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  • Response patterns in the developing social brain are organized by social and emotion features and disrupted in children diagnosed with autism spectrum disorder
    Cortex (IF 4.275) Pub Date : 2019-12-20
    Hilary Richardson; Hyowon Gweon; David Dodell-Feder; Caitlin Malloy; Hannah Pelton; Boris Keil; Nancy Kanwisher; Rebecca Saxe

    Adults and children recruit a specific network of brain regions when engaged in “Theory of Mind” (ToM) reasoning. Recently, fMRI studies of adults have used multivariate analyses to provide a deeper characterization of responses in these regions. These analyses characterize representational distinctions within the social domain, rather than comparing responses across preferred (social) and non-preferred stimuli. Here, we conducted opportunistic multivariate analyses in two previously collected datasets (Experiment 1: n = 20 5–11 year old children and n = 37 adults; Experiment 2: n = 76 neurotypical and n = 29 5–12 year old children diagnosed with Autism Spectrum Disorder (ASD)) in order to characterize the structure of representations in the developing social brain, and in order to discover if this structure is disrupted in ASD. Children listened to stories that described characters' mental states (Mental), non-mentalistic social information (Social), and causal events in the environment (Physical), while undergoing fMRI. We measured the extent to which neural responses in ToM brain regions were organized according to two ToM-relevant models: 1) a condition model, which reflected the experimenter-generated condition labels, and 2) a data-driven emotion model, which organized stimuli according to their emotion content. We additionally constructed two control models based on linguistic and narrative features of the stories. In both experiments, the two ToM-relevant models outperformed the control models. The fit of the condition model increased with age in neurotypical children. Moreover, the fit of the condition model to neural response patterns was reduced in the RTPJ in children diagnosed with ASD. These results provide a first glimpse into the conceptual structure of information in ToM brain regions in childhood, and suggest that there are real, stable features that predict responses in these regions in children. Multivariate analyses are a promising approach for sensitively measuring conceptual and neural developmental change and individual differences in ToM.

  • People represent mental states in terms of rationality, social impact, and valence: Validating the 3d Mind Model
    Cortex (IF 4.275) Pub Date : 2020-01-03
    Mark A. Thornton; Diana I. Tamir

    Humans can experience a wide variety of different thoughts and feelings in the course of everyday life. To successfully navigate the social world, people need to perceive, understand, and predict others' mental states. Previous research suggests that people use three dimensions to represent mental states: rationality, social impact, and valence. This 3d Mind Model allows people to efficiently “see” the state of another person's mind by considering whether that state is rational or emotional, more or less socially impactful, and positive or negative. In the current investigation, we validate this model using neural, behavioral, and linguistic evidence. First, we examine the robustness of the 3d Mind Model by conducting a mega-analysis of four fMRI studies in which participants considered others' mental states. We find evidence that rationality, social impact, and valence each contribute to explaining the neural representation of mental states. Second, we test whether the 3d Mind Model offers the optimal combination of dimensions for describing neural representations of mental state. Results reveal that the 3d Mind Model achieve the best performance among a large set of candidate dimensions. Indeed, it offers a highly explanatory account of mental state representation, explaining over 80% of reliable neural variance. Finally, we demonstrate that all three dimensions of the model likewise capture convergent behavioral and linguistic measures of mental state representation. Together, these findings provide strong support for the 3d Mind Model, indicating that is it is a robust and generalizable account of how people think about mental states.

  • Task-dependent changes in functional connectivity during the observation of social and non-social touch interaction
    Cortex (IF 4.275) Pub Date : 2020-01-03
    Haemy Lee Masson; Ineke Pillet; Bart Boets; Hans Op de Beeck

    Previous studies have identified a collection of brain areas that show neural selectivity for the distinction between human-to-human and human-to-object interactions, including regions implicated in sensory and social processing. It remains largely unknown, however, how the functional communication between these areas changes with the type of interaction. Combining a generalized psychophysiological interaction (gPPI) analysis and independent component analysis (ICA), the current study sought to identify the context-sensitive modulation of the functional network architecture during touch observation. Thirty-seven participants watched 75 video clips displaying social and non-social touch events during a functional imaging scan. A gPPI analysis of pre-defined regions of interest revealed that social-cognitive brain regions show enhanced interregional coupling during social touch observation, both among social-cognitive brain regions and between social-cognitive regions and sensory regions. Conversely, during non-social touch observation, a significantly stronger coupling among brain areas within the system that processes the unimodal sensory information was observed. At the level of large-scale brain networks extracted with ICA, stronger connectivity between 11 pairs of networks, including default mode networks, was observed during social touch observation, while only three pairs of networks showed stronger connectivity during non-social touch observation. The current study identifies the presence of context-dependent changes in functional brain architecture based on whether the touch recipient is a person or an object, highlighting an increased exchange of neural information for social processing.

  • Adults with high functioning autism display idiosyncratic behavioral patterns, neural representations and connectivity of the ‘Voice Area’ while judging the appropriateness of emotional vocal reactions
    Cortex (IF 4.275) Pub Date : 2019-12-05
    Felipe Pegado; Michelle H.A. Hendriks; Steffie Amelynck; Nicky Daniels; Jean Steyaert; Bart Boets; Hans Op de Beeck

    Understanding others in everyday situations requires multiple types of information processing (visual, auditory, higher order…) which implicates the use of multiple neural circuits of the human brain. Here, using a multisensory paradigm we investigate one aspect of social understanding less explored in the literature: instead of focusing on the capacity to infer what a specific person is thinking, we explore here how people with high functioning autism (HFA) and matched controls with typical development (TD) infer the “population thinking”. For this we created an audio-visual ‘social norm inference’ task. Participants were required to imagine how most people would judge the appropriateness of vocal utterances in relation to different emotional visual contexts. Behavioral findings demonstrated that HFA individuals show more interindividual variability in these judgments despite equal within-participant reliability relative to TD. This was also the case for judgements of the valence of these vocalizations when presented in isolation. At the neural level, multivoxel pattern analysis of functional magnetic resonance imaging data revealed strikingly similar neural representations between HFA and TD participants at the group level across different hierarchical levels and neural systems. However, analyses at the individual-participant level revealed that the “Temporal Voice Area” (TVA) shows more interindividual variability in the HFA group, both for neural representations and functional connectivity. Thus, this larger neural idiosyncrasy in a high-level auditory area matches with the larger behavioral idiosyncrasy in HFA individuals, when judging auditory valence and its adequacy in different social scenarios. These results suggest that idiosyncrasy in task-relevant sensory areas in HFA participants could underlie their greater difficulties to estimate how others can think.

  • Neural correlates and role of medication in reactive motor impulsivity in Tourette disorder
    Cortex (IF 4.275) Pub Date : 2019-12-30
    Cyril Atkinson-Clement; Camille-Albane Porte; Astrid de Liege; Nicolas Wattiez; Yanica Klein; Benoit Beranger; Romain Valabregue; Fuaad Sofia; Andreas Hartmann; Pierre Pouget; Yulia Worbe

    Abnormality of inhibitory control is considered to be a potential cognitive marker of tics in Tourette disorder (TD), attention deficit hyperactivity disorder (ADHD), and impulse control disorders. The results of the studies on inhibitory control in TD showed discrepant results. The aim of the present study was to assess reactive inhibitory control in adult TD patients with and without antipsychotic medication, and under emotional stimulation (visual images with positive, neutral and negative content). We assessed 31 unmedicated and 19 medicated TD patients and 26 matched healthy controls using the stop signal task as an index of reactive motor impulsivity and emotional stimulation with the aim to increase impulsivity. We performed a multimodal neuroimaging analysis using a regions of interest approach on grey matter signal, resting-state spontaneous brain activity and functional connectivity analyses. We found a higher reactive motor impulsivity in TD patients medicated with antipsychotics compared to unmedicated TD patients and controls. This propensity for reactive motor impulsivity in medicated TD patients was not influenced by ADHD or emotional stimulation. Neuroimaging results in medicated TD patients suggested that reactive motor impulsivity was underpinned by an increased grey matter signal from the right supplementary motor area and inferior frontal gyrus; decreased resting-state spontaneous activity of the left putamen; higher functional connectivity between the inferior frontal gyrus and the superior temporal gyri (bilaterally); lower functional connectivity between the cerebellum and the right subthalamic nucleus. Taken together, our data suggested (i) a deficit in reactive motor impulsivity in TD patients medicated with atypical antipsychotics that was unrelated to ADHD and (ii) that motor impulsivity was underpinned by structures and by functional connectivity of the fronto-temporo-basal ganglia-cerebellar pathway.

  • Decreased Transfer of Value to Action in Tourette Syndrome
    Cortex (IF 4.275) Pub Date : 2020-01-24
    Thomas Schüller; Adrian G. Fischer; Theo O.J. Gruendler; Juan Carlos Baldermann; Daniel Huys; Markus Ullsperger; Jens Kuhn

    Objective Tourette syndrome is a neurodevelopmental disorder putatively associated with a hyperdopaminergic state. Therefore, it seems plausible that excessive dopamine transmission in Tourette syndrome alters the ability to learn based on rewards and punishments. We tested whether Tourette syndrome patients exhibited altered reinforcement learning and corresponding feedback-related EEG deflections. Methods We used a reinforcement learning task providing factual and counterfactual feedback in a sample of 15 Tourette syndrome patients and matched healthy controls whilst recording EEG. The paradigm presented various reward probabilities to enforce adaptive adjustments. We employed a computational model to derive estimates of the prediction error, which we used for single-trial regression analysis of the EEG data. Results We found that Tourette syndrome patients showed increased choice stochasticity compared to controls. The feedback-related negativity represented an axiomatic prediction error for factual feedback, yet did not differ between groups. We observed attenuated P3a modulation specifically for factual feedback in Tourette syndrome patients, representing impaired coding of attention allocation. Conclusion Our findings indicate that cortical prediction error coding is unaffected by Tourette syndrome. Nonetheless, the transfer of learned values into choice formation is degraded, in line with increased tonic dopamine in Tourette syndrome.

  • The role of the insula in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome
    Cortex (IF 4.275) Pub Date : 2020-01-22
    Stephen R. Jackson; Joanna Loayza; Mira Crighton; Hilmar P. Sigurdsson; Katherine Dyke; Georgina M. Jackson

    Tourette syndrome (TS) is a neurological disorder of childhood onset that is characterised by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction and hyper-excitability of cortical limbic and motor regions that are thought to lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by ‘premonitory sensory/urge phenomena’ (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as a strong urge for motor discharge. While the precise role played by PU in the occurrence of tics is largely unknown, they are nonetheless of considerable theoretical and clinical importance, not least because they form the core component in many behavioural therapies used in the treatment of tic disorders. Several lines of evidence indicate that the insular cortex may play a particularly important role in the generation of PU in TS and ‘urges-for-action’ more generally. In the current study we utilised voxel-based morphometry techniques together with ‘seed-to-voxel’ structural covariance network (SCN) mapping to investigate the putative role played by the right insular cortex in the generation of motor tics and the experience of PU in a relatively large group of young people TS. We demonstrate that clinical measures of motor tic severity and PU are uncorrelated with one another, that motor tic severity and PU scores are associated with separate regions of the insular cortex, and that the insula is associated with different structural covariance networks in individuals with TS compared to a matched group of typically developing individuals.

  • Alterations in cerebellar grey matter structure and covariance networks in young people with Tourette syndrome
    Cortex (IF 4.275) Pub Date : 2020-01-22
    Hilmar P. Sigurdsson; Stephen R. Jackson; Laura Jolley; Ellie Mitchell; Georgina M. Jackson

    Tourette syndrome (TS) is a childhood-onset neurological disorder characterised by the occurrence of motor and vocal tics and the presence of premonitory sensory/urge phenomena. Functional neuroimaging studies in humans, and experimental investigations in animals, have shown that the genesis of tics in TS involve a complex interaction between cortical-striatal-thalamic-cortical brain circuits and additionally appears to involve the cerebellum. Furthermore, structural brain imaging studies have demonstrated alterations in grey matter (GM) volume in TS across a wide range of brain areas, including alterations in GM volume within the cerebellum. Until now, no study to our knowledge has yet investigated how GM structural covariance networks linked to the cerebellum may be altered in individuals with TS. In this study we employed voxel-based morphometry, and a ‘seed-to-voxel’ structural covariance network (SCN) mapping approach, to investigate alterations in GM cerebellar volume in people with TS, and alterations in cerebellar SCNs associated with TS. Data from 64 young participants was entered in the final analysis, of which 28 had TS while 36 were age-and sex-matched healthy volunteers. Using the spatially unbiased atlas template of the cerebellum and brainstem (SUIT) atlas, we found reduced GM volume in cerebellar lobule involved in higher-order cognitive functions and sensorimotor processing, in patients. In addition, we found that several areas located in frontal and cingulate cortices and sensorimotor network in addition to subcortical areas show altered structural covariance with our cerebellar seed compared to age-matched controls. These results add to the increasing evidence that cortico-basal ganglia-cerebellar interactions play an important role in tic symptomology.

  • Atypical lateralization in neurodevelopmental and psychiatric disorders: What is the role of stress?
    Cortex (IF 4.275) Pub Date : 2020-01-16
    Gesa Berretz; Oliver T. Wolf; Onur Güntürkün; Sebastian Ocklenburg

    Hemispheric asymmetries are a major organizational principle of the human brain. In different neurodevelopmental and psychiatric disorders, like schizophrenia, autism spectrum disorders, depression, dyslexia and posttraumatic stress disorder, functional and/or structural hemispheric asymmetries are altered compared to healthy controls. The question, why these disorders all share the common characteristic of altered hemispheric asymmetries despite vastly different etiologies and symptoms remains one of the unsolved mysteries of laterality research. This review is aimed at reviewing potential reasons for why atypical lateralization is so common in many neurodevelopmental and psychiatric disorders. To this end, we review the evidence for overlaps in the genetic and non-genetic factors involved in the ontogenesis of different disorders and hemispheric asymmetries. While there is evidence for genetic overlap between different disorders, only few asymmetry-related loci have also been linked to disorders and importantly, those effects are mostly specific to single disorders. However, there is evidence for shared non-genetic influences between disorders and hemispheric asymmetries. Most neurodevelopmental and psychiatric disorders show alterations in the hypothalamic-pituitary adrenocortical (HPA) axis and maternal as well as early life stress have been implicated in their etiology. Stress has also been suggested to affect hemispheric asymmetries. We propose a model in which early life stress as well as chronic stress not only increases the risk for psychiatric and neurodevelopmental disorders but also changes structural and functional hemispheric asymmetries leading to the aberrant lateralization patterns seen in these disorders. Thus, pathology-related changes in hemispheric asymmetries are not a factor causing disorders, but rather a different phenotype that is affected by partly overlapping ontogenetic factors, primarily stress.

  • Conflicting group memberships modulate neural activation in an emotional production-perception network
    Cortex (IF 4.275) Pub Date : 2020-01-14
    Miriam Steines; Johannes T. Krautheim; Gizem Neziroğlu; Tilo Kircher; Benjamin Straube

    Social group membership modulates the neural processing of emotional facial expressions, which, in turn, recruits part of the neural production system. However, little is known about how mixed – and potential conflicting – social identity cues affect this mechanism. In this study, we tested the hypothesis that incongruent cues of two group memberships (ethnic and experimentally created minimal groups) elicit conflict processing for neutral and, in particular, angry facial expressions. We further expected this interaction of ethnic group, minimal group and emotion to also modulate activation in an emotional production-perception network. Twenty-two healthy German subjects saw dynamic angry and neutral facial expressions, presented in short video clips during functional MRI scanning. All depicted actors belonged to an ethnic in- or outgroup (German or Turkish descent) as well as an ad hoc experimentally created minimal in- or outgroup. Additionally, subjects produced angry or neutral expressions themselves. The whole-brain interaction of ethnic group, minimal group and emotion revealed activity in the right parietal lobule and left cerebellum. Both showed strongest activation for angry faces with conflicting group memberships (e.g., ‘ethnic outgroup/minimal ingroup’). In addition, a sub-region of the left cerebellum cluster was also activated for both perceiving and producing angry vs. neutral expressions. These results suggest that incongruent group members displaying angry facial expressions elicit conflict processing. Group interaction effects in an emotional production-perception network further indicate stronger neural resonance for incongruent group members.

  • A function for the bicameral mind
    Cortex (IF 4.275) Pub Date : 2019-12-16
    Giorgio Vallortigara; Lesley J. Rogers

    Why do the left and right sides of the brain have different functions? Having a lateralized brain, in which each hemisphere processes sensory inputs differently and carries out different functions, is common in vertebrates, and it has now been reported for invertebrates too. Experiments with several animal species have shown that having a lateralized brain can enhance the capacity to perform two tasks at the same time. Thus, the different specializations of the left and right sides of the brain seem to increase brain efficiency. Other advantages may involve control of action that, in Bilateria, may be confounded by separate and independent sensory processing and motor outputs on the left and right sides. Also, the opportunity for increased perceptual training associated with preferential use of only one sensory or motoric organ may result in a time advantage for the dominant side. Although brain efficiency of individuals can be achieved without the need for alignment of lateralization in the population, lateral biases (such as preferences in the use of a laterally-placed eye) usually occur at the population level, with most individuals showing a similar direction of bias. Why is this the case? Not only humans, but also most non-human animals, show a similar pattern of population bias (i.e., directional asymmetry). For instance, in several vertebrate species (from fish to mammals) most individuals react faster when a predator approaches from their left side, although some individuals (a minority usually ranging from 10 to 35%) escape faster from predators arriving from their right side. Invoking individual efficiency (lateralization may increase fitness), evolutionary chance or simply genetic inheritance cannot explain this widespread pattern. Using mathematical theory of games, it has been argued that the population structure of lateralization (with either antisymmetry or directional asymmetry) may result from the type of interactions asymmetric organisms face with each other.

  • Reward Presentation Reduces On-Task Fatigue in Traumatic Brain Injury
    Cortex (IF 4.275) Pub Date : 2020-01-24
    Ekaterina Dobryakova; Helen Genova; Veronica Schneider; Nancy D. Chiaravalloti; Angela Spirou; Glenn R. Wylie; John DeLuca

    While cognitive fatigue is experienced by up to 80% of individuals with traumatic brain injury (TBI), little is known about its neural underpinnings. We previously hypothesized that presentation of rewarding outcomes leads to cognitive fatigue reduction and activation of the striatum, a brain region shown to be associated with cognitive fatigue in clinical populations and processing of rewarding outcomes. We have demonstrated this in individuals with multiple sclerosis. Here, we tested this hypothesis in individuals with TBI. Twenty-one individuals with TBI and 24 healthy participants underwent functional magnetic resonance imaging. Participants performed a task during which they were presented with 1) the Outcome condition where they were exposed to monetary rewards, and 2) the No Outcome condition that served as the control condition and was not associated with monetary rewards. In accordance with our hypothesis, results showed that attainment of rewarding outcomes leads to cognitive fatigue reduction in individuals with TBI, as well as activation of the striatum. Specifically, we observed a significant group by condition interaction on fatigue scores driven by the TBI group reporting lower levels of fatigue after the Outcome condition. fMRI data revealed a significant main-effect of condition in regions previously implicated in outcome processing, while a significant group by condition interaction was observed in the left ventral striatum as revealed by a priori region of interest analysis. Results suggest that a salient motivator can significantly reduce fatigue and that outcome presentation leads to increased activation of the ventral striatum in TBI. These findings can inform the development of future non-pharmacological cognitive fatigue treatment methods and contribute to the growing body of evidence showing the association between cognitive fatigue and the striatum.

  • Rethinking causality and data complexity in brain lesion-behaviour inference and its implications for lesion-behaviour modelling
    Cortex (IF 4.275) Pub Date : 2020-01-24
    Christoph Sperber

    Modelling behavioural deficits based on structural lesion imaging is a popular approach to map functions in the human brain, and efforts to translationally apply lesion-behaviour modelling to predict post-stroke outcomes are on the rise. The high-dimensional complexity of lesion data, however, evokes challenges in both lesion behaviour mapping and post stroke outcome prediction. This paper aims to deepen the understanding of this complexity by reframing it from the perspective of causal and non-causal dependencies in the data, and by discussing what this complexity implies for different data modelling approaches. By means of theoretical discussion and empirical examination, several common strategies and views are challenged, and future research perspectives are outlined. A main conclusion is that lesion-behaviour inference is subject to a lesion-anatomical bias that cannot be overcome by using multivariate models or any other algorithm that is blind to causality behind relations in the data. This affects the validity of lesion behaviour mapping and might even wrongfully identify paradoxical effects of lesion-induced functional facilitation – but, as this paper argues, only to a minor degree. Thus, multivariate lesion-brain inference appears to be a valuable tool to deepen our understanding of the human brain, but only because it takes into account the functional relation between brain areas. The perspective of causality and inter-variable dependence is further used to point out challenges in improving lesion behaviour models. Firstly, the dependencies in the data open up different possible strategies of data reduction, and considering those might improve post-stroke outcome prediction. Secondly, the role of non-topographical causal predictors of post stroke behaviour is discussed. The present article argues that, given these predictors, different strategies are required in the evaluation of model quality in lesion behaviour mapping and post stroke outcome prediction.

  • Anterior temporal lobe is necessary for efficient lateralised processing of spoken word identity
    Cortex (IF 4.275) Pub Date : 2020-01-24
    Thomas E. Cope; Yury Shtyrov; Lucy J. MacGregor; Rachel Holland; Friedemann Pulvermüller; James B. Rowe; Karalyn Patterson

    In the healthy human brain, the processing of language is strongly lateralised, usually to the left hemisphere, while the processing of complex non-linguistic sounds recruits brain regions bilaterally. Here we asked whether the anterior temporal lobes, strongly implicated in semantic processing, are critical to this special treatment of spoken words. Nine patients with semantic dementia (SD) and fourteen age-matched controls underwent magnetoencephalography and structural MRI. Voxel based morphometry demonstrated the stereotypical pattern of SD: severe grey matter loss restricted to the anterior temporal lobes, with the left side more affected. During magnetoencephalography, participants listened to word sets in which identity and meaning were ambiguous until word completion, for example played vs plate. Whereas left-hemispheric responses were similar across groups, patients demonstrated increased right hemisphere activity 174-294ms after stimulus disambiguation. Source reconstructions confirmed recruitment of right-sided analogues of language regions in SD: atrophy of anterior temporal lobes was associated with increased activity in right temporal pole, middle temporal gyrus, inferior frontal gyrus and supramarginal gyrus. Overall, the results indicate that anterior temporal lobes are necessary for normal and efficient lateralised processing of word identity by the language network.

  • Understanding the neural basis of episodic amnesia in logopenic progressive aphasia: a multimodal neuroimaging study
    Cortex (IF 4.275) Pub Date : 2020-01-22
    Siddharth Ramanan; Lars Marstaller; John R. Hodges; Olivier Piguet; Muireann Irish

    Logopenic progressive aphasia (LPA) is a neurodegenerative disorder characterised by profound naming and sentence repetition disturbances, attributable to disproportionately left-sided temporo-parietal atrophy. Accumulating evidence suggests, in addition to language impairments, the presence of stark verbal and nonverbal episodic memory impairments in LPA. The neurocognitive bases of such impairments, however, remain to be clarified. Here, we characterised episodic memory disruption and its corresponding grey and white matter correlates in the LPA syndrome. Nineteen LPA patients were contrasted with 23 matched typical Alzheimer’s disease (AD) patients and 31 healthy Controls on standardized verbal and nonverbal episodic delayed recall measures. Participants further underwent structural magnetic resonance and diffusion-weighted imaging. Significant verbal memory deficits were evident in both patient groups, with LPA patients performing at an intermediate level to AD and Controls. For nonverbal memory, however, LPA performance was indistinguishable from that of AD, with both groups displaying marked impairments relative to Controls. Whole-brain voxel-based morphometry analyses revealed significant left temporo-parietal and left hippocampal atrophy in the LPA group. Covariate analyses showed that verbal and nonverbal amnesia in LPA correlated with grey matter integrity of bilateral frontoparietal and left medial temporal lobe regions. Notably, the common regions underpinning verbal and nonverbal memory dysfunction in LPA were the left orbitofrontal cortex and bilateral angular gyri in the inferior parietal cortex. The bilateral angular gyri, along with prefrontal and hippocampal regions further emerged as disease-general correlates of verbal and nonverbal memory performance. Alterations in mean diffusivity in structural connections between the left angular gyrus and medial temporal lobes were further associated with verbal memory performance in all participants. Our findings reveal, for the first time, the presence of pervasive memory impairments in LPA mediated by degeneration of a distributed prefrontal-hippocampal-parietal network, and disrupted parieto-hippocampal structural connectivity.

  • Synaesthesia is linked to a Distinctive and Heritable Cognitive Profile
    Cortex (IF 4.275) Pub Date : 2020-01-22
    Jamie Ward; Gözde Filiz

    This study argues that there exists, in the general population, a distinctive profile of cognitive traits that predisposes people to develop synaesthesia (termed a ‘synaesthetic disposition’). This consists of more vivid mental imagery, better episodic memory, and greater attention-to-detail (amongst others things). Using a machine-learning classifier, we show that it is possible to distinguish synaesthetes from others using only standard cognitive and personality measures. Importantly, people with multiple forms of synaesthesia have a more distinctive profile (i.e. they can be more accurately classified). This suggests that whilst the presence/absence of synaesthesia is dichotomous, the underlying causal mechanisms are continuous. Moreover, we provide evidence that the cognitive profile constitutes a heritable endophenotype. Non-synaesthetic relatives of synaesthetes are cognitively similar to synaesthetes. This provides new insights into why synaesthesia might have evolved (i.e. it is possible to have the cognitive benefits of synaesthesia in the absence of the anomalous experiences). The notion of a synaesthetic disposition represents a novel, quantifiable individual difference in cognition/personality. This paves the way for determining if this is linked to a distinctive pattern of clinical vulnerabilities.

  • Testing the exteroceptive function of nociception: the role of visual experience in shaping the spatial representations of nociceptive inputs
    Cortex (IF 4.275) Pub Date : 2020-01-22
    Camille Vanderclausen; Marion Bourgois; Anne De Volder; Valéry Legrain

    Adequately localizing pain is crucial to protect the body against physical damage and react to the stimulus in external space having caused such damage. Accordingly, it is hypothesized that nociceptive inputs are remapped from a somatotopic reference frame, representing the skin surface, towards a spatiotopic frame, representing the body parts in external space. This ability is thought to be developed and shaped by early visual experience. To test this hypothesis, normally sighted and early blind participants performed temporal order judgment tasks during which they judged which of two nociceptive stimuli applied on each hand’s dorsum was perceived as first delivered. Crucially, tasks were performed with the hands either in an uncrossed posture or crossed over body midline. While early blinds were not affected by the posture, performances of the normally sighted participants decreased in the crossed condition relative to the uncrossed condition. This indicates that nociceptive stimuli were automatically remapped into a spatiotopic representation that interfered with somatotopy in normally sighted individuals, whereas early blinds seemed to mostly rely on a somatotopic representation to localize nociceptive inputs. Accordingly, the plasticity of the nociceptive system would not purely depend on bodily experiences but also on crossmodal interactions between nociception and vision during early sensory experience.

  • Mind-wandering in Parkinson’s disease hallucinations reflects primary visual and default network coupling
    Cortex (IF 4.275) Pub Date : 2020-01-22
    Ishan C. Walpola; Alana J. Muller; Julie M. Hall; Jessica R. Andrews-Hanna; Muireann Irish; Simon J.G. Lewis; James M. Shine; Claire O’Callaghan

    Visual hallucinations are an underappreciated symptom affecting the majority of patients during the natural history of Parkinson’s disease. Little is known about other forms of abstract and internally generated cognition – such as mind-wandering – in this population, but emerging evidence suggests that an interplay between the brain’s primary visual and default networks might play a crucial role in both internally generated imagery and hallucinations. Here, we explored the association between mind-wandering and visual hallucinations in Parkinson’s disease, and their relationship with brain network coupling. We administered a validated thought-sampling task to 38 Parkinson’s disease patients (18 with hallucinations; 20 without) and 40 controls, to test the hypothesis that individuals with hallucinations experience an increased frequency of mind-wandering. Group differences in the association between mind-wandering frequency and brain network coupling were also examined using resting state functional magnetic resonance imaging. Our results showed that patients with hallucinations exhibited significantly higher mind-wandering frequencies compared to non-hallucinators, who in turn had reduced levels of mind-wandering relative to controls. At the level of brain networks, inter-network connectivity and seed-to-voxel analyses identified that increased mind-wandering in the hallucinating vs. non-hallucinating group was associated with greater coupling between the primary visual cortex and dorsal default network. Taken together, our results suggest a relative preservation of mind-wandering in Parkinson’s disease patients who experience visual hallucinations, which is associated with increased visual cortex-default network coupling. We propose that the preservation of florid abstract and internally generated cognition in the context of the Parkinson’s disease can contribute to visual hallucinations, whereas healthy individuals experience only the vivid images of the mind’s eye. These findings refine current models of visual hallucinations by identifying a specific cognitive phenomenon and neural substrate consistent with the top-down influences over perception that have been implicated in hallucinations across neuropsychiatric disorders.

  • Executive function in children with Tourette syndrome and attention-deficit/hyperactivity disorder: Cross-disorder or unique impairments?
    Cortex (IF 4.275) Pub Date : 2019-12-03
    Thaïra J.C. Openneer; Natalie J. Forde; Sophie E.A. Akkermans; Jilly Naaijen; Jan K. Buitelaar; Pieter J. Hoekstra; Andrea Dietrich

    Findings of executive functioning deficits in Tourette syndrome (TS) have so far been inconsistent, possibly due to methodological challenges of previous studies, such as the use of small sample sizes and not accounting for comorbid attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or medication use. We aimed to address these issues by examining several areas of executive functioning (response inhibition, attentional flexibility, cognitive control, and working memory) and psychomotor speed in 174 8-to-12-year-old children with TS [n = 34 without (TS−ADHD) and n = 26 with comorbid ADHD (TS+ADHD)], ADHD without tics (ADHD−TS; n = 54), and healthy controls (n = 60). We compared executive functioning measures and psychomotor speed between these groups and related these to ADHD severity across the whole sample, and tic severity across the TS groups. Children with TS+ADHD, but not TS−ADHD, made more errors on the cognitive control task than healthy children, while TS−ADHD had a slower psychomotor speed compared to healthy controls. The ADHD group showed impairment in cognitive control and working memory versus healthy controls. Moreover, higher ADHD severity was associated with poorer cognitive control and working memory across all groups; there was no relation between any of the executive functioning measures and tic severity. OCD severity or medication use did not influence our results. In conclusion, we found little evidence for executive function impairments inherent to TS. Executive function problems appear to manifest predominantly in relation to ADHD symptomatology, with both cross-disorder and unique features of neuropsychological functioning when cross-comparing TS and ADHD.

  • Genetic effects on planum temporale asymmetry and their limited relevance to neurodevelopmental disorders, intelligence or educational attainment
    Cortex (IF 4.275) Pub Date : 2019-11-29
    Amaia Carrion-Castillo; Antonietta Pepe; Xiang-Zhen Kong; Simon E. Fisher; Bernard Mazoyer; Nathalie Tzourio-Mazoyer; Fabrice Crivello; Clyde Francks

    Previous studies have suggested that altered asymmetry of the planum temporale (PT) is associated with neurodevelopmental disorders, including dyslexia, schizophrenia, and autism. Shared genetic factors have been suggested to link PT asymmetry to these disorders. In a dataset of unrelated subjects from the general population (UK Biobank, N = 18,057), we found that PT volume asymmetry had a significant heritability of roughly 14%. In genome-wide association analysis, two loci were significantly associated with PT asymmetry, including a coding polymorphism within the gene ITIH5 that is predicted to affect the protein's function and to be deleterious (rs41298373, p = 2.01 × 10–15), and a locus that affects the expression of the genes BOK and DTYMK (rs7420166, p = 7.54 × 10-10). DTYMK showed left-right asymmetry of mRNA expression in post mortem PT tissue. Cortex-wide mapping of these SNP effects revealed influences on asymmetry that went somewhat beyond the PT. Using publicly available genome-wide association statistics from large-scale studies, we saw no significant genetic correlations of PT asymmetry with autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, educational attainment or intelligence. Of the top two individual loci associated with PT asymmetry, rs41298373 showed a tentative association with intelligence (unadjusted p = .025), while the locus at BOK/DTYMK showed tentative association with educational attainment (unadjusted Ps < .05). These findings provide novel insights into the genetic contributions to human brain asymmetry, but do not support a substantial polygenic association of PT asymmetry with cognitive variation and mental disorders, as far as can be discerned with current sample sizes.

  • Children with primary complex motor stereotypies show impaired reactive but not proactive inhibition
    Cortex (IF 4.275) Pub Date : 2019-12-20
    Giovanni Mirabella; Christian Mancini; Francesca Valente; Francesco Cardona

    Typically, the inability to control urges tends to be ascribed to a lack of inhibitory control. Primary complex motor stereotypes (p-CMS), occurring in children with an otherwise typical development, represent a remarkable example of involuntary, complex, repetitive and apparently purposeless movements. However, it has never been tested whether the core of the pathophysiology of p-CMS lies in a deficit of inhibitory control. To fill this gap, we assessed whether children with p-CMS exhibit an impairment of one or both types of inhibition, i.e., reactive inhibition (the ability of subjects to react to a stop-signal) and/or proactive inhibition (the ability of subjects to shape their response strategies according to the context in which subjects are embedded). We compared inhibitory control of 20 drug-naïve patients with p-CMS (mean age ±SD: 7.4 ± 1.1) with that of 20 age- and gender-matched typically developing children (7.5 ± 1.2) via a reaching version of the stop-signal task. We found that while reactive inhibition is significantly impaired, proactive control in children with p-CMS is similar to that of the control group. The deficit in reactive control might explain why patients are unable to inhibit involuntary movements when triggered by states of mind such as stress, fatigue, boredom or excitement. Nevertheless, the absence of a deficit in proactive control suggests that patients are aware of the environmental context and thus they quickly stop the stereotypic movements when their attention is diverted. All in all, our findings might explain two key features of the p-CMS phenotype.

  • The effects of interaction quality on neural synchrony during mother-child problem solving
    Cortex (IF 4.275) Pub Date : 2019-12-20
    Trinh Nguyen; Hanna Schleihauf; Ezgi Kayhan; Daniel Matthes; Pascal Vrtička; Stefanie Hoehl

    Understanding others is fundamental to interpersonal coordination and successful cooperation. One mechanism posited to underlie both effective communication and behavioral coordination is interpersonal neural synchrony. Although presumably foundational for children's social development, research on neural synchrony in naturalistic caregiver-child interactions is lacking. Using dual-functional near-infrared spectroscopy (fNIRS), we examined the effects of interaction quality on neural synchrony during a problem-solving task in 42 dyads of mothers and their preschool children. In a cooperation condition, mothers and children were instructed to solve a tangram puzzle together. In an individual condition, mothers and children performed the same task alone with an opaque screen between them. Wavelet transform coherence (WTC) was used to assess the cross-correlation between the two fNIRS time series. Results revealed increased neural synchrony in bilateral prefrontal cortex and temporo-parietal areas during cooperative as compared to individual problem solving. Higher neural synchrony during cooperation correlated with higher behavioral reciprocity and neural synchrony predicted the dyad's problem-solving success beyond reciprocal behavior between mothers and children. State-like factors, such as maternal stress and child agency during the task, played a bigger role for neural synchronization than trait-like factors, such as child temperament. Our results emphasize neural synchrony as a biomarker for mother-child interaction quality. These findings further highlight the role of state-like factors in interpersonal synchronization processes linked to successful coordination with others and in the long-term might improve the understanding of others.

  • Task-Merging for Finer Separation of Functional Brain Networks in Working Memory
    Cortex (IF 4.275) Pub Date : 2020-01-14
    Nicole Sanford; Jennifer C. Whitman; Todd S. Woodward

    Background In task-state functional magnetic resonance imaging (fMRI), hemodynamic response (HDR) shapes help identify cognitive process(es) supported by a brain network. However, when distinguishable networks have similar time courses, the low temporal resolution of the HDRs may result in spatial and temporal blurring of these networks. The present study demonstrated how task-merging and multivariate analysis allows data-driven separation of working memory (WM) processes. This was achieved by combining a WM task with the Thought Generation Task (TGT), a task which also requires attention to internal representations but no overt behavioral response. Methods 69 adults completed one of two tasks: (1) a Sternberg WM task, whereby participants had to remember a string of letters over a 4-second delay or no delay, and (2) the TGT task, whereby participants internally generated or listened to a function of an object. WM data were analyzed in isolation and then with the TGT data, using multi-experiment constrained principal component analysis for fMRI (fMRI-CPCA). The function of each network was interpreted by evaluating HDR shapes across conditions (within and between tasks). Results The multi-experiment analysis produced three WM networks involving frontoparietal connectivity; two of these were combined when the WM task was analyzed alone. Notably, one network exhibited HDRs consistent with volitional attention to internal representations in both tasks (i.e., strongest in WM trials with a maintenance phase and in TGT trials involving silent thought). This network was separated from visual attention and motor response networks in the multi-experiment analysis only. Conclusions Task-merging and multivariate analysis allowed us to differentiate WM networks possibly underlying internal attention (maintenance), visual attention (encoding), and response processes. Further, it allowed postulation of the cognitive operations subserved by each network by providing HDR shapes. This approach facilitates characterization of network functions by allowing direct comparisons of activity across different cognitive domains.

  • Spatial updating of allocentric landmark information in real-time and memory-guided reaching
    Cortex (IF 4.275) Pub Date : 2020-01-07
    Zijian Lu; Katja Fiehler

    The 2-streams model of vision suggests that egocentric and allocentric reference frames are utilized by the dorsal and the ventral stream for real-time and memory-guided movements, respectively. Recent studies argue against such a strict functional distinction and suggest that real-time and memory-guided movements recruit the same spatial maps. In this study we focus on allocentric spatial coding and updating of targets by using landmark information in real-time and memory-guided reaching. We presented participants with a naturalistic scene which consisted of six objects on a table that served as potential reach targets. Participants were informed about the target object after scene encoding, and were prompted by a go cue to reach to its position. After target identification a brief air-puff was applied to the participant’s right eye inducing an eye blink. During the blink the target object disappeared from the scene, and in half of the trials the remaining objects, that functioned as landmarks, were shifted horizontally in the same direction. We found that landmark shifts systematically influenced participants’ reaching endpoints irrespective of whether the movements were controlled online based on available target information (real-time movement) or memory-guided based on remembered target information (memory-guided movement). Overall, the effect of landmark shift was stronger for memory-guided than real-time reaching. Our findings suggest that humans can encode and update reach targets in an allocentric reference frame for both real-time and memory-guided movements and show stronger allocentric coding when the movement is based on memory.

  • Ever-ready for action: Spatial effects on motor system excitability
    Cortex (IF 4.275) Pub Date : 2020-01-03
    Matthieu M. de Wit; Olufunsho Faseyitan; H. Branch Coslett

    Modulation of excitability in the motor system can be observed before overt movements but also in response to covert invitations to act. We asked whether such changes can be induced in the absence of even covert motor instructions, namely, as a function of the location of the hand with reference to the body. Participants received single-pulse TMS over the motor cortex while they placed their contralateral hand (right hand in Experiment 1, left hand in Experiment 2) to the right or left of their body midline, and looked either at or away from their hand. In both experiments, greater excitability was observed when gaze was directed to the right. This finding is interpreted as a consequence of left brain lateralization of motor attention. Contrary to our expectations, we furthermore consistently observed greater excitability when gaze was directed away from the hand. To account for this finding, we introduce the concept of “surveillance attention” which, we speculate, modulates cortical gain, and thereby cortical excitability. Its function is to increase readiness to act in non-foveated regions of space. Such a process confers an advantage in environments, like those in which humans evolved, in which threatening stimuli may appear unexpectedly, and at any time.

  • Raised visual contrast thresholds with intact attention and metacognition in functional motor disorder
    Cortex (IF 4.275) Pub Date : 2020-01-03
    Julian Matthews; Kanae Nagao; Catherine Ding; Rachel Newby; Peter Kempster; Jakob Hohwy

    Functional motor disorders (FMDs) are distinguished by signs that lack congruence with recognised patterns of organic disease and show inconsistency over time. Their pathophysiology is poorly understood, but there is evidence that irregularities in perceptual and cognitive processing lie at the heart of these conditions. Here, we draw on a predictive coding account of functional neurological disorders to study perceptual decision-making in three groups: 20 patients with FMDs (14 with functional movements and 6 with functional weakness), 20 with phenotypically-matched organic motor disorders, and 20 age-matched healthy controls. We examine four cognitive domains with putative roles in FMD pathogenesis: attention, expectations, sensory processing (perceptual sensitivity), and metacognition (introspective evaluation of performance). We augmented a dual-task paradigm, manipulating the visual contrast required for target detection to examine these domains in one design. With sensory input (stimulus contrast) psychometrically adjusted to staircase target detection at a fixed level for all groups, the FMD group exhibited statistically equivalent attentional, expectational and metacognitive processing to healthy controls. However, we demonstrate Bayesian evidence and a frequentist trend that FMD patients require higher visual contrast than controls to maintain the same detection sensitivity (BF10=8.1, pholm=.066). This was statistically equivalent to the visual contrast required by the organic group, and unlikely to be accounted for by medication use or comorbid psychopathology. The organic group showed differences in processing of attention and expectations for target detection that were not observed in either healthy controls or the functional group. The distinctive behavioural profile of FMDs may arise from abnormalities in basic sensory processing, while higher attentional, expectational and metacognitive mechanisms remain intact. Conceptualising functional neurological disorders under a predictive coding account may consolidate and refine existing pathophysiological theories about them.

  • Mechanisms of smooth pursuit eye movements in schizotypy
    Cortex (IF 4.275) Pub Date : 2020-01-03
    Eliana Faiola; Inga Meyhöfer; Ulrich Ettinger

    Several studies suggest that highly schizotypal individuals display a deficit in smooth pursuit eye movements (SPEM), which are considered an important biomarker of schizophrenia. In schizophrenia, abnormal SPEM is thought to be driven by impairments in motion perception. In schizotypy, the processes underlying reduced SPEM performance have not been examined so far, and there are no studies on motion perception deficits in schizotypy. Thus, in this registered report, we aimed to investigate whether motion perception is impaired in highly schizotypal individuals, and how it contributes to SPEM performance. On an exploratory basis, we were interested in the association between schizotypy and prediction, another mechanism underlying SPEM. To address this issue, participants with high total scores of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE short form) and control participants with low scores (N = 86 in each group) performed a standard sinusoidal SPEM task, random dot kinematograms to measure motion perception, and a blanking SPEM task to assess prediction abilities. Group comparisons as well as mediator analyses were carried out to identify whether motion perception or prediction are responsible for SPEM performance in schizotypy. We found reduced blanking SPEM performance in schizotypes compared to controls, but no group differences regarding sinusoidal SPEM and motion perception. Although no significant mediators were identified for SPEM performance in schizotypes, an exploratory analysis revealed an association between motion perception and SPEM gain in high, but not in low schizotypy. Our findings imply that despite the schizotypy-related impairment in prediction, motion perception seems to be a more important predictor of SPEM performance in schizotypes. A deficit in prediction that does not relate to SPEM performance suggests that protective factors (e.g., other cognitive processes) might operate in schizotypal individuals to maintain SPEM performance on a healthy level.

  • Short- and Long-term Forms of Neural Adaptation: An ERP Investigation of Dynamic Motion Aftereffects
    Cortex (IF 4.275) Pub Date : 2020-01-02
    Sibel Akyuz; Andrea Pavan; Utku Kaya; Hulusi Kafaligonul

    Adaptation is essential to interact with a dynamic and changing environment, and can be observed on different timescales. Previous studies on a motion paradigm called dynamic motion aftereffect (dMAE) showed that neural adaptation can establish even in very short timescales. However, the neural mechanisms underlying such rapid form of neural plasticity is still debated. In the present study, short- and long-term forms of neural plasticity were investigated using dynamic motion aftereffect combined with EEG (Electroencephalogram). Participants were adapted to directional drifting gratings for either short (640 ms) or long (6.4 s) durations. Both adaptation durations led to motion aftereffects on the perceived direction of a dynamic and directionally ambiguous test pattern, but the long adaptation produced stronger dMAE. In line with behavioral results, we found robust changes in the event-related potentials elicited by the dynamic test pattern within 64-112 ms time range. These changes were mainly clustered over occipital and parieto-occipital scalp sites. Within this time range, the aftereffects induced by long adaptation were stronger than those by short adaptation. Moreover, the aftereffects by each adaptation duration were in the opposite direction. Overall, these EEG findings suggest that dMAEs reflect changes in cortical areas mediating low- and mid-level visual motion processing. They further provide evidence that short- and long-term forms of motion adaptation lead to distinct changes in neural activity, and hence support the view that adaptation is an active time-dependent process which involves different neural mechanisms.

  • Alterations to dual stream connectivity predicts response to aphasia therapy following stroke
    Cortex (IF 4.275) Pub Date : 2019-12-30
    Kartik K. Iyer; Anthony J. Angwin; Sophie Van Hees; Katie L. McMahon; Michael Breakspear; David A. Copland

    Background Predicting aphasia recovery is difficult due to a high variability in treatment response. Detailed measures of treatment response are compounded by a dearth of information that examine brain connections that contribute to clinical improvement. In this study we measure alterations to cortical connectivity pathways during a therapy paradigm to detect whether key brain connections that contribute to language recovery can be detected prior to therapy. Methods We conducted a case-control trial with twenty-three adults including eight adults with chronic, post-stroke aphasia. Aphasia patients underwent 12 naming therapy sessions over 4 weeks, consisting of semantic and phonological treatment approaches. High-density electroencephalography (128 channel EEG) was measured prior to therapy and immediately following treatment in patients with aphasia. Analysis via a dynamic causal modelling (DCM) was used to assess which cortical connections significantly correlated with therapy response. Results Altered cortical responses in aphasia patients measured bilaterally in a dual stream DCM connectivity model were predictive of treatment-induced improvement in naming. Pre-treatment DCM coupling (i.e. strength of cortical connections) significant correlated with naming improvement for items treated with semantic therapy, as indicated by increased connection strengths between left inferior parietal lobule (LIPL) and inferior frontal gyrus (LIFG, r = 0.63, pFDR=0.016). In particular, the mediating role of contralateral regions significantly influences overall treatment improvement in the latter stages of stroke recovery. Conclusions Our findings identify a potential means to stratify larger cohorts of patients in neurorehabilitation settings into distinct treatments that are tailored to their individual language deficit.

  • Combined frequency-tagging EEG and eye tracking reveal reduced social bias in boys with autism spectrum disorder
    Cortex (IF 4.275) Pub Date : 2019-12-28
    Sofie Vettori; Milena Dzhelyova; Stephanie Van der Donck; Corentin Jacques; Tim Van Wesemael; Jean Steyaert; Bruno Rossion; Bart Boets

    Developmental accounts of autism spectrum disorder (ASD) state that infants and children with ASD are spontaneously less attracted by and less proficient in processing social stimuli such as faces. This is hypothesized to partly underlie social communication difficulties in ASD. While in some studies a reduced preference for social stimuli has been shown in individuals with ASD, effect sizes are moderate and vary across studies, stimuli, and designs. Eye tracking, often the methodology of choice to study social preference, conveys information about overt orienting processes but conceals covert attention, possibly resulting in an underestimation of the effects. In this study, we recorded eye tracking and electroencephalography (EEG) during fast periodic visual stimulation to address this issue. We tested 21 boys with ASD (8-12 years old) and 21 typically developing (TD) control boys, matched for age and IQ. Streams of variable images of faces were presented at 6 Hz alongside images of houses presented at 7.5 Hz or vicNe versa, while children were engaged in an orthogonal task. While frequency-tagged neural responses were larger in response to faces than simultaneously presented houses in both groups, this effect was much larger in TD boys than in boys with ASD. This group difference in saliency of social versus non-social processing is significant after 5 seconds of stimulus presentation and holds throughout the entire trial. Although there was no interaction between group and stimulus category for simultaneously recorded eye-tracking data, eye tracking and EEG measures were strongly correlated. We conclude that frequency-tagging EEG, allowing monitoring of both overt and covert processes, provides a fast, objective and reliable measure of decreased preference for social information in ASD.

  • Diffusion tensor imaging evidence of corticospinal pathway involvement in frontotemporal lobar degeneration
    Cortex (IF 4.275) Pub Date : 2019-12-28
    Chiara Crespi; Alessandra Dodich; Sandro Iannaccone; Alessandra Marcone; Andrea Falini; Stefano F. Cappa; Chiara Cerami

    Motor neuron dysfunctions (MNDys) in Frontotemporal Lobar Degeneration (FTLD) have been consistently reported. Clinical and neurophysiological findings proved a variable range of pathological changes, also affecting the corticospinal tract (CST). This study aims to assess white-matter microstructural alterations in a sample of patients with FTLD, and to evaluate the relationship with MNDys. Fifty-four FTLD patients (21 bvFTD, 16 PPA, 17 CBS) and 36 healthy controls participated in a Diffusion Tensor Imaging (DTI) study. We analyzed distinctive and common microstructural alteration patterns across FTLD subtypes, including those affecting the CST, and performed an association analysis between CST integrity and the presence of clinical and/or neurophysiological signs of MNDys. The majority of FTLD patients showed microstructural changes in the motor pathway with a high prevalence of CST alterations also in patients not displaying clinical and/or neurophysiological signs of MNDys. Our results suggest that subtle CST alterations characterize FTLD patients regardless to the subtype. This may be due to the spread of the pathological process to the motor system, even without a clear clinical manifestation of MNDys.

  • Executive functions in schizophrenia aging: differential effects of age within specific executive functions
    Cortex (IF 4.275) Pub Date : 2019-12-26
    Flavien Thuaire; Fabien Rondepierre; Elisabeth Bacon; Guillaume T. Vallet; Isabelle Jalenques; Marie Izaute

    There are common cognitive and brain abnormalities in schizophrenia and healthy aging which may cumulate in schizophrenia aging. However, the course of executive deficits in late-life schizophrenia is still controversial as it remains unclear whether schizophrenia patients show accelerated aging. The use of specific models of executive functions might help to shed new lights on this issue. The aim of this study was then to determine how each of the four specific executive functions (shifting, updating, inhibition and access to long-term memory) is affected by aging in schizophrenia compared to healthy aging. 20 younger (age 18-34), 17 middle-aged (age 35-49) and 25 older (age 59-76) schizophrenia patients and 62 healthy comparison participants matched for gender, age and education performed a neurocognitive battery evaluating the four specific executive functions. Schizophrenia patients performed worse than comparison participants on shifting, updating and access, whereas inhibition appeared preserved. Age affected the four functions with increased degradation of shifting and access in schizophrenia patients, whereas updating and inhibition showed a normal decline with age. These results suggest a vulnerability of prefrontal and cingulate cortexes in schizophrenia aging. Moreover, as age affected the specific executive functions differently, remediation programs should be adapted to older patients. Models of specific executive functions are useful for understanding the complexity of cognition in schizophrenia and its course during later life so that healthcare can be adapted accordingly.

  • Efficacy and predictors of recovery of function after eye movement training in 296 hemianopic patients
    Cortex (IF 4.275) Pub Date : 2019-12-24
    Arash Sahraie; A. Matilda H. Cederblad; Sigrid Kenkel; Jose G. Romano

    Compensatory approaches to rehabilitation of vision loss as a result of brain injury are aimed at improving the efficacy of eye movements, enabling patients to bring the otherwise unseen stimuli into their sighted field. Eye movement training has shown promise in a large number of studies in small clinical populations nevertheless, there remain two problems; standardisation and wide accessibility. NeuroEyeCoach™ (NEC) has been developed to address both. The therapy is based on the visual search approach and is adaptive to the patient’s level of disability and the task difficulty is varied systematically through a combination of set-size and target/distractor similarity. Importantly, the therapy can be accessed online or in clinical settings, to enhance accessibility. Here we have reported on the findings from the first 296 consecutive cases who have accessed and completed NEC online, the largest cohort of patients studied to date. Patients’ performance on two objective (visual search times and errors) and one subjective (self-reported disability) measures of performance were assessed before and after therapy. The findings showed that patients improved in search time, had less errors and improved disability scores in 87% (255/294), 80% (236/294) and 66% (167/254) of all cases respectively. We examined factors age, sex, side of blindness, age at the onset of brain injury, and time elapsed between the brain injury and start of therapy as predictors of both objective and subjective measures of improvements. Age was a significant predictor of improved search errors with older patients showing larger improvements. Time between brain injury and intervention negatively influenced search reaction time, however, none of the factors could predict improved subjective reports of disability.

  • Is laterality adaptive? Pitfalls in disentangling the laterality–performance relationship
    Cortex (IF 4.275) Pub Date : 2019-12-21
    Jakub Paszulewicz; Piotr Wolski; Marek Gajdek

    Unlike non-human animal studies that have progressively demonstrated the advantages of being asymmetrical at an individual, group and population level, human studies show a quite inconsistent picture. Specifically, it is hardly clear if and how the strength of lateralization that an individual is equipped with relates to their cognitive performance. While some of these inconsistencies can be attributed to procedural and conceptual differences, the issue is aggravated by the fact that the intrinsic mathematical interdependence of the measures of laterality and performance produces spurious correlations that can be mistaken for evidence of an adaptive advantage of asymmetry. Leask and Crow [Leask, S. J., & Crow, T. J. (1997), How far does the brain lateralize?: an unbiased method for determining the optimum degree of hemispheric specialization. Neuropsychologia, 35(10), 1381–1387] devised a method of overcoming this problem that has been subsequently used in several large-sample studies investigating the asymmetry–performance relationship. In our paper we show that the original Leask and Crow method and its later variants fall victim to inherent nonlinear dependencies and produce artifacts. By applying the Leask and Crow method to random data and with mathematical analysis, we demonstrate that what has been believed to describe the true asymmetry–performance relation in fact only reflects the idiosyncrasies of the method itself. We think that the approach taken by Leask in his later paper [Leask, S. (2003), Principal curve analysis avoids assumptions of dependence between measures of hand skill. Laterality, 8(4), 307–316. doi:10.1080/13576500342000004] might be preferable.

  • Sensorimotor conflicts alter metacognitive and action monitoring
    Cortex (IF 4.275) Pub Date : 2019-12-19
    Nathan Faivre; Laurène Vuillaume; Fosco Bernasconi; Roy Salomon; Olaf Blanke; Axel Cleeremans

    While sensorimotor signals are known to modulate perception, little is known about their influence on higher-level cognitive processes. Here, we applied sensorimotor conflicts while participants performed a perceptual task followed by confidence judgments. Results showed that sensorimotor conflicts altered metacognitive monitoring by decreasing metacognitive performance. In a second experiment, we replicated this finding and extended our results by showing that sensorimotor conflicts also altered action monitoring, as measured implicitly through intentional binding. In a third experiment, we replicated the same effects on intentional binding with sensorimotor conflicts related to the hand rather than to the trunk. However, effects of hand sensorimotor conflicts on metacognitive monitoring were not significant. Taken together, our results suggest that metacognitive and action monitoring may involve endogenous, embodied processes involving sensorimotor signals which are informative regarding the state of the decider.

  • Mapping psycholinguistic features to the neuropsychological and lesion profiles in aphasia
    Cortex (IF 4.275) Pub Date : 2019-12-19
    Reem S.W. Alyahya; Ajay D. Halai; Paul Conroy; Matthew A. Lambon Ralph

    Naming and word retrieval deficits are two of the most persistent symptoms in chronic post-stroke aphasia. Naming success or failure on specific words can sometimes be predicted by the psycholinguistic properties of the word. Despite a wealth of literature investigating the influence of psycholinguistic properties in neuro-typical and clinical language processing, the underlying structure of these properties and their relation to the fundamental language components and neural correlates are unexplored. In this study, a multivariate data-decomposition approach was used to identify the underlying structure within a collection of psycholinguistic properties (word imageability, frequency, age-of-acquisition, familiarity, length, semantic diversity and phonological neighbourhood density) and their influence on naming accuracy was explored in a cohort of 42 participants with a diverse range of chronic post-stroke aphasia classifications and severities. The results extracted three principal psycholinguistic factors, which were best described as ‘lexical usage’, ‘semantic clarity’ and ‘phonological complexity’. Furthermore, a novel approach was used to systematically relate the influence of these psycholinguistic properties to participants' neuropsychological and lesion profiles. The findings did not show a one-to-one mapping between psycholinguistic features and core language components. ‘Lexical usage’ was the only factor that showed a significant difference between fluent versus non-fluent aphasia groups in terms of the influence of this lexical factor on successful naming, and it was the only factor that was related to the pattern of patients’ brain lesions. Voxel-wise whole brain lesion-symptom mapping identified left frontal regions, aligning with previous evidence that these regions are related to language production functions, including word retrieval and repetition. The evidence from the current study suggests that the functional locus of psycholinguistic properties is distributed across multiple language components rather than being localised to a single language element.

  • Hallucinatory palinopsia and paroxysmal oscillopsia as initial manifestations of sporadic Creutzfeldt-Jakob Disease: A case study
    Cortex (IF 4.275) Pub Date : 2019-12-13
    Durjoy Lahiri; Souvik Dubey; Biman Kanti Ray; Alfredo Ardila

    Background Heidenhain variant of Cruetzfeldt Jacob Disease is a rare phenotype of the disease. Early and isolated visual symptoms characterize this particular variant of CJD. Other typical symptoms pertaining to muti-axial neurological involvement usually appear in following weeks to months. Commonly reported visual difficulties in Heidenhain variant are visual dimness, restricted field of vision, agnosias and spatial difficulties. We report here a case of Heidenhain variant that presented with very unusual symptoms of palinopsia and oscillopsia. Case Presentation A 62-year-old male patient presented with symptoms of prolonged afterimages following removal of visual stimulus. It was later on accompanied by intermittent sense of unstable visual scene. He underwent surgery in suspicion of cataratcogenous vision loss but with no improvement in symptoms. Additionally he developed symptoms of cerebellar ataxia, cognitive decline and multifocal myoclonus in subsequent weeks. On the basis of suggestive MRI findings in brain, typical EEG changes and a positive result of 14-3-3 protein in CSF, he was eventually diagnosed as sCJD. Conclusion This case adds to the tally of handful reports of Heidenhain variant CJD in literature, particularly from India. Two atypical initial symptoms, namely hallucinatory palinopsia and paroxysmal oscillopsia were observed in the index case. Possible explanations of such phenomena in CJD have been explored in light of the available studies.

  • Cortical collateralization induced by language and arithmetic in non-right-handers
    Cortex (IF 4.275) Pub Date : 2019-12-13
    Tomoya Nakai; Kazuo Okanoya

    The functional overlap of language and arithmetic is debatable. Although some studies have reported independent representations of arithmetic and language in the brain, other studies have reported shared activity of the two cognitive domains in the inferior frontal gyrus. Although most previous studies have evaluated right-handed individuals, variability of hemispheric dominance in non-right-handed individuals should provide important information on the functional collateralization of these two cognitive domains. The present study evaluated the cortical lateralization patterns of the two cognitive domains using functional magnetic resonance imaging in 30 non-right-handed participants who performed language and arithmetic tasks. We found that language and arithmetic tasks demonstrated shared activity in the bilateral inferior frontal gyrus (IFG). Furthermore, the lateralization patterns of language and arithmetic tasks were correlated with each other. Most participants with language dominance in the left hemisphere also exhibited dominance of arithmetic tasks in the left hemisphere; similarly, most participants with language dominance in the right hemisphere exhibited dominance of arithmetic tasks in the right hemisphere. Among all the brain regions, the precentral gyrus, which is located slightly posterior to the IFG, exhibited the highest correlation coefficient between laterality indices of language and arithmetic tasks. These results suggest a shared functional property between language and arithmetic in the brain.

  • The focus of spatial attention during the induction of central sensitization can modulate the subsequent development of secondary hyperalgesia
    Cortex (IF 4.275) Pub Date : 2019-12-10
    Lieve Filbrich, Emanuel N. van den Broeke, Valéry Legrain, André Mouraux

    Intense or sustained activation of peripheral nociceptors can induce central sensitization. This enhanced responsiveness to nociceptive input of the central nervous system primarily manifests as an increased sensitivity to painful mechanical pinprick stimuli extending beyond the site of injury (secondary mechanical hyperalgesia) and is thought to be a key mechanism in the development of chronic pain, such as persistent post-operative pain. It is increasingly recognized that emotional and cognitive factors can strongly influence the pain experience. Furthermore, through their potential effects on pain modulation circuits including descending pathways to the spinal cord, it has been hypothesized that these emotional and cognitive factors could constitute risk factors for the susceptibility to develop chronic pain. Here, we tested whether, in healthy volunteers, the experimental induction of central sensitization by peripheral nociceptive input can be modulated by selective spatial attention. While participants performed a somatosensory detection task that required focusing attention towards one of the forearms, secondary hyperalgesia was induced at both forearms using bilateral and simultaneous high-frequency electrical stimulation (HFS) of the skin. HFS induced an increased sensitivity to mechanical pinprick stimuli at both forearms, directly (T1) and 20 minutes (T2) after HFS, confirming the successful induction of secondary hyperalgesia at both forearms. Most importantly, at T2, the HFS-induced increase in pinprick sensitivity as well as the area of secondary hyperalgesia was greater at the attended arm as compared to the non-attended arm. This indicates that top-down attentional factors can modulate the development of central sensitization by peripheral nociceptive input, and that the focus of spatial attention, besides its modulatory effects on perception, can affect activity-dependent neuroplasticity.

  • Heterogeneous correlations between hippocampus volume and cognitive map accuracy among healthy young adults
    Cortex (IF 4.275) Pub Date : 2019-12-10
    Qiliang He, Thackery I. Brown

    Marked individual differences in the ability to mentally map our environment are pronounced not only among people of different ages or clinical conditions, but also within healthy young adults. Previous studies have shown that hippocampus size positively correlated with spatial navigation ability in healthy young adults, navigation experts, and patients with hippocampus lesions. However, a recent pre-registered study (Weisberg, Newcombe, & Chatterjee, 2019) with a large sample size (n = 90) did not observe this correlation in healthy young adults. Motivated by evidence that self-report sense of direction (SOD) could have a profound impact on how individuals utilize environmental cues, and that different navigation strategies could have opposite impacts on wayfinding performance in individuals with different cognitive map formation (CMF) abilities, we reanalyzed the publicly available dataset from Weisberg et al’s study. We tested the influence of participants’ SOD and CMF abilities on hippocampal volume-performance relationships. We find evidence that the non-significant correlation could envelop heterogeneous correlations among subgroups of individuals: the correlation between the right posterior hippocampal volume and spatial learning performance is significantly higher among individuals with high spatial ability than individuals with low spatial ability. This pattern of performance was observed for both SOD and CMF moderations of the relationship between hippocampal volume and spatial learning. While our re-analyses are fundamentally exploratory in nature, the new results imply that the relationship between hippocampal volume and spatial learning performance might be more complicated than previously thought.

  • Rhinal and hippocampal contributions to spontaneous inter-item binding and verbal memory recall: Evidence from temporal lobe epilepsy
    Cortex (IF 4.275) Pub Date : 2019-12-10
    Philip Grewe, Dominik Neu, Joerg Aengenendt, Friedrich G. Woermann, Markus Mertens, Christian G. Bien, Johanna Kissler

    The medial temporal lobes (MTL) play a prominent role in associative memory processing. Still, it is unclear to what extent specific structures within the MTL sub-serve distinct aspects of associative memory. Here, the role of the MTL in forming spontaneous associations in a “naturalistic” setting is investigated applying a word-list memory test not presenting items in an associative fashion. This allows for the differential investigation of item recall and associative binding. Participants included patients with medial temporal lobe epilepsy (mTLE, n = 79) and healthy controls (n = 58). Memory performance in a verbal list-learning paradigm was analyzed by (1) inter-trial repetitions (“binding”, i.e., number of word-pairs consistently recalled over two consecutive trials), and (2) single item recall. In patients, behavioral results were correlated with rhinal cortex and hippocampal volumetric data. Results showed that binding was specifically diminished for patients with mTLE during learning and delayed recall. Moreover, binding predicted behavioral differences in item recall. Notably, hippocampal volumes were correlated with item recall during delayed recall, whereas rhinal cortex volumes were correlated with binding during learning. Our results provide evidence that diminished verbal memory in patients with mTLE at least partly can be attributed to functional reductions in spontaneous inter-trial stimulus binding. Moreover, they demonstrate a process-dependent functional dissociation between rhinal cortex and hippocampus for verbal encoding and recall: While the rhinal cortex is mainly engaged in detecting novel associations, the hippocampus primarily subserves consolidation and recall of associations between stimuli. Our study thus advances current models of the sub-specialization of MTL structures and offers novel evidence that memory formation in the MTL is mediated by associative item-processing, even when stimuli are not presented in an associative fashion per se. Thus, our results provide valuable qualitative insights into mechanisms of memory formation and memory failures in patients with MTL dysfunctions.

  • Unified tactile detection and localisation in split-brain patients
    Cortex (IF 4.275) Pub Date : 2019-12-07
    Edward H.F. de Haan, Mara Fabri, H. Chris Dijkerman, Nicoletta Foschi, Simona Lattanzi, Yair Pinto

    In ‘split-brain’ patients, the corpus callosum has been surgically severed to alleviate medically intractable, severe epilepsy. The classic claim is that after removal of the corpus callosum an object presented in the right visual field will be identified correctly verbally and with the right hand but not with the left hand. When the object is presented in the left visual field the patient verbally states that he saw nothing but nevertheless identifies it accurately with the left hand. This interaction suggests that perception, recognition and responding are separated in the two isolated hemispheres. However, there is now accumulating evidence that this interaction is not absolute. Recently, we (Pinto et al., 2017) showed that accurate detection and location of stimuli anywhere in the visual field could be performed with both hands. In this study, we explored detection and localisation of tactile stimulation on the body. In line with our previous results, we observed that split-brain patients can signal detection and localisation with either hand anywhere on the body (be it the arm or the leg) but they remain unable to match positions touched on both arms or legs simultaneously. These results add to the evidence suggesting that the effects of removal of the corpus callosum may be less severe than sometimes claimed.

  • How alliteration enhances conceptual-attentional interactions in reading
    Cortex (IF 4.275) Pub Date : 2019-11-28
    Ciara Egan, Filipe Cristino, Joshua S. Payne, Guillaume Thierry, Manon W. Jones

    In linguistics, the relationship between phonological word form and meaning is mostly considered arbitrary. Why, then, do literary authors traditionally craft sound relationships between words? We set out to characterise how dynamic interactions between word form and meaning may account for this literary practice. Here, we show that alliteration influences both meaning integration and attentional engagement during reading. We presented participants with adjective-noun phrases, having manipulated semantic relatedness (congruent, incongruent) and form repetition (alliterating, non-alliterating) orthogonally, as in “dazzling-diamond”; “sparkling-diamond”; “dangerous-diamond”; and “creepy-diamond”. Using simultaneous recording of event-related brain potentials and pupil dilation (PD), we establish that, whilst semantic incongruency increased N400 amplitude as expected, it reduced PD, an index of attentional engagement. Second, alliteration affected semantic evaluation of word pairs, since it reduced N400 amplitude even in the case of unrelated items (e.g., “dangerous-diamond”). Third, alliteration specifically boosted attentional engagement for related words (e.g., “dazzling-diamond”), as shown by a sustained negative correlation between N400 amplitudes and PD change after the window of lexical integration. Thus, alliteration strategically arouses attention during reading and when comprehension is challenged, phonological information helps readers link concepts beyond the level of literal semantics. Overall, our findings provide a tentative mechanism for the empowering effect of sound repetition in literary constructs.

  • Complexity in neuropsychological assessments of cognitive impairment: A network analysis approach.
    Cortex (IF 4.275) Pub Date : 2019-11-27
    Giorgia Tosi, Carolina Borsani, Stefania Castiglioni, Roberta Daini, Massimo Franceschi, Daniele Romano

    In a neuropsychological assessment, each test aims at measuring a single cognitive function. However, test performance depends on an interconnected system of cognitive functions and individual characteristics. For a better understanding of cognitive deficits, it is fundamental to recognize this complexity and study the relationships between test performances. This study aims to evaluate complexity in neuropsychological assessment through network analysis (NA) in 165 healthy older adults, 191 patients with Alzheimer's disease (AD), and 129 patients with vascular encephalopathy (VaE). NA is a flexible method to explore different domains where many variables are correlated with each other, and the relationships are key for understanding the domains. We included general aspects of individual differences (i.e., age, sex, years of education) and the raw scores of a clinically used neuropsychological battery in the network. Healthy subjects showed a segregated pattern, suggesting a good specificity of each test in measuring a specific cognitive function. Moreover, the scores were related to age and education. In the patient groups, the identified patterns changed in a consistent manner, showing less specificity and new relationships between the various tests, thereby reducing the impact of age and education on the performance. In particular, AD patients showed worse performance on the tests but also a different balance between different tasks, suggesting a reorganization of the cognitive system and not a mere decline. These results provide a new perspective in looking at the complexity of cognitive function assessment.

  • The role of the fornix in human navigational learning
    Cortex (IF 4.275) Pub Date : 2019-11-26
    Carl J. Hodgetts, Martina Stefani, Angharad N. Williams, Branden S. Kolarik, Andrew P. Yonelinas, Arne D. Ekstrom, Andrew D. Lawrence, Jiaxiang Zhang, Kim S. Graham

    Experiments on rodents have demonstrated that transecting the white matter fibre pathway linking the hippocampus with an array of cortical and subcortical structures - the fornix - impairs flexible navigational learning in the Morris Water Maze (MWM), as well as similar spatial learning tasks. While diffusion magnetic resonance imaging (dMRI) studies in humans have linked inter-individual differences in fornix microstructure to episodic memory abilities, its role in human spatial learning is currently unknown. We used high-angular resolution diffusion MRI combined with constrained spherical deconvolution-based tractography, to ask whether inter-individual differences in fornix microstructure in healthy young adults would be associated with spatial learning in a virtual reality navigation task. To efficiently capture individual learning across trials, we adopted a novel curve fitting approach to estimate a single index of learning rate. We found a statistically significant correlation between learning rate and the microstructure (mean diffusivity) of the fornix, but not that of a comparison tract linking occipital and anterior temporal cortices (the inferior longitudinal fasciculus, ILF). Further, this correlation remained significant when controlling for both hippocampal volume and participant gender. These findings extend previous animal studies by demonstrating the functional relevance of the fornix for human spatial learning in a virtual reality environment, and highlight the importance of a distributed neuroanatomical network, underpinned by key white matter pathways, such as the fornix, in complex spatial behaviour.

  • Longitudinal Flortaucipir ([18F]AV-1451) PET Imaging in Primary Progressive Apraxia of Speech
    Cortex (IF 4.275) Pub Date : 2019-11-19
    Rene L. Utianski, Peter R. Martin, Hugo Botha, Christopher G. Schwarz, Joseph R. Duffy, Ronald C. Petersen, David S. Knopman, Heather M. Clark, Alissa M. Butts, Mary M. Machulda, Clifford R. Jack, Val J. Lowe, Jennifer L. Whitwell, Keith A. Josephs

    Primary progressive apraxia of speech (PPAOS) is a term used to describe a neurodegenerative condition in which apraxia of speech (AOS; a planning and/or programming deficit) occurs in the absence of aphasia (a language deficit). PPAOS is strongly associated with 4-repeat tau pathology. Elevated flortaucipir ([18F]AV-1451; FTP) uptake has been observed cross-sectionally in patients with PPAOS and those with aphasia. Here, we evaluated longitudinal changes in previously-identified regions of uptake and their relationship with clinical presentation. Thirteen patients who were diagnosed with PPAOS (5 female) at presentation underwent FTP PET imaging at two visits (mean 1 year interval). Median age was 72, with a median of 4 years disease duration at initial testing. Beta-amyloid status was assessed with Pittsburgh Compound B (PiB), where a global PiB ratio>1.48 was deemed amyloid positive (n=4). FTP uptake was assessed as cortical to cerebellar crus ratios (SUVr) in cortical regions of interest. A single hierarchical linear model (HLM) compared PPAOS patients to 52 cognitively unimpaired controls of similar age and sex. Annualized SUVr change was the outcome, predicted by region, clinical status, and age. Person-specific effects accounted for intra-patient correlations and contralateral regions were included as repeated measures. Changes in clinical measures were assessed using Wilcoxon signed-rank tests; statistically significant changes in the Montreal Cognitive Assessment, MDS-UPDRS, motor section, and PSP Rating Scale were noted between visits. Changes in FTP SUVr were greater for patients than controls. The strongest changes in PPAOS patients were in the precentral gyrus, pallidum, and mid and superior frontal gyri, per the HLM. Qualitatively, larger changes were seen in patients who had developed aphasia by the time of their baseline scan (n=5). While the biological mechanisms of FTP signal in non-AD tauopathies are unknown, this study demonstrates the utility of FTP in tracking disease progression in 4R tauopathies.

  • Cognitive and language performance predicts effects of spelling intervention and tDCS in Primary Progressive Aphasia
    Cortex (IF 4.275) Pub Date : 2019-11-19
    Vânia de Aguiar, Yi Zhao, Bronte N. Ficek, Kimberly Webster, Adrià Rofes, Haley Wendt, Constantine Frangakis, Brian Caffo, Argye E. Hillis, Brenda Rapp, Kyrana Tsapkini

    Predictors of treatment effects allow individual tailoring of treatment characteristics, thereby saving resources and optimizing outcomes. Electrical stimulation coupled with language intervention has shown promising results in improving language performance in individuals with Primary Progressive Aphasia (PPA). The current study aimed to identify language and cognitive variables associated with response to therapy consisting of language intervention combined with transcranial direct current stimulation (tDCS). Forty individuals with PPA received written naming/spelling intervention combined with anodal tDCS or Sham, using a between-subjects, randomized design, with intervention delivered over a period of 3 weeks. Participants were assessed using a battery of neuropsychological tests before and after each phase. We measured letter accuracy during spelling of trained and untrained words, before, immediately after, 2 weeks, and 2 months after therapy. We used step-wise regression methods to identify variables amongst the neuropsychological measures and experimental factors that were significantly associated with therapy outcomes at each time-point. For trained words, improvement was related to pre-therapy scores, in RAVLT (5 trials sum), pseudoword spelling, object naming, digit span backward, spatial span backward and years post symptom onset. Regarding generalization to untrained words, improvement in spelling was associated with pseudoword spelling, RAVLT proactive interference, RAVLT immediate recall. Generalization effects were larger under tDCS compared to Sham at the 2-month post training measurement. We conclude that, for trained words, patients who improve the most are those who retain for longer language skills such as sublexical spelling processes (phoneme-to-grapheme correspondences) and word retrieval, and other cognitive functions such as executive functions and working memory, and those who have a better learning capacity. Generalization to untrained words occurs through improvement in knowledge of phoneme-to-grapheme correspondences. Furthermore, tDCS enhances the generalizability and duration of therapy effects.

  • Neurophysiological markers discriminate different forms of motor imagery during action observation
    Cortex (IF 4.275) Pub Date : 2019-11-16
    Adam M. Bruton, Paul S. Holmes, Daniel L. Eaves, Zoë C. Franklin, David J. Wright

    The dual-action simulation hypothesis proposes that both an observed and an imagined action can be represented simultaneously in the observer’s brain. These two sensorimotor streams would either merge or compete depending on their relative suitability for action planning. To test this hypothesis, three forms of combined action observation and motor imagery (AO+MI) instructions were used in this repeated-measures experiment. Participants observed index finger abduction-adduction movements while imagining the same action (congruent AO+MI), little finger abduction-adduction (coordinative AO+MI), or a static hand (conflicting AO+MI). Single-pulse transcranial magnetic stimulation was applied to the left primary motor cortex. The amplitude of motor evoked potential responses were recorded from both the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles of the right-hand while eye movements were tracked. When controlling for the influence of relevant eye movements, corticospinal excitability was facilitated relative to control conditions in the concurrently observed and imagined muscles for both congruent and coordinative AO+MI conditions. Eye-movement metrics and social validation data from post-experiment interviews provided insight into the cognitive mechanisms underlying these effects. The findings provide empirical support for the dual-action simulation hypothesis, indicating for the first time that it is possible to co-represent observed and imagined actions simultaneously.

  • Structural Correlates of Commission Errors in Prospective Memory Registered Report
    Cortex (IF 4.275) Pub Date : 2019-11-16
    Michael K. Scullin, Hunter Ball, Julie M. Bugg

    Prospective memory refers to remembering to perform an intended future action, such as remembering to take medication with breakfast. Historically, the field has focused on failures to initially remember a prospective memory task (omission errors), but interestingly, individuals will occasionally repeat a prospective memory action after it has been completed (e.g., double dosing). These failures in prospective memory deactivation/forgetting are termed commission errors. The current pre-registered study investigated structural neuroimaging correlates of a laboratory measure of commission errors in 47 healthy older adults. Extant theories differed in their predicted outcomes: commission error risk was predicted to be highest in individuals with smaller medial temporal lobe volume (output monitoring theory), larger lateral prefrontal cortex volume (residual activation theory), or a combination of larger medial temporal lobe volume and smaller lateral prefrontal cortex volume (dual mechanisms theory). In registered analyses, we found that a higher number of commission errors was associated with larger medial temporal lobe/hippocampal grey matter volume (supporting dual mechanism’ hypothesis), but not with grey or white matter volume in the lateral parietal lobe, frontal pole, or a composite of ventrolateral/dorsolateral prefrontal cortex (not supporting dual mechanisms’ hypothesis). In post hoc analyses, smaller volume in the lateral orbitofrontal cortex was associated with a higher number of commission errors, possibly indicating that the dual mechanisms’ view of PFC control was conceptually correct, but that a different PFC subregion than anticipated exerts control over commission errors. Collectively, the registered and post hoc analysis findings showed a functional dissociation across MTL/PFC regions that were more consistent with the dual mechanisms view than the alternative views.

  • Functional connectivity of the orbitofrontal cortex, anterior cingulate cortex, and inferior frontal gyrus in humans
    Cortex (IF 4.275) Pub Date : 2019-11-16
    Jingnan Du, Edmund T. Rolls, Wei Cheng, Yu Li, Weikang Gong, Jiang Qiu, Jianfeng Feng

    Parcellation of the orbitofrontal cortex, anterior cingulate cortex, and inferior frontal gyrus based on their functional connectivity with the whole brain in resting state fMRI with 654 participants was performed to investigate how these regions with different functions in reward, emotion and their disorders are functionally connected to each other and to the whole brain. The human medial and lateral orbitofrontal cortex, the ventromedial prefrontal cortex, the anterior cingulate cortex, and the right and left inferior frontal gyrus have different functional connectivity with other brain areas and with each other; and each of these regions has several parcels with different functional connectivity with other brain areas. In terms of functional connectivity, the lateral orbitofrontal cortex extends especially on the right into the orbital part of the inferior frontal gyrus and provides connectivity with premotor cortical areas. The orbitofrontal cortex, especially the lateral orbitofrontal cortex, has connectivity not only with language-related areas in the inferior frontal gyrus (Broca's area), but also with the angular and supramarginal gyri. In this context, whereas the connectivity of the orbitofrontal cortex, ventromedial prefrontal cortex, and anterior cingulate cortex is symmetrical, the connectivity of the inferior frontal gyrus triangular and opercular parts is asymmetrical for the right and the left hemispheres. These findings have implications for understanding the neural bases of human emotion and decision-making, and for their disorders including depression.

  • Representation of shape, space, and attention in monkey cortex
    Cortex (IF 4.275) Pub Date : 2019-06-24
    Anne B. Sereno, Sidney R. Lehky, Margaret E. Sereno

    Attentional deficits are core to numerous developmental, neurological, and psychiatric disorders. At the single-cell level, much knowledge has been garnered from studies of shape and spatial properties, as well as from numerous demonstrations of attentional modulation of those properties. Despite this wealth of knowledge of single-cell responses across many brain regions, little is known about how these cellular characteristics relate to population level representations and how such representations relate to behavior; in particular, how these cellular responses relate to the representation of shape, space, and attention, and how these representations differ across cortical areas and streams. Here we will emphasize the role of population coding as a missing link for connecting single-cell properties with behavior. Using a data-driven intrinsic approach to population decoding, we show that both ‘what’ and ‘where’ cortical visual streams encode shape, space, and attention, yet demonstrate striking differences in these representations. We suggest that both pathways fully process shape and space, but that differences in representation may arise due to their differing functions and input and output constraints. Moreover, differences in the effects of attention on shape and spatial population representations in the two visual streams suggest two distinct strategies: in a ventral area, attention or task demands modulate the population representations themselves (perhaps to expand or enhance one part at the expense of other parts) while in a dorsal area, at a population representation level, attention effects are weak and nearly non-existent, perhaps in order to maintain veridical representations needed for visuomotor control. We show that an intrinsic approach, as opposed to theory-driven and labeled approaches, is useful for understanding how representations develop and differ across brain regions. Most importantly, these approaches help link cellular properties more tightly with behavior, a much-needed step to better understand and interpret cellular findings and key to providing insights to improve interventions in human disorders.

  • Ipsilesional perceptual deficits in hemispatial neglect: Case reports
    Cortex (IF 4.275) Pub Date : 2019-04-10
    Tony Ro, Michael Beauchamp

    Hemispatial neglect, usually after right hemisphere lesions, is characterized by contralesional deficits in attention and perception. However, little is known about impairments of perceptual processing in the ipsilesional region of visual space (the right visual field for right hemisphere lesions). In two right hemisphere neglect patients, we used a metacontrast masking paradigm to characterize systematic spatial and temporal visual processing deficits in the ipsilesional right visual field. The presence of a visual mask caused the neglect patients to miss targets in ipsilesional space, even when a mask was presented as long as 1.5 sec after the target and in a different spatial position. These prolonged and spatially extended masking effects were not measured in age-matched healthy controls or in two control patients with hemianopsia but without neglect. The results show that perceptual processing is distorted and delayed in a region of the visual field that has been thought to be unaffected – the ipsilesional hemifield in patients with neglect.

  • Emotional capture during emotion-induced blindness is not automatic
    Cortex (IF 4.275) Pub Date : 2019-03-27
    James E. Hoffman, Minwoo Kim, Matt Taylor, Kelsey Holiday

    The present research used behavioral and event-related brain potentials (ERP) measures to determine whether emotional capture is automatic in the emotion-induced blindness (EIB) paradigm. The first experiment varied the priority of performing two concurrent tasks: identifying a negative or neutral picture appearing in a rapid serial visual presentation (RSVP) stream of pictures and multiple object tracking (MOT). Results showed that increased attention to the MOT task resulted in decreased accuracy for identifying both negative and neutral target pictures accompanied by decreases in the amplitude of the P3b component. In contrast, the early posterior negativity (EPN) component elicited by negative pictures was unaffected by variations in attention. Similarly, there was a decrement in MOT performance for dual-task versus single task conditions but no effect of picture type (negative vs neutral) on MOT accuracy which isn't consistent with automatic emotional capture of attention. However, the MOT task might simply be insensitive to brief interruptions of attention. The second experiment used a more sensitive reaction time (RT) measure to examine this possibility. Results showed that RT to discriminate a gap appearing in a tracked object was delayed by the simultaneous appearance of to-be-ignored distractor pictures even though MOT performance was once again unaffected by the distractor. Importantly, the RT delay was the same for both negative and neutral distractors suggesting that capture was driven by physical salience rather than emotional salience of the distractors. Despite this lack of emotional capture, the EPN component, which is thought to reflect emotional capture, was still present. We suggest that the EPN doesn't reflect capture but rather downstream effects of attention, including object recognition. These results show that capture by emotional pictures in EIB can be suppressed when attention is engaged in another difficult task. The results have important implications for understanding capture effects in EIB.

  • Impairments in action and perception after right intraparietal damage
    Cortex (IF 4.275) Pub Date : 2019-02-21
    Jared Medina, Steven A. Jax, H. Branch Coslett

    We examined visually-guided reaching and perception in an individual who underwent resection of a small tumor in right intraparietal sulcus (pIPS). In the first experiment, she reached to targets presented on a touch screen. Vision was occluded from reach onset on half of the trials, whereas on the other half she had vision during the entire reach. For visually-guided reaching, she demonstrated significantly more reach errors for targets left of fixation versus right of fixation. However, there were no hemispatial differences when reaching without vision. Furthermore, her performance was consistent for reaches with either hand, providing evidence that pIPS encodes location based on an eye-centered reference frame. Second, previous studies reported that optic ataxics are more accurate when reaching to remembered versus visible target locations. We repeated the first experiment, adding a five second delay between stimulus presentation and reach initiation. In contrast to prior reports, she was less accurate in delayed versus immediate reaching. Finally, we examined whether a small pIPS resection would disrupt visuospatial processing in a simple perceptual task. We presented two small circles in succession in either the same location or offset at varying distances, and asked whether the two circles were presented in the same or different position. She was significantly more impaired left of fixation compared to right of fixation, providing evidence for a perceptual deficit after a dorsal stream lesion.

  • Perturbation-driven paradoxical facilitation of visuo-spatial function: Revisiting the ‘Sprague effect’
    Cortex (IF 4.275) Pub Date : 2019-02-10
    Antoni Valero-Cabré, Monica N. Toba, Claus C. Hilgetag, R. Jarrett Rushmore

    The ‘Sprague Effect’ described in the seminal paper of James Sprague (Science 153:1544–1547, 1966a) is an unexpected paradoxical effect in which a second brain lesion reversed functional deficits induced by an earlier lesion. It was observed initially in the cat where severe and permanent contralateral visually guided attentional deficits generated by the ablation of large areas of the visual cortex were reversed by the subsequent removal of the superior colliculus (SC) opposite to the cortical lesion or by the splitting of the collicular commissure. Physiologically, this effect has been explained in several ways-most notably by the reduction of the functional inhibition of the ipsilateral SC by the contralateral SC, and the restoration of normal interactions between cortical and midbrain structures after ablation. In the present review, we aim at reappraising the ‘Sprague Effect’ by critically analyzing studies that have been conducted in the feline and human brain. Moreover, we assess applications of the ‘Sprague Effect’ in the rehabilitation of visually guided attentional impairments by using non-invasive therapeutic approaches such as transcranial magnetic stimulation (TMS) and transcranial direct-current stimulation (tDCS). We also review theoretical models of the effect that emphasize the inhibition and balancing between the two hemispheres and show implications for lesion inference approaches. Last, we critically review whether the resulting inter-hemispheric rivalry theories lead toward an efficient rehabilitation of stroke in humans. We conclude by emphasizing key challenges in the field of ‘Sprague Effect’ applications in order to design better therapies for brain-damaged patients.

  • Circadian circuits in humans: White matter microstructure predicts daytime sleepiness
    Cortex (IF 4.275) Pub Date : 2019-01-30
    Kristin Koller, Robert D. Rafal, Paul G. Mullins

    The suprachiasmatic nucleus of the hypothalamus is the chief circadian pacemaker in the brain, and is entrained to day-night cycles by visual afferents from melanopsin containing retinal ganglion cells via the inferior accessory optic tract. Tracer studies have demonstrated efferents from the suprachiasmatic nucleus projecting to the paraventricular nucleus of the hypothalamus, which in turn project to first-order sympathetic neurons in the intermedio-lateral grey of the spinal cord. Sympathetic projections to the pineal gland trigger the secretion of the sleep inducing hormone melatonin. The current study reports the first demonstration of potential sympathopetal hypothalamic projections involved in circadian regulation in humans with in vivo virtual white matter dissections using probabilistic diffusion tensor imaging (DTI) tractography. Additionally, our data shows a correlation between individual differences in white matter microstructure (measured with fractional anisotropy) and increased daytime sleepiness [measured with the Epworth Sleepiness Scale (ESS, Johns, 1991)]. Sympathopetal connections with the hypothalamus were virtually dissected using designated masks on the optic chiasm, which served as an anatomical landmark for retinal fibres projecting to the suprachiasmatic nucleus, and a waypoint mask on the lateral medulla, where hypothalamic projections to the sympathetic nervous system traverse in humans. Sympathopetal projections were demonstrated in each hemisphere in twenty-six subjects. The tract passed through the suprachiasmatic nucleus of the hypothalamus and its trajectory corresponds to the dorsal longitudinal fasciculus traversing the periaqueductal region and the lateral medulla. White matter microstructure (FA) in the left hemisphere correlated with high scores on the ESS, suggesting an association between circadian pathway white matter microstructure, and increased daytime sleepiness.

  • Right hemisphere superiority for executive control of attention
    Cortex (IF 4.275) Pub Date : 2018-12-29
    Alfredo Spagna, Tae Hyeong Kim, Tingting Wu, Jin Fan

    Over forty years have passed since the first evidence showing the unbalanced attentional allocation of humans across the two visual fields, and since then, a wealth of behavioral, neurophysiological, and clinical data increasingly showed a right hemisphere dominance for orienting of attention. However, inconsistent evidence exists regarding the right-hemisphere dominance for executive control of attention, possibly due to a lack of consideration of its dynamics with the alerting and orienting functions. In this study, we used a version of the Attentional Network Test with lateralized presentation of the stimuli to the left visual field (processed by the right hemisphere, RH) and right visual field (processed by the left hemisphere, LH) to examine visual field differences in executive control of attention under alerting and orienting of attention. Analyses of behavioral performance (reaction time and error rate) showed a more efficient executive control (reduced conflict effect) in the RH compared to the LH for the reaction time, under conditions of increased alerting and of informative spatial orienting. These results demonstrate the right-hemisphere superiority for executive control, and that this effect depends on the involvement of the alerting and orienting functions.

  • Evidence for the world as an external memory: A trade-off between internal and external visual memory storage
    Cortex (IF 4.275) Pub Date : 2019-01-03
    Rosyl S. Somai, Martijn J. Schut, Stefan Van der Stigchel

    We use visual working memory (VWM) to maintain the visual features of objects in our world. Although the capacity of VWM is limited, it is unlikely that this limit will pose a problem in daily life, as visual information can be supplemented with input from our external visual world by using eye movements. In the current study, we influenced the trade-off between eye movements and VWM utilization by introducing a cost to a saccade. Higher costs were created by adding a delay in stimulus availability to a copying task. We show that increased saccade cost results in less saccades towards the model and an increased dwell time on the model. These results suggest a shift from making eye movements towards taxing internal VWM. Our findings reveal that the trade-off between executing eye-movements and building an internal representation of our world is based on an adaptive mechanism, governed by cost-efficiency.

  • Increased inhibition following negative cues: A possible role for enhanced processing
    Cortex (IF 4.275) Pub Date : 2018-12-21
    Hadas Okon-Singer, Avishai Henik, Shai Gabay

    Based on findings showing that attention is captured by aversive stimuli, previous studies have hypothesized that inhibition of return (IOR) is reduced at spatial locations previously occupied by threat cues. Yet evidence for this view is limited: Only a few studies have demonstrated a reduced degree of IOR following threat cues, while most have not found differences in IOR between aversive and neutral cues. In contrast to previous studies that used the spatial cuing paradigm and for the most part employed mild negative stimuli as cues, we examined the influence of highly aversive, colored and complex pictures of real life situations. As opposed to the stimuli used in previous studies, these pictures are thought to result in enhanced processing as well as in specific enhancement for threat pictures in comparison to neutral ones. Based on evidence indicating that enhanced processing of spatial cues results in increased IOR, we hypothesized that the negative picture cues employed in the present study would yield increased IOR. This hypothesis was confirmed in two experiments. We suggest that the enhancement of IOR following highly threatening cues may be related to efficient spatial orienting of attention in response to stimuli that are important from an evolutionary point of view. The results are discussed in the context of neurocognitive mechanisms that may underlie the modulation of IOR by emotional information.

  • Voluntary modulation of saccadic peak velocity associated with individual differences in motivation
    Cortex (IF 4.275) Pub Date : 2018-12-14
    Kinan Muhammed, Edwin Dalmaijer, Sanjay Manohar, Masud Husain

    Saccadic peak velocity increases in a stereotyped manner with the amplitude of eye movements. This relationship, known as the main sequence, has classically been considered to be fixed, although several recent studies have demonstrated that velocity can be modulated to some extent by external incentives. However, the ability to voluntarily control saccadic velocity and its association with motivation has yet to be investigated. Here, in three separate experimental paradigms, we measured the effects of incentivisation on saccadic velocity, reaction time and preparatory pupillary changes in 53 young healthy participants. In addition, the ability to voluntarily modulate saccadic velocity with and without incentivisation was assessed. Participants varied in their ability to increase and decrease the velocity of their saccades when instructed to do so. This effect correlated with motivation level across participants, and was further modulated by addition of monetary reward and avoidance of loss. The findings show that a degree of voluntary control of saccadic velocity is possible in some individuals, and that the ability to modulate peak velocity is associated with intrinsic levels of motivation.

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