Abreaction was once a common treatment for functional neurological disorder (FND) but has since fallen out of use. Norman Poole argues that abreaction is compatible with many findings from modern neuroscience, and should be studied and tested as a treatment for FND.

Medial temporal lobe structures are among the first areas impacted by neurofibrillary tangle pathology, making volumetric changes of these areas promising biomarkers for Alzheimer's disease. To date, little is known about the integrity of these regions in individuals with Down syndrome, a population which almost invariably develops Alzheimer's disease and thus offers a unique opportunity to determine

Atypical parkinsonian syndromes are distinguished from Parkinson’s disease by additional neurological signs and characteristic underlying neuropathology. However, they can be diagnostically challenging, rapidly progressive, and are often diagnosed late in disease course. Their different demographic features and prognoses are well studied, but the accompanying cognitive and psychiatric features may

Partial phenotypic overlap has been suggested between multiple system atrophy (MSA) and spinocerebellar ataxia 27B, the autosomal dominant ataxia caused by an intronic GAA•TTC repeat expansion in FGF14. This study investigated the frequency of FGF14 GAA•TTC repeat expansion in clinically diagnosed and pathologically confirmed multiple system atrophy cases. We screened 657 multiple system atrophy cases

Focal cortical dysplasia (FCD) type 2 is the most common malformation of cortical development associated with pharmaco-resistant focal epilepsy and frequently located in the frontal cortex. Neuropathological hallmarks comprise abnormal cortical layering and enlarged, dysmorphic neuronal elements. Fundamentally altered local neuronal activity has been reported in human FCD type 2 epilepsy surgical biopsies

Two of the most well-studied types of reasoning are analogical reasoning (AR) and deductive reasoning (DR). Yet, our understanding of the relationship between reasoning abilities and their neuroanatomical basis remains surprisingly limited. We aimed to conduct fine-grained anatomical mapping of performance on tests of AR, DR and fluid intelligence (Gf), in a large sample of patients with unilateral

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder with 4-repeat (R) tau protein deposition. The substantia nigra (SN) and midbrain tegmentum nuclei (MBT) are consistently affected. Lymphocyte infiltrates are scarce in the brain of neurodegenerative diseases, although a few reports have described this feature in brains with the α-synucleinopathy, Parkinson’s disease (PD). To evaluate

Remote digital monitoring of Huntington’s disease (HD) has potential to enhance the development of therapeutics, but no data-driven digital motor score exists to quantify the diversity of disease manifestations and track their progression. The Huntington’s Disease Digital Motor progression Score (HDDMS), co-designed by people with HD and neurologists, is a composite score for measuring motor progression

Glioblastoma (GBM) is the most aggressive and lethal adult brain tumor. The cellular heterogeneity within the tumor microenvironment (TME) plays a critical role in the complexity of treatment and poor survival. GBM is typically classified into 3 molecular subtypes—Classical, Mesenchymal, and Proneural—associated with EGFR, NF1, and PDGFRA genetic drivers, respectively. Yet, the role of these driver

Autism spectrum disorder is a complex neurodevelopmental disease characterized by altered cortical network excitability. Recent genetic studies have identified deep layer V cortical pyramidal neurons in the frontal cortex as central to autism pathophysiology, yet the cortical circuits, plasticity mechanisms and molecular signalling pathways involved remain poorly understood. Layer V pyramidal neurons

Gain-of-function (GoF) variants in the GRIN2D gene, encoding the GluN2D subunit of the N-methyl-D-aspartate receptor (NMDAR), cause a severe developmental and epileptic encephalopathy (DEE), characterized by intractable seizures, hypotonia, and neurodevelopmental delay. We generated mice carrying the GoF V664I variant, orthologous to V667I, which is present in ∼25% of GRIN2D-DEE patients. Heterozygous

5q-Spinal muscular atrophy (SMA) has been a trailblazer in the development of advanced therapies for inherited diseases. SMA is an autosomal recessive disorder affecting mainly motor neurons in the anterior horn of the spinal cord and brainstem motor nuclei, but currently considered a systemic disease. Advances in understanding of the genetics of SMA led to the development of disease modifying therapies

Polymyositis with mitochondrial pathology (PM-Mito) was first identified in 1997 as a subtype of idiopathic inflammatory myopathy. Recent findings demonstrated significant molecular similarities between PM-Mito and Inclusion Body Myositis (IBM), suggesting a trajectory from early to late IBM and prompting the inclusion of PM-Mito as an IBM precursor (early IBM) within the IBM spectrum. Both PM-Mito

Chronic facial pain, a frequent and disabling condition, is maintained by central sensitization, which results in pain hypersensitivity. Although it is well established that reactive astrocytes play a key role in persistent pain mechanisms, the role of disruption of the normal capacity of astrocytes to maintain neuronal homeostasis is much less known. Here we show that persistent facial inflammation

Paralysis is assumed permanent in persons with motor-complete spinal cord injury (SCI). However, spinal epidural stimulation combined with activity-based locomotor training (ABLT) and cognitive intent enabled two adults with motor-complete SCI to walk with a walker. Transcutaneous spinal stimulation (scTS), also capable of promoting a cyclic step-like pattern, might be a viable alternative in children

Spreading depolarization (SD) is a slowly propagating wave of massive cellular depolarization that transiently impairs the function of affected brain regions. While SD typically arises as an isolated hemispheric event, we previously reported that reducing M-type potassium current (IKM) by ablation of Kcnq2 in forebrain excitatory neurons results in tightly coupled spontaneous bilateral seizure-SD complexes

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of the motor system marked by significant phenotypic heterogeneity. Motor symptoms in the limbs consistently emerge focally and asymmetrically and, whilst variable, the pattern of regional progression related to the balance of clinical upper and lower motor neuron signs, upper versus lower limb onset and hand dominance to some

SNAREopathies constitute a group of severe genetic neurodevelopmental disorders caused by de novo variants that disturb the synaptic release machinery. These neurodevelopmental disorders comprise highly diverse clinical phenotypes, usually including developmental delay, epilepsy, intellectual disability, and sometimes autism spectrum disorder. Despite major progress in genetic testing, current treatments

Collagen VI-related dystrophies (COL6-RDs) manifest with a spectrum of clinical phenotypes, ranging from Ullrich congenital muscular dystrophy (UCMD), presenting with prominent congenital symptoms and characterised by progressive muscle weakness, joint contractures and respiratory insufficiency, to Bethlem muscular dystrophy, with milder symptoms typically recognised later and at times resembling a

Exposure to traumatic brain injury (TBI) and/or repetitive head impacts (RHI) increases the risk of a range of neurodegenerative pathologies, including chronic traumatic encephalopathy neuropathologic change (CTE-NC). Astrocytic tau pathology reminiscent of aging-related tau astrogliopathy (ARTAG) is a component feature of CTE-NC in many cases. Yet the relationship between TBI/RHI exposure and wider

Although neuropsychiatric symptoms are not part of diagnostic criteria for sporadic Creutzfeldt-Jakob disease a few retrospective studies and our clinical experience have suggested they are prominent and often occur early. The objective of our study was to assess prospectively the neuropsychiatric features in sCJD (and their impact on caregivers) and compare them with five other neurodegenerative diseases:

SEEG cortical stimulation enables individualised mapping of language networks. Regions associated with induced language deficits are marked as ‘language-positive’ and considered important in supporting function. It remains unclear, however, whether small lesions in ‘language-positive’ sites created by radiofrequency thermocoagulation are sufficient to cause language deficits. Thirty-six consecutive

RAB3A encodes a small GTP-binding protein that is abundant in brain synaptic vesicles and crucial for the release of neurotransmitters and synaptic plasticity. Here we identified RAB3A as a candidate gene for autosomal dominant cerebellar ataxia by two independent approaches: linkage in a large dominant ataxia family and, in parallel, an untargeted computational genetic association approach, analyzing

Combinatorial approaches targeting multiple aspects of spinal cord injury (SCI) pathophysiology are needed to maximize functional recovery. We hypothesized that strengthening corticospinal synapses via Hebbian stimulation and increasing neuronal transmission with 4-aminopyridine (4-AP, a potassium blocker) could accelerate locomotor recovery in individuals with chronic SCI. Participants were randomly

This scientific commentary refers to ‘The inferior fronto-occipital fasciculus: bridging phylogeny, ontogeny and functional anatomy’ by Giampiccolo et al. (https://doi.org/10.1093/brain/awaf055).

Intracerebral haemorrhage (ICH), a subtype of stroke, carries a grim prognosis. Inflammatory response during the early phase of ICH is a major perpetuator of neurological damage. Recent clinical studies suggest the possible participation of the CXC chemokine receptor 3 (CXCR3)-chemokine system in mediating neuroimmune crosstalk, which exacerbates neurological dysfunction and may serve as a potential

The ADAT2/ADAT3 (ADAT) complex catalyzes the adenosine to inosine modification at the wobble position of eukaryotic tRNAs. Mutations in ADAT3, the catalytically inactive subunit of the ADAT2/ADAT3 complex, have been identified in patients presenting with severe neurodevelopmental disorders. Yet, the physiological function of ADAT2/ADAT3 complex during brain development remains totally unknown. Here

Neurodegenerative diseases are multi-faceted disorders influenced by and affecting more than just the brain and nervous system. Here, we provide a review of the potential links, including mechanistic and genetic, between kidney health and neurodegeneration, mainly dementia and the two most prevalent late-onset neurodegenerative disorders, Alzheimer’s disease and Parkinson’s disease. We also discuss

Intense political behavior is associated with brain regions involved in emotional and cognitive processing. However, it remains unclear if this neuroanatomy is causal, compensatory, or otherwise correlated. We employed lesion network mapping in a cross-sectional study of 124 male military Veterans with penetrating head trauma. 40-45 years after the injury, participants reported current political behavior

Treatment for drug-resistant epilepsy in poor candidates for resection surgeries remains challenging. The prevailing deep brain stimulation of subcortical nuclei is effective but exhibits heterogeneous efficacy and unpredictable side effects. Therefore, the investigation of novel DBS targets holds paramount importance. Here, we focused on the unique structure known as the extreme capsule (EC), being

Up to 30% of older adults meet pathological criteria for a diagnosis of Alzheimer’s disease at autopsy yet never show signs of cognitive impairment. Recent work has highlighted genetic drivers of this resilience, or better-than-expected cognitive performance given a level of neuropathology, that allow the aged brain to protect itself from the downstream consequences of amyloid and tau deposition. However

Willingness to exert effort for a given goal is dependent on the magnitude of the potential rewards and effort costs of an action. Such effort-based decision making is an essential component of motivation, in which the dopaminergic system plays a key role. Depression in Parkinson's disease (PD) is common, disabling and has poor outcomes. Motivational symptoms such as apathy and anhedonia, are prominent

Risk-taking behaviour is a symptom of multiple neuropsychiatric disorders and often lacks effective treatments. Reward circuitry regions including the amygdala, orbitofrontal cortex, insula, and anterior cingulate have been implicated in risk-taking, but electrophysiological activity predictive of risk taking in these regions is not well understood in humans. Identifying local field potential frequency

Guillain-Barré syndrome is an acute polyradiculoneuropathy in which preceding infections often elicit the production of antibodies that target peripheral nerve antigens, principally gangliosides. Anti-ganglioside antibodies are thought to play a key role in the clinical diversity of the disease and can be helpful in clinical practice. Extensive research into clinical associations of individual anti-ganglioside

Anti-Leucine-rich glioma inactivated-1 (LGI1) and anti-contactin-associated-protein-2 (CASPR2) autoimmune encephalitis (AIE) are common and characterized by pathogenic antibodies targeting neuronal autoantigens. However, the drivers of the antibody-secreting cells (ASC) and involvement of T cells remain unresolved. We performed single cell RNA-sequencing of fresh cerebrospinal fluid (CSF) and parallel

Studies assessing genetic associations with neuropathological features in Lewy body disease (LBD) have been limited to candidate gene investigations, and therefore information is lacking regarding the genetic architecture of the neuropathology of LBD. In the current study, we examined a large series of neuropathologically-confirmed LBD cases (N=980 in the discovery series, N=503 in the replication

This scientific commentary refers to ‘Visual feature processing in a large stroke cohort: evidence against modular organization’ by Lugtmeijer, Sobolewska et al. (https://doi.org/10.1093/brain/awaf009).

Parkinson’s disease is characterized, in part, by hypoactivity of direct pathway inhibitory projections from striatum to the globus pallidus internus (GPi) and indirect pathway inhibitory projections from globus pallidus externus (GPe) to the subthalamic nucleus (STN). In people with Parkinson’s disease (n=32), we explored the potential use of intracranial stimulation for eliciting long-term potentiation

Patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, often present with severe psychiatric symptoms, yet the neuropathological mechanisms underlying their cognitive deficits remain insufficiently understood. In this study, we constructed an animal model using anti-NMDAR IgG purified from the serum of patients with anti-NMDAR encephalitis, and we used IgG obtained from healthy

Ischemic strokes disrupt brain networks, leading to remote effects in key regions like the thalamus, a critical hub for brain functions. However, non-invasive methods to quantify these remote consequences still need to be explored. This study aimed to demonstrate that MRI-derived R2* changes can capture iron accumulation linked with inflammation secondary to stroke-induced disconnection. In order to

After stroke, upper extremity (UE) motor recovery may be mediated in part by transcallosal projections between hemispheres. The interhemispheric competition model posits that transcallosal inhibition (TI) from the contralesional hemisphere is abnormally strengthened following stroke and interferes with motor recovery. This model has recently been questioned. In this longitudinal study, we aimed to

Raised intracranial pressure (ICP) is associated with altered cerebral hemodynamics and cephalic pain. The relationship between the algetic response and cortical neurovascular changes in raised ICP is unclear. This study aimed to evaluate this relationship and determine if lowering ICP (using a glucagon like peptide-1 receptor agonist) could ameliorate the algetic response. We also sought to explore

This scientific commentary refers to ‘Distinctive clinical features in biopsy-proven nerve large-arteriole vasculitis and microvasculitis’ by Soontrapa et al. (https://doi.org/10.1093/brain/awae406).

Epilepsy surgery can eliminate seizures in patients with drug-resistant focal epilepsy. Surgical intervention requires proper identification of the epileptic network and often involves implanting stereo-EEG electrodes in patients where non-invasive methods are insufficient. However, only ∼60% of patients achieve seizure-freedom following surgery. Quantitative methods have been developed to help improve

Malformations of cortical development (MCDs) are a heterogeneous family of congenital brain malformations that originate from disturbed development of the cerebral cortex. MCDs can arise from primary genetic disorders that lead to dysfunction of the molecular processes controlling neuronal proliferation, neuronal migration, cortical folding, or cortical organization. MCDs can also result from secondary

Epilepsy is recognised as one of the leading targets for precision medicine, following on from the successes in cancer therapy, due to its substantial clinical heterogeneity and divergent therapeutic options. To bring personalised care to the epilepsies, there is a need for appropriate precision biomarkers that can identify disease processes or predict treatment outcomes at the individual patient level

Yang et al. propose that psychedelics hold untapped potential for improving stroke recovery through their unique ability to modulate neuroplasticity, reduce neuroinflammation, and enhance cognitive and psychological resilience.

Impulse control disorders (ICDs) are frequent and particularly distressing neuropsychiatric symptoms in patients with Parkinson’s disease (PD) which are related to impaired behavioural inhibition. Multiple PET imaging studies indicate that striatal dopaminergic abnormalities contribute to hyperdopaminergic functioning in PD patients with ICD (PDICD+) and to the dysregulation of the limbic fronto-striatal

Neuromyelitis optica (NMO) is an acute inflammatory demyelinating disease of the CNS. The presence of astrocyte-targeted AQP4-immunoglobulin G (IgG) in peripheral blood is a major factor in its diagnosis. Previous studies show that AQP4-IgG directly contributes to CNS inflammation, and B cells play a central pathogenic role in NMO. However, where and how B cell response is altered remains controversial

Whiplash Associated Disorders (WAD) affect 20-50 million individuals globally each year, with up to 50% developing persistent pain. WAD grade II (WADII) is the most common type and is characterised by neck symptoms and musculoskeletal signs without apparent nerve injury on routine diagnostic testing. However, emerging evidence suggests nerve pathology may be present in some people with WADII. This

Children who experienced moderate perinatal hypoxia are at risk of developing long-lasting subtle cognitive and behavioural deficits, including learning disabilities and emotional problems. Understanding the underlying mechanisms is an essential step for designing targeted therapy. Fast-spiking, parvalbumin-positive (PV) GABAergic interneurons modulate the generation of gamma oscillations, which in

While neuropathological and genetic studies have established the crucial involvement of TDP-43 proteinopathy in the pathogenesis of ALS (Amyotrophic Lateral Sclerosis), FTD (Frontotemporal Dementia) and related neurodegenerative disorders, multiple studies have described the presence of TDP-43 inclusions in muscular disorders, including inclusion body myositis but also other related rimmed vacuole

Neuroinflammation is a feature of many neurodegenerative diseases, and is quantified in vivo by PET imaging with radioligands for the translocator protein (TSPO, e.g. [11C]-PK11195). TSPO radioligand binding correlates with clinical severity and predicts clinical progression. However, the cellular substrate of altered TSPO binding is controversial and requires neuropathological validation. We used

Tuberous sclerosis complex (TSC) is an inherited multi-system neurocutaneous disorder where patients often present with neurodevelopmental manifestations such as epilepsy and TSC-associated neuropsychiatric disorder (TAND) that includes autism spectrum disorder (ASD). TSC is caused by inactivating mutations in TSC1 or TSC2 tumor suppressor genes, with encoded proteins hamartin (TSC1) and tuberin (TSC2)