Prefrontal activation and pupil dilation during n-back task performance: A combined fNIRS and pupillometry study
Introduction
Human short-term memory has a limited capacity (Baddeley, 2012; Miller, 1956). Therefore, the ability to replace old, irrelevant information with information that is relevant to the current context is a core aspect of executive function essential for the pursuit of goals (Miyake et al., 2000). In cognitive neuroscience, the n-back task has been one of the most widely used working memory (WM) paradigms (Kirchner, 1958). Studies using this task have shown that accuracy and reaction time (RT) worsen with increasing WM load across ages and materials (Boisgueheneuc et al., 2006; Bopp and Verhaeghen, 2020). Additionally, meta-analyses of the positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) literature have identified activity in the bilateral dorsolateral and ventrolateral prefrontal cortex (PFC), premotor cortex, supplementary motor area, and parietal cortex that increases with increasing WM load during the n-back task (Mencarelli et al., 2019; Owen et al., 2005; Rottschy et al., 2012; Yaple et al., 2019). Studies using functional near-infrared spectroscopy (fNIRS) have also generated converging evidence of the involvement of the bilateral lateral PFC during this task (Ito et al., 2011; Koike et al., 2013; Kopf et al., 2013; Yeung et al., 2016, 2019). It is generally assumed that activation in various PFC subregions during the n-back task reflects the active operation of the cognitive processes associated with the executive control of WM, such as the storage and manipulation of internal representations, monitoring incoming information, the implementation of stimulus response mapping, and the use of organizational strategies (Mencarelli et al., 2019; Owen et al., 2005).
Accumulated evidence indicates that the pupil size of the eye increases in response to an increasing cognitive load during a variety of tasks (Beatty, 1982; Kahneman and Beatty, 1966; van der Wel and van Steenbergen, 2018). In the context of the n-back task, the pupil size increases with an increasing WM load (Belayachi et al., 2015; Karatekin et al., 2007; Niezgoda et al., 2015; Scharinger et al., 2015). It is well known that the pupil size is influenced by the sympathetic and parasympathetic branches of the autonomic nervous system, which is modulated by the locus-coeruleus (LC) norepinephrine system (Joshi et al., 2016; McDougal and Gamlin, 2011; Murphy et al., 2014; Samuels and Szabadi, 2008). The LC has been implicated in the regulation of arousal and vigilance (Sara and Bouret, 2012). Therefore, the task-evoked pupillary response has been and can be employed as a proxy measure for arousal and mental effort (i.e., LC activity; Bradley et al., 2008; Mathôt, 2018). In the present study, arousal refers to the degree of vigilance and alertness during periods of wakefulness, manifesting as motor activation, responsiveness to sensory inputs, emotional reactivity, and enhanced cognitive processing (Carter et al., 2013). Arousal is expected to occur during the n-back task because individuals have to detect incoming sensory stimuli, operate on the information, and generate an efferent response in a timely manner.
The LC extensively innervates the cerebral cortex of all hemispheric lobes, including the dorsolateral and the dorsomedial PFC (Arnsten and Goldman-Rakic, 1984; Aston-Jones and Cohen, 2005). Neurons in this small pontine nucleus are the primary source of cortical norepinephrine (Samuels and Szabadi, 2008). Thus, the LC is implicated in the regulation of arousal and mental effort across many tasks, playing a general, modulatory role in neocortical functions. In contrast, the lateral PFC is implicated in executive control and goal-directed behavior (Petrides, 2005). This region represents a primary site of WM and plays a crucial role in n-back task performance (Barbey et al., 2013; Levy and Goldman-Rakic, 2000; Tsuchida and Fellows, 2009). Although lateral PFC activation and pupil dilation have been separately observed during n-back task performance, whether they are functionally related to each other remains elusive. In addition, the effect of WM demand on the relationship between activity in the lateral PFC and the LC during the n-back task, if any, remains unclear. A high WM load may enhance the functional integration of the two systems due to the increased general, modulatory effects exerted by the LC system on the cortex. Alternatively, it may reduce the functional coupling between the lateral PFC and the LC, or remove the co-dependence of the two systems, due to the specialized role of the lateral PFC in WM and to a LC or norepinephrine-induced increase in local neural communications within network during task performance (Eldar et al., 2013).
The aim of this study was to examine the relationship between changes in lateral PFC activity and the pupil diameter (a proxy for LC activity) during n-back task performance. In addition, the effect of WM load on such relationship was investigated by evaluating the correlation between the moment-to-moment changes in lateral PFC activity and the pupil size at two WM load levels (i.e., 0- and 3-back conditions). A significant positive correlation between the observed [oxy-Hb] changes and the [oxy-Hb] changes predicted from the pupil signal would suggest that lateral PFC activity and pupil dilation were subtended by common mechanisms. In contrast, a nonsignificant zero correlation between the observed and the predicted [oxy-Hb] changes would indicate that the two proxies might be underpinned by distinct mechanisms, and more evidence is needed to elucidate the relationship. Clarifying the functional relationship between the lateral PFC and the LC during the n-back task would give us insights into the meaning of lateral PFC activity (e.g., lateral PFC activity correlating with arousal level) during this task.
There is growing recognition that fNIRS is relatively tolerant to motion and is free from environmental interference (Ferrari and Quaresima, 2012). Thus, fNIRS is a suitable tool to use in conjunction with eye trackers, and it is an excellent tool for monitoring brain activity in a natural setting (Hosseini et al., 2017; İşbilir et al., 2019). For these reasons, we used fNIRS to probe prefrontal hemodynamic changes. Due to the use of a blocked design and fast trial presentation to increase power, the distinction between a shift in tonic and phase LC activity (Aston-Jones and Cohen, 2005) in response to increased WM load would not and could not be made in the present study.
Section snippets
Participants
Thirty-nine right-handed college students (10 males, 29 females) aged between 18 and 24 years (Mean = 19.8 years; SD = 1.5 years) were recruited from the subject pool of the Chinese University of Hong Kong. This sample size was larger than those in most of the previous fNIRS and pupillometry studies using the n-back task (e.g., Ito et al., 2011; Karatekin et al., 2007; Niezgoda et al., 2015; Yeung et al., 2016). No participant reported a history of psychiatric or neurological disorder, and none
Behavioral performance
First, performance in terms of A′ and the mean RT during the n-back task was examined. Table 1a presents the means and SDs of these two variables in the 0- and 3-back conditions. Paired t-tests comparing the two conditions showed that A’ was significantly lower in the 3-back condition than in the 0-back condition, t(38) = 8.56, p < 0.001, d = 1.37. Additionally, the mean RT was significantly slower in the 3-back condition than in the 0-back condition, t(38) = 7.85, p < 0.001, d = 1.26. These
Discussion
This study's aim was to determine the relationship between changes in lateral PFC activity and the pupil size (a proxy for LC activity), as well as the effect of WM load on such relationship. It is the first to examine changes in PFC activity and the pupil size simultaneously measured during the n-back task. In keeping with the existing fMRI (Mencarelli et al., 2019; Owen et al., 2005) and fNIRS (Koike et al., 2013; Yeung et al., 2016, 2019) literature, we found negligible PFC activation at a
Credit author statement
MKY: Conceptualization, Methodology, Data Curation, Software, Formal Analysis, Writing - Original Draft, Visualization TLL: Conceptualization, Data Curation, Writing - Review & Editing YMYH: Writing - Review & Editing ASC: Conceptualization, Methodology, Supervision, Writing - Review & Editing.
Declaration of competing interest
The authors have no conflict of interest to declare.
References (71)
- et al.
Neuroticism and the pupillary response to a brief exposure to noise
Biol. Psychol.
(1983) - et al.
Selective prefrontal cortical projections to the region of the locus coeruleus and raphe nuclei in the rhesus monkey
Brain Res.
(1984) - et al.
Dorsolateral prefrontal contributions to human working memory
Cortex
(2013) - et al.
Are the carrot and the stick the two sides of same coin? A neural examination of approach/avoidance motivation during cognitive performance
Behav. Brain Res.
(2015) - et al.
Functional near infrared spectroscopy (NIRS) signal improvement based on negative correlation between oxygenated and deoxygenated hemoglobin dynamics
Neuroimage
(2010) - et al.
A quantitative comparison of NIRS and fMRI across multiple cognitive tasks
Neuroimage
(2011) - et al.
Reduced lateral prefrontal activation in adult patients with attention-deficit/hyperactivity disorder (ADHD) during a working memory task: a functional near-infrared spectroscopy (fNIRS) study
J. Psychiatr. Res.
(2008) - et al.
A brief review on the history of human functional near-infrared spectroscopy (fNIRS) development and fields of application
Neuroimage
(2012) - et al.
Event-related fMRI: characterizing differential responses
Neuroimage
(1998) - et al.
Gaze position regulates memory accessibility during competitive memory retrieval
Cognition
(2020)
Relationships between pupil diameter and neuronal activity in the locus coeruleus, colliculi, and cingulate cortex
Neuron
Automated cortical projection of EEG sensors: anatomical correlation via the international 10–10 system
Neuroimage
Reduced but broader prefrontal activity in patients with schizophrenia during n-back working memory tasks: a multi-channel near-infrared spectroscopy study
J. Psychiatr. Res.
Exploring brain-behavior relationships in the N-back task
Neuroimage
The unity and diversity of executive functions and their contributions to complex “frontal lobe” tasks: A latent variable analysis
Cognit. psychol.
Towards testing auditory–vocal interfaces and detecting distraction while driving: a comparison of eye-movement measures in the assessment of cognitive workload
Transport. Res. F Traffic Psychol. Behav.
Three-dimensional probabilistic anatomical cranio-cerebral correlation via the international 10–20 system oriented for transcranial functional brain mapping
Neuroimage
Event-related functional near-infrared spectroscopy (fNIRS): are the measurements reliable?
Neuroimage
Modelling neural correlates of working memory: a coordinate-based meta-analysis
Neuroimage
Orienting and reorienting: the locus coeruleus mediates cognition through arousal
Neuron
Disentangling reward anticipation with simultaneous pupillometry/fMRI
Neuroimage
Age dependency of the hemodynamic response as measured by functional near-infrared spectroscopy
Neuroimage
Investigating the post-stimulus undershoot of the BOLD signal—a simultaneous fMRI and fNIRS study
Neuroimage
Modulation of large-scale cortical coupling by transcranial alternating current stimulation
Brain Stimul.
Multiple frontal systems controlling response speed
Neuropsychologia
Meta-analyses of the n-back working memory task: fMRI evidence of age-related changes in prefrontal cortex involvement across the adult lifespan
Neuroimage
Right-lateralized frontal activation underlies successful updating of verbal working memory in adolescents with high-functioning autism spectrum disorder
Biol. Psychol.
An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance
Annu. Rev. Neurosci.
Working memory: theories, models, and controversies
Annu. Rev. Psychol.
Frontal lobe mechanisms that resolve proactive interference
Cerebr. Cortex
Task-evoked pupillary responses, processing load, and the structure of processing resources
Psychol. Bull.
Functions of the left superior frontal gyrus in humans: a lesion study
Brain
Aging and n-back performance: a meta-analysis
J. Gerontol.: Ser. Bibliogr.
The pupil as a measure of emotional arousal and autonomic activation
Psychophysiology
Physiological characteristics of capacity constraints in working memory as revealed by functional MRI
Cerebr. Cortex
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