Topographical Distribution of Neuroanatomical Abnormalities Following COVID-19 Invasion : A Systematic Literature Review.

PURPOSE: This systematic review is aimed at synthesising the literature base to date on the frequency and topographical distribution of neuroanatomical changes seen on imaging following COVID-19 invasion with a focus on both the acute and chronic phases of the disease. METHODS: In this study, 8 databases were systematically searched to identify relevant articles published from December 2019 to March 2022 and supplemented with a manual reference search. Data were extracted from the included studies and narrative synthesis was employed to integrate the findings. RESULTS: A total of 110 studies met the inclusion criteria and comprised 119,307 participants (including 31,073 acute and 143 long COVID-19 patients manifesting neurological alterations) and controls. Considerable variability in both the localisation and nature of neuroanatomical abnormalities are noted along the continuum with a wide range of neuropathologies relating to the cerebrovascular/neurovascular system, (sub)cortical structures (including deep grey and white matter structures), brainstem, and predominant regional and/or global alterations in the cerebellum with varying degrees of spinal involvement. CONCLUSION: Structural regional alterations on neuroimaging are frequently demonstrated in both the acute and chronic phases of SARS-CoV­2 infection, particularly prevalent across subcortical, prefrontal/frontal and cortico-limbic brain areas as well as the cerebrovascular/neurovascular system. These findings contribute to our understanding of the acute and chronic effects of the virus on the nervous system and has the potential to provide information on acute and long-term treatment and neurorehabilitation decisions.

The effect of negative arousal on declarative memory.

Arousing events influence retrieval success, with a number of studies supporting a context-dependent effect of arousal on episodic memory retrieval. An improvement in speed and accuracy of episodic memories is observed when negative arousal is attached to them. In contrast, enhancing effects of negative arousal have not been reported to improve semantic memory retrieval. Episodic and semantic memory are highly interactive and yet differ based on their embedded contextual content. Although differences in brain activity exist between episodic and semantic memory, the two types of memory retrieval are part of a common long-term memory system. Considering the shared processes between episodic and semantic memory, the objectives of the current study were twofold: i) to examine, employing a novel paradigm, whether performance on episodic and semantic memory retrieval would be influenced differently by varying levels of arousal, between negative and neutral valence; and ii) to explore the neural patterns underlying these processes. Forty-seven healthy young adults were recruited and completed the experiment in the MRI scanner. The results demonstrated a negative arousal effect on the brain circuitry subserving both memory conditions as well as on behavioural performance, as indicated by better accuracy and faster reaction times. The study provides an insight into the role of negative arousal in memory processes and contributes to our understanding of the interplay between cognitive and emotional factors in memory modulation. Our work also highlights the highly interactive nature of episodic and semantic memory, and emphasises the importance in understanding how negative arousal interacts with the contextual content of a memory, on a behavioural and neurofunctional level.

The effects of age bias on neural correlates of successful and unsuccessful response inhibition in younger and older adults.

Facilitating communication between generations has become increasingly important. However, individuals often demonstrate a preference for their own age group, which can impact social interactions, and such bias in young adults even extends to inhibitory control. To assess whether older adults also experience this phenomenon, a group of younger and older adults completed a Go/NoGo task incorporating young and old faces, while undergoing functional magnetic resonance imaging. Within the networks subserving successful and unsuccessful response inhibition, patterns of activity demonstrated distinct neural age bias effects in each age group. During successful inhibition, the older adult group demonstrated significantly increased activity to other-age faces, whereas unsuccessful inhibition in the younger group produced significantly enhanced activity to other-age faces. Consequently, the findings of the study confirm that neural responses to successful and unsuccessful inhibition can be contingent on the stimulus-specific attribute of age in both younger and older adults. These findings have important implications in regard to minimizing the emergence of negative consequences, such as ageism, as a result of related implicit biases.

Spikes with and without concurrent high-frequency oscillations: Topographic relationship and neural correlates using EEG-fMRI.

OBJECTIVE: Epilepsy surgery is the best therapeutic option for patients with drug-resistant focal epilepsy. During presurgical investigation, interictal spikes can provide important information on eligibility, lateralisation and localisation of the surgical target. However, their relationship to epileptogenic tissue is variable. Interictal spikes with concurrent high-frequency oscillations (HFOs) have been postulated to reflect epileptogenic tissue more reliably. Here, we studied the voltage distribution of scalp-recorded spikes with and without concurrent HFO and identified their respective haemodynamic correlates using simultaneous electroencephalography and functional Magnetic Resonance Imaging (EEG-fMRI). METHODS: The scalp topography of spikes with and without concurrent HFOs were assessed in 31 consecutive patients with focal drug-resistant epilepsy who showed interictal spikes during presurgical evaluation. Simultaneous EEG-fMRI was then used in 17 patients with spikes and concurrent HFOs. Haemodynamic changes were obtained from the spatial correlation between the patient-specific voltage map of each spike population and the intra-scanner EEG. The haemodynamic response of spikes with and without HFOs were compared in terms of their spatial similarity, strength, the distance between activation peaks and concordance with interictal localisation. RESULTS: Twenty-five patients showed spikes with and without concurrent HFOs. Among patients with both types of spikes, most spikes were not associated with HFOs (p < 0.0001, Mann-Whitney test). Twenty of the 25 patients showed an average of 8 ± 6 (standard deviation) electrodes with significant voltage differences (p = 0.025, permutation test corrected for multiple comparisons) on scalp electrodes within and distant to the spike field. Comparing the haemodynamic response between both spike populations, we found no significant differences in the peak strength (p = 0.71, Mann-Whitney test), spatial distribution (p = 0.113, One-sample Wilcoxon test) and distance between activation peaks (p = 0.5, One-sample Wilcoxon test), with all peaks being co-localised in the same lobe. SIGNIFICANCE: Our data showed that spikes with and without HFOs have different scalp voltage distributions. However, when assessing the haemodynamic changes of each spike type, we found that both elicit similar haemodynamic changes and share high spatial similarity suggesting that the epileptic networks of spikes with and without HFOs have the same underlying neural substrate.

The effects of age-bias on neural correlates of successful and unsuccessful response inhibition.

Response inhibition is important for adherence to social norms, especially when norms conflict with biases based on one's social identity. While previous studies have shown that in-group bias generally modulates neural activity related to stimulus appraisal, it is unclear whether and how an in-group bias based on age affects neural information processing during response inhibition. To assess this potential influence, young adults completed a Go/NoGo task incorporating younger face (in-group) and older face (out-group) stimuli while undergoing functional magnetic resonance imaging (fMRI). Our results replicated previous findings by demonstrating higher accuracy in successful Go compared to NoGo trials, as well as the engagement of nodes of the response inhibition network during successful response inhibition, and brain regions comprising the salience network during unsuccessful response inhibition. Importantly, despite a lack of behavioural differences, our results showed that younger and older face stimuli modulated activity in the response inhibition and salience networks during successful and unsuccessful inhibition, respectively. Interestingly, these effects were not uniform across networks. During successful response inhibition, in-group stimuli increased activity in medial prefrontal cortex and temporo-parietal junction, whereas out-group stimuli more strongly engaged pre-supplemental motor area. During unsuccessful response inhibition, in-group stimuli increased activity in posterior insula, whereas out-group stimuli more strongly engaged angular gyrus and intraparietal sulcus. Consequently, the results infer the presence of an age-bias effect in the context of inhibitory control, which has substantial implications for future experimental design and may also provide the means of investigating the neural correlates of implicit beliefs that contribute to ageism.

Weaker connectivity in resting state networks is associated with disinhibited eating in older adults.

BACKGROUND/OBJECTIVES: Obesity affects more than forty percent of adults over the age of sixty. Aberrant eating styles such as disinhibition have been associated with the engagement of brain networks underlying executive functioning, attentional control, and interoception. However, these effects have been exclusively studied in young samples overlooking those most at risk of obesity related harm. METHODS: Here we assessed associations between resting-state functional connectivity and disinhibited eating (using the Three Factor Eating Questionnaire) in twenty-one younger (aged 19-34 years, BMI range: 18-31) and twenty older (aged 60-73 years, BMI range: 19-32) adults matched for BMI. The Alternative Healthy Eating Index was used to quantify diet quality. RESULTS: Older, compared to younger, individuals reported lower levels of disinhibited eating, consumed a healthier diet, and had weaker connectivity in the frontoparietal (FPN) and default mode (DMN) networks. In addition, associations between functional connectivity and eating behaviour differed between the two age groups. In older adults, disinhibited eating was associated with weaker connectivity in the FPN and DMN--effects that were absent in the younger sample. Importantly, these effects could not be explained by differences in habitual diet. CONCLUSIONS: These findings point to a change in interoceptive signalling as part of the ageing process, which may contribute to behavioural changes in energy intake, and highlight the importance of studying this under researched population.

Salience and default-mode network connectivity during threat and safety processing in older adults.

The appropriate assessment of threat and safety is important for decision-making but might be altered in old age due to neurobiological changes. The literature on threat and safety processing in older adults is sparse and it is unclear how healthy ageing affects the brain's functional networks associated with affective processing. We measured skin conductance responses as an indicator of sympathetic arousal and used functional magnetic resonance imaging and independent component analysis to compare young and older adults' functional connectivity in the default mode (DMN) and salience networks (SN) during a threat conditioning and extinction task. While our results provided evidence for differential threat processing in both groups, they also showed that functional connectivity within the SN - but not the DMN - was weaker during threat processing in older compared to young adults. This reduction of within-network connectivity was accompanied by an age-related decrease in low frequency spectral power in the SN and a reduction in inter-network connectivity between the SN and DMN during threat and safety processing. Similarly, we found that skin conductance responses were generally lower in older compared to young adults. Our results are the first to demonstrate age-related changes in brain activation during aversive conditioning and suggest that the ability to adaptively filter affective information is reduced in older adults.

Functional Interplay Between Posterior Parietal Cortex and Hippocampus During Detection of Memory Targets and Non-targets.

Posterior parietal cortex is frequently activated during episodic memory retrieval but its role during retrieval and its interactions with the hippocampus are not yet clear. In this fMRI study, we investigated the neural bases of recognition memory when study repetitions and retrieval goals were manipulated. During encoding participants studied words either once or three times, and during retrieval they were rewarded more to detect either studied words or new words. We found that (1) dorsal parietal cortex (DPC) was more engaged during detection of items studied once compared to three times, whereas regions in the ventral parietal cortex (VPC) responded more to items studied multiple times; (2) DPC, within a network of brain regions functionally connected to the anterior hippocampus, responded more to items consistent with retrieval goals (associated with high reward); (3) VPC, within a network of brain regions functionally connected to the posterior hippocampus, responded more to items not aligned with retrieval goals (i.e., unexpected). These findings support the hypothesis that DPC and VPC regions contribute differentially to top-down vs. bottom-up attention to memory. Moreover, they reveal a dissociation in the functional profile of the anterior and posterior hippocampi.

Functional connectivity of the irritative zone identified by electrical source imaging, and EEG-correlated fMRI analyses.

OBJECTIVE: The irritative zone - the area generating epileptic spikes - can be studied non-invasively during the interictal period using Electrical Source Imaging (ESI) and simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI). Although the techniques yield results which may overlap spatially, differences in spatial localization of the irritative zone within the same patient are consistently observed. To investigate this discrepancy, we used Blood Oxygenation Level Dependent (BOLD) functional connectivity measures to examine the underlying relationship between ESI and EEG-fMRI findings. METHODS: Fifteen patients (age 20-54), who underwent presurgical epilepsy investigation, were scanned using a single-session resting-state EEG-fMRI protocol. Structural MRI was used to obtain the electrode localisation of a high-density 64-channel EEG cap. Electrical generators of interictal epileptiform discharges were obtained using a distributed local autoregressive average (LAURA) algorithm as implemented in Cartool EEG software. BOLD activations were obtained using both spike-related and voltage-map EEG-fMRI analysis. The global maxima of each method were used to investigate the temporal relationship of BOLD time courses and to assess the spatial similarity using the Dice similarity index between functional connectivity maps. RESULTS: ESI, voltage-map and spike-related EEG-fMRI methods identified peaks in 15 (100%), 13 (67%) and 8 (53%) of the 15 patients, respectively. For all methods, maxima were localised within the same lobe, but differed in sub-lobar localisation, with a median distance of 22.8 mm between the highest peak for each method. The functional connectivity analysis showed that the temporal correlation between maxima only explained 38% of the variance between the time course of the BOLD response at the maxima. The mean Dice similarity index between seed-voxel functional connectivity maps showed poor spatial agreement. SIGNIFICANCE: Non-invasive methods for the localisation of the irritative zone have distinct spatial and temporal sensitivity to different aspects of the local cortical network involved in the generation of interictal epileptiform discharges.

Motor neuroplasticity: A MEG-fMRI study of motor imagery and execution in healthy ageing.

Age-related decline in motor function is associated with over-activation of the sensorimotor circuitry. Using a multimodal MEG-fMRI paradigm, we investigated whether this neural over-recruitment in old age would be related to changes in movement-related beta desynchronization (MRBD), a correlate of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), and whether it would characterize compensatory recruitment or a reduction in neural specialization (dedifferentiation). We used MEG to assess age-related changes in beta band oscillations in primary motor cortices, fMRI to localize age-related changes in brain activity, and the Finger Configuration Task to measure task performance during overt and covert motor processing: motor execution (ME) and motor imagery (MI). The results are threefold: first, showing age-related neuroplasticity during ME of older adults, compared to young adults, as evidenced by increased MRBD in motor cortices and over-recruitment of sensorimotor areas; second, showing similar age-related neuroplastic changes during MI; and finally, showing signs of dedifferentiation during ME in older adults whose performance negatively correlated with connectivity to bilateral primary motor cortex. Together, these findings demonstrate that elevated MRBD levels, reflecting greater GABAergic inhibitory activity, and over-activation of the sensorimotor network during ME may not be compensatory, but rather might reflect an age-related decline of the quality of the underlying neural signal.

Stria terminalis, amygdala, and temporoparietal junction networks facilitate efficient emotion processing under expectations.

Rapid emotion processing is an ecologically essential ability for survival in social environments in which threatening or advantageous encounters dynamically and rapidly occur. Efficient emotion recognition is subserved by different processes, depending on one's expectations; however, the underlying functional and structural circuitry is still poorly understood. In this study, we delineate brain networks that subserve fast recognition of emotion in situations either congruent or incongruent with prior expectations. For this purpose, we used multimodal neuroimaging and investigated performance on a dynamic emotion perception task. We show that the extended amygdala structural and functional networks relate to speed of emotion processing under threatening conditions. Specifically, increased microstructure of the right stria terminalis, an amygdala white-matter pathway, was related to faster detection of emotion during actual presentation of anger or after cueing anger. Moreover, functional connectivity of right amygdala with limbic regions was related to faster detection of anger congruent with cue, suggesting selective attention to threat. On the contrary, we found that faster detection of anger incongruent with cue engaged the ventral attention "reorienting" network. Faster detection of happiness, in either expectancy context, engaged a widespread frontotemporal-subcortical functional network. These findings shed light on the functional and structural circuitries that facilitate speed of emotion recognition and, for the first time, elucidate a role for the stria terminalis in human emotion processing.

Towards Establishing Age-Related Cortical Plasticity on the Basis of Somatosensation.

Age-related somatosensory processing appears to remain intact where tasks engage centrally- as opposed to peripherally-mediated mechanisms. This distinction suggests that insight into alterations in neural plasticity could be derived via metrics of vibrotactile performance. Such an approach could be used to support the early detection of global changes in brain health but current evidence is limited. Knowledge of the precise conditions in which older adults are expected to sustain somatosensory performance is largely unknown. For this purpose, the study aimed to characterize age-related performance on tactile detection and discrimination-based tests. Accordingly, a group of young and older adult participants took part in simple reaction time and amplitude discrimination tasks. Participants' ability to distinguish between stimuli on the basis of amplitude was assessed with and without dual-site adaptation, which has been proposed to refine cortical responses and improve behavioral performance. The results show that while older adults exhibited significantly prolonged (p < .001, d = 1.116) and more variable (p = .022, d = 0.578) information processing speed compared to young adults, they were able to achieve similar scores in baseline discrimination (p = .179, d = 0.336). We also report, for the first time, that older adults displayed similar performance improvements to young adults, under conditions of dual-site adaptation (p = .948, d = 0.016). The findings support the argument that centrally-mediated mechanisms remain intact in the ageing population. Accordingly, dual-site adaptation data provide compelling new evidence of somatosensation in ageing that will contribute towards the development of an assessment tool to ascertain pre-clinical, age-related changes in the status of cortical function.

Differentiation of functional networks during long-term memory retrieval in children and adolescents.

The processes that characterize the neural development of long-term memory (LTM) are largely unknown. In young adults, the degree of activation of a single large-scale memory network corresponds to the level of contextual detail involved; thus, differentiating between autobiographical, episodic, and semantic retrieval. In contrast to young adults, children and adolescents retrieve fewer contextual details, suggesting that they might not yet engage the entire memory circuitry and that this brain recruitment might lack the characteristic contextual differentiation found in adults. Twenty-one children (10-12 years of age), 20 adolescents (14-16 years of age), and 22 young adults (20-35 years of age) were assessed on a previously validated LTM retrieval task, while their brain activity was measured with functional magnetic resonance imaging. The results demonstrate that children, adolescents, and adults recruit a left-lateralized subset of the large-scale memory network, comprising semantic and language processing regions, with neither developmental group showing evidence of contextual differentiation within this network. Additionally, children and adolescents recruited occipital and parietal regions during all memory recall conditions, in contrast to adults who engaged the entire large-scale memory network, as described previously. Finally, a significant covariance between age and brain activation indicates that the reliance on occipital and parietal regions during memory retrieval decreases with age. These results suggest that both children and adolescents rely on semantic processing to retrieve long-term memories, which, we argue, may restrict the integration of contextual detail required for complex episodic and autobiographical memory retrieval.

Evidence for a functional specialization of ventral anterior temporal lobe for language.

The controlled semantic cognition framework proposes that the ventral anterior temporal lobes (vATL) in the left and right hemisphere function as an integrated hub region supporting transmodal semantic representations. The clinical evidence for the transmodal function of vATL is largely based on studies of semantic dementia patients with severe anomia, who also show impaired performance on nonverbal tasks that involve the retrieval of knowledge about objects and their prototypical use, such as the production of tool use pantomimes. Yet, evidence from patients with apraxia and functional neuroimaging studies in healthy adults does not implicate vATL in pantomime production. We, therefore, compared semantic retrieval of object-action associations for overt verb and pantomime production from picture and word stimuli. Our results show that, independent of stimulus modality, the retrieval of object-action associations for verb, but not pantomime, production is related to activity in bilateral vATL. Bilateral vATL activation was also observed for meaningless verbal responses that did not require the retrieval of object-action associations. Taken together, our results suggest that bilateral vATL is not engaged in the retrieval of object-action associations per se, but rather supports semantic representations that are functionally specialized for language. These findings have implications for the semantic cognition framework and our understanding of the dependence of conceptual knowledge on language.

Neural correlates of dynamic emotion perception in schizophrenia and the influence of prior expectations.

Impaired emotion perception is a well-established and stable deficit in schizophrenia; however, there is limited knowledge about the underlying aberrant cognitive and brain processes that result in emotion perception deficits. Recent influential work has shown that perceptual deficits in schizophrenia may result from aberrant precision in prior expectations, associated with disrupted activity in frontal regions. In the present study, we investigated the perception of dynamic, multisensory emotion, the influence of prior expectations and the underlying aberrant brain processes in schizophrenia. During a functional Magnetic Resonance Imaging scan, participants completed the Dynamic Emotion Perception task, which induces prior expectations with emotion instruction cues. We delineated neural responses and functional connectivity in whole-brain large-scale networks underlying emotion perception. Compared to healthy individuals, schizophrenia patients had lower accuracy specifically for emotions that were congruent with prior expectations. At the neural level, schizophrenia patients had less engagement of right inferior frontal and parietal regions, as well as right amygdala dysconnectivity during discrimination of emotions congruent with prior expectations. The results indicate that individuals with schizophrenia may have aberrant prior expectations about emotional expressions, associated with under-activity in inferior frontoparietal regions and right amygdala dysconnectivity, which results in impaired perception of emotion.

Association between schizophrenia polygenic risk and neural correlates of emotion perception.

The neural correlates of emotion perception have been shown to be significantly altered in schizophrenia (SCZ) patients as well as their healthy relatives, possibly reflecting genetic susceptibility to the disease. The aim of the study was to investigate the association between SCZ polygenic risk and brain activity whilst testing perception of multisensory, dynamic emotional stimuli. We created SCZ polygenic risk scores (PRS) for a sample of twenty-eight healthy individuals. The PRS was based on data from the Psychiatric Genomics Consortium and was used as a regressor score in the neuroimaging analysis. The results of a multivariate brain-behaviour analysis show that higher SCZ PRS are related to increased activity in brain regions critical for emotion during the perception of threatening (angry) emotions. These results suggest that individuals with higher SCZ PRS over-activate the neural correlates underlying emotion during perception of threat, perhaps due to an increased experience of fear or neural inefficiency in emotion-regulation areas. Moreover, over-recruitment of emotion regulation regions might function as a compensation to maintain normal emotion regulation during threat perception. If replicated in larger studies, these findings may have important implications for understanding the neurophysiological biomarkers relevant in SCZ.

Altered functional connectivity in mesial temporal lobe epilepsy.

Growing evidence of altered functional connectivity suggests that mesial temporal lobe epilepsy (mTLE) alters not only hippocampal networks, but also a number of resting state networks. These highly coherent, yet functionally distinct brain circuits interact dynamically with each other in order to mediate consciousness, memory, and attention. However, little is currently known about the modulation of these networks by epileptiform activity, such as interictal spikes and seizures. The objective of the study was to use simultaneous EEG-fMRI to investigate functional connectivity in three resting state networks: default mode network (DMN), salience network (SN), and dorsal attentional network (DAN) in patients with mTLE compared to a healthy cohort, and in relation to the onset of interictal spikes and the period immediately prior to the spikes. Compared to the healthy participants, mTLE patients showed significant alterations in functional connectivity of all three resting state networks, generally characterized by a lack of functional connectivity to prefrontal areas and increased connectivity to subcortical and posterior areas. Critically, prior to the onset of interictal spikes, compared to resting state, mTLE patients showed a lack of functional connectivity to the DMN and decreased synchronization within the SN and DAN, demonstrating alterations in functional coherence that may be responsible for the generation of epileptiform activity. Our findings demonstrate mTLE-related alterations of connectivity during the resting state as well as in relation to the onset of interictal spikes. These functional changes may underlie epilepsy-related cognitive abnormalities, because higher cognitive functions, such as memory or attention, rely heavily on the coordinated activity of all three resting state networks.

Proactive Recruitment of Frontoparietal and Salience Networks for Voluntary Decisions.

There is evidence that neural patterns are predictive of voluntary decisions, but findings come from paradigms that have typically required participants to make arbitrary choices decisions in highly abstract experimental tasks. It remains to be seen whether proactive neural activity reflects upcoming choices for individuals performing decisions in more complex, dynamic, scenarios. In this functional Magnetic Resonance Imaging (fMRI) study, we investigated proactive neural activity for voluntary decisions compared with instructed decisions in a virtual environment, which more closely mimicked a real-world decision. Using partial least squares (PLS) analysis, we found that the frontoparietal and salience networks were associated with voluntary choice selection from a time at which decisions were abstract and preceded external stimuli. Using multi-voxel pattern analysis (MVPA), we showed that participants' choices, which were decodable from motor and visual cortices, could be predicted with lower accuracy for voluntary decisions than for instructed decisions. This corresponded to eye-tracking data showing that participants made a greater number of fixations to alternative options during voluntary choices, which might have resulted in less stable choice representations. These findings suggest that voluntary decisions engage proactive choice selection, and that upcoming choices are encoded in neural representations even while individuals continue to consider their options in the environment.

The method of educational assessment affects children's neural processing and performance: behavioural and fMRI Evidence.

Standardised educational assessments are now widespread, yet their development has given comparatively more consideration to what to assess than how to optimally assess students' competencies. Existing evidence from behavioural studies with children and neuroscience studies with adults suggest that the method of assessment may affect neural processing and performance, but current evidence remains limited. To investigate the impact of assessment methods on neural processing and performance in young children, we used functional magnetic resonance imaging to identify and quantify the neural correlates during performance across a range of current approaches to standardised spelling assessment. Results indicated that children's test performance declined as the cognitive load of assessment method increased. Activation of neural nodes associated with working memory further suggests that this performance decline may be a consequence of a higher cognitive load, rather than the complexity of the content. These findings provide insights into principles of assessment (re)design, to ensure assessment results are an accurate reflection of students' true levels of competency.

Grey matter volume differences in the left caudate nucleus of people who stutter.

The cause of stuttering has many theoretical explanations. A number of research groups have suggested changes in the volume and/or function of the striatum as a causal agent. Two recent studies in children and one in adults who stutter (AWS) report differences in striatal volume compared that seen in controls; however, the laterality and nature of this anatomical volume difference is not consistent across studies. The current study investigated whether a reduction in striatal grey matter volume, comparable to that seen in children who stutter (CWS), would be found in AWS. Such a finding would support claims that an anatomical striatal anomaly plays a causal role in stuttering. We used voxel-based morphometry to examine the structure of the striatum in a group of AWS and compared it to that in a group of matched adult control subjects. Results showed a statistically significant group difference for the left caudate nucleus, with smaller mean volume in the group of AWS. The caudate nucleus, one of three main structures within the striatum, is thought to be critical for the planning and modulation of movement sequencing. The difference in striatal volume found here aligns with theoretical accounts of stuttering, which suggest it is a motor control disorder that arises from deficient articulatory movement selection and sequencing. Whilst the current study provides further evidence of a striatal volume difference in stuttering at the group level compared to controls, the significant overlap between AWS and controls suggests this difference is unlikely to be diagnostic of stuttering.