Action viewing and language in adolescents with autism spectrum disorder.

The mirror neuron system consists of fronto-parietal regions and responds to both goal-directed action execution and observation. The broader action observation network is specifically involved in observation of actions and is thought to play a role in understanding the goals of the motor act, the intention of others, empathy, and language. Many, but not all, studies have found mirror neuron system or action observation network dysfunction in autism spectrum disorder. The objective of this study was to use observation of a goal-directed action fMRI paradigm to examine the action observation network in autism spectrum disorder and to determine whether fronto-parietal activation is associated with language ability. Adolescents with autism spectrum disorder (n = 23) were compared to typically developing adolescents (n = 20), 11-17 years. Overall, there were no group differences in activation, however, the autism spectrum group with impaired expressive language (n = 13) had significantly reduced inferior frontal and inferior parietal activation during action viewing. In controls, right supramarginal gyrus activation was associated with higher expressive language; bilateral supramarginal and left pars opercularis activation was associated with better verbal-gesture integration. Results suggest that action-observation network dysfunction may characterize a subgroup of individuals with autism spectrum disorder with expressive language deficits. Therefore, interventions that target this dysfunctional network may improve expressive language in this autism spectrum subgroup. Future treatment studies should individualize therapeutic approaches based on brain-behavior relationships.

Frontal lesions predict response to prism adaptation treatment in spatial neglect: A randomised controlled study.

Spatial neglect commonly follows right hemisphere stroke. It is defined as impaired contralesional stimulus detection, response, or action, causing functional disability. While prism adaptation treatment is highly promising to promote functional recovery of spatial neglect, not all individuals respond. Consistent with a primary effect of prism adaptation on spatial movements, we previously demonstrated that functional improvement after prism adaptation treatment is linked to frontal lobe lesions. However, that study was a treatment-only study with no randomised control group. The current study randomised individuals with spatial neglect to receive 10 days of prism adaptation treatment or to receive only standard care (control group). Replicating our earlier results, we found that the presence of frontal lesions moderated response to prism adaptation treatment: among prism-treated patients, only those with frontal lesions demonstrated functional improvements in their neglect symptoms. Conversely, among individuals in the standard care control group, the presence of frontal lesions did not modify recovery. These results suggest that further research is needed on how frontal lesions may predict response to prism adaptation treatment. Additionally, the results help elucidate the neural network involved in spatial movement and could be used to aid decisions about treatment.

Limb Apraxia: a Disorder of Learned Skilled Movement.

PURPOSE OF REVIEW: This chapter focuses on limb apraxia, a cognitive-motor disorder of learned skilled movement, and the nature of the spatiotemporal errors that disrupt movement sequences. RECENT FINDINGS: A cognitive model that attempts to reconcile conceptual and preparatory aspects of the motor program with perceptual and kinematic features will be discussed. An update on the localization of the praxis network will be provided. In addition, a long-held view that limb apraxia does not have ecological relevance will be disputed in the context of studies that have shown that limb apraxia (i) is one of the most important predictors of increased caregiver burden and (ii) is associated with impaired activities of daily living in post-stroke patients. This review summarizes current screening tools and the few randomized clinical controlled treatment studies to date. Limb apraxia is underdiagnosed and very few therapeutic options are available. Cognitive process models should be used to inform future controlled multi-modal treatment strategies.

Atypical PT anatomy in children with autism spectrum disorder with expressive language deficits.

Deficits in communication are a core feature of autism spectrum disorder (ASD), however, structural language abilities are highly variable, ranging from minimally verbal to superior linguistic skills. Differences in the anatomy of cortical language regions, including anterior and posterior areas, have been found in ASD. It remains unclear, however, if anatomical differences distinguish individuals with impaired expressive language from those without such deficits. In addition, anatomical differences have not been explored in children with extremely low expressive language. This study included 34 boys with ASD, 7-11 years old, including an expressive language impaired group (n = 17) and an average-high language group (n = 17). The language impaired group was subdivided into a low (n = 9) and extremely low (n = 8) language subgroup for exploratory analyses to determine whether children with ASD with extremely low expressive language abilities exhibit distinct anatomy. Gray matter volume of the pars triangularis, pars opercularis, and planum temporale (PT) were measured on MRIs. PT volume was smaller in the ASD group with expressive language impairment relative to those without language deficits. The right PT volume was also positively correlated with language scores. The exploratory analyses revealed differences in the left PT, with smaller volume in the extremely low language subgroup, relative to the average and moderately low language groups. Results suggest that smaller PT volumes in both hemispheres are associated with severe language impairments in ASD. The PT may therefore, be a biomarker of language outcome in young children with ASD, with more studies of PT anatomy necessary.

Unilateral repetitive transcranial magnetic stimulation differentially affects younger and older adults completing a verbal working memory task.

Functional neuroimaging studies have found that lateralization of activity in the dorsolateral prefrontal cortex (dlPFC) is reduced with aging. In the present study, repetitive transcranial magnetic stimulation (rTMS) was used to disrupt dlPFC activity in order to test the relationship of dlPFC laterality and age in verbal working memory (WM). Young (n=36) and older (n=35) subjects received 1Hz-rTMS (sham or active) to left or right dlPFC and WM performance was assessed pre- and post-stimulation via the n-back task. Significant increases in WM accuracy were observed following rTMS in the right dlPFC and sham conditions, but not with the left dlPFC stimulation. This was accompanied by a decrease in left P1 latency was also observed following left dlPFC stimulation. In contrast, older adults did not show a disruption in WM performance following rTMS in any of the stimulation conditions and exhibited increased left P3 amplitude following left stimulation. Our results show that changes in prefrontal laterality are evident with increasing age (left stimulation affects younger adults while older adults are not affected by stimulation) and this change is associated with specific neurophysiologic measures.

Atypical activation of action-semantic network in adolescents with autism spectrum disorder.

In typical adults, fMRI studies have shown activation of primary and pre-motor regions during action word processing. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments. ASD studies have shown atypical semantic processing and motor deficits. The objective of this study was to examine semantic processing of verbs in ASD. 15 ASD adolescents and 19 typically developing adolescents, 11-16years, completed a semantic similarity judgment task during fMRI. There were no differences in task accuracy or reaction time. At the group level, both groups had activation in left language areas; controls, but not ASD, also had activation in the left pre-supplementary motor area (pre-SMA). In ASD, less left frontal activation and reduced left lateralization of activation within these regions was associated with shorter reaction times and better language skills. More left temporal activation was associated with better language abilities in ASD. Differences in pre-SMA activation may relate to motor planning deficits or differences in approach to the semantic task in ASD. Results suggest that left frontal language areas may be less efficient in ASD and those who can compensate by recruiting more right hemisphere homologues may result in better language abilities.

Cortical activity during cued picture naming predicts individual differences in stuttering frequency.

OBJECTIVE: Developmental stuttering is characterized by fluent speech punctuated by stuttering events, the frequency of which varies among individuals and contexts. Most stuttering events occur at the beginning of an utterance, suggesting neural dynamics associated with stuttering may be evident during speech preparation. METHODS: This study used EEG to measure cortical activity during speech preparation in men who stutter, and compared the EEG measures to individual differences in stuttering rate as well as to a fluent control group. Each trial contained a cue followed by an acoustic probe at one of two onset times (early or late), and then a picture. There were two conditions: a speech condition where cues induced speech preparation of the picture's name and a control condition that minimized speech preparation. RESULTS: Across conditions stuttering frequency correlated to cue-related EEG beta power and auditory ERP slow waves from early onset acoustic probes. CONCLUSIONS: The findings reveal two new cortical markers of stuttering frequency that were present in both conditions, manifest at different times, are elicited by different stimuli (visual cue, auditory probe), and have different EEG responses (beta power, ERP slow wave). SIGNIFICANCE: The cue-target paradigm evoked brain responses that correlated to pre-experimental stuttering rate.

Handedness in Children With Autism Spectrum Disorder.

The left hemisphere is usually predominant in manual skills and language, suggesting a link between hand dominance and language. Studies of autism spectrum disorder show atypical handedness; however, few have examined language-handedness associations. Handedness, assessed by task performance, and standardized receptive and expressive language tests were completed in 110 autism spectrum disorder children (96 boys; M age = 8.3 years, SD = 3.8) and 45 typically developing children (37 boys; M age = 8.6 years, SD = 4.3), 3 to 17 years of age. The autism spectrum disorder group had a lower handedness score (was less strongly lateralized) than the control group. In the autism spectrum disorder group, there was a small effect of handedness on language; right-handers had better language than non-right-handers. Results suggest poorer language prognosis may be associated with left- or mixed-handedness in autism spectrum disorder.

Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic: Phase I single group and phase II randomized placebo-controlled studies.

OBJECTIVES: Phase I (PhI): assess the safety of Polyphenon E in people with multiple sclerosis (MS) and determine the futility of Polyphenon E as a neuroprotective agent. Correlate plasma levels of EGCG with neuroprotective effects. Phase II (PhII): Further assess safety and confirm the neuroprotective effects of Polyphenon E. DESIGN: PhI: single group futility study. PhII: parallel group randomized double-blind placebo-controlled study. PARTICIPANTS: Recruitment area (both studies): LSU MS Center, New Orleans, LA and general public from surrounding areas. Inclusion criteria (both studies): 1) MS per 2005 McDonald criteria; 2) relapsing remitting or secondary progressive MS; 3) stable for six months prior to enrollment on either no therapy or glatiramer acetate (GA) for the PhI study and on either on GA or Interferon ß for the PhII study. Exclusion criteria (both studies): 1) complete bone marrow ablation or alentuzumab use at any time; 2) mitoxantrone, cyclophosphamide, natalizumab or fingolimod use in the prior nine months; 3) liver problems or significant medical problems. INTERVENTIONS: PhI: Polyphenon E, a green tea extract containing 50% of the antioxidant Epigallocatechin-gallate (EGCG), two capsules twice daily (200mg of EGCG per capsule; total daily dose 800mg) for six months. PhII: Polyphenon E or matching placebo capsules, same dose for one year. Only the research pharmacist knew treatment assignment and she randomized participants (one-to-one, stratified by GA or Interferon ß, blocks of 4 or 6). Outcome evaluators did not discuss side effects with participants. OUTCOME MEASURES: PhI: 1) adverse events (AE); 2) futility: decrease in N-acetyl aspartate (NAA) from baseline to six months of 10% or more; 3) association between EGCG plasma levels and change in NAA. PhII: 1) AEs; 2) difference in the rate of change of NAA-levels over twelve months.We measured NAA using a point resolved magnetic resonance spectroscopic imaging sequence (TE30/TR2000) on a 10cm×10cm×1cm volume of interest (VOI) located just superior to the lateral ventricles. The field of view was 16×16 resulting in 1cm(3) voxels. We quantified NAA and creatine/phosphocreatine (Cr) levels using LCModel for post-processing. RESULTS: PhI: Ten participants enrolled and completed all assessments with no serious AEs. One discontinued therapy due to grade (G) I abnormal liver function tests (LFTs). We included all participants in the analysis. NAA adjusted for creatine increased by 10% [95% CI(3.4%,16.2%), p<0.01] rejecting the futility endpoint. PhII: Thirteen participants enrolled and twelve started treatment. The DSMB stopped the study because 5/7 participants on Polyphenon E had abnormal LFTs (G I, and 1G III). Median time to onset of abnormal LFTs was 20 weeks [Inter-Quartile Range (IQR) (10,23)]. Only two participants completed the six-month visit, so we could not analyze the NAA levels. PhI participants took capsules from lot 189I1107 while 6/7 PhII participants took capsules from a new lot (L0206306). Both lots had similar levels of EGCG but differed in the levels of minor catechins. There were no significant differences between the lots on participants' median free EGCG plasma levels at either 3h or 8h as well as conjugated EGCG levels at 3h (all p>0.4, Wilcoxon exact test). Free EGCG levels at 8h correlated with changes in NAA adjusted by water content. A 1ng/ml higher EGCG plasma concentration correlated with a 0.9% increase in NAA[95% CI(0.5%,1.4%), visit*level interaction F=14.4, p<0.001]. However, EGCG plasma concentrations did not correlate with NAA adjusted by creatine (1ng/ml higher EGCG was associated with 0.02%,[95% CI(-0.27%,0.3%) change in NAA, p>0.5]). There was a trend towards an increase in creatine levels (referenced to water content) from baseline to exit (1 5% increase, [95% CI(-6%,17%), p=0.4]). The free EGCG levels at 8hours correlated significantly with change in creatine levels (1ng/ml higher EGCG level at 8h was associated with a 1.1% increase in creatine [95% CI(0.6%,1.6%)]). Thus it is possible that the discrepancy between the correlation of the EGCG 8h levels with NAA changes referenced to water and the 8h EGCG levels with NAA changes referenced to creatine was due to a change in creatine among the subjects with higher EGCG levels. Conjugated 3h and 8h levels and free 3h levels did not correlate with NAA changes (all p >0.5). CONCLUSIONS/CLASSIFICATION OF EVIDENCE: Class III evidence: Polyphenon E at a dose of 400mg of EGCG twice a day is not futile at increasing brain NAA levels. Class I evidence: some lots of Polyphenon E have a high risk of hepatotoxicity. FUNDING: National Center for Complementary and Alternative Medicine K23AT004433, National Multiple Sclerosis Society RG4816-A-1 and National Institute of General Medical Sciences 1 U54 GM104940. Mitsui Norin provided Polyphenon E and placebo and their representative reviewed the manuscript prior to publication. Mitsui Norin was not involved in other aspects of the study. The decision to submit the manuscript remained with the investigators. REGISTRATION: NCT00836719 and NCT01451723

Speech preparation in adults with persistent developmental stuttering.

Motor efference copy conveys movement information to sensory areas before and during vocalization. We hypothesized speech preparation would modulate auditory processing, via motor efference copy, differently in men who stutter (MWS) vs. fluent adults. Participants (n=12/group) had EEG recorded during a cue-target paradigm with two conditions: speech which allowed for speech preparation, while a control condition did not. Acoustic stimuli probed auditory responsiveness between the cue and target. MWS had longer vocal reaction times (p<0.01) when the cue-target differed (10% of trials), suggesting a difficulty of rapidly updating their speech plans. Acoustic probes elicited a negative slow wave indexing motor efference copy that was smaller in MWS vs. fluent adults (p<0.03). Current density responses in MWS showed smaller left prefrontal responses and auditory responses that were delayed and correlated to stuttering rate. Taken together, the results provide insight into the cortical mechanisms underlying atypical speech planning and dysfluencies in MWS.

Ipsilesional neglect: behavioral and anatomical correlates.

UNLABELLED: [Correction Notice: An Erratum for this article was reported in Vol 29(2) of Neuropsychology (see record 2014-42242-001). The funding source information was missing from the author note, and A. M. Barrett's institutional affiliation was incorrect. The funding source information and Barrett's correct institutional affiliation are provided in the erratum.] OBJECTIVE: The sparse existing research on ipsilesional neglect supports an association of this disorder with damage to the right frontal and subcortical brain networks. It is believed that dysfunction in these networks may result in primarily "aiming" motor-intentional spatial errors. The purpose of this study was to confirm whether frontal-subcortical circuits are indeed commonly affected in ipsilesional neglect and to determine the relative presence of "aiming" motor-intentional versus "where" perceptual-attentional spatial errors in these individuals. METHODS: We identified 12 participants with ipsilesional neglect based on a computerized line bisection task and used the line bisection data to quantify participants' perceptual-attentional and motor-intentional errors. We were able to discriminate between these 2 biases using the algebraic solutions for 2 separate equations, one for "aiming" and one for "where" biases. Lesion mapping was conducted for all participants using MRIcron software; lesion checklist and overlap analysis were created from these images. RESULTS: A greater percentage of participants with ipsilesional neglect had frontal/subcortical damage (83%) compared with the expected percentage (27%) observed in published patient samples with contralesional neglect. We observed the greatest area of lesion overlap in frontal lobe white matter pathways. Nevertheless, participants with ipsilesional neglect made primarily "where" rather than "aiming" spatial errors. CONCLUSION: Our data confirm previous research suggesting that ipsilesional neglect may result from lesions to the right frontal-subcortical networks. Furthermore, in our group, ipsilesional neglect was also strongly associated with primarily "where" perceptual-attentional bias, and less so with "aiming" motor-intentional spatial bias.

Integrity of medial temporal structures may predict better improvement of spatial neglect with prism adaptation treatment.

Prism adaptation treatment (PAT) is a promising rehabilitative method for functional recovery in persons with spatial neglect. Previous research suggests that PAT improves motor-intentional "aiming" deficits that frequently occur with frontal lesions. To test whether presence of frontal lesions predicted better improvement of spatial neglect after PAT, the current study evaluated neglect-specific improvement in functional activities (assessment with the Catherine Bergego Scale) over time in 21 right-brain-damaged stroke survivors with left-sided spatial neglect. The results demonstrated that neglect patients' functional activities improved after two weeks of PAT and continued improving for four weeks. Such functional improvement did not occur equally in all of the participants: Neglect patients with lesions involving the frontal cortex (n = 13) experienced significantly better functional improvement than did those without frontal lesions (n = 8). More importantly, voxel-based lesion-behavior mapping (VLBM) revealed that in comparison to the group of patients without frontal lesions, the frontal-lesioned neglect patients had intact regions in the medial temporal areas, the superior temporal areas, and the inferior longitudinal fasciculus. The medial cortical and subcortical areas in the temporal lobe were especially distinguished in the "frontal lesion" group. The findings suggest that the integrity of medial temporal structures may play an important role in supporting functional improvement after PAT.

Presence of Motor-Intentional Aiming Deficit Predicts Functional Improvement of Spatial Neglect With Prism Adaptation.

UNLABELLED: Background Spatial neglect is a debilitating disorder for which there is no agreed on course of rehabilitation. The lack of consensus on treatment may result from systematic differences in the syndrome's characteristics, with spatial cognitive deficits potentially affecting perceptual-attentional "Where" or motor-intentional "Aiming" spatial processing. Heterogeneity of response to treatment might be explained by different treatment impacts on these dissociated deficits: prism adaptation, for example, might reduce Aiming deficits without affecting Where spatial deficits. OBJECTIVE: Here, we tested the hypothesis that classifying patients by their profile of Where-versus-Aiming spatial deficit would predict response to prism adaptation and specifically that patients with Aiming bias would have better recovery than those with isolated Where bias. Methods We classified the spatial errors of 24 subacute right stroke survivors with left spatial neglect as (1) isolated Where bias, (2) isolated Aiming bias, or (3) both. Participants then completed 2 weeks of prism adaptation treatment. They also completed the Behavioral Inattention Test and Catherine Bergego Scale (CBS) tests of neglect recovery weekly for 6 weeks. Results As hypothesized, participants with only Aiming deficits improved on the CBS, whereas those with only Where deficits did not improve. Participants with both deficits demonstrated intermediate improvement. Conclusion These results support behavioral classification of spatial neglect patients as a potential valuable tool for assigning targeted, effective early rehabilitation.

Atypical caudate anatomy in children who stutter.

A temporal motor defect in speech preparation and/or planning may contribute to the development of stuttering. This defect may be linked to a dysfunctional cortical-subcortical network at the level of the striatum. To determine whether structural differences exist and whether group differences are associated with stuttering severity or manual laterality, the caudate was measured in 14 children who stutter (CWS) and in a control group of right-handed boys, ages 8-13 years. There was a statistically significant hemisphere by group effect for caudate volume. CWS had reduced right caudate volume and atypical leftward asymmetry compared to controls. Nine of the 13 CWS with atypical caudate asymmetry had atypical manual laterality. These anomalies may represent a vulnerability that perturbs speech planning/preparation and contributes to inefficiencies in action-perception coupling that may be an indicator of stuttering susceptibility. These results suggest that right-handed boys who stutter may have a defect in the feedforward cortico-striato-thalamo-cortical networks.

The SpeechEasy device in stuttering and nonstuttering adults: fluency effects while speaking and reading.

The SpeechEasy is an electronic device designed to alleviate stuttering by manipulating auditory feedback via time delays and frequency shifts. Device settings (control, default, custom), ear-placement (left, right), speaking task, and cognitive variables were examined in people who stutter (PWS) (n=14) compared to controls (n=10). Among the PWS there was a significantly greater reduction in stuttering (compared to baseline) with custom device settings compared to the non-altered feedback (control) condition. Stuttering was reduced the most during reading, followed by narrative and conversation. For the conversation task, stuttering was reduced more when the device was worn in the left ear. Those individuals with a more severe stuttering rate at baseline had a greater benefit from the use of the device compared to individuals with less severe stuttering. Our results support the view that overt stuttering is associated with defective speech-language monitoring that can be influenced by manipulating auditory feedback.

Apraxia: neural mechanisms and functional recovery.

Apraxia is a cognitive-motor disorder that impacts the performance of learned, skilled movements. Limb apraxia, which is the topic of this chapter, is specific to disordered movements of the upper limb that cannot be explained by weakness, sensory loss, abnormalities of posture/tone/movement, or a lack of understanding/cooperation. Patients with limb apraxia have deficits in the control or programming of the spatial-temporal organization and sequencing of goal-directed movements. People with limb apraxia can have difficulty manipulating and using tools including cutting with scissors or making a cup of coffee. Two praxis systems have been identified including a production system (action plan and production) and a conceptual system (action knowledge). Dysfunction of the former produces ideomotor apraxia (e.g., difficulty using scissors), and dysfunction of the latter induces ideational apraxia (e.g., difficulty making a cup of coffee). Neural mechanisms, including how to evaluate apraxia, will be presented in the context of these two praxis systems. Information about these praxis systems, including the nature of the disordered limb movement, is important for rehabilitation clinicians to understand for several reasons. First, limb apraxia is a common disorder. It is common in patients who have had a stroke, in neurodegenerative disorders like Alzheimer disease, in traumatic brain injury, and in developmental disorders. Second, limb apraxia has real world consequences. Patients with limb apraxia have difficulty managing activities of daily living. This factor impacts healthcare costs and contributes to increased caregiver burden. Unfortunately, very few treatments have been systematically studied in large numbers of patients with limb apraxia. This overview of limb apraxia should help rehabilitation clinicians to educate patients and caregivers about this debilitating problem, and should facilitate the development of better treatments that could benefit many people in the future.

Atypical brain torque in boys with developmental stuttering.

The counterclockwise brain torque, defined as a larger right prefrontal and left parietal-occipital lobe, is a consistent brain asymmetry. Reduced or reversed lobar asymmetries are markers of atypical cerebral laterality and have been found in adults who stutter. It was hypothesized that atypical brain torque would be more common in children who stutter. Magnetic resonance imaging-based morphology measures were completed in boys who stutter (n = 14) and controls (n = 14), ages 8-13. The controls had the expected brain torque configurations whereas the boys who stutter were atypical. These results support the hypothesis that developmental stuttering is associated with atypical prefrontal and parietal-occipital lobe asymmetries.

Sylvian fissure and parietal anatomy in children with autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by deficits in social functioning and language and communication, with restricted interests or stereotyped behaviors. Anatomical differences have been found in the parietal cortex in children with ASD, but parietal subregions and associations between Sylvian fissure (SF) and parietal anatomy have not been explored. In this study, SF length and anterior and posterior parietal volumes were measured on MRI in 30 right-handed boys with ASD and 30 right-handed typically developing boys (7-14 years), matched on age and non-verbal IQ. There was leftward SF and anterior parietal asymmetry, and rightward posterior parietal asymmetry, across groups. There were associations between SF and parietal asymmetries, with slight group differences. Typical SF asymmetry was associated with typical anterior and posterior parietal asymmetry, in both groups. In the atypical SF asymmetry group, controls had atypical parietal asymmetry, whereas in ASD there were more equal numbers of individuals with typical as atypical anterior parietal asymmetry. We did not find significant anatomical-behavioral associations. Our findings of more individuals in the ASD group having a dissociation between cortical asymmetries warrants further investigation of these subgroups and emphasizes the importance of investigating anatomical relationships in addition to group differences in individual regions.

Prefrontal and occipital asymmetry and volume in boys with autism spectrum disorder.

OBJECTIVE: To examine prefrontal and occipital asymmetry (brain torque) in boys with autism spectrum disorder (ASD) and controls. A secondary aim was to study age-related changes in gray and white matter volume. BACKGROUND: Several studies have found atypical early cortical development in ASD. Atypical brain torque, defined as a greater-than-normal left prefrontal and right occipital asymmetry, has been found in some studies of children and adults with ASD. This configuration may be an early neural marker of ASD risk. METHODS: We studied 24 right-handed boys with ASD and 27 typically developing right-handed boys, 7 to 15 years old, obtaining neuropsychological profiles and measuring prefrontal and occipital volumes on magnetic resonance images. RESULTS: Most participants had the expected rightward prefrontal and leftward occipital asymmetry, with no group differences in direction or degree of asymmetry. We found a trend toward larger prefrontal volume in the ASD group than in the controls. The controls also had a trend toward differences in age associations, correlating with total and left prefrontal white matter volumes. CONCLUSIONS: Our findings suggest that atypical brain torque may not be a neural signature of ASD, although our sample was limited to high-functioning, right-handed boys. Our results provide support for aberrant cortical development in ASD, continuing into adolescence, with prefrontal regions being disproportionally affected.