Biomedical subjects

S H Mostofsky

Publications and source records attributed to S H Mostofsky.

14 recordsLinked to original sources

PubMed2006

Sex differences in cerebral laterality of language and visuospatial processing.

Sex differences on language and visuospatial tasks are of great interest, with differences in hemispheric laterality hypothesized to exist between males and females. Some functional imaging studies examining sex differences have shown that males are more left lateralized on language tasks and females are more right lateralized on visuospatial tasks; however, findings are inconsistent. Here we used functional magnetic resonance imaging to study thirty participants, matched on task performance, during phonological and visuospatial tasks. For each task, region-of-interest analyses were used to test differences in cerebral laterality. Results indicate that lateralization differences exist, with males more left lateralized during the phonological task and showing greater bilateral activity during the visuospatial task, whereas females showed greater bilateral activity during the phonological task and were more right lateralized during the visuospatial task. Our data provide clear evidence for differences in laterality between males and females when processing language versus visuospatial information.

Adult↗

PubMed2006

Normal physiological emotions but differences in expression of conscious feelings in children with high-functioning autism.

To provide insight into what aspects of the emotional circuit might be affected in high-functioning autism, we measured indices of physiological emotions and of the expression of conscious feelings in 10 children with high-functioning autism or Asperger syndrome and 10 comparison participants. Pleasant, unpleasant, and neutral pictures were presented while skin conductance responses were measured. Self-report ratings of pleasantness and interestingness were taken between pictures. Skin conductance responses did not differ between the groups. Self report ratings were different, with the children with autism giving more similar answers to the two questions than the comparison children. Impairments in socio-emotional expression in autism may be related to deficits in perception and/or expression of conscious feelings; physiological emotions may be relatively preserved.

Adolescent↗

PubMed2005

Subtle executive impairment in children with autism and children with ADHD.

BACKGROUND: The executive functions of inhibition, planning, flexible shifting of actions, and working memory are commonly reported to be impaired in neurodevelopmental disorders. METHOD: We compared these abilities in children (8-12 years) with high functioning autism (HFA, n = 17), attention deficit-hyperactivity disorder (ADHD, n = 21) and healthy controls (n = 32). Response inhibition was assessed using the Stroop Color and Word Test (Golden, 1978). Problem solving, set-shifting, and nonverbal memory were assessed using three tasks, respectively, from the CANTAB (Cambridge Cognition, 1996): the Stockings of Cambridge task; the Intra-Dimensional/Extra-Dimensional set-shifting task; and the Spatial Working Memory task (SWM) with tokens hidden behind 3, 4, 6, and 8 boxes. RESULTS: There were no group differences on the response inhibition, planning, or set-shifting tasks. On the SWM task, children with HFA made significantly more between-search errors compared with controls on both the most difficult problems (8-box) and on the mid-difficulty problems (6-box); however, children with ADHD made significantly more errors compared to controls on the most difficult (8-box) problems only. CONCLUSION: Our findings suggest that spatial working memory is impaired in both ADHD and HFA, and more severely in the latter. More detailed investigation is needed to examine the mechanisms that differentially impair spatial working memory, but on this set of tasks there appears to be sparing of other executive functions in these neuropsychiatric developmental disorders.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

Megalencephaly in NF1: predominantly white matter contribution and mitigation by ADHD.

BACKGROUND: Megalencephaly is a frequent CNS manifestation in neurofibromatosis type 1 (NF1); however, its tissue composition, modification by attention deficit hyperactivity disorder (ADHD), and relationship with unidentified bright objects (UBO) remain controversial. METHODS: Eighteen male patients with NF1, seven of whom had ADHD (NF1+ADHD), were compared with 18 age- and sex-matched controls in terms of MRI-, Talairach-based brain, cerebral, lobar, and sublobar gray and white matter volumes. Twelve subjects with NF1 had UBO in the centrencephalic region, whereas six had no UBO or exclusively infratentorial lesions. RESULTS: Patients with NF1 without ADHD (NF1-pure) had the largest total cerebral, gray, and white matter volumes with larger parietal/somatosensory white matter volumes than controls, particularly if UBO were present in the basal ganglia. All subjects with NF1 (including NF1+ADHD) had larger total and frontal white matter volumes than controls. Smaller frontal/right prefrontal gray matter volumes were found in NF1+ADHD when compared with NF1-pure patients. CONCLUSIONS: The increase in frontal and parietal white matter volumes in male patients with NF1, including the preferential centrencephalic distribution, supports the hypothesis that NF1's white matter pathology encompasses but is not limited to visible UBO. Male patients with NF1+ADHD, as compared with NF1-pure patients, showed frontal reductions that are largely consistent with those found in idiopathic ADHD.

Adolescent↗

PubMed2002

Disproportionate increases of white matter in right frontal lobe in Tourette syndrome.

OBJECTIVE: Based on previous findings implicating abnormalities of cortico-striatal-thalamo-cortical circuitry in Tourette syndrome (TS), the authors performed a volumetric analysis of frontal and nonfrontal tissue (gray + white matter) in boys with TS, with and without attention deficit hyperactivity disorder (ADHD). METHODS: Frontal and nonfrontal gray and white matter compartment volumes, obtained by a MRI protocol, were analyzed with a 2 x 2 factorial multivariate analysis of variance approach for associations with a TS or ADHD factor in 11 boys with TS only, 14 with TS + ADHD, 12 with ADHD only, and 26 healthy boys. RESULTS: In subjects with TS, the right frontal lobe showed a larger proportion of white matter. In addition, results were consistent with previous reports of reduced frontal lobe volumes associated with ADHD. Our analyses suggested these reductions to be mainly the consequence of smaller gray matter volumes, particularly on the left. CONCLUSIONS: These findings, suggesting the volumetric composition of frontal lobe tissue to be different in TS, support the hypothesis proposing frontostriatal pathway involvement in the pathophysiology of the disorder. Differences in composition of right frontal lobe attributable to white matter do not definitively implicate the hypothesized fiber pathways; however, considered in the context of the unilateral directionality of frontal-striatal circuitry, these results suggest the white matter connections as one explanation for basal ganglia anomalies (loss of normal left > right asymmetry) in TS.

Adolescent↗

PubMed2001

Oculomotor abnormalities in attention deficit hyperactivity disorder: a preliminary study.

BACKGROUND: Prevailing hypotheses suggest that attention deficit hyperactivity disorder (ADHD) is secondary to dysfunction of motor intentional systems mediated by prefrontal circuitry. Oculomotor paradigms provide a mechanism for examining and localizing dysfunction at the interface between movement and cognition. OBJECTIVE: Three different saccade tasks (reflexive or prosaccades, antisaccades, and memory-guided saccades) were used to examine functions necessary for the planning and the execution of eye movements, including motor response preparation, response inhibition, and working memory. METHODS: The study included 19 children with ADHD, divided into two groups: a group of 8 children on methylphenidate at the time of testing and a group of 11 children not taking any psychoactive medication. Results from the two groups were compared with those from 25 age- and gender-matched normal control children. RESULTS: Both groups of children with ADHD made significantly more directional errors than did controls on the antisaccade task and significantly more anticipatory errors than did controls on the memory-guided saccade task, findings that are consistent with deficits in response inhibition. There were no significant differences in prosaccade latency, although unmedicated children with ADHD showed significantly greater variability in latency on the prosaccade task than did controls. On the memory-guided saccade task there were no significant differences in saccade accuracy; however, unmedicated children with ADHD showed longer saccade latency than did either controls or medicated children with ADHD. CONCLUSIONS: Oculomotor findings suggest that deficits in prefrontal functions, in particular response inhibition, contribute to behavioral abnormalities observed in ADHD. Findings also suggest that the administration of methylphenidate is associated with improvements in the consistency of motor response. Although there were no observed improvements in response inhibition with methylphenidate, conclusions await a design in which subjects complete testing both on and off medication.

Adolescent↗

PubMed2001

Oculomotor abnormalities in boys with tourette syndrome with and without ADHD.

OBJECTIVE: To assess saccadic eye movements in boys with Tourette syndrome (TS) with and without attention-deficit hyperactivity disorder (ADHD), comparing performance with that of an age-matched group of male controls. METHOD: Three different saccade tasks (prosaccades, antisaccades, and memory-guided saccades) were used to examine functions necessary for the planning and execution of eye movements, including motor response preparation, response inhibition, and working memory. The study included 14 boys with TS without ADHD (TS-only), 11 boys with TS and ADHD (TS+ADHD), and 10 male controls. RESULTS: Latency of prosaccades was prolonged in boys with TS (both with and without ADHD) compared with controls. Variability in prosaccade latency was greater in the groups of boys with TS+ADHD compared with both the TS-only and control groups. Response inhibition errors on both the antisaccade task (directional errors) and memory-guided saccade task (anticipatory errors) were increased in boys with TS+ADHD compared with those with TS-only. There were no significant differences among the three groups in accuracy of memory-guided saccades. CONCLUSIONS: Oculomotor findings suggest that TS is associated with delay in initiation of motor response as evidenced by excessive latency on prosaccades. Signs of impaired response inhibition and variability in motor response appear to be associated with the presence of ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2000

Evidence for a deficit in procedural learning in children and adolescents with autism: implications for cerebellar contribution.

To examine the hypothesis that abnormalities in those cognitive functions for which cerebellar components have been implicated contribute to the pathophysiology of autism, tests of judgment of explicit time intervals and procedural learning were administered to 11 participants with autism and 17 age-and-IQ-matched controls. Results indicated that the group with autism demonstrated significant impairments in procedural learning compared with the group of controls. No significant difference in judgment of explicit time intervals was found. The data suggest that deficits in procedural learning may contribute to the cognitive and behavioral phenotype of autism; these deficits may be secondary to abnormalities in cerebellar-frontal circuitry.

Adolescent↗

PubMed2000

Judgment of duration in individuals with ataxia-telangiectasia.

Several clinical investigations with adults suggest that the cerebellum may be critical for judgment of explicit time intervals; however, little work has been done in populations with lesions of the cerebellum acquired during development. We evaluated 17 individuals with ataxia-telangiectasia (AT), an autosomal recessive disorder with on-set in early childhood characterized by diffuse, almost selective, degeneration of the cerebellar cortex, and 21 normal controls, matched for age. Because patients with AT have motor impairment, verbal IQ (VIQ) was used to estimate intelligence; VIQ was significantly lower in the group with AT (p < .0001). Participants were tested using a test of judgment of duration that has been found to be impaired in adults with cerebellar lesions and a contrasting auditory control task (not impaired in adults with cerebellar lesions) involving judgment of pitch. After statistically controlling for VIQ, the 2 groups did not differ significantly on judgment of pitch, but those with AT performed significantly worse than controls on judgment of duration (p = .01). Children and adolescents with AT show deficits in judgment of duration but not of pitch, suggesting that the cerebellum may be critical for judgment of explicit time intervals at all ages.

Adolescent↗

PubMed1999

Corpus callosum measurements in girls with Tourette syndrome.

The objective of this study was to examine whether abnormalities in corpus callosum morphology, previously reported in boys with Tourette syndrome (TS), were also present in girls with this disorder. Among the three groups of girls-TS, TS and attention deficit hyperactivity disorder, and controls-there were no significant differences in the size of the corpus callosum or any of five individual subregions. The findings suggest that abnormalities in corpus callosum morphology in TS are a gender-related phenomenon.

Adolescent↗

PubMed1998

Neuroanatomical and neurocognitive differences in a pair of monozygous twins discordant for strictly defined autism.

In this study, we investigated the neuroanatomical similarities and differences between a pair of monozygotic, 7.5-year-old twin boys discordant for strictly defined autism, to identify neuroanatomical pathways that are impaired in individuals with autism. Although the unaffected twin did not fulfill the traditional diagnostic criteria for autism, he displayed constrictions in social interaction and play that were consistent with the broader phenotype for autism that has been described in nonautistic co-twins. Magnetic resonance imaging scans were obtained for each brother and compared with the scans of 5 age- and sex-matched unaffected peers. Quantitative analysis of brain anatomy revealed that the affected twin had markedly smaller caudate, amygdaloid, and hippocampal volumes, and smaller cerebellar vermis lobules VI and VII, in comparison with his brother. Both twins evidenced disproportionately reduced volumes of the superior temporal gyrus and the frontal lobe relative to the comparison sample. The results suggest the dysfunction of two separate but overlapping neuroanatomical pathways, ie, one subcortical network differentiating the twins from each other that may underlie the traditional neurobehavioral phenotype for strictly defined autism, and a second cortical network differentiating the twins from the comparison sample that may lead to the broader phenotype for autism.

Autistic Disorder↗

PubMed1998

Evaluation of cerebellar size in attention-deficit hyperactivity disorder.

Evidence from animal and human research suggests that the cerebellum may play a role in cognition. This includes domains of executive function that are normally attributed to the prefrontal cortex and are typically deficient in individuals with attention-deficit hyperactivity disorder (ADHD). To investigate cerebellar structure in ADHD, magnetic resonance imaging morphometry was used to measure the area of the cerebellar vermis in 12 males with ADHD and 23 male controls matched for age and Wechsler Full-Scale IQ. Analyses were conducted to evaluate group differences, as well as differences between matched pairs of subjects with ADHD and those without ADHD. All measurements were corrected for overall brain size. Both analyses revealed that the size of the posterior vermis was significantly decreased in males with ADHD (P < .05 in both analyses), and that within the posterior vermis, the inferior posterior lobe (lobules VIII-X) was involved in this reduction (P < .05 for group analysis, P < .005 for matched pair analysis), while the superior posterior lobe (lobules VI/VII) was not involved in the reduction. The finding of abnormal inferior posterior vermal size suggests that dysfunction within this region of the cerebellum may underlie clinical deficits seen in individuals with ADHD.

Adolescent↗

PubMed1998

Decreased cerebellar posterior vermis size in fragile X syndrome: correlation with neurocognitive performance.

We examined whether posterior vermis size is smaller in individuals with fragile X syndrome (fra X) than in control subjects and whether this decreased size is associated with cognitive performance. Cognitive and behavioral dysfunctions have been identified in fra X; however, underlying neuropathogenic mechanisms remain unclear. MRI was used to investigate the posterior fossa in 32 males with fra X, 28 males with other causes of cognitive disability (CD), and 38 males with normal development (ND) as well as and in 37 females with fra X and 53 female control subjects. Among females with fra X, neurocognitive correlates of posterior vermis size were examined. Posterior vermis size (cross-sectional area) in males with fra X was significantly smaller compared with CD and ND groups, particularly when corrected for intracranial area. Posterior vermis size corrected for intracranial area was significantly smaller in females with fra X compared with control subjects. Compared with males with fra X and non-fra X control subjects, posterior vermis size in females with fra X was intermediate. After statistically removing the effect of mean parental IQ, posterior vermis size predicted a significant proportion of the variance (10 to 23%) of performance on full-scale, verbal, and performance IQ; block design; categories achieved on the Wisconsin Card Sorting Test; and the Rey inventory score. The size of the posterior vermis is significantly decreased in fra X, more so in males than in females. In females with fra X, posterior vermis size predicts performance on selected cognitive measures.

Adolescent↗

PubMed1996

Autosomal dominant torsion dystonia with onset in infancy.

We report a man and his daughter who had onset of dystonia during the first year of life, primarily involving their legs and consisting of both sustained postures and rhythmical 2-3 Hz twisting movements. They also had eccentric and irregularly shaped pupils, but no other neurological abnormalities. This disorder differs from all familial dystonia syndromes described in the literature, including classic idiopathic torsion dystonia, which has a later age of onset. This disorder probably represents a new autosomal dominant dystonia syndrome.

Adolescent↗