Hooman Ganjavi

Cortical thickness correlates of specific cognitive performance accounted for by the general factor of intelligence in healthy children aged 6 to 18

Prevailing psychometric theories of intelligence posit that individual differences in cognitive performance are attributable to three main sources of variance: the general factor of intelligence (g), cognitive ability domains, and specific test requirements and idiosyncrasies. Cortical thickness has been previously associated with g. In the present study, we systematically analyzed associations between cortical thickness and cognitive performance with and without adjusting for the effects of g in a representative sample of children and adolescents (N=207, Mean age=11.8; SD=3.5; Range=6 to 18.3 years). Seven cognitive tests were included in a measurement model that identified three first-order factors (representing cognitive ability domains) and one second-order factor representing g. Residuals of the cognitive ability domain scores were computed to represent g-independent variance for the three domains and seven tests. Cognitive domain and individual test scores as well as residualized scores were regressed against cortical thickness, adjusting for age, gender and a proxy measure of brain volume. g and cognitive domain scores were positively correlated with cortical thickness in very similar areas across the brain. Adjusting for the effects of g eliminated associations of domain and test scores with cortical thickness. Within a psychometric framework, cortical thickness correlates of cognitive performance on complex tasks are well captured by g in this demographically representative sample.

The effect of dopamine therapy on ventral and dorsal striatum-mediated cognition in Parkinson's disease: support from functional MRI.

The central aim of our study was to elucidate functions mediated by the ventral and dorsal striatum, respectively, to better understand the cognitive effects of dopamine replacement in Parkinsons disease. We proposed that the ventral striatum underlies general learning of stimulus associations, whereas the dorsal striatum promotes integration of various influences on selecting. In Parkinsons disease, dopamine depletion is substantially less notable in the ventral relative to the dorsal striatum, and therefore greater improvements are expected for dorsal striatum-mediated functions with dopamine replacement. Using a simple selection task, we found that dopamine replacement impaired encoding and facilitation of consistent stimulus-stimulus relations across trials. This finding was in line with our contention that ventral striatum mediates learning stimulus associations, even when explicit feedback or reward is not provided. In contrast, dopamine replacement enhanced interference related to assimilating conflicting influences on selection across trials, consistent with our hypothesis that the dorsal striatum supports deciding in ambiguous contexts. We further confirmed these separable roles for the ventral and dorsal striatum in our selection task with healthy young volunteers using functional magnetic resonance imaging. In summary, we present a within-subject, double dissociation of the effects of dopamine replacement in patients with Parkinsons disease for ventral striatum-mediated facilitation and dorsal striatum-mediated interference, confirmed in a separate functional magnetic resonance imaging experiment. Defining the distinct functions of the ventral and dorsal striatum will have direct clinical implications. Titration of therapy in Parkinsons disease is generally geared towards optimizing dorsal striatum-mediated motor symptoms, possibly at the expense of ventral striatum operations, a consequence that is only beginning to be recognized. Enhanced awareness of these different processes will translate into medication strategies that take into account those symptoms that dopamine replacement might hinder, as well as improve. Here, we show impairments in learning new stimulus associations compared with improvements in integrating varied influences related to selection. Ultimately, this knowledge will lead clinicians to survey a broader range of symptoms in determining optimal therapy based on individual patient priorities.

Right Anterior Cingulate Cortical Thickness and Bilateral Striatal Volume Correlate with Child Behavior Checklist Aggressive Behavior Scores in Healthy Children

BACKGROUND The anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and basal ganglia have been implicated in pathological aggression. This study aimed at identifying neuroanatomical correlates of impulsive aggression in healthy children. METHODS Data from 193 representative 6- to 18-year-old healthy children were obtained from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development after a blinded quality control. Cortical thickness and subcortical volumes were obtained with automated software. Aggression levels were measured with the Aggressive Behavior scale (AGG) of the Child Behavior Checklist. AGG scores were regressed against cortical thickness and basal ganglia volumes using first- and second-order linear models while controlling for age, gender, scanner site, and total brain volume. Gender by AGG interactions were analyzed. RESULTS There were positive associations between bilateral striatal volumes and AGG scores (right: r = .238, p = .001; left: r = .188, p = .01). A significant association was found with right ACC and subgenual ACC cortical thickness in a second-order linear model (p < .05, corrected). High AGG scores were associated with a relatively thin right ACC cortex. An AGG by gender interaction trend was found in bilateral OFC and ACC associations with AGG scores. CONCLUSIONS This study shows the existence of relationships between impulsive aggression in healthy children and the structure of the striatum and right ACC. It also suggests the existence of gender-specific patterns of association in OFC/ACC gray matter. These results may guide research on oppositional-defiant and conduct disorders.

Parkinson's disease duration determines effect of dopaminergic therapy on ventral striatum function

We investigated the hypothesis that variation in endogenous dopamine (DA) across brain regions explains dissimilar effects of dopaminergic therapy on aspects of cognition in early Parkinsons disease (PD). Extensive degeneration of DA‐producing cells in the substantia nigra cause dorsal striatum (DS) DA deficiency and movement abnormalities. Particularly in early PD, this contrasts with relative sparing of the dopaminergic cells of the ventral tegmental area (VTA). The hypothesis predicts that DS‐mediated cognitive functions are deficient at baseline and improved by DA replacement, whereas functions depending upon VTA‐innervated brain regions are normal off medication and worsen with treatment. The latter pattern presumably owes to overdose of relatively DA‐replete VTA‐supplied brain regions with medication levels titrated to DS‐mediated motor symptoms. As PD progresses, however, VTA degeneration increases. Impairment in cognitive operations performed by VTA‐innervated brain regions, such as the ventral striatum (VS), is expected. We compared the performance of early and late PD patients, on and off dopaminergic medication, relative to age‐matched controls, on reward learning, previously shown to implicate the VS. As expected, in early PD, stimulus‐reward learning was normal off medication, but worsened with DA replacement. At more advanced disease stages, PD patients learned stimulus‐reward contingencies more poorly than controls and early PD patients off medication. Furthermore, dopaminergic medication did not worsen reward learning in late PD patients, in line with the dopamine overdose hypothesis. Unlike its effect on DS‐mediated functions, however, DA‐replacement therapy did not improve reward learning in late PD patients.

Negative associations between corpus callosum midsagittal area and IQ in a representative sample of healthy children and adolescents.

Documented associations between corpus callosum size and cognitive ability have heretofore been inconsistent potentially owing to differences in sample characteristics, differing methodologies in measuring CC size, or the use of absolute versus relative measures. We investigated the relationship between CC size and intelligence quotient (IQ) in the NIH MRI Study of Normal Brain Development sample, a large cohort of healthy children and adolescents (aged six to 18, n = 198) recruited to be representative of the US population. CC midsagittal area was measured using an automated system that partitioned the CC into 25 subregions. IQ was measured using the Wechsler Abbreviated Scale of Intelligence (WASI). After correcting for total brain volume and age, a significant negative correlation was found between total CC midsagittal area and IQ (r = −0.147; p = 0.040). Post hoc analyses revealed a significant negative correlation in children (age<12) (r = −0.279; p = 0.004) but not in adolescents (age≥12) (r = −0.005; p = 0.962). Partitioning the subjects by gender revealed a negative correlation in males (r = −0.231; p = 0.034) but not in females (r = 0.083; p = 0.389). Results suggest that the association between CC and intelligence is mostly driven by male children. In children, a significant gender difference was observed for FSIQ and PIQ, and in males, a significant age-group difference was observed for FSIQ and PIQ. These findings suggest that the correlation between CC midsagittal area and IQ may be related to age and gender.

Investigating the relation between striatal volume and IQ

The volume of the input region of the basal ganglia, the striatum, is reduced with aging and in a number of conditions associated with cognitive impairment. The aim of the current study was to investigate the relation between the volume of striatum and general cognitive ability in a sample of 303 healthy children that were sampled to be representative of the population of the United States. Correlations between the WASI-IQ and the left striatum, composed of the caudate nucleus and putamen, were significant. When these data were analyzed separately for male and female children, positive correlations were significant for the left striatum in male children only. This brain structure-behavior relation further promotes the increasingly accepted view that the striatum is intimately involved in higher order cognitive functions. Our results also suggest that the importance of these brain regions in cognitive ability might differ for male and female children.

Examining dorsal striatum in cognitive effort using Parkinson's disease and fMRI

Understanding cognition mediated by the striatum can clarify cognitive deficits in Parkinsons disease (PD). Previously, we claimed that dorsal striatum (DS) mediates cognitive flexibility. To refute the possibility that variation in cognitive effort confounded our observations, we reexamined our data to dissociate cognitive flexibility from effort. PD provides a model for exploring DS‐mediated functions. In PD, dopamine‐producing cells supplying DS are significantly degenerated. DS‐mediated functions are impaired off and improved on dopamine replacement medication. Functional magnetic resonance imaging (fMRI) can confirm striatum‐mediated functions.

Dopaminergic therapy affects learning and impulsivity in Parkinson's disease

The aim was to examine the effect of dopaminergic medication on stimulus‐response learning versus performing decisions based on learning.

A fourth case of Feingold syndrome type 2: psychiatric presentation and management

Feingold syndrome (FGLDS1) is an autosomal dominant disorder caused by mutations in the MYCN oncogene on the short arm of chromosome 2 (2p24.1). It is characterised by microcephaly, digital abnormalities, oesophageal and duodenal atresias, and often learning disability or mental retardation. In 2011, individuals sharing the skeletal abnormalities of FGLDS1 but lacking mutations in MYCN, were found to harbour hemizygous deletions of the MIR17HG gene on chromosome 13q31.3. These individuals share many of the characteristics of FGLDS1 except for gastrointestinal atresia. The condition was termed Feingold syndrome type 2 (FGLDS2). We describe the presentation and management of a fourth known case of FGLDS2 in an 18-year-old girl with microcephaly, short stature, mildly dysmorphic features, digital malformations and significant cognitive and psychiatric symptoms. Comparative genomic hybridisation array testing confirmed a 7.4 Mb microdeletion in chromosome region 13q31.1q.31.3 corresponding to the MIR17HG gene.

ON-OFF Effects of Dopaminergic Therapy on Psychiatric Symptoms in Parkinson’s Disease

Psychiatric manifestations of Parkinsons disease (PD) are a cause of significant disability and the impact of dopaminergic medications is unclear. Using standardized rating scales, the authors tested the hypothesis that anxiety, depression, and apathy vary in the ON versus OFF states in PD in 33 PD patients and 29 healthy age- and education-matched controls. PD patients had significantly higher anxiety, depression, and apathy scores than control participants, regardless of ON-OFF state. Anxiety scores were higher in PD patients on relative to off dopaminergic medication. The ON-OFF difference in anxiety related to degree of improvement in motor function but not illness duration.