Identification of neuroanatomical substrates of set-shifting ability: evidence from patients with focal brain lesions.
ABSTRACT This work concerns the investigation of executive functions in patients with focal brain lesion. In order to identify the underlying substrates for executive functions, 54 patients with focal cortical (n=30), subcortical (n=13) and cerebellar damage (n=10) (M=9; F=1) in the age range of 24-65 years with a minimum of Class V education have been investigated. The patients were admitted to the Department of Neuromedicine of Bangur Institute of Neurology, Calcutta. Each patient with focal lesion was matched with a healthy normal subject controlling for age and education. The socio-economic background was also taken into consideration. Controls were selected from the families of other patients admitted to the institution and also from individuals who volunteered to act as controls. Here too, rigid criteria have been followed to select the normals. Mini Mental State Examination (MMSE) and General Health Questionnaire (GHQ) were administered to screen out the neurological and psychiatric abnormalities in selection of normal control and Wisconsin Card Sorting Test (WCST) was administered to find out the executive function, in terms of set-shifting ability. Since standard anatomical groupings can obscure more specific brain-behavior relations, group-comparison design does not always allow determination of the effective lesion responsible for a particular deficit (Godefroy et al., 1998). The Classification and Regression Tree (CART) analysis has been used to determine the brain-behavior relationships. The result reveals that the frontal lobes are essential determinants of set-shifting capacity. However, for optimal execution of set-shifting function, the frontal lobes require participation of other cortical, subcortical and cerebellar regions. The result has been discussed in the light of the existing theories and research reports.
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ABSTRACT: The aged rhesus macaque exhibits brain atrophy and behavioral deficits similar to normal aging in humans. Here we studied the association between cognitive and motor performance and anatomic and microstructural brain integrity measured with 3T magnetic resonance imaging in aged monkeys. About half of these animals were maintained on moderate calorie restriction (CR), the only intervention shown to delay the aging process in lower animals. T1-weighted anatomic and diffusion tensor images were used to obtain gray matter (GM) volume and fractional anisotropy (FA) and mean diffusivity (MD), respectively. We tested the extent to which brain health indexed by GM volume, FA, and MD were related to executive and motor function, and determined the effect of the dietary intervention on this relationship. We hypothesized that fewer errors on the executive function test and faster motor response times would be correlated with higher volume, higher FA, and lower MD in frontal areas that mediate executive function, and in motor, premotor, subcortical, and cerebellar areas underlying goal-directed motor behaviors. Higher error percentage on a cognitive conceptual shift task was significantly associated with lower GM volume in frontal and parietal cortices, and lower FA in major association fiber bundles. Similarly, slower performance time on the motor task was significantly correlated with lower volumetric measures in cortical, subcortical, and cerebellar areas and decreased FA in several major association fiber bundles. Notably, performance during the acquisition phase of the hardest level of the motor task was significantly associated with anterior mesial temporal lobe volume. Finally, these brain-behavior correlations for the motor task were attenuated in CR animals compared to controls, indicating a potential protective effect of the dietary intervention.Frontiers in Aging Neuroscience 01/2012; 4:31. · 5.20 Impact Factor
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ABSTRACT: The ability to learn a rule to guide behavior is crucial for cognition and executive function. However, in a constantly changing environment, flexibility in terms of learning and changing rules is paramount. Research suggests there may be common underlying causes for the similar rule learning impairments observed in many psychiatric disorders. One of these common anatomical manifestations involves deficits to the GABAergic system, particularly in the frontal cerebral cortical regions. Many common anti-epileptic drugs and mood stabilizers activate the GABA system with the reported adverse side effects of cognitive dysfunction. The mouse reversal/set-shifting test was used to evaluate effects in mice given topiramate, which is reported to impair attention in humans. Here we report that in mice topiramate prevents formation of the attentional set, but does not alter reversal learning. Differences in the GABA system are also found in many neuropsychiatric disorders that are more common in males, including schizophrenia and autism. Initial findings with the reversal/set-shifting task excluded female subjects. In this study, female mice tested on the standard reversal/set-shifting task showed similar reversal learning, but were not able to form the attentional set. The behavioral paradigm was modified and when presented with sufficient discrimination tasks, female mice performed the same as male mice, requiring the same number of trials to reach criterion and form the attentional set. The notable difference was that female mice had an extended latency to complete the trials for all discriminations. In summary, the reversal/set-shifting test can be used to screen for cognitive effects of potential therapeutic compounds in both male and female mice.Physiology & Behavior 06/2012; · 3.16 Impact Factor
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ABSTRACT: The present study aimed to examine the relationships of insight with symptomatology and executive function, both cross-sectionally and longitudinally in patients with first-episode schizophrenia-spectrum disorders. Ninety-two medication-naïve patients were recruited and 71 completed the assessments. Insight, symptoms and executive function were assessed at baseline, 6 months and 1 year. Insight was measured with the abridged version of Scale of Unawareness of Mental Disorder (SUMD). Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Executive function was measured with the Modified Wisconsin Card Sorting Test (MCST). The most significant improvement of insight and symptomatology was found over the first 6 months, whereas the perseverative errors of MCST were significantly improved between 6 and 12 months. Differential correlations of perseverative errors of the MCST and PANSS scores with SUMD were found at different time points. This suggests the involvement of different mechanisms in insight deficit at different stages of the illness. The baseline MCST perseverative errors were correlated significantly with the SUMD total score at 6 months and the change of SUMD scores over the first 6 months. Although the variance explained was small, it suggests better set-shifting capacity facilitates the improvement of insight at an early stage of the illness.Psychiatry research. 12/2013;