J. Keshav Kumar

Neuropsychological functioning in obsessive-compulsive disorder: are executive functions the key deficit?

OBJECTIVE Although several studies have examined neuropsychological functions in obsessive-compulsive disorder (OCD), findings are not conclusive, predominantly due to small samples and assessment of limited domains. We aim to map the neuropsychological profile of OCD in a large sample with a comprehensive battery of tests. METHOD Neuropsychological functions were tested in 150 subjects with DSM-IV OCD and 205 healthy control subjects. RESULTS Subjects with OCD performed significantly worse than healthy control subjects on Colour Trails 1 time, Tower of Hanoi 3-disk time, Wisconsin Card Sorting Test categories completed, Iowa Gambling Task, Complex Figure Test immediate and delayed recall (p<0.001). CONCLUSIONS Subjects with OCD evince deficits in scanning, planning time, concept formation, decision making and encoding of non-verbal memory after controlling for the effects of age, gender and education. The profile is suggestive of a predominantly executive dysfunction, with difficulties in strategizing and organizing stimuli and cognitive resources for maximum efficiency. The findings implicate dorsolateral prefrontal, superior medial prefrontal and anterior cingulate cortices, suggesting that OCD might not be a purely orbitofronto-striatal disorder as previously conceptualized.

Schizophrenia patients experience substantial social cognition deficits across multiple domains in remission

Knowledge about SC (social cognition) during remission would inform us whether such deficits are trait- or state-markers of the disorder, as well as highlight its relevance for rehabilitation. We aimed to compare SC deficits and their relative independence from NC (neuro-cognition) deficits in remitted schizophrenia patients and matched health controls using comprehensive, culturally sensitive standardized tools. 60 schizophrenia patients meeting modified standardized criteria for remission and 60 age, gender and education matched healthy controls were compared on culturally validated tests of SC-Social Cognition Rating Tool in Indian Setting (SOCRATIS) & Tool for Recognition of Emotions in Neuropsychiatric Disorders (TRENDS) to assess theory of mind, attributional bias, social perception and emotion recognition and NC-(attention/vigilance, speed of processing, visual and verbal learning, working memory and executive functions). Patients had deficits in both SC and NC compared to healthy controls. Deficits in SC were largely independent of NC performance, and SC deficits persisted after adjusting for deficits in NC function. The effect sizes (Cohens d) for SC deficits ranged from 0.37 to 2.23. All patients scored below a defined cut-off in at least one SC domain. SC deficits are likely to be state-independent in schizophrenia, as they are present in remission phase of the illness. This supports their status as a possible composite-endophenotype in schizophrenia.

Similar and contrasting dimensions of social cognition in schizophrenia and healthy subjects

Schizophrenia patients experience substantial impairments in social cognition (SC) and these deficits are associated with their poor functional outcome. Though SC is consistently shown to emerge as a cognitive dimension distinct from neurocognition, the dimensionality of SC is poorly understood. Moreover, comparing the components of SC between schizophrenia patients and healthy comparison subjects would provide specific insights on the construct validity of SC. We conducted principal component analyses of eight SC test scores (representing four domains of SC, namely, theory of mind, emotion processing, social perception and attributional bias) independently in 170 remitted schizophrenia patients and 111 matched healthy comparison subjects. We also conducted regression analyses to evaluate the relative contribution of individual SC components to other symptom dimensions, which are important clinical determinants of functional outcome (i.e., neurocognition, negative symptoms, motivational deficits and insight) in schizophrenia. A three-factor solution representing socio-emotional processing, social-inferential ability and external attribution components emerged in the patient group that accounted for 64.43% of the variance. In contrast, a two-factor solution representing socio-emotional processing and social-inferential ability was derived in the healthy comparison group that explained 56.5% of the variance. In the patient group, the social-inferential component predicted negative symptoms and motivational deficits. Our results suggest the presence of a multidimensional SC construct. The dimensionality of SC observed across the two groups, though not identical, displayed important parallels. Individual components also demonstrated distinct patterns of association with other symptom dimensions, thus supporting their external validity.

Cascading and combined effects of cognitive deficits and residual symptoms on functional outcome in schizophrenia - A path-analytical approach.

Understanding the complex relationship among determinants of real-world functioning in schizophrenia patients in remission is important in planning recovery-oriented interventions. We explored two path-analytical models of functioning in schizophrenia. 170 Schizophrenia patients remitted from positive symptoms underwent fairly comprehensive assessments of cognition - neurocognition (NC) and social cognition (SC), residual symptoms - insight, motivation and other negative symptoms, and socio-occupational functioning. We explored (a) a cascading model, where NC predicted functional outcome through its effects on other determinants and (b) a combined model, incorporating additional direct paths from each of the determinants. The combined model, and not the cascading model demonstrated a good fit. Post-hoc trimming of the combined model by elimination of non-significant paths maintained the goodness-of-fit and was retained as the final model. In addition to the direct paths, this final model demonstrated that (a) NC influenced functioning through SC and insight and (b) SC influenced functioning through motivation and negative symptoms. This suggests that NC and SC may influence functional outcome directly, as well as indirectly, via specific impact on insight, and motivation and negative symptoms respectively.

Clinico-pathological factors influencing surgical outcome in drug resistant epilepsy secondary to mesial temporal sclerosis

BACKGROUND Mesial temporal sclerosis (MTS) is the most common cause of drug resistant epilepsy amenable for surgical treatment and seizure control. METHODS This study analyzed the outcome of patients with MTS following anterior temporal lobectomy and amygdalohippocampectomy (ATL-AH) over 10 years and correlated the electrophysiological and radiological factors with the post operative seizure outcome. RESULTS Eighty seven patients were included in the study. Sixty seven (77.2%) patients had an Engel Class 1 outcome, 9 (11.4%) had Class 2 outcome. Engels class 1 outcome was achieved in 89.9% at 1 year, while it reduced slightly to 81.9% at 2 years and 76.2% at 5 year follow up. Seventy seven (88.5%) patients had evidence of hippocampal sclerosis on histopathology. Dual pathology was observed in 19 of 77 specimens with hippocampal sclerosis, but did not influence the outcome. Factors associated with an unfavorable outcome included male gender (p=0.04), and a higher frequency of pre-operative seizures (p=0.005), whereas the presence of febrile seizures (p=0.048) and loss of hippocampal neurons in CA4 region on histopathology (p=0.040) were associated with favorable outcome. The effect of CA4 loss on outcome is probably influenced by neuronal loss in other subfields as well since isolated CA4 loss was rare. Abnormal post operative EEG at the end of 1 week was found to be a significant factor predicting unfavorable outcome (p=0.005). On multivariate analysis, the pre-operative seizure frequency was the only significant factor affecting outcome. CONCLUSIONS The present study observed excellent seizure free outcome in a carefully selected cohort of patients with MTS with refractory epilepsy. The presence of dual pathology did not influence the outcome.

Negative symptoms mediate the influence of theory of mind on functional status in schizophrenia

We aimed to assess the relationship between social cognition, neurocognition, negative symptoms and functional status in a homogeneous schizophrenia patient group remitted from positive symptoms. Sixty patients underwent assessments of social and neurocognition dimensions recommended by expert panels. A blind rater assessed their functional status. Second order theory of mind (ToM) and negative symptoms had significant correlations with functional status. A bootstrapping analysis used to test for specific mediation models revealed that the effect of second order ToM on functioning was mediated by negative symptoms. Future studies should examine if targeted remediation of ToM improves negative symptoms and thus functioning.

Stroke with supernumerary phantom limb: case study, review of literature and pathogenesis.

Objective: Constitute hypothesis for origin of supernumerary phantom limb (SPL) after stroke. Method: Single case description, review of literature and formulation of hypothesis. Results: A 59-year-old lady was evaluated for complaints of left-sided hemiparesis and extra limbs attached to her left shoulder for the past 7 months. Neuropsychological assessment revealed left hemineglect with SPL, and profile suggested bilateral frontal, right parietotemporal and basal ganglia involvement. Magnetic resonance imaging brain scan showed gliotic cavity secondary to the old haematoma in right putamen with white matter changes in the right frontoparietotemporal lobes. Conclusions: The conceptual framework of body schema can be used to classify many of the neurological disorders of body representation. Generation of SPL comes under the subtype of pathology of updating among the disorders of body schema. The continuous updating allows the body schema to modulate perceptual processing of objects according to their position in space. Brain areas classified as parts of motor system can, under pathological conditions (haemorrhage), influence body perception. So, when she used to move her arm, the representation of the estimated position was not updated by the motor commands. Sensory and motor information therefore becomes discrepant, and failure to integrate these two sources of information leads to loss of normal coherence, and the perceived shape of the body was altered by adding a SPL to accommodate the discrepancy.

Neuropsychological and imaging profile of patients with Parkinson's disease and freezing of gait

BACKGROUND Neuropsychological evaluation with advanced neuroimaging may be a useful tool to determine the anatomical substrates that play crucial role in freezing of gait (FOG) in patients with Parkinsons Disease (PD). OBJECTIVES To compare the cognitive profile and gray matter (GM) changes (using Voxel Based Morphometry - VBM) between patients with PD with and without FOG (FOG+ve and FOG-ve). METHODS Seventeen FOG+ve (M:F = 11:6) and 21 FOG-ve (M:F = 11:10) were evaluated clinically and with a structured neuropsychological battery. All patients underwent 3 T MRI. In order to determine areas of GM atrophy, T1W volumetric MRI data of the two groups were compared using VBM and Statistical Parametric Mapping 8. RESULTS The mean age of FOG+ve and FOG-ve patients were 56.9 ± 6.6 and 47.4 ± 9.1 years respectively. There was no significant difference in the duration (6.0 ± 4.9 vs 5.2 ± 3.5 years, p < 0.05) and stage of PD (Hoehn & Yahr stage: 1.96 ± 0.53 vs 1.78 ± 0.37) between the two groups. Compared to the FOG-ve group, the FOG+ve group had (i) significant impairment in memory, attention, executive and visuospatial functions on neuropsychological tests, and (ii) significant GM atrophy in the right cerebellum (pyramis, declive), left cerebrum (Brodmann area (BA) 21 and 22) and right cerebrum (BA 10 and 6) on VBM analysis. CONCLUSIONS The FOG+ve group showed widespread involvement of cognition localizing to frontal, temporal (especially left) and parietal areas. VBM analysis showed significant GM atrophy in FOG+ve group in left temporal, right frontal areas (coinciding with that observed in neuropsychological tests) and significant involvement of right cerebellum.

Relationships between neuropsychological variables and factor-analysed symptom dimensions in obsessive compulsive disorder

Despite mounting evidence for the distinctiveness of symptom dimensions in obsessive-compulsive disorder, neuropsychological studies have been few, focused on small samples, and relying on classification of participants based on mutually exclusive symptom categories, resulting in lack of concordance across neuropsychological and imaging studies. Neuropsychological assessment was undertaken with 150 individuals with DSM IV OCD, and neuropsychological variables were analysed in relation to symptom dimension scores derived from factor analysis. Five dimensions were derived from principal components analysis with varimax rotation - contamination/washing, doubts/checking, symmetry/ordering, forbidden thoughts, and hoarding. After controlling for severity of depression and OCD, antipsychotic and benzodiazepine use, and all other symptom dimensions, washing was associated with poorer attention/working memory, visuo-spatial construction and better planning time; checking was related to poorer alternation learning; symmetry linked with poorer verbal fluency; forbidden thoughts with better visuospatial scanning and working memory; hoarding with poorer immediate verbal recall and better visuospatial working memory. The neuropsychological associations are explained in the context of existing neuroimaging evidence, and the clinical picture of each symptom dimension. The use of factor-analysed symptom dimensions and a large sample of individuals with OCD are strengths of the study.

Neuropsychology in India

Abstract Objective: This is an invited paper for a special issue with the objective to provide information on neuropsychology in India. Method: Information was gathered from a literature search and personal communication with professionals working in the field of neuropsychology. Results: Neuropsychology as a specialization started in India approximately 40 years ago. The early years witnessed the use of Western tools for assessing patients with organic brain damage. Subsequent years saw the development of indigenous tools for use with the vast majority of the Indian population and also a few Western tests adapted to suit the needs of the unique Indian clientele. The starting of the Neuropsychology unit at the National Institute of Mental Health and Neurosciences (NIMHANS) in Bangalore in 1975 resulted in changing of the course of training and practice of Neuropsychology. The field of assessments has witnessed indigenous tests being developed, while rehabilitation programs have brought about a decline in cognitive deficits in several clinical conditions. Currently, work within the field of neuropsychology has focused on child, geriatric, acquired brain injury, and forensic populations with a development of unique rehabilitations to suit needs of several clinical conditions. However, there are very few neuropsychologists in the country, and only one nodal training center, which limits the availability of training to the large population of the country. Conclusion: Despite the shortcomings, the field of neuropsychology has received much attention in the recent years with the number of referrals and professionals increasing.