Neural Correlates of a Perspective-taking Task Using in a Realistic Three-dimmensional Environment Based Task: A Pilot Functional Magnetic Resonance Imaging Study

OBJECTIVE: Perspective-taking ability is an essential spatial faculty that is of much interest in both health and neuropsychiatric disorders. There is limited data on the neural correlates of perspective taking in the context of a realistic three-dimensional environment. We report the results of a pilot study exploring the same in eight healthy volunteers. METHODS: Subjects underwent two runs of an experiment in a 3 Tesla magnetic resonance imaging (MRI) involving alternate blocks of a first-person perspective based allocentric object location memory task (OLMT), a third-person perspective based egocentric visual perspective taking task (VPRT), and a table task (TT) that served as a control. Difference in blood oxygen level dependant response during task performance was analyzed using Statistical Parametric Mapping software, version 12. Activations were considered significant if they survived family-wise error correction at the cluster level using a height threshold of p<0.001, uncorrected at the voxel level. RESULTS: A significant difference in accuracy and reaction time based on task type was found. Subjects had significantly lower accuracy in VPRT compared to TT. Accuracy in the two active tasks was not significantly different. Subjects took significantly longer in the VPRT in comparison to TT. Reaction time in the two active tasks was not significantly different. Functional MRI revealed significantly higher activation in the bilateral visual cortex and left temporoparietal junction (TPJ) in VPRT compared to OLMT. CONCLUSION: The results underscore the importance of TPJ in egocentric manipulation in healthy controls in the context of reality-based spatial tasks.

Transcranial Direct Current Stimulation in Schizophrenia

Transcranial direct current stimulation (tDCS) is an upcoming treatment modality for patients with schizophrenia. A series of recent observations have demonstrated improvement in clinical status of schizophrenia patients with tDCS. This review summarizes the research work that has examined the effects of tDCS in schizophrenia patients with respect to symptom amelioration, cognitive enhancement and neuroplasticity evaluation. tDCS is emerging as a safe, rapid and effective treatment for various aspects of schizophrenia symptoms ranging from auditory hallucinations-for which the effect is most marked, to negative symptoms and cognitive symptoms as well. An interesting line of investigation involves using tDCS for altering and examining neuroplasticity in patients and healthy subjects and is likely to lead to new insights into the neurological aberrations and pathophysiology of schizophrenia. The mechanistic aspects of the technique are discussed in brief. Future work should focus on establishing the clinical efficacy of this novel technique and on evaluating this modality as an adjunct to cognitive enhancement protocols. Understanding the mechanism of action of tDCS as well as the determinants and neurobiological correlates of clinical response to tDCS remains an important goal, which will help us expand the clinical applications of tDCS for the treatment of patients with schizophrenia.

A Longitudinal Study of Relation between Side-effects and Clinical Improvement in Schizophrenia: Is There a Neuro-metabolic Threshold for Second Generation Antipsychotics?

OBJECTIVE: Classical studies demonstrated Neuroleptic Induced Extrapyramidal Side-effects (NIES; Neuroleptic threshold) to correlate with the efficacy of first generation antipsychotics. Second generation antipsychotics (SGAs), in addition to the extrapyramidal side effects, are also associated with metabolic side effects. This prospective study on antipsychotic-naive schizophrenia patients, for the first-time, examined concurrently the relationship between clinical improvement and these side-effects NIES and Neuroleptic Induced Metabolic Side-effects. METHODS: Thirty six-antipsychotic-naive schizophrenia (DSM-IV) patients were examined at baseline and after 5 weeks of treatment with antipsychotics. At baseline and follow-up, we recorded the body mass index (BMI) and assessed psychopathology using Scale for Assessment of Positive-symptoms (SAPS) and Scale for Assessment of Negative-symptoms (SANS), extrapyramidal symptoms using Simpson-Angus Extra Pyramidal Scale (SAEPS) and improvement using Clinical Global Impression Improvement (CGI). RESULTS: After treatment, patients showed significant reduction in SAPS (baseline, 27.97+/-14.47; follow-up, 14.63+/-13.25; p<0.001) and SANS total scores (baseline, 63.77+/-28.96; follow-up, 49.30+/-28.77; p=0.001) and a significant increase in BMI (baseline, 18.5+/-3.37; follow-up, 19.13+/-3.17; p<0.001). At follow-up CGI-Improvement score was (2.55+/-0.65) and SAEPS score was (0.8+/-1.32). CGI-Improvement score had a significant negative correlation with magnitude of increase in BMI (rs=-0.39; p=0.01) and SAEPS symptom score at follow-up (rs=-0.58; p<0.001). In addition, magnitude of increase in BMI showed positive correlation with the magnitude of reduction in SAPS total score (rs=0.33; p=0.04). CONCLUSION: The study findings suggest a possible relation between clinical improvement and antipsychotic-induced neuroleptic as well as metabolic side-effects in schizophrenia. Though the mechanism of this relation is yet to be elucidated, insulin signaling pathways and lipid homeostasis are potential mechanisms in addition to the established neurotransmitter hypothesis. Theoretically findings support the novel hypothetical construct of 'Neuro-Metabolic threshold' in the treatment of schizophrenia.