Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative.

BACKGROUND: Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2-3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. METHODS: We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. DISCUSSION: Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it.

Integrative Medicine Enhances Motor and Sensory Recovery in Guillain-Barre Syndrome - A Case Study.

Guillain-Barre syndrome (GBS) is a heterogenous group of immune-mediated conditions affecting peripheral nerves. About 40% of patients treated with standard dosage of plasma exchange or intravenous immunoglobulins do not improve in the first 4 weeks following treatment. Add-on treatment from traditional medical approaches such as Yoga therapy and Ayurveda are increasingly being sought for rehabilitation of patients with chronic neurological disorders. The current case study reports the clinical utility of adjunct Yoga and Ayurveda treatment in the treatment of residual symptoms of GBS.

Auditory signal detection in schizophrenia: Correlates with auditory verbal hallucinations & effect of single session transcranial direct current stimulation (tDCS).

INTRODUCTION: Transcranial Direct Current Stimulation (tDCS) has been beneficial for treating auditory verbal hallucinations (AVH) in schizophrenia (SZ). Aberrant auditory signal detection (ASD) is one of the pathogenetic mechanisms for AVH. We investigated the correlates of ASD with AVH and the impact of single-session tDCS on ASD in SZ patients. METHODS: The ASD performance in SZ patients was compared with matched healthy controls (HC) (N = 24). Subsequently, the effect of single-session tDCS on ASD in SZ patients (N = 24) with AVH was examined in a randomized, double-blind, sham-controlled, cross-over design. The true and sham tDCS were administered (anode at the left dorsolateral prefrontal cortex and cathode at the left temporoparietal junction) on two different days. ASD task was performed before and after each session of tDCS. RESULTS: Auditory hallucination rating scores correlated significantly with false alarm rate, discriminability index, and response bias. SZ patients had a significantly lesser discriminability index in ASD than HC. Single-session tDCS (true versus sham) did not have any significant effect on ASD in SZ patients. CONCLUSION: The study findings support the pathogenetic role of ASD in AVH in SZ. Lack of effect on ASD following single-session tDCS suggests the need for multi-session studies in the future.

A Primer on Interoception and its Importance in Psychiatry

Interoception is the perception of signals from inside the body. It plays a significant role in the nervous, cardiovascular, respiratory, gastrointestinal, genitourinary, and endocrine systems. It is also closely related to the autonomic nervous system and inflammatory pathways and plays a significant role in our optimal functioning. Recently, interoception has gained more attention in neuropsychiatric research. Anatomical and physiological aspects of interoception like relevant brain areas, the role of the vagus nerve, and the autonomic nervous system are gradually being understood. Different facets of interoception like interoceptive attention, detection, magnitude, discrimination, accuracy, awareness, and appraisal have been proposed and their assessments and importance are being evaluated. Further, interoception is often dysregulated or abnormal in psychiatric disorders. It has been implicated in the psychopathology, etiopathogenesis, clinical features and treatment of mood, anxiety, psychotic, personality and addiction-related disorders. This narrative review attempts to provide a nuanced understanding of the pathway(s), components, functions, assessments, and problems of interoception and will help us to detect its disturbances and evaluate its impact on psychiatric disorders, leading to a better perspective and management. This will also advance interoception-related research.

Pars Triangularis Volume Asymmetry and Schneiderian First Rank Symptoms in Antipsychotic-naïve Schizophrenia

Objective@#Schizophrenia is a disorder of language and self, with first-rank symptoms (FRS) as one of the predominant features in a subset of patients. Abnormal language lateralization is hypothesized to underlie the neurobiology of FRS in schizophrenia. The role of Broca’s area with its right-hemispheric counterpart, consisting of pars triangularis (PTr) and pars opercularis (POp) of the inferior frontal gyrus in FRS is undetermined. We compared the volumes and asymmetries of PTr & POp in anti-psychotic-naive schizophrenia patients with FRS (FRS[＋]) with those without FRS (FRS[−]) and healthy-controls (HC) using three dimensional, interactive, semi-automated volumetric morphometry. @*Methods@#Antipsychotic naïve FRS(＋) (n = 27), FRS(−) (n = 24) and HC (n = 51) were carefully assessed with structured and semi-structured clinical tools. T1-weighted images were acquired in a 3T scanner. Volumes of regions of interest were measured independently for both sides using slicer-3D software, and asymmetry indices were calculated. @*Results@#FRS(＋) but not FRS(−) had a significant volume deficit in right PTr after controlling for the potential confounding effects of age, sex, and intracranial volume (p = 0.029). There was a significant leftward asymmetry of PTr in patients with FRS (i.e., leftward asymmetry in patients) (p = 0.026). No significant volume/asymmetry abnormalities were observed in POp. @*Conclusion@#Study findings suggest reduced right PTr volume with leftward asymmetry to be associated with FRS in schizophrenia. This is consistent with the loss of Yakovlevian torque in schizophrenia. Role of PTr in the neurobiology of schizophrenia as a disorder of self, speech, and social cognition needs further systematic evaluation in future research.

Pars Triangularis Volume Asymmetry and Schneiderian First Rank Symptoms in Antipsychotic-naïve Schizophrenia

Objective@#Schizophrenia is a disorder of language and self, with first-rank symptoms (FRS) as one of the predominant features in a subset of patients. Abnormal language lateralization is hypothesized to underlie the neurobiology of FRS in schizophrenia. The role of Broca’s area with its right-hemispheric counterpart, consisting of pars triangularis (PTr) and pars opercularis (POp) of the inferior frontal gyrus in FRS is undetermined. We compared the volumes and asymmetries of PTr & POp in anti-psychotic-naive schizophrenia patients with FRS (FRS[＋]) with those without FRS (FRS[−]) and healthy-controls (HC) using three dimensional, interactive, semi-automated volumetric morphometry. @*Methods@#Antipsychotic naïve FRS(＋) (n = 27), FRS(−) (n = 24) and HC (n = 51) were carefully assessed with structured and semi-structured clinical tools. T1-weighted images were acquired in a 3T scanner. Volumes of regions of interest were measured independently for both sides using slicer-3D software, and asymmetry indices were calculated. @*Results@#FRS(＋) but not FRS(−) had a significant volume deficit in right PTr after controlling for the potential confounding effects of age, sex, and intracranial volume (p = 0.029). There was a significant leftward asymmetry of PTr in patients with FRS (i.e., leftward asymmetry in patients) (p = 0.026). No significant volume/asymmetry abnormalities were observed in POp. @*Conclusion@#Study findings suggest reduced right PTr volume with leftward asymmetry to be associated with FRS in schizophrenia. This is consistent with the loss of Yakovlevian torque in schizophrenia. Role of PTr in the neurobiology of schizophrenia as a disorder of self, speech, and social cognition needs further systematic evaluation in future research.

A Functional Domain Based Approach in Neurocognitive Rehabilitation with Transcranial Direct Current Stimulation: A Case Report

Transcranial direct current stimulation (tDCS) is a novel brain stimulation technique which has kindled hope in alleviating motor, language as well as cognitive deficits in neuronal injury. Current case report describes application of tDCS in two phases using two different protocols in a patient with hypoxic injury. In the first phase anodal stimulation of dorsolateral prefrontal cortex improved the language fluency. Subsequently, after 6 months second phase application of anodal stimulation over posterior parietal region targeted arithmetic and working memory deficits. Individualising the treatment protocols of brain stimulation, based on the lesion and the functional deficits, for neuro-rehabilitation is emphasised.

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.