Vaibhav A Diwadkar

Wayne State University | WSU · Department of Psychiatry and Behavioral Neurosciences

Background: Patients with schizophrenia show abnormal gaze processing, which is associated with social dysfunction. These abnormalities are associated with aberrant connectivity among brain regions associated with visual processing, social cognition, and cognitive control. In this study, we investigated 1) how effective connectivity during gaze pr...

The human brain is a prediction device, a view widely accepted in neuroscience. Prediction is a rational and efficient response that relies on the brain's ability to create and employ generative models to optimize actions over unpredictable time horizons. We argue that extant predictive frameworks while compelling, have not explicitly accounted for...

Motivational deficits in schizophrenia may interact with foundational cognitive processes including learning and memory to induce impaired cognitive proficiency. If such a loss of synergy exists, it is likely to be underpinned by a loss of synchrony between the brains learning and reward sub-networks. Moreover, this loss should be observed even dur...

Introduction Asymmetries in processing by the healthy brain demonstrate regularities that facilitate the modeling of brain operations. The goal of the present study was to determine asymmetries in saccadic metrics during visual exploration, devoid of confounding clutter in the visual field. Methods Twenty healthy adults searched for a small, low-c...

Objectives: Schizophrenia is characterized by deficits across multiple cognitive domains and altered glutamate related neuroplasticity. The purpose was to investigate whether glutamate deficits are related to cognition in schizophrenia, and whether glutamate-cognition relationships are different between schizophrenia and controls. Methods: Magne...

Intensive cognitive tasks induce inefficient regional and network responses in schizophrenia (SCZ). fMRI-based studies have naturally focused on gray matter, but appropriately titrated visuo-motor integration tasks reliably activate inter- and intra-hemispheric white matter pathways. Such tasks can assess network inefficiency without demanding inte...

There is a paucity of graph-theoretic methods applied to task-based data in schizophrenia (SCZ). Tasks are useful for modulating brain network dynamics, and topology. Understanding how changes in task conditions impact inter-group differences in topology can elucidate unstable network characteristics in SCZ. Here, in a group of patients and healthy...

Schizophrenia (SCZ) is characterized by deficits across multiple cognitive domains presumed to be associated with altered glutamate (Glu) related neuroplasticity in the dorsolateral prefrontal cortex (dlPFC) and the hippocampus. However, how Glu deficits, are related to cognition in SCZ, and whether the relationship between Glu and cognition is dif...

Abnormal function of the thalamo-cortical relay is considered a hallmark of obsessive-compulsive disorder (OCD) and aberrant network interactions may underpin many of the clinical and cognitive symptoms that characterize the disorder. Several statistical approaches have been applied to in vivo fMRI data to support the general loss of thalamo-cortic...

Background: Impaired emotion processing constitutes a key dimension of schizophrenia and a possible endophenotype of this illness. Empirical studies consistently report poorer emotion recognition performance in patients with schizophrenia as well as in individuals at enhanced risk of schizophrenia (“at risk”). fMRI studies also report consistent pa...

Background Impaired emotion processing constitutes a key dimension of schizophrenia and a possible endophenotype of this illness. Empirical studies consistently report poorer emotion recognition performance in patients with schizophrenia as well as in individuals at enhanced risk of schizophrenia (“at risk”). fMRI studies also report consistent pat...

Homeostatic centers in the mammalian brainstem are critical in responding to thermal challenges. These centers play a prominent role in human thermoregulation, but humans also respond to thermal challenges through behavior modification. Behavioral modifications are presumably sub served by interactions between the brainstem and interoceptive, cogni...

Time-series data are amongst the most widely-used in biomedical sciences, including domains such as functional Magnetic Resonance Imaging (fMRI). Structure within time series data can be captured by the tools of topological data analysis (TDA). Persistent homology is the mostly commonly used data-analytic tool in TDA, and can effectively summarize...

fMRI is the preeminent method for collecting signals from the human brain in vivo , for using these signals in the service of functional discovery, and relating these discoveries to anatomical structure. Numerous computational and mathematical techniques have been deployed to extract information from the fMRI signal. Yet, the application of Topolog...

Neuropsychiatric disorders are among the most intractable of medical conditions. They are acknowledged as conditions of the lifespan, tied to the bookends of neurodevelopment and neurodegeneration, thus implying that they cannot be “cured.” Though psychiatric nosology is relatively tractable and characterized by high reliability, the etiology of ne...

Background Borderline personality disorder (BPD) is characterized by instability in affective regulation that can result in a loss of cognitive control. Triggers may be neuronal responses to emotionally valenced context and/or stimuli. ‘Neuronal priming’ indexes the familiarity of stimuli, and may capture the obligatory effects of affective valence...

Background Panic Disorder (PD) is characterized by unexpected and repeated moments of intense fear or anxiety, which manifest themselves through strong cognitive and behavioural symptoms. However, a clear picture of how impairments in recognition and processing of facial emotions affect the everyday life of PD patients has yet to be delineated. Thi...

Sex-related differences are tied into neurodevelopmental and lifespan processes, beginning early in the perinatal and developmental phases and continue into adulthood. The present study was designed to investigate sexual dimorphism of changes in gray matter (GM) volume in post-adolescence, with a focus on early and middle-adulthood using a structur...

Extinction learning is the dominant laboratory model for exposure therapy, a treatment involving both experience of safety near the feared object, and safety instructions relayed by a therapist. While the experiential aspect of extinction learning is well researched, less is known about instructed extinction learning and its neurocircuitry. Here, i...

Interest in the pathology of Obsessive-Compulsive Disorder\has focused on brain network profiles of the dorsal Anterior Cingulate Cortex (dACC), given its role as a principal control region. Both motor control and working memory tasks induce dysfunctional dACC profiles in OCD. H H We contrasted dACC network profiles in OCD and age-comparable contro...

Brain network function and dysfunction is the dominant model for understanding how the brain gives rise to normal and abnormal behavior. Moreover, neuropsychiatric illnesses continue to resist attempts to reveal an understanding of their bases. Thus, this timely volume provides a synthesis of the uses of multiple analytic methods as they are applie...

In humans, dynamic thermoregulation is (presumably) underpinned by a complex hierarchy of functional interactions between constituents of the human thermoregulatory large-scale network. However, these interactions have not been quantified from in vivo fMRI signals acquired during the experimental delivery of whole-body thermal stress. Here, we used...

Directional network interactions underpin normative brain function in key domains including associative learning. Schizophrenia (SCZ) is characterized by altered learning dynamics, yet dysfunctional directional functional connectivity (dFC) evoked during learning is rarely assessed. Here, nonlinear learning dynamics were induced using a paradigm al...

Functional connectivity analyses for task-based fMRI data are generally preceded by methods for identification of network nodes. As there is no general canonical approach to identifying network nodes, different identification techniques may exert different effects on inferences drawn regarding functional network properties. Here, we compared the im...

Neurodevelopment represents a period of increased opportunity and vulnerability, during which a complex confluence of genetic and environmental factors influences brain growth trajectories, cognitive and mental health outcomes. Recently, magnetic resonance imaging (MRI) studies on twins have increased our knowledge of the extent to which genes, the...

Background: Disentangling psychopathological heterogeneity in schizophrenia is challenging, and previous results remain inconclusive. We employed advanced machine learning to identify a stable and generalizable factorization of the Positive and Negative Syndrome Scale and used it to identify psychopathological subtypes as well as their neurobiolog...

Stress is known to influence smoking relapse. Experimental studies indicate that acute stress increases nicotine‐seeking behavior, yet neurobiological mechanisms remain poorly understood. Herein, we investigated disrupted excitatory neural activity in the dorsolateral prefrontal cortex (dlPFC) as a mechanism of stress‐induced nicotine‐seeking behav...

Predominant concepts assert that conscious willful processes do not assert a significant influence on autonomic functions associated with physiological homeostasis (e.g., thermal regulation). The singular purpose of this review is to promote a reappraisal of concepts regarding the circumscribed role of hierarchical control systems. To effect this r...

Functional connectivity (FC) analysis of fMRI data typically rests on prior identification of network nodes from activation profiles. We compared Activation Likelihood Estimate (ALE) and the Experimentally Derived Estimate (EDE) approaches to network node identification and functional inference for both verbal and visual forms of working memory. AL...

We investigated the flexible modulation of undirected functional connectivity (uFC) of brain pathways during simple uni-manual responding. Two questions were central to our interests: (1) does response hand (dominant vs. non-dominant) differentially modulate connectivity and (2) are these effects related to responding under varying motor sets. fMRI...

Working memory processes are associated with the dorsolateral prefrontal cortex (dlPFC). Prior research using proton functional magnetic resonance spectroscopy (¹H fMRS) observed significant dlPFC glutamate modulation during letter 2-back performance, indicative of working memory-driven increase in excitatory neural activity. Acute stress has been...

Because the visual cortices are contra-laterally organized, inter-hemispheric transfer tasks have been used to behaviorally probe how information briefly presented to one hemisphere of the visual cortex is integrated with responses resulting from the ipsi- or contra-lateral motor cortex. By forcing rapid information exchange across diverse regions,...

The original version of this article unfortunately contained a mistake. The family name of Paolo Brambilla was incorrectly spelled as Bambilla.

Bipolar disorder (BD) is highly heritable. Thus, studies in first-degree relatives of individuals with BD could lead to the discovery of objective risk markers of BD. Abnormalities in white matter structure reported in at-risk individuals could play an important role in the pathophysiology of BD. Due to the lack of studies with other at-risk offspr...

Glutamate is involved in excitatory neurotransmission and metabolic processes related to brain function. Previous studies using proton functional magnetic resonance spectroscopy (1H fMRS) have demonstrated elevated cortical glutamate levels by 2–4% during visual and motor stimulation, relative to periods of no stimulation. Here, we extended this ap...

Background The DSM-5 separates the diagnostic criteria for mood and behavioral disorders. Both types of disorders share neurocognitive deficits of executive function and reading difficulties in childhood. Children with dyslexia also have executive function deficits, revealing a role of executive function circuitry in reading. The aim of the current...

Details of subject groups by recruitment cohort, diagnostic group, age, including behavioral reading measures and global efficiency estimates for each subject.

Descriptive statistics from reading measures and global efficiency measures in each group and network along with results of 4-way ANOVA showing significance of difference in these measures between the 4 groups.

The defense of body temperature against environmental thermal challenges is a core objective of homeostatic regulation governed by the autonomic nervous system. Autonomous mechanisms of thermoregulation are only weakly affected by top-down modulation, allowing only transient tolerance for extreme cold. There is however, anecdotal evidence of a uniq...

To maintain thermal homeostasis, specific thermogenic tissues are under the control of central thermoregulatory networks that regulate the body's response to thermal challenges. One of these mechanisms involves non-shivering thermogenesis in brown adipose tissue (BAT), which is activated in cold environments in order to defend the body against phys...

Although schizophrenia (SCZ) and bipolar disorder (BD) share elements of pathology, their neural underpinnings are still under investigation. Here, structural Magnetic Resonance Imaging (MRI) data collected from a large sample of BD and SCZ patients and healthy controls (HC) were analyzed in terms of gray matter volume (GMV) using both voxel based...

Database information. Demographic and clinical information on Dataset1 and Dataset2. (XLSX)

Statistics of the significant ROIs (p<0.05, cFWE corrected) of the VBM analysis of Dataset2. Degrees of freedom: [1 284]. t-stat threshold: 3.12. SCZ: schizophrenia. HC: healthy controls. FWE: family wise error. AAL: Automated Anatomical Labeling. R: right hemisphere. L: left hemisphere. (DOCX)

Significant AAL regions of the region-based analysis of Dataset2 (p<0.05, Bonferroni corrected). SCZ: schizophrenia. HC: healthy controls. AAL: Automated Anatomical Labeling. (DOCX)

Results of the VBM analysis of Dataset2. (DOCX)

Left: Results of the VBM analysis of Dataset2. Significant regions emerging from the SCZ<HC t-contrast (p<0.05, cFWE corrected). Right: Results of the ROI analysis of Dataset2. AAL regions with significant GMV differences between SCZ and HC (p<0.05, Bonferroni corrected). VBM: voxel based morphometry. ROI: region of interest. AAL: Automated Anatomi...

We studied modulation of undirected functional connectivity (uFC) in cortical-hippocampal sub-networks during associative learning. Nineteen healthy individuals were studied (fMRI acquired on a Siemens Verio 3T), and uFC was studied between nodes in a network of regions identified by standard activation models based on bivariate correlational analy...

Difficulty regulating positive mood and energy is a feature that cuts across different pediatric psychiatric disorders. Yet, little is known regarding the neural mechanisms underlying different developmental trajectories of positive mood and energy regulation in youth. Recent studies indicate that machine learning techniques can help elucidate the...

Mood disorders and behavioral are broad psychiatric diagnostic categories that have different symptoms and neurobiological mechanisms, but share some neurocognitive similarities, one of which is an elevated risk for reading deficit. Our aim was to determine the influence of mood versus behavioral dysregulation on reading ability and neural correlat...

Motor control is a ubiquitous aspect of human function, and from its earliest origins, abnormal motor control has been proposed as being central to schizophrenia. The neurobiological architecture of the motor system is well understood in primates and involves cortical and sub-cortical components including the primary motor cortex, supplementary mot...

The dorsal Anterior Cingulate Cortex (dACC) and the Supplementary Motor Area (SMA) are known to interact during motor coordination behavior. We previously discovered that the directional influences underlying this interaction in a visuo-motor coordination task are asymmetric, with the dACC→SMA influence being significantly greater than that in the...

Working memory paradigm data: Eigenvariate values based on data extraction from each of the M1, the SMA and the dACC, for each of the study participants are included in ?S2 File.xls?. (XLS)

Motor paradigm data: Eigenvariate values based on data extraction from each of the M1, the SMA and the dACC, for each of the study participants are included in ?S1 File.xls?. (XLS)

Background: Schizophrenia (SCZ) is associated with structural impairments in the corpus callosum (CC; Diwadkar, et al., 2004; Zhuo, et al., 2016), yet structural deficits do not necessarily predict dysfunction (Diwadkar et al., 2011). Here we explored CC dysfunction in SCZ using fMRI. Whereas the use of fMRI to identify activations in white matter...

Background: Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth. Method: LASSO regression for variable selection was used to predict substance use 24.3 months aft...

Fronto-limbic brain networks involved in regulation of impulsivity and aggression are abnormal in Borderline Personality Disorder (BPD). However, it is unclear whether, or to what extent, these personality traits actually modulate brain responses during cognitive processing. Using fMRI, we examined the effects of trait impulsivity, aggression, and...

Emotion dysregulation is a core characteristic of patients with Borderline Personality Disorder (BPD), and is often attributed to an imbalance in fronto-limbic network function. Hyperarousal of amygdala, especially in response to negative affective stimuli, results in affective interference with cognitive processing of executive functions. Clinical...

Objective: Both bipolar spectrum disorders (BPSD) and attention deficit hyperactivity disorder (ADHD) present with emotion-regulation deficits, but require different clinical management. We examined how the neurobiological underpinnings of emotion regulation might differentiate youth with BPSD versus ADHD (and healthy controls, HCs), specifically...

Schizophrenia has long been considered one of the most intractable psychiatric conditions. Its etiology is likely polygenic, and its symptoms are hypothesized to result from complex aberrations in network-level neuronal activity. While easily identifiable by psychiatrists based on clear behavioral signs, the biological substrate of the disease rema...

Background: Changes in neural circuitry function may be associated with longitudinal changes in psychiatric symptom severity. Identification of these relationships may aid in elucidating the neural basis of psychiatric symptom evolution over time. We aimed to distinguish these relationships using data from the Longitudinal Assessment of Manic Symp...

Schizophrenia is a disorder characterized by brain network dysfunction, particularly during behavioral tasks that depend on frontal and hippocampal mechanisms. Here, we investigated network profiles of the regions of the frontal cortex during memory encoding and retrieval, phases of processing essential to associative memory. Schizophrenia patients...

Behavioral and emotional dysregulation in childhood may be understood as prodromal to adult psychopathology. Additionally, there is a critical need to identify biomarkers reflecting underlying neuropathological processes that predict clinical/behavioral outcomes in youth. We aimed to identify such biomarkers in youth with behavioral and emotional d...

Objectives: Genotype and drug pharmacology may contribute to variations in brain response to antidepressants. We examined the impact of two antidepressants with differential actions on serotonin transporter and the 5-HHTLPR-S/Lg polymorphisms on amygdala responses in major depressive disorder (MDD). Methods: Caucasians with MDD were given either...

Introduction: High comorbidity among pediatric disorders characterized by behavioral and emotional dysregulation poses problems for diagnosis and treatment, and suggests that these disorders may be better conceptualized as dimensions of abnormal behaviors. Furthermore, identifying neuroimaging biomarkers related to dimensional measures of behavior...

Response inhibition is an aspect of executive function (EF) that has been found to be impaired in children with fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD) (Kodituwakku et al 1995; Mattson et al 2011). Studies comparing typically developing children to children diagnosed with FASD using event related potentials (ERP) to...