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Author: Vaibhav A Diwadkar (77)


Feb
2018

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 unique set of individuals known for extreme cold tolerance.

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Dec
1969

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 physical damage as a result of hypothermia. The objective of our study was to assess the interaction between CNS thermoregulatory pathways and sympathetic innervation in BAT during a cold exposure paradigm.

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Dec
1969

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 morphometry (VBM) and a region of interest (ROI) approach.
The analysis was conducted on two datasets, Dataset1 (802 subjects: 243 SCZ, 176 BD, 383 HC) and Dataset2, a homogeneous subset of Dataset1 (301 subjects: 107 HC, 85 BD and 109 SCZ).

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Oct
2017

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 analyses of time series data. The paradigm alternated between Memory Encoding, Rest and Retrieval.

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Aug
2017

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, these tasks robustly activate not only gray matter regions, but also white matter tracts. It is likely that the response hand itself (dominant or non-dominant) modulates gray and white matter activations during within and inter-hemispheric transfer.

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Dec
1969

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 correlates supporting these skills in youth, using diffusion tensor imaging in 11- to 17-year-old children and youths with mood disorders or behavioral disorders and age-matched healthy controls. The three groups differed only in phonological processing and passage comprehension.

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Dec
1969

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 role of neuroimaging measures in classifying individual subjects by specific symptom trajectory.

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Aug
2017

Suppression of aversive memories through memory control has historically been proposed as a central psychological defense mechanism. Inability to suppress memories is considered a central psychological trait in several psychiatric disorders, including Generalized Anxiety Disorder (GAD). Yet, few studies have attempted the focused identification of dysfunctional brain activation profiles when patients with Generalized Anxiety Disorders attempt memory control.

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May
2017

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 Symptoms (LAMS) cohort.

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Jun
2017

fMRI has provided vibrant characterization of regional and network responses associated with associative learning and memory; however, their relationship to functional neurochemistry is unclear. Here, we introduce a novel application of in vivo proton functional magnetic resonance spectroscopy (H fMRS) to investigate the dynamics of hippocampal glutamate during paired-associated learning and memory in healthy young adults. We show that the temporal dynamics of glutamate differed significantly during processes of memory consolidation and retrieval.

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May
2017

Psychosis - an impaired contact with reality - is a hallmark of schizophrenia. Many psychotic symptoms are associated with disruptions in agency - the sense that 'I' cause my actions. A failure to predict sensory consequences of one's own actions may underlie agency disturbances.

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Dec
1969

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 reverse direction. To assess the specificity of this effect, here we undertook an analysis of the interaction between dACC and SMA in two distinct contexts.

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Feb
2017

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 depressed mood on regional brain responses in 31 female BPD and 25 control subjects during a Go No-Go task using Ekman faces as targets.

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Feb
2017

In an effort to elucidate differences in functioning brain networks between youth with obsessive-compulsive disorder and controls, we used fMRI signals to analyze brain network interactions of the dorsal anterior cingulate cortex (dACC) during visually coordinated motor responses. Subjects made a uni-manual response to briefly presented probes, at periodic (allowing participants to maintain a "motor set") or random intervals (demanding reactive responses). Network interactions were assessed using psycho-physiological interaction (PPI), a basic model of functional connectivity evaluating modulatory effects of the dACC in the context of each task condition.

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Jan
2017

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 assessing functional connectivity (FxC) of amygdala-prefrontal circuitry during an implicit emotion processing task.
We scanned a subset of the Longitudinal Assessment of Manic Symptoms (LAMS) sample, a clinically recruited cohort with elevated behavioral and emotional dysregulation, and age/sex-ratio matched HCs.

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Dec
1969

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 remains poorly understood.

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Dec
1969

Extensive studies in rodents have established the role of neural pathways that are activated during thermoregulation. However, few studies have been conducted in humans to assess the complex, hierarchically organized thermoregulatory network in the CNS that maintains thermal homeostasis, especially as it pertains to cold exposure. To study the human thermoregulatory network during whole body cold exposure, we have used functional MRI to characterize changes in the BOLD signal within the constituents of the thermoregulatory network in 20 young adult controls during non-noxious cooling and rewarming of the skin by a water-perfused body suit.

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Dec
1969

Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals [dynamic causal modeling (DCM)] to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands.

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Dec
1969

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 (n = 12) and healthy control (HC) subjects (n = 10) participated in an established object-location associative memory paradigm that drives frontal-hippocampal interactions.

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Mar
2016

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).
Caucasians with MDD were given either citalopram or quetiapine extended release for 8 weeks.

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Dec
1969

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 may provide targets to guide individualized treatment. We aimed to use functional neuroimaging and pattern regression techniques to determine whether patterns of brain activity could accurately decode individual-level severity on a dimensional scale measuring behavioural and emotional dysregulation at two different time points.

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Jan
2016

The rate of biological change in middle-adulthood is relatively under-studied. Here, we used behavioral testing in conjunction with structural magnetic resonance imaging to examine the effects of chronological age on associative learning proficiency and on brain regions that previous functional MRI studies have closely related to the domain of associative learning.
Participants (n=66) completed a previously established associative learning paradigm, and consented to be scanned using structural magnetic resonance imaging.

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Dec
1969

Motor control is integral to all types of human behavior, and the dorsal Anterior Cingulate Cortex (dACC) is thought to play an important role in the brain network underlying motor control. Yet the role of the dACC in motor control is under-characterized. Here we aimed to characterize the dACC's role in adolescent brain network interactions during a simple motor control task involving visually coordinated unimanual finger movements.

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Jul
2015

Emotion dysregulation in borderline personality disorder (BPD) is associated with loss of cognitive control in the face of intense negative emotion. Negative emotional context may interfere with cognitive processing through the dysmodulation of brain regions involved in regulation of emotion, impulse control, executive function and memory. Structural and metabolic brain abnormalities have been reported in these regions in BPD.

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Sep
2015

Cognitive control includes processes that facilitate execution of effortful cognitive tasks, including associative memory. Regions implicated in cognitive control during associative memory include the dorsal prefrontal (dPFC) and dorsal anterior cingulate cortex (dACC). Here we investigated the relative degrees of network-related interactions originating in the dPFC and dACC during oscillating phases of associative memory: encoding and cued retrieval.

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Dec
1969

Brain network dysfunction is emerging as a central biomarker of interest in psychiatry, in large part, because psychiatric conditions are increasingly seen as disconnection syndromes. Understanding dysfunctional brain network profiles in task-active states provides important information on network engagement in an experimental context. This in turn may be predictive of many of the cognitive and behavioral deficits associated with complex behavioral phenotypes.

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Apr
2015

Psychiatric disorders in youth characterized by behavioral and emotional dysregulation are often comorbid and difficult to distinguish. An alternative approach to conceptualizing these disorders is to move toward a diagnostic system based on underlying pathophysiologic processes that may cut across conventionally defined diagnoses. Neuroimaging techniques have potentials for the identification of these processes.

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Dec
1969

Brain changes in schizophrenia evolve along a dynamic trajectory, emerging before disease onset and proceeding with ongoing illness. Recent investigations have focused attention on functional brain interactions, with experimental imaging studies supporting the disconnection hypothesis of schizophrenia. These studies have revealed a broad spectrum of abnormalities in brain connectivity in patients, particularly for connections integrating the frontal cortex.

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Nov
2014

Previous neuroimaging studies of youth with bipolar disorder (BD) have identified abnormalities in emotion regulation circuitry. Using data from the Longitudinal Assessment of Manic Symptoms Cohort (a clinical sample recruited for behavioral and emotional dysregulation), we examined the impact of BD and medication on activation in these regions. Functional neuroimaging data were obtained from 15 youth with BD who currently were unmedicated with a mood stabilizer or antipsychotic (U-BD), 19 youth with medicated BD (M-BD), a non-bipolar clinical sample with high rates of disruptive behavioral disorders (non-BD, n = 59), and 29 healthy controls (HC) while they were shown task-irrelevant morphing emotional faces and shapes.

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Oct
2014

Inflammation and psychopathology: what we now know, and what we need to know.

Soc Psychiatry Psychiatr Epidemiol 2014 Oct 30;49(10):1537-9. Epub 2014 Jul 30.
Monica Uddin, Vaibhav A Diwadkar

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Dec
1969

The recent sociodevelopmental cognitive model of schizophrenia/psychosis is a highly influential and compelling compendium of research findings. Here, we present logical extensions to this model incorporating ideas drawn from epigenetic mediation of psychiatric disease, and the plausible effects of epigenetics on the emergence of brain network function and dysfunction in adolescence. We discuss how gene-environment interactions, effected by epigenetic mechanisms, might in particular mediate the stress response (itself heavily implicated in the emergence of schizophrenia).

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Dec
1969

Abnormalities in the brain's attention network may represent early identifiable neurobiological impairments in individuals at increased risk for schizophrenia or bipolar disorder. Here, we provide evidence of dysfunctional regional and network function in adolescents at higher genetic risk for schizophrenia or bipolar disorder [henceforth higher risk (HGR)]. During fMRI, participants engaged in a sustained attention task with variable demands.

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Dec
2013

Pediatric bipolar disorder involves poor social functioning, but the neural mechanisms underlying these deficits are not well understood. Previous neuroimaging studies have found deficits in emotional face processing localized to emotional brain regions. However, few studies have examined dysfunction in other regions of the face processing circuit.

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Jan
2014

Pediatric disorders characterized by behavioral and emotional dysregulation pose diagnostic and treatment challenges because of high comorbidity, suggesting that they may be better conceptualized dimensionally rather than categorically. Identifying neuroimaging measures associated with behavioral and emotional dysregulation in youth may inform understanding of underlying dimensional vs disorder-specific pathophysiologic features.
To identify, in a large cohort of behaviorally and emotionally dysregulated youth, neuroimaging measures that (1) are associated with behavioral and emotional dysregulation pathologic dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory 10-Item Mania Scale [PGBI-10M], mania, depression, and anxiety) or (2) differentiate diagnostic categories (bipolar spectrum disorders, attention-deficit/hyperactivity disorder, anxiety, and disruptive behavior disorders).

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Nov
2014

Thermoregulatory events are associated with activity in the constituents of the spinothalamic tract. Whereas studies have assessed activity within constituents of this pathway, in vivo functional magnetic resonance imaging (fMRI) studies have not determined if neuronal activity in the constituents of the tract is temporally ordered. Ordered activity would be expected in naturally occurring thermal events, such as menopausal hot flashes (HFs), which occur in physiological sequence.

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Aug
2013

Schizophrenia (SCZ) is characterized by disordered activation and disordered connectivity, yet few fMRI studies have convergently investigated both. Here, we compared differences in activation and connectivity between SCZ and controls (HC). Twenty-two subjects (18≤age≤35yrs) participated in a paired-associative learning task, a behavioral domain particularly dependent on fronto-hippocampal connectivity and of relevance to the schizophrenia diathesis.

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Jul
2013

Evidence from neuroimaging studies indicate that individuals with bipolar disorder (BD) exhibit altered functioning of fronto-limbic systems implicated in voluntary emotion regulation. Few studies, however, have examined the extent to which unaffected youth at familial risk for BD exhibit such alterations. Using an fMRI emotional working memory paradigm, we investigated the functioning of fronto-limbic systems in fifteen healthy bipolar offspring (8-17 years old) with at least one parent diagnosed with BD (HBO), and 16 age-matched healthy control (HC) participants.

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Dec
1969

There is general consensus that second-generation antipsychotics are at least as effective as and more tolerable than first-generation antipsychotics. We address questions of safety and tolerability in both the short-term and long-term use of these medications by reviewing the existing literature in youth and adults.
A MEDLINE search was conducted via PubMed using the following keywords (in various combinations): typical antipsychotics, atypical antipsychotics, children, adolescents, side effects, weight gain, diabetes, metformin, metabolic syndrome, and CATIE.

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Aug
2013

Although children with heavy prenatal alcohol exposure may exhibit the distinctive facial dysmorphology seen in full or partial fetal alcohol syndrome (FAS/PFAS), many lack that dysmorphology. This study examined the functional organization of working memory in the brain in three groups of children-those meeting diagnostic criteria for FAS or PFAS, heavily exposed (HE) nonsyndromal children, and healthy controls. A verbal n-back task (1-back and 0-back) was administered to 47 children (17 with FAS/PFAS, 13 HE, and 17 controls) during fMRI.

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Mar
2012

Disordered functional architecture of brain networks may contribute to the well-documented increased risk for psychiatric disorders in offspring of patients with schizophrenia.
To investigate aberrant interactions between regions associated with affective processing in children and adolescent offspring of patients with schizophrenia (HR-SCZ group) and healthy control subjects using dynamic causal modeling of functional magnetic resonance imaging data.
Subjects participated in a continuous affective processing task during which positive, negative, and neutral valenced faces were presented.

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May
2012

Reverse speech has often been used as a control task in brain-mapping studies of language utilizing various non-invasive modalities. The rationale is that reverse speech is comparable to forward speech in terms of auditory characteristics, while omitting the linguistic components. Thus, it may control for non-language auditory functions.

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Feb
2012

Fronto-limbic regions of the brain including the sub-genual (sgPFC) and medial prefrontal (mPFC) cortices are central to processing emotionally salient and hedonic stimuli (Mayberg, 2009) and implicated in depression. The relevance of cortico-limbic models of emotion and reward processing in children with genetic risk for psychiatric disorders has not been assessed.
Here we studied adolescents at risk for schizophrenia (HRS) and controls (HC) using an event-related fMRI continuous affective appraisal task.

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Jan
2012

Efforts to predict psychosis in individuals at high risk for schizophrenia have focused on the identification of sub-threshold clinical criteria and neurobiological markers, including neuropsychological assessment, structural and functional brain imaging, and psychophysiological testing. We sought to evaluate the relative utility of "psychosis-proneness" measures for prospective prediction of psychotic disorders in a group of young relatives at familial risk for schizophrenia.
We examined the receiver operating characteristics of sub-threshold symptoms in predicting conversion to psychosis in a group of 97 young first- and second- degree relatives of persons with schizophrenia over a 2-year period.

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Jan
2012

fMRI studies indicate that schizophrenia patients and their adult relatives require greater prefrontal activation to maintain performance at levels equal to controls, but studies have not established if this pattern of inefficiency is observed in child and adolescent offspring of schizophrenia patients (SCZ-Off).
Using a task with visual working memory demands, we investigated activation in cortico-striatal networks and dorsal prefrontal modulation of regions underlying visual working memory in a group of SCZ-Off (n = 19) and controls with no family history of psychosis (n = 25 subjects) using an event-related design. Trials were divided based on memory performance (correct vs.

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Sep
2011

Adolescent offspring of schizophrenia patients (HR-S) are an important group in whom to study impaired brain function and structure, particularly of the frontal cortices. Studies of working memory have suggested behavioral deficits and fMRI-measured hypoactivity in fronto-parietal regions in these subjects. Independent structural MRI (sMRI) studies have suggested exaggerated frontal gray matter decline.

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