scholarly journals Acute Ketamine Modulated Functional Brain Coupling and Dissociative and Affective States in Human Subjects: Interim Analyses

2021 ◽  
Author(s):  
Laura M Hack ◽  
Katherine G Warthen ◽  
Xue Zhang ◽  
Boris D Heifets ◽  
Trisha Suppes ◽  
...  
Keyword(s):  
Functional Neuroimaging ◽  
Therapeutic Potential ◽  
Neural Mechanisms ◽  
Self Report ◽  
Affective States ◽  
Brain Response ◽  
Functional Brain ◽  
Functional Connections ◽  
Reward Responsiveness ◽  
Acute Responses

Ketamine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor that is both a drug of abuse and an FDA-approved anesthetic used off-label for treatment-resistant depression. Despite its growing clinical use for depression and pain, the relationships between the acute dissociative and affective effects of ketamine that contribute to its abuse liability and therapeutic potential, along with the neural mechanisms underlying these effects, are not well established. To address this need, we have implemented a randomized, double-blinded, placebo-controlled, within-subjects mechanistic trial. Healthy adult subjects undergo infusion with two fixed doses of subanesthetic racemic intravenous (IV) ketamine and placebo and their acute responses are assessed with self-report questionnaires, behavioral measures, hormone levels, and neuroimaging. As planned in our analysis strategy, we present interim results for the first 7 subjects of our study, focusing on dissociative and affective states and resting functional brain coupling signatures of these states. The first key finding was that ketamine induced dose-dependent increases in dissociation and related intoxication. Ketamine also altered affective states, reducing emotional insensitivity but increasing stress assessed by cortisol. Second, ketamine had an effect on altering brain connectivity, particularly for specific connections between regions of the reward and negative affect circuits and involving thalamic sub-regions. Third, regarding brain-response associations, ketamine-induced increases in amygdala-anteroventral thalamus coupling were correlated with greater dissociation and intoxication, whereas decreases in the coupling of the anteromedial thalamus and posterior parietal thalamus were correlated with increased sensory aspects of reward responsiveness. Additional specific correlations were observed between affective measures relevant to reward responsiveness or its absence and drug-altered changes in localized functional connections involving the nucleus accumbens (NAcc), amygdala, and thalamic sub-regions. We also discovered a consistent profile of negative associations between ketamine altered connectivity involving the NAcc and specific thalamic sub-regions and effects of anxiety. Further, drug-altered increases in the coupling of the amygdala and anteroventral thalamus were associated with increases in cortisol, an indicator of biochemical stress. The findings highlight the utility of integrating self-reports, objective measures, and functional neuroimaging to disentangle the brain states underlying specific acute responses induced by ketamine. With the likely continued expansion of FDA indications for ketamine, understanding acute responses and underlying neural mechanisms is important for maximizing the therapeutic potential of ketamine while minimizing the risk of promoting misuse or abuse of this substance. Clinical Trial Registration ID #: NCT03475277

The Oxford Handbook of Functional Brain Imaging in Neuropsychology and Cognitive Neurosciences

2014 ◽  
Keyword(s):  
Brain Imaging ◽  
Diffusion Tensor ◽  
Functional Neuroimaging ◽  
Functional Brain Imaging ◽  
Affective States ◽  
Source Imaging ◽  
Magnetic Source Imaging ◽  
Functional Brain ◽  
Positron Emission ◽  
Cognitive Neurosciences

A large part of the contemporary literature involves functional neuroimaging. Yet few readers are sufficiently familiar with the various imaging methods, their capabilities and limitations, to appraise it correctly. To fulfill that need is the purpose of this Handbook, which consists of an accessible description of the methods and their clinical and research applications. The Handbook begins with an overview of basic concepts of functional brain imaging, magnetoencephalography and the use of magnetic source imaging (MSI), positron emission tomography (PET), diffusion tensor imaging (DTI), and transcranial magnetic stimulation (TMS). The authors then discuss the various research applications of imaging, such as white matter connectivity; the function of the default mode network; the possibility and the utility of imaging of consciousness; the search for mnemonic traces of concepts the mechanisms of the encoding, consolidation, and retrieval of memories; executive functions and their neuroanatomical mechanisms; voluntary actions, human will and decision-making; motor cognition; language and the mechanisms of affective states and pain. The final chapter discusses the uses of functional neuroimaging in the presurgical mapping of the brain.

scholarly journals Color naming and categorization depend on distinct functional brain networks

2020 ◽  
Author(s):  
Katarzyna Siuda-Krzywicka ◽  
Christoph Witzel ◽  
Paolo Bartolomeo ◽  
Laurent Cohen
Keyword(s):  
Resting State ◽  
Response Times ◽  
Brain Networks ◽  
Color Naming ◽  
Neural Mechanisms ◽  
Angular Gyrus ◽  
Functional Brain ◽  
Functional Connections ◽  
Functional Brain Networks ◽  
Color Categorization

AbstractNaming a color can be understood as an act of categorization, i.e. identifying it as a member of category of colors that are referred to by the same name. But are naming and categorization equivalent cognitive processes, and consequently rely on same neural substrates? Here, we used task and resting-state fMRI, as well as behavioral measures to identify functional brain networks that modulated naming and categorization of colors. Color naming and categorization response times were modulated by different resting state connectivity networks spanning from the color-sensitive regions in the ventro-occipital cortex. Color naming correlated with the connectivity between the left posterior color region, the left medial temporal gyrus, and the left angular gyrus; whereas color categorization involved the connectivity between the bilateral posterior color regions, the left frontal, right temporal and bilateral parietal areas. The networks supporting naming and categorization did not overlap, suggesting that the two processes rely on different neural mechanisms.SignificanceWhen we name a color, we also identify it as a member of a color category, e.g. blue or yellow. Are neural processes underlying color categorization equivalent to those of color naming? Here, we address this question by measuring how individual differences in color categorization and naming response times relate to the strength of functional connections in the brain. Color naming speed correlated with left-hemispheric connectivity between the color-sensitive visual regions and the anterior temporal lobe. Color categorization speed was modulated by a different brain network, encompassing bilateral color-sensitive visual areas, and high-level executive and semantic regions. Thus, color categorization and naming performance involved distinct, non-overlapping brain networks, suggesting that the two processes depend on different neural mechanisms.

An Alternative to Self-Reports of Trait and State Affect

2014 ◽  
Vol 30 (3) ◽  
pp. 231-237 ◽  
Author(s):  
Markus Quirin ◽  
Regina C. Bode
Keyword(s):  
Self Report ◽  
Factorial Validity ◽  
Artificial Language ◽  
Cognitive Representation ◽  
Affective States ◽  
Novel Variants ◽  
Self Reports ◽  
State Affect ◽  
Affective Experiences ◽  
Automatic Activation

Self-report measures for the assessment of trait or state affect are typically biased by social desirability or self-delusion. The present work provides an overview of research using a recently developed measure of automatic activation of cognitive representation of affective experiences, the Implicit Positive and Negative Affect Test (IPANAT). In the IPANAT, participants judge the extent to which nonsense words from an alleged artificial language express a number of affective states or traits. The test demonstrates appropriate factorial validity and reliabilities. We review findings that support criterion validity and, additionally, present novel variants of this procedure for the assessment of the discrete emotions such as happiness, anger, sadness, and fear.

Childhood trauma moderates morphometric associations between orbitofrontal cortex and amygdala: implications for pathological personality traits

2020 ◽  
pp. 1-10
Author(s):  
Nadia Bounoua ◽  
Rickie Miglin ◽  
Jeffrey M. Spielberg ◽  
Curtis L. Johnson ◽  
Naomi Sadeh
Keyword(s):  
Personality Traits ◽  
Childhood Trauma ◽  
Orbitofrontal Cortex ◽  
Functional Neuroimaging ◽  
Trauma Exposure ◽  
Diagnostic Interview ◽  
Emotional Dysregulation ◽  
Self Report ◽  
Traumatic Experiences ◽  
Pathological Personality Traits

Abstract Background Research has demonstrated that chronic stress exposure early in development can lead to detrimental alterations in the orbitofrontal cortex (OFC)–amygdala circuit. However, the majority of this research uses functional neuroimaging methods, and thus the extent to which childhood trauma corresponds to morphometric alterations in this limbic-cortical network has not yet been investigated. This study had two primary objectives: (i) to test whether anatomical associations between OFC–amygdala differed between adults as a function of exposure to chronic childhood assaultive trauma and (ii) to test how these environment-by-neurobiological effects relate to pathological personality traits. Methods Participants were 137 ethnically diverse adults (48.1% female) recruited from the community who completed a clinical diagnostic interview, a self-report measure of pathological personality traits, and anatomical MRI scans. Results Findings revealed that childhood trauma moderated bilateral OFC–amygdala volumetric associations. Specifically, adults with childhood trauma exposure showed a positive association between medial OFC volume and amygdalar volume, whereas adults with no childhood exposure showed the negative OFC–amygdala structural association observed in prior research with healthy samples. Examination of the translational relevance of trauma-related alterations in OFC–amygdala volumetric associations for disordered personality traits revealed that trauma exposure moderated the association of OFC volume with antagonistic and disinhibited phenotypes, traits characteristic of Cluster B personality disorders. Conclusions The OFC–amygdala circuit is a potential anatomical pathway through which early traumatic experiences perpetuate emotional dysregulation into adulthood and confer risk for personality pathology. Results provide novel evidence of divergent neuroanatomical pathways to similar personality phenotypes depending on early trauma exposure.

scholarly journals From cognitive to neural models of working memory

2007 ◽  
Vol 362 (1481) ◽  
pp. 761-772 ◽  
Author(s):  
Mark D'Esposito
Keyword(s):  
Working Memory ◽  
Functional Neuroimaging ◽  
Empirical Studies ◽  
Brain Regions ◽  
Cognitive Models ◽  
Neural Mechanisms ◽  
Long Term Memory ◽  
Cognitive Mechanisms ◽  
Internal Representations ◽  
Active Maintenance

Working memory refers to the temporary retention of information that was just experienced or just retrieved from long-term memory but no longer exists in the external environment. These internal representations are short-lived, but can be stored for longer periods of time through active maintenance or rehearsal strategies, and can be subjected to various operations that manipulate the information in such a way that makes it useful for goal-directed behaviour. Empirical studies of working memory using neuroscientific techniques, such as neuronal recordings in monkeys or functional neuroimaging in humans, have advanced our knowledge of the underlying neural mechanisms of working memory. This rich dataset can be reconciled with behavioural findings derived from investigating the cognitive mechanisms underlying working memory. In this paper, I review the progress that has been made towards this effort by illustrating how investigations of the neural mechanisms underlying working memory can be influenced by cognitive models and, in turn, how cognitive models can be shaped and modified by neuroscientific data. One conclusion that arises from this research is that working memory can be viewed as neither a unitary nor a dedicated system. A network of brain regions, including the prefrontal cortex (PFC), is critical for the active maintenance of internal representations that are necessary for goal-directed behaviour. Thus, working memory is not localized to a single brain region but probably is an emergent property of the functional interactions between the PFC and the rest of the brain.

scholarly journals Exploring negative affect dynamics in high resolution: within-person relationship of inertia and instability with depression is mediated by affect intensity

2021 ◽  
Author(s):  
Levente Rónai ◽  
Bertalan Polner
Keyword(s):  
Depressive Symptoms ◽  
Multilevel Models ◽  
Negative Mood ◽  
Population Sample ◽  
Self Report ◽  
Affective States ◽  
Affect Intensity ◽  
Individual Level ◽  
Affective Functioning ◽  
Affect Dynamics

Background: Temporal patterns of affective functioning such as emotional inertia and instability may indicate changes in emotion regulation that predict depression. However, affect dynamics’ incremental validity over affect intensity and exposure to stressors in predicting depression has been questioned.Methods: We collected longitudinal data regarding momentary affective states (measured multiple times a day), perceived stressors and depressive symptoms (measured every three days) from a general population sample during the COVID-19 pandemic’s first wave in Hungary. The final dataset included 7165 affective states surveys from 125 participants, which were aggregated in 464 three-day measurement windows. Using multilevel models, we explored the unique effects of within-person changes in mean level, inertia, and instability of negative affective states (NA), and stressor-exposure on two domains of depression (anhedonia and negative mood and thoughts) within the three-day windows.Results: Within-person increases in NA inertia and NA instability showed significant positive associations with negative mood and thoughts. These effects did not remain significant after adjusting for mean levels of NA. Multilevel mediation analysis revealed that within individuals, NA inertia and instability indirectly predicted negative mood and thoughts through elevated NA mean.Limitations: The application of self-report questionnaires might bias the results, and the overrepresentation of female participants could limit the generalizability of the findings.Conclusions: Specific patterns of temporal affective functioning are indirect predictors of depressive symptoms at the within-individual level. Our findings may facilitate automated depression risk assessment on the basis of simple affective time series.

scholarly journals Brain-behaviour modes of covariation in healthy and clinically depressed young people

2018 ◽  
Author(s):  
Agoston Mihalik ◽  
Fabio S. Ferreira ◽  
Maria J. Rosa ◽  
Michael Moutoussis ◽  
Gabriel Ziegler ◽  
...  
Keyword(s):  
Brain Connectivity ◽  
Demographic Data ◽  
Strong Association ◽  
Early Adulthood ◽  
Well Being ◽  
Self Report ◽  
Multivariate Statistical ◽  
Functional Brain ◽  
Clinically Depressed ◽  
Critical Developmental Period

AbstractUnderstanding how variations in dimensions of psychometrics, IQ and demographics relate to changes in brain connectivity during the critical developmental period of adolescence and early adulthood is a major challenge. This has particular relevance for mental health disorders where a failure to understand these links might hinder the development of better diagnostic approaches and therapeutics. Here, we investigated this question in 306 adolescents and young adults (14-24y, 25 clinically depressed) using a multivariate statistical framework, based on canonical correlation analysis (CCA). By linking individual functional brain connectivity profiles to self-report questionnaires, IQ and demographic data we identified two distinct modes of covariation. The first mode mapped onto an externalization/internalization axis and showed a strong association with sex. The second mode mapped onto a well-being/distress axis independent of sex. Interestingly, both modes showed an association with age. Crucially, the changes in functional brain connectivity associated with changes in these phenotypes showed marked developmental effects. The findings point to a role for the default mode, frontoparietal and limbic networks in psychopathology and depression.

scholarly journals Functional neuroimaging studies of the effects of psychotherapy

2014 ◽  
Vol 16 (1) ◽  
pp. 75-81 ◽  
Keyword(s):  
Functional Neuroimaging ◽  
Brain Activity ◽  
Behavioral Changes ◽  
Neural Mechanisms ◽  
Psychological Interventions ◽  
Emotional States ◽  
Major Depressive ◽  
Psychotherapeutic Interventions ◽  
Functional Brain Activity ◽  
Neuroimaging Techniques

It has been long established that psychological interventions can markedly alter patients' thinking patterns, beliefs, attitudes, emotional states, and behaviors. Little was known about the neural mechanisms mediating such alterations before the advent of functional neuroimaging techniques. Since the turn of the new millenium, several functional neuroimaging studies have been conducted to tackle this important issue. Some of these studies have explored the neural impact of various forms of psychotherapy in individuals with major depressive disorder. Other neuroimaging studies have investigated the effects of psychological interventions for anxiety disorders. I review these studies in the present article, and discuss the putative neural mechanisms of change in psychotherapy. The findings of these studies suggest that mental and behavioral changes occurring during psychotherapeutic interventions can lead to a normalization of functional brain activity at a global level.

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