scholarly journals Alprazolam modulates persistence energy during emotion processing in first-degree relatives of individuals with schizophrenia: a network control study

2021 ◽  
Author(s):  
Arun S. Mahadevan ◽  
Eli J. Cornblath ◽  
David M. Lydon-Staley ◽  
Dale Zhou ◽  
Linden Parkes ◽  
...  
Keyword(s):  
Visual Processing ◽  
Emotion Processing ◽  
Brain Regions ◽  
Facial Affect ◽  
Network Control ◽  
State Transitions ◽  
Compensatory Mechanism ◽  
Pharmacological Modulation ◽  
First Degree Relatives ◽  
Affect Processing

AbstractSchizophrenia is marked by deficits in facial affect processing associated with abnormalities in GABAergic circuitry, deficits also found in first-degree relatives. Facial affect processing involves a distributed network of brain regions including limbic regions like amygdala and visual processing areas like fusiform cortex. Pharmacological modulation of GABAergic circuitry using benzodiazepines like alprazolam can be useful for studying this facial affect processing network and associated GABAergic abnormalities in schizophrenia. Here, we use pharmacological modulation and computational modeling to study the contribution of GABAergic abnormalities toward emotion processing deficits in schizophrenia. Specifically, we apply principles from network control theory to model persistence energy – the control energy required to maintain brain activation states – during emotion identification and recall tasks, with and without administration of alprazolam, in a sample of first-degree relatives and healthy controls. Here, persistence energy quantifies the magnitude of theoretical external inputs during the task. We find that alprazolam increases persistence energy in relatives but not in controls during threatening face processing, suggesting a compensatory mechanism given the relative absence of behavioral abnormalities in this sample of unaffected relatives. Further, we demonstrate that regions in the fusiform and occipital cortices are important for facilitating state transitions during facial affect processing. Finally, we uncover spatial relationships (i) between regional variation in differential control energy (alprazolam versus placebo) and (ii) both serotonin and dopamine neurotransmitter systems, indicating that alprazolam may exert its effects by altering neuromodulatory systems. Together, these findings reveal differences in emotion-processing circuitry associated with genetic vulnerability to schizophrenia.

Evidence of diagnostic specificity in the neural correlates of facial affect processing in bipolar disorder and schizophrenia: a meta-analysis of functional imaging studies

2012 ◽  
Vol 43 (3) ◽  
pp. 553-569 ◽  
Author(s):  
G. Delvecchio ◽  
G. Sugranyes ◽  
S. Frangou
Keyword(s):  
Bipolar Disorder ◽  
Visual Processing ◽  
Emotional Regulation ◽  
Emotional Processing ◽  
Meta Analysis ◽  
Likelihood Estimation ◽  
Facial Affect ◽  
Healthy Individuals ◽  
Processing Network ◽  
Affect Processing

BackgroundSchizophrenia (SZ) and bipolar disorder (BD) may overlap in etiology and phenomenology but differ with regard to emotional processing. We used facial affect as a probe for emotional processing to determine whether there are diagnosis-related differences between SZ and BD in the function of the underlying neural circuitry.MethodFunctional magnetic resonance imaging (fMRI) studies published up to 30 April 2012 investigating facial affect processing in patients with SZ or BD were identified through computerized and manual literature searches. Activation foci from 29 studies encompassing 483 healthy individuals, 268 patients with SZ and 267 patients with BD were subjected to voxel-based quantitative meta-analysis using activation likelihood estimation (ALE).ResultsCompared to healthy individuals, when emotional facial stimuli were contrasted to neutral stimuli, patients with BD showed overactivation within the parahippocampus/amygdala and thalamus and reduced engagement within the ventrolateral prefrontal cortex (PFC) whereas patients with SZ showed underactivation throughout the entire facial affect processing network and increased activation in visual processing regions within the cuneus. Patients with BD showed greater thalamic engagement compared to patients with SZ; in the reverse comparison, patients with SZ showed greater engagement in posterior associative visual cortices.ConclusionsDuring facial affect processing, patients with BD show overactivation in subcortical regions and underactivation in prefrontal regions of the facial affect processing network, consistent with the notion of reduced emotional regulation. By contrast, overactivation within visual processing regions coupled with reduced engagement of facial affect processing regions points to abnormal visual integration as the core underlying deficit in SZ.

scholarly journals Changes in dynamic transitions between integrated and segregated states underlie visual hallucinations in Parkinson's disease

2021 ◽  
Author(s):  
Angeliki Zarkali ◽  
Andrea Luppi ◽  
Emmanuel A Stamatakis ◽  
Suzanne Reeves ◽  
Peter McColgan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Visual Processing ◽  
Temporal Dynamics ◽  
Expression Profiles ◽  
Receptor Gene ◽  
Structural Connectivity ◽  
Brain Regions ◽  
State Transitions ◽  
Visual Hallucinations ◽  
Density Profiles

Background: Visual hallucinations in Parkinsons disease (PD) are transient, suggesting a change in dynamic brain states. However, the causes underlying these dynamic brain changes are not known. Methods: Focusing on fundamental network properties of integration and segregation, we used rsfMRI to examine alterations in temporal dynamics in PD patients with hallucinations (n=16) compared to those without hallucinations (n=75) and a group of normal controls (n=32). We used network control theory to examine how structural connectivity guides transitions between functional states. We then studied the brain regions most involved in these state transitions, and examined corresponding neurotransmitter density profiles and receptor gene expression in health. Results: There were significantly altered temporal dynamics in PD with hallucinations, with an increased proportion of time spent in the Segregated state compared to non-hallucinators and controls; less between-state transitions; and increased dwell time in the Segregated state. The energy cost needed to transition from integrated-to-segregated state was lower in PD-hallucinators compared to non-hallucinators. This was primarily driven by subcortical and transmodal cortical brain regions, including the thalamus and default mode network regions. The regional energy needed to transition from integrated-to-segregated state was significantly correlated with regional neurotransmitter density and gene expression profiles for serotoninergic (including 5HT2A), GABAergic, noradrenergic and cholinergic but not dopaminergic density profiles. Conclusions: We describe the patterns of temporal functional dynamics in PD-hallucinations, and link these with neurotransmitter systems involved in early sensory and complex visual processing. Our findings provide mechanistic insights into visual hallucinations in PD and highlighting potential therapeutic targets.

scholarly journals Facial affect processing deficits in schizophrenia: A meta-analysis of antipsychotic treatment effects

2014 ◽  
Vol 29 (2) ◽  
pp. 224-229 ◽  
Author(s):  
Anthony S Gabay ◽  
Matthew J Kempton ◽  
Mitul A Mehta
Keyword(s):  
Meta Analysis ◽  
Treatment Options ◽  
Emotion Processing ◽  
Facial Affect ◽  
Cognitive Domain ◽  
Antipsychotic Treatment ◽  
Emotion Identification ◽  
Positive Effect ◽  
Affect Processing ◽  
Small Positive Effect

Social cognition, including emotion processing, is a recognised deficit observed in patients with schizophrenia. It is one cognitive domain which has been emphasised as requiring further investigation, with the efficacy of antipsychotic treatment on this deficit remaining unclear. Nine studies met our criteria for entry into a meta-analysis of the effects of medication on facial affect processing, including data from 1162 patients and six antipsychotics. Overall we found a small, positive effect (Hedge’s g = 0.13, 95% CI 0.05 to 0.21, p = 0.002). In a subgroup analysis this was statistically significant for atypical, but not typical, antipsychotics. It should be noted that the pooled sample size of the typical subgroup was significantly lower than the atypical. Meta-regression analyses revealed that age, gender and changes in symptom severity were not moderating factors. For the small, positive effect on facial affect processing, the clinical significance is questionable in terms of treating deficits in emotion identification in schizophrenia. We show that antipsychotic medications are poor at improving facial affect processing compared to reducing symptoms. This highlights the need for further investigation into the neuropharmacological mechanisms associated with accurate emotion processing, to inform treatment options for these deficits in schizophrenia.

Alexithymia and automatic processing of emotional stimuli: a systematic review

2017 ◽  
Vol 28 (3) ◽  
pp. 247-264 ◽  
Author(s):  
Uta-Susan Donges ◽  
Thomas Suslow
Keyword(s):  
Visual Processing ◽  
Web Of Science ◽  
Emotion Processing ◽  
Affective Response ◽  
Automatic Processing ◽  
Brain Regions ◽  
Future Research ◽  
Healthy Individuals ◽  
Emotional Stimuli ◽  
Emotional Information

AbstractAlexithymia is a personality trait characterized by difficulties in recognizing and verbalizing emotions and the utilization of a cognitive style that is oriented toward external events, rather than intrapsychic experiences. Alexithymia is considered a vulnerability factor influencing onset and course of many psychiatric disorders. Even though emotions are, in general, elicited involuntarily and emerge without conscious effort, it is surprising that little attention in etiological considerations concerning alexithymia has been given to deficits in automatic emotion processing and their neurobiological bases. In this article, results from studies using behavioral or neurobiological research methods were systematically reviewed in which automatic processing of external emotional information was investigated as a function of alexithymia in healthy individuals. Twenty-two studies were identified through a literature search of Psycinfo, PubMed, and Web of Science databases from 1990 to 2016. The review reveals deficits in the automatic processing of emotional stimuli in alexithymia at a behavioral and neurobiological level. The vast majority of the reviewed studies examined visual processing. The alexithymia facets externally oriented thinking and difficulties identifying feelings were found to be related to impairments in the automatic processing of threat-related facial expressions. Alexithymic individuals manifest low reactivity to barely visible negative emotional stimuli in brain regions responsible for appraisal, encoding, and affective response, e.g. amygdala, occipitotemporal areas, and insula. Against this background, it appears plausible to assume that deficits in automatic emotion processing could be factors contributing to alexithymic personality characteristics. Directions for future research on alexithymia and automatic emotion perception are suggested.

scholarly journals A Computational Network Control Theory Analysis of Depression Symptoms

2018 ◽  
Vol 1 ◽  
Author(s):  
Yoed N. Kenett ◽  
Roger E. Beaty ◽  
John D. Medaglia
Keyword(s):  
Control Theory ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Brain Network ◽  
Network Control ◽  
Depression Symptoms ◽  
Theory Approach ◽  
Imaging Data ◽  
The Brain ◽  
Subclinical Depression

AbstractRumination and impaired inhibition are considered core characteristics of depression. However, the neurocognitive mechanisms that contribute to these atypical cognitive processes remain unclear. To address this question, we apply a computational network control theory approach to structural brain imaging data acquired via diffusion tensor imaging in a large sample of participants, to examine how network control theory relates to individual differences in subclinical depression. Recent application of this theory at the neural level is built on a model of brain dynamics, which mathematically models patterns of inter-region activity propagated along the structure of an underlying network. The strength of this approach is its ability to characterize the potential role of each brain region in regulating whole-brain network function based on its anatomical fingerprint and a simplified model of node dynamics. We find that subclinical depression is negatively related to higher integration abilities in the right anterior insula, replicating and extending previous studies implicating atypical switching between the default mode and Executive Control Networks in depression. We also find that subclinical depression is related to the ability to “drive” the brain system into easy to reach neural states in several brain regions, including the bilateral lingual gyrus and lateral occipital gyrus. These findings highlight brain regions less known in their role in depression, and clarify their roles in driving the brain into different neural states related to depression symptoms.

scholarly journals Increased hypothalamic–pituitary–adrenal drive is associated with decreased appetite and hypoactivation of food-motivation neurocircuitry in anorexia nervosa

2013 ◽  
Vol 169 (5) ◽  
pp. 639-647 ◽  
Author(s):  
Elizabeth A Lawson ◽  
Laura M Holsen ◽  
Rebecca DeSanti ◽  
McKale Santin ◽  
Erinne Meenaghan ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Visual Processing ◽  
Serum Cortisol ◽  
Brain Regions ◽  
Cross Sectional Study ◽  
Food Motivation ◽  
Cross Sectional ◽  
Hypothalamic Pituitary Adrenal ◽  
Cortisol Levels ◽  
The Relationship

ObjectiveCorticotrophin-releasing hormone (CRH)-mediated hypercortisolemia has been demonstrated in anorexia nervosa (AN), a psychiatric disorder characterized by food restriction despite low body weight. While CRH is anorexigenic, downstream cortisol stimulates hunger. Using a food-related functional magnetic resonance imaging (fMRI) paradigm, we have demonstrated hypoactivation of brain regions involved in food motivation in women with AN, even after weight recovery. The relationship between hypothalamic–pituitary–adrenal (HPA) axis dysregulation and appetite and the association with food-motivation neurocircuitry hypoactivation are unknown in AN. We investigated the relationship between HPA activity, appetite, and food-motivation neurocircuitry hypoactivation in AN.DesignCross-sectional study of 36 women (13 AN, ten weight-recovered AN (ANWR), and 13 healthy controls (HC)).MethodsPeripheral cortisol and ACTH levels were measured in a fasting state and 30, 60, and 120 min after a standardized mixed meal. The visual analog scale was used to assess homeostatic and hedonic appetite. fMRI was performed during visual processing of food and non-food stimuli to measure the brain activation pre- and post-meal.ResultsIn each group, serum cortisol levels decreased following the meal. Mean fasting, 120 min post-meal, and nadir cortisol levels were high in AN vs HC. Mean postprandial ACTH levels were high in ANWR compared with HC and AN subjects. Cortisol levels were associated with lower fasting homeostatic and hedonic appetite, independent of BMI and depressive symptoms. Cortisol levels were also associated with between-group variance in activation in the food-motivation brain regions (e.g. hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula).ConclusionsHPA activation may contribute to the maintenance of AN by the suppression of appetitive drive.

Neurocircuitries of Emotion Processing Affected in Major Depressive Disorder

2019 ◽  
pp. 101-114
Author(s):  
Anjali Sankar ◽  
Cynthia H.Y. Fu
Keyword(s):  
Major Depression ◽  
Predictive Accuracy ◽  
Emotion Processing ◽  
Affective State ◽  
Brain Regions ◽  
First Episode ◽  
Neuroimaging Data ◽  
Multivariate Pattern ◽  
Future Work ◽  
Hallmark Feature

Impairments in processing emotions are a hallmark feature of depression. Advances in neuroimaging techniques have rapidly improved our understanding of the pathophysiology underlying major depression. In this chapter, we provide an overview of influential neural models of emotion perception and regulation and discuss the neurocircuitries of emotion processing that are affected. Major depression is characterized by impairments in widespread brain regions that are evident in the first episode. Models have sought to distinguish the neural circuitry associated with recognition of the emotion, integration of somatic responses, and monitoring of the affective state. In particular, there has been a preponderance of research on the neurocircuitries affected during processing of mood-congruent negative emotional stimuli in depression. While neuroimaging correlates have been investigated and models proposed, these findings have had limited clinical applicability to date. Novel methods such as multivariate pattern recognition applied to neuroimaging data might enable identification of reliable, valid, and robust biomarkers with high predictive accuracy that can be applied to an individual. Last, we discuss avenues for extension and future work.

Glutamate in the pathophysiology of schizophrenia

2020 ◽  
pp. 287-296
Author(s):  
Daniel C. Javitt
Keyword(s):  
Visual System ◽  
Visual Processing ◽  
Negative Symptoms ◽  
Glutamate Release ◽  
Critical Role ◽  
Brain Regions ◽  
Long Term Memory ◽  
Subcortical Structures ◽  
Impaired Metabolism

Glutamate theories of schizophrenia were first proposed over 30 years ago and since that time have become increasingly accepted. Theories are supported by the ability of N-methyl-D-aspartate receptor (NMDAR) antagonists such as phencyclidine (PCP) or ketamine to induce symptoms that closely resemble those of schizophrenia. Moreover, NMDAR antagonists uniquely reproduce the level of negative symptoms and cognitive deficits observed in schizophrenia, suggesting that such models may be particularly appropriate to poor outcome forms of the disorder. As opposed to dopamine, which is most prominent within frontostriatal brain regions, glutamate neurons are present throughout cortex and subcortical structures. Thus, NMDAR theories predict widespread disturbances across cortical and thalamic pathways, including sensory brain regions. In auditory cortex, NMDAR play a critical role in the generation of mismatch negativity (MMN), which may therefore serve as a translational marker of NMDAR dysfunction across species. In the visual system, NMDAR play a critical role in function of the magnocellular visual system. Deficits in both auditory and visual processing contribute to social and communication deficits, which, in turn, lead to poor functional outcome. By contrast, NMDAR dysfunction within the frontohippocampal system may contribute to well described deficits in working memory, executive processing and long-term memory formation. Deficits in NMDAR function may be driven by disturbances in presynaptic glutamate release, impaired metabolism of NMDAR modulators such as glycine or D-serine, or intrinsic abnormalities in NMDAR themselves.

scholarly journals C-19 An fMRI Study of Age-Associated Changes in Basic Visual Discrimination

2019 ◽  
Vol 34 (6) ◽  
pp. 1048-1048
Author(s):  
T Seider ◽  
E Porges ◽  
A Woods ◽  
R Cohen
Keyword(s):  
Visual Processing ◽  
Visual Discrimination ◽  
Community Sample ◽  
Visual Assessment ◽  
Brain Regions ◽  
Brain Response ◽  
Match To Sample ◽  
Fmri Study ◽  
Perceptual Skill ◽  
Cluster Level

Abstract Objective The study was conducted to determine age-associated changes in functional brain response, measured with fMRI, during visual discrimination with regard to three elementary components of visual perception: shape, location, and velocity. A secondary aim was to validate the method used to isolate the hypothesized brain regions associated with these perceptual functions. Method Items from the Visual Assessment Battery (VAB), a simultaneous match-to-sample task, assessed visual discrimination in 40 healthy adults during fMRI. Participants were aged 51-91 and recruited from a larger community sample for a study on normal aging. The tasks were designed to isolate neural recruitment during discrimination of either location, shape, or velocity by using tasks that were identical aside from the perceptual skill required to complete them. Results The Location task uniquely activated the dorsal visual processing stream, the Shape task the ventral stream, and the Velocity task V5/MT. Greater age was associated with greater neural recruitment, particularly in frontal areas (uncorrected voxel-level p < .001, family-wise error cluster-level p□.05). Conclusions Results validated the specialization of brain regions for spatial, perceptual, and movement discriminations and the use of the VAB to assess functioning localized to these regions. Anterior neural recruitment during visual discrimination increases with age.

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