Sex differences in effective fronto-limbic connectivity during negative emotion processing

Lungu, Ovidiu; Potvin, Stéphane; Tikàsz, Andràs; Mendrek, Adrianna

doi:10.1016/j.psyneuen.2015.08.012

Cited by 76 publications

(49 citation statements)

References 45 publications

(62 reference statements)

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“…First, to allow an evaluation of the training independent of menstrual-cycle or gender effects on ER and associated neural activity [46, 47, 49], our proof-of-concept study focused on male participants. The question of whether training success generalizes to female subjects and potential sex differences therefore remains to be addressed.…”

Section: Discussionmentioning

confidence: 99%

“…Given that the main aim was to evaluate the feasibility and functional relevance of connectivity-informed rt-fMRI NFT potential confounding effects of menstrual cycle-related variation in ER [46], as well as sex differences in ER capacity [47], ER strategies [48] and associated connectivity in the target pathway [49] were controlled for by focusing on a male sample. Detailed eligibility criteria and sample characteristics are provided in the online supplementary materials (for all online suppl.…”

Section: Methodsmentioning

confidence: 99%

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Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety

Zhao

Yao

et al. 2019

Psychother Psychosom

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Background: Deficient emotion regulation and exaggerated anxiety represent a major transdiagnostic psychopathological marker. On the neural level these deficits have been closely linked to impaired, yet treatment-sensitive, prefrontal regulatory control over the amygdala. Gaining direct control over these pathways could therefore provide an innovative and promising intervention to regulate exaggerated anxiety. To this end the current proof-of-concept study evaluated the feasibility, functional relevance and maintenance of a novel connectivity-informed real-time fMRI neurofeedback training. Methods: In a randomized crossover sham-controlled design, 26 healthy subjects with high anxiety underwent real-time fMRI-guided neurofeedback training to enhance connectivity between the ventrolateral prefrontal cortex (vlPFC) and the amygdala (target pathway) during threat exposure. Maintenance of regulatory control was assessed after 3 days and in the absence of feedback. Training-induced changes in functional connectivity of the target pathway and anxiety ratings served as primary outcomes. Results: Training of the target, yet not the sham control, pathway significantly increased amygdala-vlPFC connectivity and decreased levels of anxiety. Stronger connectivity increases were significantly associated with higher anxiety reduction on the group level. At the follow-up, volitional control over the target pathway was maintained in the absence of feedback. Conclusions: The present results demonstrate for the first time that successful self-regulation of amygdala-prefrontal top-down regulatory circuits may represent a novel intervention to control anxiety. As such, the present findings underscore both the critical contribution of amygdala-prefrontal circuits to emotion regulation and the therapeutic potential of connectivity-informed real-time neurofeedback.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety

Zhao

Yao

et al. 2019

Psychother Psychosom

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“…Animal studies demonstrated sex differences (greater in females than males) in a number of domains, including greater immobility in tasks associated with mood-related phenotypic behavior 29 , increased ACTH, corticosterone, and glucocorticoid receptor binding 30,31 , and increased corticosterone sensitivity 32 . A recent neuroimaging study in humans reported sex differences in fronto-limbic connectivity with women having more affective and men more evaluative responses to negative affective stimuli 33 . In the study reported here, we hypothesized that hyperactivity in subcortical arousal regions and hypoactivity in cortical regions and hippocampus would be associated with severity of dysphoric mood, and that these deficits in ability to regulate neural response to negative affective stimuli will be greater among women than men.…”

Section: Introductionmentioning

confidence: 99%

Brain activity and connectivity in response to negative affective stimuli: Impact of dysphoric mood and sex across diagnoses

Marečková

Holsen

Admon

et al. 2016

Human Brain Mapping

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Negative affective stimuli elicit behavioral and neural responses which vary on a continuum from adaptive to maladaptive, yet are typically investigated in a dichotomous manner (healthy controls vs. psychiatric diagnoses). This practice may limit our ability to fully capture variance from acute responses to negative affective stimuli to psychopathology at the extreme end. To address this, we conducted a functional magnetic resonance imaging (fMRI) study to examine the neural responses to negative valence/high arousal and neutral valence/low arousal images as a function of dysphoric mood and sex across individuals (n=99) who represented traditional categories of healthy controls, major depressive disorder, bipolar psychosis, and schizophrenia. Observation of negative (vs. neutral) stimuli elicited BOLD responses in the following circuitry: periaqueductal gray [PAG], hypothalamus [HYPO], amygdala [AMYG], hippocampus [HIPP], orbitofrontal cortex [OFC], medial prefrontal cortex [mPFC], and greater connectivity between AMYG and mPFC. Across all subjects, severity of dysphoric mood was associated with hyperactivity of HYPO, and, among females, right (R) AMYG. Females also demonstrated inverse relationships between severity of dysphoric mood and connectivity between HYPO - R OFC, R AMYG - R OFC, and R AMYG - R HIPP. Overall, our findings demonstrated sex-dependent deficits in response to negative affective stimuli increasing as a function of dysphoric mood state. Females demonstrated greater inability to regulate arousal as mood became more dysphoric. These findings contribute to elucidating biosignatures associated with response to negative stimuli across disorders and suggest the importance of a sex-dependent lens in determining these biosignatures.

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“…In order to account for modulation in Granger effective connectivity by the task, we used an approach similar to the psychophysiological interaction (PPI) technique (40), whereby we included in the regression model the values of the BOLD signal time series originating from a seed cluster multiplied with the weights of the regressor corresponding to the task (i.e., the PPI term). This approach allowed to evaluate the variations in GC effective connectivity between pairs of ROIs during experimental conditions (i.e., Tobacco, Negative, and Neutral) relative to one another or to rest periods (26, 41). …”

Section: Methodsmentioning

confidence: 99%

Impaired Coupling between the Dorsomedial Prefrontal Cortex and the Amygdala in Schizophrenia Smokers Viewing Anti-smoking Images

et al. 2017

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BackgroundCigarette smoking is highly prevalent in schizophrenia and is one of the main factors contributing to the significantly decreased life expectancy in this population. Schizophrenia smokers, compared to their counterparts with no comorbid psychiatric disorder, are largely unaware and indifferent to the long-term negative consequences of cigarette smoking. The objective of this study was to determine, for the first time, if these meta-cognitive deficits are associated with neuro-functional alterations in schizophrenia smokers.MethodsTwenty-four smokers with no psychiatric disorder and 21 smokers with schizophrenia (DSM-IV criteria) were scanned using functional magnetic resonance imaging and exposed to anti-smoking images. Granger causality analyses were used to examine the effective connectivity between brain regions found to be significantly activated.ResultsAcross groups, potent activations were observed in the left ventro-lateral prefrontal cortex, the left amygdala (AMG), and the dorsomedial prefrontal cortex (dmPFC). Using the dmPFC as a seed region, we found an abnormal negative connectivity from the dmPFC to the AMG in schizophrenia smokers during the viewing of anti-smoking stimuli. This abnormal connectivity was not present during the viewing of aversive stimuli unrelated to tobacco.DiscussionGiven the well-established roles of the dmPFC in social cognition and of the AMG in emotional processing, our results suggest that the relative indifference of schizophrenia smokers regarding the negative consequences of tobacco smoking could be explained by a cognitive-affective dissonance.

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Sex differences in effective fronto-limbic connectivity during negative emotion processing

Cited by 76 publications

References 45 publications

Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety

Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety

Brain activity and connectivity in response to negative affective stimuli: Impact of dysphoric mood and sex across diagnoses

Impaired Coupling between the Dorsomedial Prefrontal Cortex and the Amygdala in Schizophrenia Smokers Viewing Anti-smoking Images

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