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BioRxiv : the Preprint Server For... Jun 2024The amygdala responds to a large variety of socially and emotionally salient environmental and interoceptive stimuli. The context in which these stimuli occur determines...
The amygdala responds to a large variety of socially and emotionally salient environmental and interoceptive stimuli. The context in which these stimuli occur determines their social and emotional significance. In canonical neurophysiological studies, the fast-paced succession of stimuli and events induce phasic changes in neural activity. During inter-trial intervals neural activity is expected to return to a stable and relatively featureless baseline. Context, such as the presence of a social partner, or the similarity of trials in a blocked design, induces brain states that can transcend the fast-paced succession of stimuli and can be recovered from the baseline firing rate of neurons. Indeed, the baseline firing rates of neurons in the amygdala change between blocks of trials of gentle grooming touch, delivered by a trusted social partner, and non-social airflow stimuli, delivered by a computer-controlled air valve. In this experimental paradigm, the presence of the groomer alone was sufficient to induce small but significant changes in baseline firing rates. Here, we examine local field potentials (LFP) recorded during these baseline periods to determine whether context was encoded by network dynamics that emerge in the local field potentials from the activity of large ensembles of neurons. We found that machine learning techniques can reliably decode social vs. non-social context from spectrograms of baseline local field potentials. Notably, decoding accuracy improved significantly with access to broad-band information. No significant differences were detected between the nuclei of the amygdala that receive direct or indirect inputs from areas of the prefrontal cortex known to coordinate flexible, context-dependent behaviors. The lack of nuclear specificity suggests that context-related synaptic inputs arise from a shared source, possibly interoceptive inputs that signal the sympathetic- vs. parasympathetic-dominated states characterizing non-social and social blocks, respectively.
PubMed: 38915563
DOI: 10.1101/2024.06.14.598974 -
Social Cognitive and Affective... Jun 2024Malfunctioning in executive functioning has been proposed as a risk factor for intimate partner violence (IPV). This is not only due to its effects on behavioral...
Malfunctioning in executive functioning has been proposed as a risk factor for intimate partner violence (IPV). This is not only due to its effects on behavioral regulation, but also because of its association with other variables such as sexism. Executive dysfunctions have been associated with frontal and prefrontal cortical thickness. Therefore, our first aim was to assess differences in cortical thickness in frontal and prefrontal regions, as well as levels of sexism, between two groups of IPV perpetrators (with and without executive dysfunctions) and a control group of non-violent men. Second, we analyzed whether the cortical thickness in the frontal and prefrontal regions would explain sexism scores. Our results indicate that IPV perpetrators classified as dysexecutive exhibited a lower cortical thickness in the right rostral anterior cingulate superior frontal bilaterally, caudal middle frontal bilaterally, right medial orbitofrontal, right paracentral, and precentral bilaterally when compared with controls. Furthermore, they exhibited higher levels of sexism than the rest of the groups. Most importantly, in the brain structures that distinguished between groups, lower thickness was associated with higher sexism scores. This research emphasizes the need to incorporate neuroimaging techniques to develop accurate IPV profiles or subtypes based on neuropsychological functioning.
PubMed: 38915189
DOI: 10.1093/scan/nsae046 -
Social Cognitive and Affective... Jun 2024Understanding others involves inferring traits and intentions, a process complicated by our reliance on stereotypes and generalized information when we lack personal...
Understanding others involves inferring traits and intentions, a process complicated by our reliance on stereotypes and generalized information when we lack personal information. Yet, as relationships are formed, we shift towards nuanced and individualized perceptions of others. This study addresses how relationship strength influences the creation of unique or normative representations of others in key regions known to be involved in social cognition. Employing a round-robin interpersonal perception paradigm (N = 111, 20 groups of 5-6 people), we used functional magnetic resonance imaging (fMRI) to examine whether the strength of social relationships modulated the degree to which multivoxel patterns of activity that represented a specific other were similar to a normative average of all others in the study. Behaviorally, stronger social relationships were associated with more normative trait endorsements. Neural findings reveal that closer relationships lead to more unique representations in the medial prefrontal cortex and anterior insula, areas associated with mentalizing and person perception. Conversely, more generalized representations emerge in posterior regions like the posterior cingulate cortex, indicating a complex interplay between individuated and generalized processing of social information in the brain. These findings suggest that cortical regions typically associated with social cognition may compute different kinds of information when representing the distinctiveness of others.
PubMed: 38915187
DOI: 10.1093/scan/nsae045 -
Nature Communications Jun 2024Idling brain activity has been proposed to facilitate inference, insight, and innovative problem-solving. However, it remains unclear how and when the idling brain can...
Idling brain activity has been proposed to facilitate inference, insight, and innovative problem-solving. However, it remains unclear how and when the idling brain can create novel ideas. Here, we show that cortical offline activity is both necessary and sufficient for building unlearned inferential knowledge from previously acquired information. In a transitive inference paradigm, male C57BL/6J mice gained the inference 1 day after, but not shortly after, complete training. Inhibiting the neuronal computations in the anterior cingulate cortex (ACC) during post-learning either non-rapid eye movement (NREM) or rapid eye movement (REM) sleep, but not wakefulness, disrupted the inference without affecting the learned knowledge. In vivo Ca imaging suggests that NREM sleep organizes the scattered learned knowledge in a complete hierarchy, while REM sleep computes the inferential information from the organized hierarchy. Furthermore, after insufficient learning, artificial activation of medial entorhinal cortex-ACC dialog during only REM sleep created inferential knowledge. Collectively, our study provides a mechanistic insight on NREM and REM coordination in weaving inferential knowledge, thus highlighting the power of idling brain in cognitive flexibility.
Topics: Animals; Sleep, REM; Male; Mice, Inbred C57BL; Prefrontal Cortex; Learning; Mice; Gyrus Cinguli; Wakefulness; Sleep, Slow-Wave; Knowledge; Entorhinal Cortex; Neurons
PubMed: 38914541
DOI: 10.1038/s41467-024-48816-x -
ELife Jun 2024Downregulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is...
Downregulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is critical for top-down modulatory processes, and despite previous studies adopting repetitive transcranial magnetic stimulation (rTMS) over this region provided encouraging results in enhancing extinction, no studies have hitherto explored the effects of stimulating the medial anterior PFC (aPFC, encompassing the Brodmann area 10) on threat memory and generalization. Here we showed that rTMS over the aPFC applied before threat memory retrieval immediately decreases implicit reactions to learned and novel stimuli in humans. These effects enduringly persisted 1 week later in the absence of rTMS. No effects were detected on explicit recognition. Critically, rTMS over the aPFC resulted in a more pronounced reduction of defensive responses compared to rTMS targeting the dorsolateral PFC. These findings reveal a previously unexplored prefrontal region, the modulation of which can efficiently and durably inhibit implicit reactions to learned threats. This represents a significant advancement toward the long-term deactivation of exaggerated responses to threats.
Topics: Humans; Fear; Prefrontal Cortex; Transcranial Magnetic Stimulation; Male; Young Adult; Female; Adult; Extinction, Psychological
PubMed: 38913410
DOI: 10.7554/eLife.85951 -
Frontiers in Aging Neuroscience 2024To explore the structural and functional changes in cognition-related brain regions in patients with chronic low back pain (CLBP) at earlier ages, and explore the impact...
OBJECTIVE
To explore the structural and functional changes in cognition-related brain regions in patients with chronic low back pain (CLBP) at earlier ages, and explore the impact of the interaction between CLBP and age on the brain.
METHODS
Seventy-six patients with CLBP were recruited and divided into "younger" age group (20-29 years, YA), "middle" age group (30-39 years, MA), and "older" age group (40-49 years, OA). All patients underwent functional magnetic resonance imaging (fMRI) as well as clinical psychological and pain-related symptoms assessments.
RESULTS
Structural analysis showed that patients in OA group had lower gray matter (GM) volumes in the orbitofrontal cortex (OFC) bilaterally and the right superior frontal gyrus (SFG) compared to YA group. The resting-state brain activity analysis showed that amplitude of low-frequency fluctuation (ALFF) values in the bilateral postcentral gyrus and left ventral medial prefrontal cortex (mPFC) were significantly different in the OA group. The functional connectivity (FC) in the right ventral dorsolateral prefrontal cortex (DLPFC) and the right insula was significantly decreased in the OA group compared to the YA and MA groups. Likewise, the FC in the left caudal parahippocampal gyrus (PHG) and left inferior parietal lobule (IPL) were significantly lower in the MA and OA groups compared to the YA group. In addition, both the structural properties and the FC values of these brain regions were significantly correlated with age.
CONCLUSION
This preliminary study concludes that CLBP affects the aging process. The synergistic effects of CLBP and aging accelerate the functional and structural decline of certain areas of the brain, which not only affects pain processing, but are also may be associated with cognitive declines.
PubMed: 38912520
DOI: 10.3389/fnagi.2024.1356507 -
International Journal of Tryptophan... 2024Alterations in the composition of the gut microbiota may be causally associated with several brain diseases. Indole-3-propionic acid (IPrA) is a tryptophan-derived...
Alterations in the composition of the gut microbiota may be causally associated with several brain diseases. Indole-3-propionic acid (IPrA) is a tryptophan-derived metabolite, which is produced by intestinal commensal microbes, rapidly enters the circulation, and crosses the blood-brain barrier. IPrA has neuroprotective properties, which have been attributed to its antioxidant and bioenergetic effects. Here, we evaluate an alternative and/or complementary mechanism, linking IPrA to kynurenic acid (KYNA), another neuroprotective tryptophan metabolite. Adult Sprague-Dawley rats received an oral dose of IPrA (200 mg/kg), and both IPrA and KYNA were measured in plasma and frontal cortex 90 minutes, 6 or 24 hours later. IPrA and KYNA levels increased after 90 minutes and 6 hours (brain IPrA: ~56- and ~7-fold; brain KYNA: ~4- and ~3-fold, respectively). In vivo microdialysis, performed in the medial prefrontal cortex and in the striatum, revealed increased KYNA levels (~2.5-fold) following the administration of IPrA (200 mg/kg, p.o), but IPrA failed to affect extracellular KYNA when applied locally. Finally, treatment with 100 or 350 mg IPrA, provided daily to the animals in the chow for a week, resulted in several-fold increases of IPrA and KYNA levels in both plasma and brain. These results suggest that exogenously supplied IPrA may provide a novel strategy to affect the function of KYNA in the mammalian brain.
PubMed: 38911967
DOI: 10.1177/11786469241262876 -
Biological Psychiatry. Cognitive... Jun 2024Binge Eating Disorder (BED) is thought of as a disorder of cognitive control but evidence regarding its neurocognitive mechanisms is inconclusive. Key limitations in...
BACKGROUND
Binge Eating Disorder (BED) is thought of as a disorder of cognitive control but evidence regarding its neurocognitive mechanisms is inconclusive. Key limitations in prior research are a lack of consistent separation between effects of BED and obesity, and a disregard for self-report evidence suggesting that neurocognitive alterations may emerge primarily in loss- or harm-avoidance contexts.
METHODS
Addressing these gaps, this longitudinal study investigated behavioral flexibility and its underlying neuro-computational processes in reward-seeking and loss-avoidance contexts. Obese participants with BED (BED), without BED (OB), and healthy normal-weight participants (NW) (N=96) performed a probabilistic reversal learning task during functional imaging, with different blocks focused on obtaining wins or avoiding losses. They were reinvited for a 6-months follow-up.
RESULTS
Analyses informed by computational models of reinforcement learning showed that unlike BED, OB performed worse in the win than the loss condition. Computationally, this was explained by differential learning sensitivities in the win vs loss conditions between groups. In the brain, this was echoed in differential neural learning signals in the ventromedial prefrontal cortex (vmPFC) per condition. The differences were subtle, but scaled with BED symptoms, such that more severe BED symptoms were associated with increasing bias towards improved learning from wins vs losses. Across conditions, OB switched more between choice options than NW. This was reflected in diminished representation of choice certainty in the vmPFC.
CONCLUSIONS
Our study highlights the importance of distinguishing between obesity with and without BED to identify unique neuro-computational alterations underlying different styles of maladaptive eating behavior.
PubMed: 38909896
DOI: 10.1016/j.bpsc.2024.06.002 -
Neuroscience Jun 2024Chronic ethanol consumption increased extracellular glutamate concentrations in several reward brain regions. Glutamate homeostasis is regulated in majority by...
Effects of MC-100093 on Ethanol Drinking and the Expression of Astrocytic Glutamate Transporters in the Mesocorticolimbic Brain Regions of Male and Female Alcohol-Preferring Rats.
Chronic ethanol consumption increased extracellular glutamate concentrations in several reward brain regions. Glutamate homeostasis is regulated in majority by astrocytic glutamate transporter 1 (GLT-1) as well as the interactive role of cystine/glutamate antiporter (xCT). In this study, we aimed to determine the attenuating effects of a novel beta-lactam MC-100093, lacking the antibacterial properties, on ethanol consumption and GLT-1 and xCT expression in the subregions of nucleus accumbens (NAc core and NAc shell) and medial prefrontal cortex (Infralimbic, mPFC-IL and Prelimbic, mPFC-PL) in male and female alcohol-preferring (P) rats. Female and male rats were exposed to free access to ethanol (15% v/v) and (30% v/v) for five weeks, and on Week 6, rats were administered 100 mg/kg (i.p) of MC-100093 or saline for five days. MC-100093 reduced ethanol consumption in both male and female P rats from Day 1-5. Additionally, MC-100093 upregulated GLT-1 and xCT expression in mPFC and NAc subregions as compared to ethanol-saline groups in female and male rats. Chronic ethanol intake reduced GLT-1 and xCT expression in the IL and PL in female and male rats, except there was no reduction in GLT-1 expression in the mPFC-PL in female rats. Although, MC-100093 upregulated GLT-1 and xCT expression in the subregions of NAc, we didn't observe any reduction in GLT-1 and xCT expression with chronic ethanol intake in female rats. These findings strongly suggest that MC-100093 treatment effectively reduced ethanol intake and upregulated GLT-1 and xCT expression in the mPFC and NAc subregions in male and female P rats.
PubMed: 38909675
DOI: 10.1016/j.neuroscience.2024.06.017 -
Journal of Affective Disorders Jun 2024We conducted a meta-analysis and qualitative review on the randomized controlled trials investigating the effects of transcranial direct current stimulation and... (Review)
Review
BACKGROUND
We conducted a meta-analysis and qualitative review on the randomized controlled trials investigating the effects of transcranial direct current stimulation and transcranial magnetic stimulation on fear extinction and the return of fear in non-primate animals and humans.
METHODS
The meta-analysis was conducted by searching PubMed, Web of science, PsycINFO, and Cochrane Library and extracting fear response in the active and sham groups in the randomized controlled trials. The pooled effect size was quantified by Hedges' g using a three-level meta-analytic model in R.
RESULTS
We identified 18 articles on the tDCS effect and 5 articles on the TMS effect, with 466 animal subjects and 621 human subjects. Our findings show that tDCS of the prefrontal cortex significantly inhibit fear retrieval in animal models (Hedges' g = -0.50). In human studies, TMS targeting the dorsolateral/ventromedial prefrontal cortex has an inhibiting effect on the return of fear (Hedges' g = -0.24).
LIMITATIONS
The limited number of studies and the heterogeneous designs of the selected studies made cross-study and cross-species comparison difficult.
CONCLUSIONS
Our findings shed light on the optimal non-invasive brain stimulation protocols for targeting the neural circuitry of threat extinction in humans.
PubMed: 38908557
DOI: 10.1016/j.jad.2024.06.060