Closed-loop brain stimulation to reduce pathologic fear DOI Open Access
Rodrigo O. Sierra, Lizeth K. Pedraza, Lívia Barcsai

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: July 24, 2022

ABSTRACT Maladaptive processing of trauma related memory engrams leads to dysregulated fear reactions. In post-traumatic stress disorder (PTSD), dysfunctional extinction learning prevents discretization trauma-related and generalized responses. PTSD is postulated as a mnemonic-based disorder, but we lack markers or treatments targeting pathological processing. Hippocampal sharp wave-ripples (SWRs) concurrent neocortical oscillations are scaffolds consolidate contextual memory, their role during remains poorly understood. We demonstrate that closed-loop SWRs triggered neuromodulation the medial forebrain bundle (MFB) can enhance consolidation extinction. It modified memories became resistant induced recall (i.e., ‘renewal’ ‘reinstatement’) did not reemerge spontaneously PTSD-like phenotype. The effects mediated by D2 receptor signaling synaptic remodeling in basolateral amygdala. These results suggest help consolidating memories. Furthermore, enhancing SWR-triggered induction reward signals alleviate pathologic reactions rodent model PSTD. No adverse were seen, suggesting this potential therapy for anxiety disorders.

Language: Английский

Circadian rhythms in conditioned threat extinction reflect time-of-day differences in ventromedial prefrontal cortex neural processing DOI
Matthew J. Hartsock,

Catherine T Levy,

Maria Jose Guillén Navarro

et al.

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(39), P. e0878242024 - e0878242024

Published: Sept. 9, 2024

Circadian rhythms in conditioned threat extinction emerge from a tissue-level circadian timekeeper, or local clock, the ventromedial prefrontal cortex (vmPFC). Yet it remains unclear how this clock contributes to extinction-dependent adaptations. Here we used single-unit and field potential analyses interrogate neural activity male rat vmPFC during repeated sessions at different times of day. In association with superior recall remote memory active phase, putative principal neurons exhibited phasic firing that was amplified for cue presentations diminished transitions freezing behavior. Coupling gamma amplitude phase low-frequency oscillations greater than mobility, difference augmented highlighting time-of-day dependence organization freezing- versus mobility-associated cell assemblies. Additionally, proportion were phase-locked consistent heightened excitability time Our results suggest daily fluctuations precipitate enhanced recruitment into extinction-based assemblies providing mechanism by which modulates circuit behavioral plasticity extinction.

Language: Английский

Citations

1

Transcriptomic diversity of amygdalar subdivisions across humans and nonhuman primates DOI Creative Commons
Michael S. Totty, Rita Cervera‐Juanes, Svitlana V. Bach

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 19, 2024

The amygdaloid complex mediates learning, memory, and emotions. Understanding the cellular anatomical features that are specialized in amygdala of primates versus other vertebrates requires a systematic, anatomically-resolved molecular analysis constituent cell populations. We analyzed five nuclear subdivisions primate with single-nucleus RNA sequencing macaques, baboons, humans to examine gene expression profiles for excitatory inhibitory neurons confirmed our results single-molecule FISH analysis. identified distinct subtypes

Language: Английский

Citations

1

Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear DOI Creative Commons
Michael S. Totty, Karthik R. Ramanathan, Jingji Jin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 13, 2022

Abstract Traumatic events result in vivid and enduring fear memories. Suppressing the retrieval of these memories is central to behavioral therapies for pathological fear. The medial prefrontal cortex (mPFC) hippocampus (HPC) have been implicated suppression, but how mPFC-HPC activity coordinated during extinction unclear. Here we show that after training, coherent theta oscillations (6-9 Hz) HPC mPFC are correlated with suppression conditioned freezing male female rats. Inactivation nucleus reuniens (RE), a thalamic hub interconnecting HPC, reduces extinction-related Fos expression both dampens coherence, impairs retrieval. Conversely, theta-paced optogenetic stimulation RE augments relapse extinguished Collectively, results demonstrate novel role coordinating interactions suppress extinction.

Language: Английский

Citations

4

Influence of chronic stress on network states governing valence processing: potential relevance to the risk for psychiatric illnesses DOI Creative Commons

Pantelis Antonoudiou,

Bradly T. Stone, Phillip L.W. Colmers

et al.

Journal of Neuroendocrinology, Journal Year: 2023, Volume and Issue: 35(9)

Published: April 1, 2023

Stress is a major risk factor for psychiatric illnesses and understanding the mechanisms through which stress disrupts behavioral states imperative to underlying pathophysiology of mood disorders. Both chronic early life alter valence processing, process assigning value sensory inputs experiences (positive or negative), determines subsequent behavior essential emotional processing ultimately survival. in both humans preclinical models, favoring negative impairing positive processing. Valence assignment involves neural computations performed hubs, including amygdala, prefrontal cortex, ventral hippocampus, can be influenced by neuroendocrine mediators. Oscillations within between these regions are critical necessary perform functions. Major advances field have demonstrated role oscillatory under physiological conditions emerging studies exploring how network altered pathophysiological impacted factors. The current review highlights what currently known regarding impact mediators on Further, we propose model alters information routing resulting facilitation suppression

Language: Английский

Citations

2

Dopamine D1-like receptors modulate synchronized oscillations in the hippocampal–prefrontal–amygdala circuit in contextual fear DOI Creative Commons
Christine Stubbendorff,

Ed Hale,

Tobias Bast

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Oct. 17, 2023

Contextual fear conditioning (CFC) is mediated by a neural circuit that includes the hippocampus, prefrontal cortex, and amygdala, but neurophysiological mechanisms underlying regulation of CFC neuromodulators remain unclear. Dopamine D1-like receptors (D1Rs) in this regulate local synaptic plasticity, which facilitated synchronized oscillations between these areas. In rats, we determined effects systemic D1R blockade on oscillatory synchrony dorsal hippocampus (DH), prelimbic (PL) basolateral amygdala (BLA), ventral (VH), sends hippocampal projections to PL BLA. altered DH-VH reduced VH-PL VH-BLA during CFC, as inferred from theta gamma coherence theta-gamma coupling. also impaired indicated decreased freezing at retrieval, was characterized VH-PL, VH-BLA, PL-BLA synchrony. This reduction VH-PL-BLA not fully accounted for non-specific locomotor effects, revealed comparing epochs movement controls. These results suggest D1Rs modulating within hippocampus-prefrontal-amygdala circuit. They add growing evidence indicating retrieval reflects signature learned fear.

Language: Английский

Citations

2

Respiratory Coupled Oscillations as a Mechanism of Attention to the Olfactory Environment DOI Creative Commons
Ana Luiza Alves Dias,

Joseph Andrews Alves Belo,

Davi Carvalho Drieskens

et al.

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(8), P. e1866232024 - e1866232024

Published: Feb. 21, 2024

Language: Английский

Citations

0

Neural Decoding and Feature Selection Techniques for Closed-Loop Control of Defensive Behavior DOI Creative Commons
Jinhan Liu,

Rebecca Younk,

Lauren M Drahos

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 6, 2024

Abstract Objective Many psychiatric disorders involve excessive avoidant or defensive behavior, such as avoidance in anxiety and trauma rituals obsessive-compulsive disorders. Developing algorithms to predict these behaviors from local field potentials (LFPs) could serve foundational technology for closed-loop control of A significant challenge is identifying the LFP features that encode behaviors. Approach We analyzed signals infralimbic cortex basolateral amygdala rats undergoing tone-shock conditioning extinction, standard investigating utilized a comprehensive set neuro-markers across spectral, temporal, connectivity domains, employing SHapley Additive exPlanations feature importance evaluation within Light Gradient-Boosting Machine models. Our goal was decode three commonly studied avoidance/defensive behaviors: freezing, bar-press suppression, motion (accelerometry), examining impact different on decoding performance. Main results Band power band ratio between channels emerged optimal sessions. High-gamma (80-150 Hz) power, ratios, inter-regional correlations were more informative than other bands are classically linked Focusing highly enhanced Across 4 recording sessions with 16 subjects, we achieved an average coefficient determination 0.5357 0.3476, Pearson correlation coefficients 0.7579 0.6092 accelerometry jerk bar press rate, respectively. Utilizing only most revealed differential encoding former primarily through spectral latter via connectivity. methodology demonstrated remarkably low time complexity, requiring < 110 ms training 1 inference. Significance demonstrate feasibility accurately minimal latency, using neural circuits strongly This holds promise real-time identify physiological targets neuromodulation.

Language: Английский

Citations

0

Breathing modulates network activity in frontal brain regions during anxiety DOI Creative Commons

Ana L.A. Dias,

Davi Carvalho Drieskens,

Joseph Andrews Alves Belo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 25, 2024

Abstract Anxiety elicits various physiological responses, including changes in respiratory rate and neuronal activity within specific brain regions such as the medial prefrontal cortex (mPFC). Previous research suggests that olfactory bulb (OB) modulates mPFC through respiration-coupled oscillations (RCOs), which have been linked to fear-related freezing behavior. Nevertheless, impact of breathing on frontal networks during other negative emotional anxiety-related states characterized by higher rates, remains unclear. To address this, we subjected rats elevated plus maze (EPM) paradigm while simultaneously recording respiration local field potentials OB mPFC. Our findings demonstrate distinct patterns EPM exploration: slower frequencies prevailed closed arms, whereas faster were observed open independent locomotor activity, indicating anxiety-like are associated with increased rates. Additionally, identified RCOs at different frequencies, mirroring bimodal distribution frequencies. exhibited power arm exploration, when they showed greater coherence Furthermore, confirmed nasal drives regions, found a stronger effect breathing. Interestingly, frequency gamma modulated heightened anxiety levels frequency. Overall, our study provides evidence for significant influence anxious states, shedding light complex interplay between physiology processing. Significance Statement Understanding how influences could pave way novel therapeutic interventions targeting control alleviate symptoms. uncovers crucial link neural brain. By investigating breathing, oscillations, reveal induces patterns, rates correlating Importantly, oscillatory cortex, this is potentiated fast anxiety. cycle emergence differentially across levels. This discovery sheds new intricate relationship

Language: Английский

Citations

0

Neural decoding and feature selection methods for closed-loop control of avoidance behavior DOI
Jinhan Liu,

Rebecca Younk,

Lauren M Drahos

et al.

Journal of Neural Engineering, Journal Year: 2024, Volume and Issue: 21(5), P. 056041 - 056041

Published: Oct. 1, 2024

Abstract Objective. Many psychiatric disorders involve excessive avoidant or defensive behavior, such as avoidance in anxiety and trauma rituals obsessive-compulsive disorders. Developing algorithms to predict these behaviors from local field potentials (LFPs) could serve the foundational technology for closed-loop control of A significant challenge is identifying LFP features that encode behaviors. Approach. We analyzed signals infralimbic cortex basolateral amygdala rats undergoing tone-shock conditioning extinction, standard investigating utilized a comprehensive set neuro-markers across spectral, temporal, connectivity domains, employing SHapley Additive exPlanations feature importance evaluation within Light Gradient-Boosting Machine models. Our goal was decode three commonly studied avoidance/defensive behaviors: freezing, bar-press suppression, motion (accelerometry), examining impact different on decoding performance. Main results. Band power band ratio between channels emerged optimal sessions. High-gamma (80–150 Hz) power, ratios, inter-regional correlations were more informative than other bands are classically linked Focusing highly enhanced Across 4 recording sessions with 16 subjects, we achieved an average coefficient determination 0.5357 0.3476, Pearson correlation coefficients 0.7579 0.6092 accelerometry jerk bar press rate, respectively. Utilizing only most revealed differential encoding former primarily through spectral latter via connectivity. methodology demonstrated remarkably low training/inference time memory usage, requiring < 310 ms training, 0.051 inference, 16.6 kB memory, using single core AMD Ryzen Threadripper PRO 5995WX CPU. Significance. results demonstrate feasibility accurately minimal latency, neural circuits strongly This holds promise real-time identify physiological targets neuromodulation.

Language: Английский

Citations

0

Efficacy of Transcranial Direct Current Stimulation (tDCS) on Neuropsychiatric Symptoms in Multiple Sclerosis (MS)—A Review and Insight into Possible Mechanisms of Action DOI Open Access

James Chmiel,

Marta Stępień-Słodkowska

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(24), P. 7793 - 7793

Published: Dec. 20, 2024

Introduction: Neuropsychiatric symptoms such as depression and anxiety are a significant burden on patients with multiple sclerosis (MS). Their pathophysiology is complex yet to be fully understood. There an urgent need for non-invasive treatments that directly target the brain help MS. One possible treatment transcranial direct current stimulation (tDCS), popular effective technique. Methods: This mechanistic review explores efficacy of tDCS in treating MS while focusing underlying mechanisms action. Understanding these crucial, neuropsychiatric arise from neuroinflammatory neurodegenerative processes. offers insights may more focused efficient therapeutic approaches by investigating ways which affects inflammation, plasticity, neural connections. Searches were conducted using PubMed/Medline, ResearchGate, Cochrane, Google Scholar databases. Results: The literature search yielded 11 studies included this review, total 175 participating studies. In most studies, did not significantly reduce or scores studied have elevated indicating anxiety. few where had mild/moderate dysfunction, was effective. risk bias assessed moderate. Despite null near-null results, still prove option MS, because produces neurobiological effect nervous system. To facilitate further work, several action been reported, modulation frontal-midline theta, reductions neuroinflammation, HPA axis, cerebral blood flow regulation. Conclusions: Although overall demonstrate positive effects reducing patients, role area should underestimated. Evidence other indicates effectiveness anxiety, but include sufficient Future needed confirm dysfunctions

Language: Английский

Citations

0