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Psychophysiology Jun 2024Adapting to the ever-changing demands of the environment requires a complex interplay between cognitive-affective, neuronal, and autonomic processes. Vagally mediated...
The dynamic role of the left dlPFC in neurovisceral integration: Differential effects of theta burst stimulation on vagally mediated heart rate variability and cognitive-affective processing.
Adapting to the ever-changing demands of the environment requires a complex interplay between cognitive-affective, neuronal, and autonomic processes. Vagally mediated heart rate variability (vmHRV) is positively associated with both cognitive-affective functioning and prefrontal cortex (PFC) activity. Accordingly, the Neurovisceral Integration Model has posited a shared role of the PFC in the regulation of cognitive-affective processes and autonomic nervous system (ANS) activity. While there are numerous correlational findings in this regard, no study so far has investigated whether the manipulation of PFC activity induces changes in vmHRV and cognitive-affective processing in an inter-dependent manner. In a sample of 64 participants, we examined the effects of continuous (cTBS; n = 21) and intermittent theta-burst stimulation (iTBS; n = 20) compared to sham stimulation (n = 23) over the left dorsolateral PFC (dlPFC) on vmHRV and cognitive-affective processing within an emotional stop-signal task (ESST). Our results revealed that both resting vmHRV and vmHRV reactivity predicted cognitive-affective processing. Furthermore, we found a dampening effect of cTBS on resting and on-task vmHRV, as well as an enhancing effect of iTBS on ESST performance. Our results show no direct association between vmHRV changes and ESST performance alterations following stimulation. We interpret our results in the light of a hierarchical model of neurovisceral integration, suggesting a dynamical situation-dependent recruitment of higher-order cortical areas like the dlPFC in the regulation of the ANS. In conclusion, our results highlight the complex interplay between PFC activity, autonomic regulation, and cognitive-affective processing, emphasizing the need for further research to understand the causal dynamics of the underlying neural mechanisms.
PubMed: 38867447
DOI: 10.1111/psyp.14606 -
The Journal of Neuroscience : the... Jun 2024We investigated sex differences in dopamine (DA) release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) using a chronic 16-channel carbon fiber electrode...
Sex Differences in Dopamine Release in Nucleus Accumbens and Dorsal Striatum Determined by Chronic Fast Scan Cyclic Voltammetry: Effects of social housing and repeated stimulation.
We investigated sex differences in dopamine (DA) release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) using a chronic 16-channel carbon fiber electrode and fast-scan cyclic voltammetry (FSCV). Electrical stimulation (ES; 60 Hz) induced DA release was recorded in the NAc of single or pair-housed male and female rats. When core (NAcC) and shell (NAcS) were recorded simultaneously, there was greater ES DA release in NAcC of pair-housed females compared with single females and males. Housing did not affect ES NAc DA release in males. In contrast, there was significantly more ES DA release from the DLS of female rats than male rats. This was true prior to and after treatment with methamphetamine. Furthermore, in castrated (CAST) males and ovariectomized (OVX) females, there were no sex differences in ES DA release from the DLS, demonstrating the hormone dependence of this sex difference. However, in the DLS of both intact and gonadectomized rats, DA reuptake was slower in females than in males. Finally, DA release following ES of the medial forebrain bundle at 60 Hz was studied over four weeks. ES DA release increased over time for both CAST males and OVX females, demonstrating sensitization. Using this novel 16-channel chronic FSCV electrode, we found sex differences in the effects of social housing in the NAcS, sex differences in DA release from intact rats in DLS, sex differences in DA reuptake in DLS of intake and gonadectomized rats, and we report sensitization of ES-induced DA release in DLS in vivo. Dopamine release is not uniform or fixed. In the nucleus accumbens, pair housing, compared with individual housing, is shown to differentially affect dopamine responsiveness to stimulation in a sex-dependent and region-specific way. There are also sex differences in stimulated dopamine release in the dorsolateral striatum of intact rats, which are not seen in gonadectomized rats, indicating the hormone dependence of this sex difference. However, reuptake of dopamine was slower in females than in males, independent of gonadal hormones. Importantly, the electrical stimulation-induced dopamine release in the dorsolateral striatum of gonadectomized rats demonstrated sensitization of dopamine release in vivo within animals for the first time. Thus, stimulated dopamine release exhibits sex-specific neuroplasticity that is modified in females by the housing conditions.
PubMed: 38866486
DOI: 10.1523/JNEUROSCI.1527-23.2024 -
Clinical Neurophysiology : Official... May 2024Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (dlPFC) is an effective treatment for depression, but the neural effects after TMS remains...
BACKGROUND
Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (dlPFC) is an effective treatment for depression, but the neural effects after TMS remains unclear. TMS paired with electroencephalography (TMS-EEG) can causally probe these neural effects. Nonetheless, variability in single pulse TMS-evoked potentials (TEPs) across dlPFC subregions, and potential artifact induced by muscle activation, necessitate detailed mapping for accurate treatment monitoring.
OBJECTIVE
To characterize early TEPs anatomically and temporally (20-50 ms) close to the TMS pulse (EL-TEPs), as well as associated muscle artifacts (<20 ms), across the dlPFC. We hypothesized that TMS location and angle influence EL-TEPs, and specifically that conditions with larger muscle artifact may exhibit lower observed EL-TEPs due to over-rejection during preprocessing. Additionally, we sought to determine an optimal group-level TMS target and angle, while investigating the potential benefits of a personalized approach.
METHODS
In 16 healthy participants, we applied single-pulse TMS to six targets within the dlPFC at two coil angles and measured EEG responses.
RESULTS
Stimulation location significantly influenced observed EL-TEPs, with posterior and medial targets yielding larger EL-TEPs. Regions with high EL-TEP amplitude had less muscle artifact, and vice versa. The best group-level target yielded 102% larger EL-TEP responses compared to other dlPFC targets. Optimal dlPFC target differed across subjects, suggesting that a personalized targeting approach might boost the EL-TEP by an additional 36%.
SIGNIFICANCE
EL-TEPs can be probed without significant muscle-related confounds in posterior-medial regions of the dlPFC. The identification of an optimal group-level target and the potential for further refinement through personalized targeting hold significant implications for optimizing depression treatment protocols.
PubMed: 38865780
DOI: 10.1016/j.clinph.2024.05.008 -
Integrative and Comparative Biology Jun 2024Strong selective pressure on phenotype can arise when habitat transitions fundamentally alter the physical media in which animals live, such as the invasion of land by...
Strong selective pressure on phenotype can arise when habitat transitions fundamentally alter the physical media in which animals live, such as the invasion of land by lobe-finned fishes and insects. When environmental gradients differ drastically among habitats and multiple lineages transition between these habitats, we expect phenotypic convergence to be prevalent. One transition where widespread convergence has been observed is the shift from aboveground to subterranean environments in fossorial animals. Subterranean environments are low-light, confined spaces and tend to be hypoxic or anoxic, not to mention that the act of burrowing itself demands morphological specializations for excavation. Research suggests burrowing promotes morphological convergence in crayfish, with non-burrowing forms having a dorsoventrally compressed carapace and long, slender claws (chelae) while primary burrowing forms have a dorsolaterally compressed carapace and shorter, more powerful claws. However, earlier ecomorphological comparisons relied on qualitative, rather than quantitative assessments of phenotypic differences. This study tested for convergence in North American crayfishes using a geometric morphometric approach. We photographed the carapace and claw for representative species across thirteen North American genera. We hypothesized that crayfishes which occur in similar habitats and exhibit similar burrowing behaviors will converge in their carapace and claw shapes. We found evidence for convergence in carapace and claw morphologies in burrowing crayfishes. However, claw phenotypes did not converge as strongly as carapace shape, an example of "imperfect" or "incomplete" convergence we attribute to the multiple competing demands on claw form and function. We argue that nuances in habitat characteristics, like soil type or compaction, make complete convergence unlikely for range- and dispersal-limited fossorial crayfishes.
PubMed: 38862199
DOI: 10.1093/icb/icae067 -
Journal of Affective Disorders Jun 2024Research into the shared and distinct brain dysfunctions in patients with schizophrenia (SCZ) and major depressive disorder (MDD) has been increasing. However, few...
BACKGROUND
Research into the shared and distinct brain dysfunctions in patients with schizophrenia (SCZ) and major depressive disorder (MDD) has been increasing. However, few studies have explored the application of functional near-infrared spectroscopy (fNIRS) in investigating brain dysfunction and enhancing diagnostic methodologies in these two conditions.
METHODS
A general linear model was used for analysis of brain activation following task-state fNIRS from 131 patients with SCZ, 132 patients with MDD and 130 healthy controls (HCs). Subsequently, seventy-seven time-frequency analysis methods were used to construct new features of fNIRS, followed by the implementation of five machine learning algorithms to develop a differential diagnosis model for the three groups. This model was evaluated by comparing it to both a diagnostic model relying on traditional fNIRS features and assessments made by two psychiatrists.
RESULTS
Brain activation analysis revealed significantly lower activation in Broca's area, the dorsolateral prefrontal cortex, and the middle temporal gyrus for both the SCZ and MDD groups compared to HCs. Additionally, the SCZ group exhibited notably lower activation in the superior temporal gyrus and the subcentral gyrus compared to the MDD group. When distinguishing among the three groups using independent validation datasets, the models utilizing new fNIRS features achieved an accuracy of 85.90 % (AUC = 0.95). In contrast, models based on traditional fNIRS features reached an accuracy of 52.56 % (AUC = 0.66). The accuracies of the two psychiatrists were 42.00 % (AUC = 0.60) and 38.00 % (AUC = 0.50), respectively.
CONCLUSION
This investigation brings to light the shared and distinct neurobiological abnormalities present in SCZ and MDD, offering potential enhancements for extant diagnostic systems.
PubMed: 38862077
DOI: 10.1016/j.jad.2024.06.013 -
Nature Communications Jun 2024Single administration of low-dose ketamine has both acute and sustained anti-depressant effects. Sustained effect is associated with restoration of glutamatergic...
Single administration of low-dose ketamine has both acute and sustained anti-depressant effects. Sustained effect is associated with restoration of glutamatergic synapses in medial prefrontal cortic (mFPC) neurons. Ketamine induced profound changes in a number of molecular pathways in a mouse model for chronic stress. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling was decreased after chronic administration of corticosterone but increased following ketamine administration in most of the excitatory neurons. Similar decrease of PCP signaling in excitatory neurons was predicted in dorsolateral prefrontal cortical (dl-PFC) neurons of patients with major depressive disorder (MDD). We showed that the basolateral amygdala (BLA)-projecting infralimbic prefrontal cortex (IL PFC) neurons regulate immobility time in the tail suspension test and food consumption. Conditionally knocking out Celsr2 and Celsr3 or Prickle2 in the BLA-projecting IL PFC neurons abolished ketamine-induced synapse restoration and behavioral remission. Therefore, PCP proteins in IL PFC-BLA neurons mediate synapse restoration induced by of low-dose ketamine.
Topics: Animals; Ketamine; Prefrontal Cortex; Synapses; Neurons; Mice; Disease Models, Animal; Male; Humans; Cell Polarity; Depressive Disorder, Major; Mice, Knockout; Stress, Psychological; Corticosterone; Basolateral Nuclear Complex; Mice, Inbred C57BL; LIM Domain Proteins; Glutamic Acid; Antidepressive Agents
PubMed: 38858386
DOI: 10.1038/s41467-024-48257-6 -
Alcohol (Fayetteville, N.Y.) Jun 2024Many drugs of abuse, including alcohol, disrupt long-term synaptic depression (LTD) at dorsal striatal glutamate synapses. This disruption is common to many forms of LTD...
Many drugs of abuse, including alcohol, disrupt long-term synaptic depression (LTD) at dorsal striatal glutamate synapses. This disruption is common to many forms of LTD that are mediated by G protein coupled receptors (GPCRs) that signal through the inhibitory G class of G proteins. A loss of LTD is thought to mediate behavioral changes associated with the development of substance use disorders. We have previously shown in multiple studies that LTD mediated by the G-coupled mu opioid receptor is disrupted by in vivo opioid and alcohol exposure in adolescent and adult mice. One of our previous studies suggested that LTD mediated by delta and kappa opioid receptors was resistant to the LTD-disrupting properties of in vivo opioid exposure. We hypothesized that delta and kappa opioid receptor-mediated LTD would be exceptions to the generalizable observation that forms of dorsal striatal G-coupled receptor LTD are disrupted by drugs of abuse. Specifically, we predicted that these forms of LTD would be resistant to the deleterious effects of alcohol consumption, just as they were resistant to opioid exposure. Indeed, in adult male mice that drank alcohol for 3 weeks, delta and kappa opioid receptor-mediated LTD at glutamatergic inputs to direct pathway and indirect pathway medium spiny neurons in the dorsolateral striatum was unaffected by alcohol. These data demonstrate that alcohol effects on GPCR-mediated LTD are not generalizable across all types of G-coupled GPCRs.
PubMed: 38857678
DOI: 10.1016/j.alcohol.2024.06.002 -
Pflugers Archiv : European Journal of... Jun 2024To assess the possible interactions between the dorsolateral periaqueductal gray matter (dlPAG) and the different domains of the nucleus ambiguus (nA), we have examined...
To assess the possible interactions between the dorsolateral periaqueductal gray matter (dlPAG) and the different domains of the nucleus ambiguus (nA), we have examined the pattern of double-staining c-Fos/FoxP2 protein immunoreactivity (c-Fos-ir/FoxP2-ir) and tyrosine hydroxylase (TH) throughout the rostrocaudal extent of nA in spontaneously breathing anaesthetised male Sprague-Dawley rats during dlPAG electrical stimulation. Activation of the dlPAG elicited a selective increase in c-Fos-ir with an ipsilateral predominance in the somatas of the loose (p < 0.05) and compact formation (p < 0.01) within the nA and confirmed the expression of FoxP2 bilaterally in all the domains within the nA. A second group of experiments was made to examine the importance of the dlPAG in modulating the laryngeal response evoked after electrical or chemical (glutamate) dlPAG stimulations. Both electrical and chemical stimulations evoked a significant decrease in laryngeal resistance (subglottal pressure) (p < 0.001) accompanied with an increase in respiratory rate together with a pressor and tachycardic response. The results of our study contribute to new data on the role of the mesencephalic neuronal circuits in the control mechanisms of subglottic pressure and laryngeal activity.
PubMed: 38856775
DOI: 10.1007/s00424-024-02976-3 -
Alzheimer's & Dementia : the Journal of... Jun 2024The ɛ4 allele of the apolipoprotein E gene (APOE ɛ4) is the strongest genetic risk factor for Alzheimer's disease (AD), but the mechanisms connecting APOE ɛ4 to AD...
INTRODUCTION
The ɛ4 allele of the apolipoprotein E gene (APOE ɛ4) is the strongest genetic risk factor for Alzheimer's disease (AD), but the mechanisms connecting APOE ɛ4 to AD are not clear.
METHODS
Participants (n = 596) were from two clinical-pathological studies. Tissues from dorsolateral prefrontal cortex were examined to identify 8425 proteins. Post mortem pathological assessment used immunohistochemistry to obtain amyloid beta (Aβ) load and tau tangle density.
RESULTS
In separate models, APOE ɛ4 was associated with 18 proteins, which were associated with Aβ and tau tangles. Examining the proteins in a single model identified Netrin-1 and secreted frizzled-related protein 1 (SFRP1) as the two proteins linking APOE ɛ4 with Aβ with the largest effect sizes and Netrin-1 and testican-3 linking APOE ɛ4 with tau tangles.
DISCUSSION
We identified Netrin-1, SFRP1, and testican-3 as the most promising proteins that link APOE ɛ4 with Aβ and tau tangles.
HIGHLIGHTS
Of 8425 proteins extracted from prefrontal cortex, 18 were related to APOE ɛ4. The 18 proteins were also related to amyloid beta (Aβ) and tau. The 18 proteins were more related to APOE ɛ4 than other AD genetic risk variants. Netrin-1 and secreted frizzled-related protein 1 were the two most promising proteins linking APOE ɛ4 with Aβ. Netrin-1 and testican-3 were two most promising proteins linking APOE ɛ4 with tau.
PubMed: 38856164
DOI: 10.1002/alz.13867 -
World Journal of Otorhinolaryngology -... Jun 20242019 novel coronavirus disease (COVID-19) infection is commonly associated with olfactory dysfunctions, but the basic pathogenesis of these complications remains...
OBJECTIVES
2019 novel coronavirus disease (COVID-19) infection is commonly associated with olfactory dysfunctions, but the basic pathogenesis of these complications remains controversial. This study seeks to evaluate the value of magnetic resonance spectroscopy (MRS) in determining the molecular neurometabolite alterations within the main brain olfactory areas in patients with COVID-19-related anosmia.
METHODS
In a cross-sectional study, seven patients with persistent COVID-19-related anosmia (mean age: 29.57 years) and seven healthy volunteers (mean age: 27.28 years) underwent MRS in which N-acetyl-aspartate (NAA), choline (Cho), creatine (Cr), and their ratios were measured in the anterior cingulate cortex, dorsolateral prefrontal cortex, orbitofrontal cortex (OFC), insular cortex, and ventromedial prefrontal cortex. Data were analyzed using TARQUIN software (version 4.3.10), and the results were compared with an independent sample -test and nonparametric Mann-Whitney test based on the normality of the MRS data distribution.
RESULTS
The mean duration of anosmia before imaging was 8.5 months in COVID-19-related anosmia group. MRS analysis elucidated a significant association between MRS findings within OFC and COVID-19-related anosmia ( < 0.01), and NAA was among the most important neurometabolites ( = 0.006). Reduced levels of NAA ( < 0.001), Cr ( < 0.001) and / ratio ( = 0.007) within OFC characterize COVID-19-related anosmia.
CONCLUSIONS
This study emphasizes that MRS can be illuminating in COVID-19-related anosmia and indicates a possible association between central nervous system impairment and persistent COVID-19-related anosmia.
PubMed: 38855283
DOI: 10.1002/wjo2.132