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Adaptive behavior requires the ability to shift responding within (intra-dimensional) or between (extra-dimensional) stimulus dimensions when reward contingencies change. Studies of shifting in humans have focused mainly on the prefrontal cortex and/ or have been restricted to indirect measures of neural activity such as fMRI and lesions. Here, we demonstrate the importance of the amygdala and hippocampus by recording local field potentials directly from these regions intracranially in human epilepsy patients. Reward signals were coded in the high frequency gamma activity (HFG; 60-250 Hz) of both regions and synchronised via low frequency (3-5 Hz) phase-locking only after a shift when patients did not already know the rule and it signalled to stop shifting ("Win-Stay"). In contrast, HFG punishment signals were only seen in the amygdala when the rule then changed and it signalled to start shifting ("Lose-Shift"). During decision-making, hippocampal HFG was more inhibited on non-shift relative to shift trials, suggesting a role in preventing interference in rule representation and amygdala HFG was sensitive to stimulus novelty. The findings expand our understanding of human amygdala-hippocampal function and shifting processes, the disruption of which could contribute to shifting deficits in neuropsychiatric disorders. Studies of rule shifts have focused mainly on prefrontal cortex. Here, the authors show that activity in amygdala and hippocampus and their connectivity is important for several processes involved in rule shifts. [ABSTRACT FROM AUTHOR]

Introduction: Social anxiety disorder (SAD) is a prevalent psychiatric condition characterized by an intense fear of and avoidance of social situations. Traditional assessment methods for SAD primarily rely on subjective self-report questionnaires and clinical interviews, which can be prone to biases and inaccuracies. This study aims to explore the functional excitation-inhibition (fEI) ratio derived from EEG data as a potential objective biomarker for assessing SAD severity. Methods: Resting-state EEG data were collected from 20 control subjects and 60 individuals with varying degrees of SAD severity (mild, moderate, and severe). The fEI ratio was estimated across different EEG bands and analyzed, focusing on differences between control subjects and SAD groups. Results: Significantly higher fEI ratios were observed in the alpha and low beta EEG bands in individuals with SAD compared to controls, especially within the prefrontal cortex. Additionally, a positive correlation was found between the fEI ratio and the severity of social anxiety symptoms across SAD severity levels. Discussion: The findings indicate that the fEI ratio in the alpha and low beta bands may serve as a promising biomarker for assessing SAD severity. These results contribute to a deeper understanding of the neural mechanisms underlying social anxiety, offering a potentially more objective approach to SAD assessment compared to traditional methods. [ABSTRACT FROM AUTHOR]

Introduction: Inadequate exposure to real-life operating can impede timely acquisition of technical competence among surgical residents, and is a major challenge faced in the current training climate. Mental rehearsal (MR)--the cognitive rehearsal of a motor task without overt physical movement--has been shown to accelerate surgical skills learning. However, the neuroplastic effect of MR of a complex bimanual surgical task is unknown. The aim of this study is to use functional near-infrared spectroscopy (fNIRS) to assess the impact of MR on prefrontal and motor cortical activation during a laparoscopic knot tying task. Methods: Twelve surgical residents performed a laparoscopic knot tying task before and after either mental rehearsal (MR, intervention group) or textbook reading (TR, control group). In both groups, fNIRS was used to measure changes in oxygenated hemoglobin concentration (HbO2) in the prefrontal (24 channels) and motor cortices (22 channels). Technical performance was measured using leak volume, objective performance score and task progression score. Results: MR led to a decrease in HbO2 (reduced activation) in the bilateral prefrontal cortex (PFC), and an increase in HbO2 (increased activation) in the left middle frontal gyrus, left precentral gyrus, and left postcentral gyrus. No discernible changes in activation were observed after TR in either the PFC or motor cortex. Moreover, smaller ΔHbO2 responses in the right PFC and greater ΔHbO2 responses in the left motor cortex were observed in the MR group compared with the TR group. Leak volume was significantly less following MR (p = 0.019), but not after TR (p = 0.347). Mean objective performance score was significantly higher following MR compared with TR (p = 0.043). Conclusion: Mental rehearsal may enhance surgical skill acquisition and technical proficiency by reducing utilization of attentional resources in the prefrontal cortex and improving neural efficiency in motor areas during a laparoscopic surgical task. [ABSTRACT FROM AUTHOR]

Several studies in both animal models and in humans have provided substantial evidence that early life stress (ELS) induces long-term changes in behavior and brain function, making it a significant risk factor in the aetiology of various mental disorders, including anxiety and depression. In this study, we tested the hypothesis that ELS in male rats (i) leads to increased anxiety and depressive-like symptoms; and (ii) that these behavioral changes are associated with functional alterations in the endocannabinoid system of the medial prefrontal cortex (mPFC). We further assessed whether the predicted changes in the gene expression of two key components of the endocannabinoid system, cannabinoid receptor 1 (CB1R) and the fatty acid amide hydrolase (FAAH), are regulated by epigenetic mechanisms. Behavioral profiling revealed that the proportion of behaviorally affected animals was increased in ELS exposed male rats compared to control animals, specifically showing symptoms of anhedonia and impaired social behavior. On the molecular level we observed a decrease in CB1R and FAAH mRNA expression in the mPFC of adult ELS exposed animals. These gene expression changes were accompanied by reduced global histone 3 acetylation in the mPFC, while no significant changes in DNA methylation and no significant changes of histone-acetylation at the promoter regions of the analyzed genes were detected. Taken together, our data provide evidence that ELS induces a long-term reduction of CB1R and FAAH expression in the mPFC of adult male rats, which may partially contribute to the ELS-induced changes in adult socio-emotional behavior. [ABSTRACT FROM AUTHOR]

Introduction: Repetitive transcranial magnetic stimulation (rTMS) can improve post stroke motor function. However, there is little research on targets. The purpose of this study is to investigate the effects of rTMS therapy with different targets on post stroke motor function and neural plasticity. Methods: Fifty-four subjects were randomly divided into M1 (Primary motor area) group, SMA (supplementary motor area) group and Sham group, and were given 10 Hz on the affected M1 area, SMA area and sham stimulation rTMS. The primary outcomes included Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), Fugl-Meyer Assessment Lower Extremity Scale (FMA-LE) and Berg balance scale (BBS). Secondary outcomes: amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were analyzed by functional magnetic resonance imaging (fMRI) to evaluate brain functional activation and functional connectivity changes. Results: The 2-way repeated-measures ANOVA revealed a significant group × time interaction (F = 23.494, p < 0.001; F = 10.801, p < 0.001; F = 17.812, p < 0.001) in the FMA-UE, FMA-LE and BBS scores. Post hoc analysis indicated that 4 weeks of SMA rTMS resulted in an increase in FMA-UE, FMA-LE and BBS scores compared with Sham group (p = 0.006; p = 0.033; p = 0.012), SMA group was significantly increased in BBS compared with M1 group (p = 0.034). Moreover, there were significant effects of time in all 3 groups in the FMA-UE, FMA-LE and BBS scores (p < 0.001). In addition, the increase of ALFF in the supramarginal gyrus on the affected side was correlated with better FMA-UE recovery, the increase of ALFF in the middle temporal gyrus and the middle frontal gyrus on the affected side was positively correlated with the improvement of BBS, and the ALFF in the cerebellum on the healthy side was negatively correlated with the improvement of BBS. There was a positive correlation between FC (SMA – ipsilateral cerebellum) changes and BBS changes in SMA group. Discussion: In conclusion, SMA-rTMS intervention has a better recovery effect on motor dysfunction after stroke than Sham-rTMS. SMA-rTMS led to similar improvement on motor function but significantly greater improvement on balance compared to M1-rTMS, and this may pave a new way for stroke rehabilitation. Clinical trial registration: Registration number: ChiCTR2200060955, https://www.chictr.org.cn/. [ABSTRACT FROM AUTHOR]

Cholinergic disruptions underlie attentional deficits following traumatic brain injury (TBI). Yet, drugs specifically targeting acetylcholinesterase (AChE) inhibition have yielded mixed outcomes. Therefore, we hypothesized that galantamine (GAL), a dual-action competitive AChE inhibitor and α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator, provided chronically after injury, will attenuate TBI-induced deficits of sustained attention and enhance ACh efflux in the medial prefrontal cortex (mPFC), as assessed by in vivo microdialysis. In Experiment 1, adult male rats (n = 10–15/group) trained in the 3-choice serial reaction time (3-CSRT) test were randomly assigned to controlled cortical impact (CCI) or sham surgery and administered GAL (0.5, 2.0, or 5.0 mg/kg; i.p.) or saline vehicle (VEH; 1 mL/kg; i.p) beginning 24-h post-surgery and once daily thereafter for 27 days. Measures of sustained attention and distractibility were assessed on post-operative days 21–25 in the 3-CSRT, following which cortical lesion volume and basal forebrain cholinergic cells were quantified on day 27. In Experiment 2, adult male rats (n = 3–4/group) received a CCI and 24 h later administered (i.p.) one of the three doses of GAL or VEH for 21 days to quantify the dose-dependent effect of GAL on in vivo ACh efflux in the mPFC. Two weeks after the CCI, a guide cannula was implanted in the right mPFC. On post-surgery day 21, baseline and post-injection dialysate samples were collected in a temporally matched manner with the cohort undergoing behavior. ACh levels were analyzed using reverse phase high-performance liquid chromatography (HPLC) coupled to an electrochemical detector. Cortical lesion volume was quantified on day 22. The data were subjected to ANOVA, with repeated measures where appropriate, followed by Newman–Keuls post hoc analyses. All TBI groups displayed impaired sustained attention versus the pooled SHAM controls (p's < 0.05). Moreover, the highest dose of GAL (5.0 mg/kg) exacerbated attentional deficits relative to VEH and the two lower doses of GAL (p's < 0.05). TBI significantly reduced cholinergic cells in the right basal forebrain, regardless of treatment condition, versus SHAM (p < 0.05). In vivo microdialysis revealed no differences in basal ACh in the mPFC; however, GAL (5.0 mg/kg) significantly increased ACh efflux 30 min following injection compared to the VEH and the other GAL (0.5 and 2.0 mg/kg) treated groups (p's < 0.05). In both experiments, there were no differences in cortical lesion volume across treatment groups (p's > 0.05). In summary, albeit the higher dose of GAL increased ACh release, it did not improve measures of sustained attention or histopathological markers, thereby partially supporting the hypothesis and providing the impetus for further investigations into alternative cholinergic pharmacotherapies such as nAChR positive allosteric modulators. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) has garnered significant interest for its potential to enhance cognitive functions and as a therapeutic intervention in various cognitive disorders. However, the clinical application of tDCS has been hampered by significant variability in its cognitive outcomes. Furthermore, the widespread use of tDCS has raised concerns regarding its safety and efficacy, particularly in light of our limited understanding of its underlying neural mechanisms at the cellular level. We still do not know 'where', 'when' and 'how' tDCS modulates information encoding by neurons, in order to lead to the observed changes in cognitive functions. Without elucidating these fundamental unknowns, the root causes of its outcome variability and long-term safety remain elusive, challenging the effective application of tDCS in clinical settings. Addressing this gap, our study investigates the effects of tDCS, applied over the dorsolateral prefrontal cortex, on cognitive abilities and individual neuron activity in macaque monkeys performing cognitive tasks. Like humans performing a delayed match-to-sample task, monkeys exhibited practice-related slowing in their responses (within-session behavioural adaptation). Concurrently, there were practice-related changes in simultaneously recorded activity of prefrontal neurons (within-session neuronal adaptation). Anodal tDCS attenuated both these behavioural and neuronal adaptations when compared with sham stimulation. Furthermore, tDCS abolished the correlation between response time of monkeys and neuronal firing rate. At a single-cell level, we also found that following tDCS, neuronal firing rate was more likely to exhibit task-specific modulation than after sham stimulation. These tDCS-induced changes in both behaviour and neuronal activity persisted even after the end of tDCS stimulation. Importantly, multiple applications of tDCS did not alter burst-like firing rates of individual neurons when compared with sham stimulation. This suggests that tDCS modulates neural activity without enhancing susceptibility to epileptiform activity, confirming a potential for safe use in clinical settings. Our research contributes unprecedented insights into the 'where', 'when' and 'how' of tDCS effects on neuronal activity and cognitive functions by showing that modulation of the behaviour of monkeys by the tDCS of the prefrontal cortex is accompanied by alterations in prefrontal cortical cell activity ('where') during distinct trial phases ('when'). Importantly, tDCS led to task-specific and state-dependent alterations in prefrontal cell activities ('how'). Our findings suggest a significant shift from the view that the effects of tDCS are merely attributable to polarity-specific shifts in cortical excitability and instead propose a more complex mechanism of action for tDCS that encompasses various aspects of cortical neuronal activity without increasing burst-like epileptiform susceptibility. [ABSTRACT FROM AUTHOR]

The use of psilocybin to treat alcohol use disorder is very promising, but its mechanisms of action remain poorly understood. We combined behavioural, pharmacological and gene expression analyses to decipher the mechanisms of action of psilocybin, for the first time, when injected into the brain. Male Long Evans rats underwent chronic operant ethanol self-administration before testing the effect of intraperitoneal psilocybin or directly within the nucleus accumbens core or the ventral tegmental area. Transcripts from the dopaminergic system were quantified in the nucleus accumbens and prefrontal cortex. Psilocybin significantly reduced (by 50%) ethanol self-administration when injected 4 h before the session either intraperitoneally (1 mg/kg) or directly within the left nucleus accumbens (0.15 μg) but not the right nucleus accumbens or the left ventral tegmental area. The effect of intraperitoneal injection of psilocybin was prevented by intra-left nucleus accumbens injection of 0.3 μg of the 5-HT2A receptor antagonist ketanserin. In rats that self-administered ethanol but not in those self-administering saccharin, dopamine D2 receptor (D2R) mRNA was increased in both the nucleus accumbens and the prefrontal cortex by psilocybin, while dopamine D1 receptor mRNA was increased only in the prefrontal cortex. As in humans, psilocybin reduced ethanol self-administration in rats through the 5-HT2A receptor within the left nucleus accumbens, possibly through increased D2R expression. Our results open unexpected perspectives regarding the hemispheric lateralization of psychedelic effects. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (SVD) is known to contribute to cognitive impairment, apathy and gait dysfunction. Although associations between cognitive impairment and either apathy or gait dysfunction have been shown in SVD, the inter-relations among these three clinical features and their potential common neural basis remain unexplored. The dopaminergic meso-cortical and meso-limbic pathways have been known as the important brain circuits for both cognitive control, emotion regulation and motor function. Here, we investigated the potential inter-relations between cognitive impairment, apathy and gait dysfunction, with a specific focus on determining whether these clinical features are associated with damage to the meso-cortical and meso-limbic pathways in SVD. In this cross-sectional study, we included 213 participants with SVD for whom MRI and comprehensive neurobehavioural assessments were performed. These assessments comprised six clinical measures: processing speed, executive function, memory, apathy (based on the Apathy Evaluation Scale) and gait function (based on the time and steps in the Timed Up and Go Test). We reconstructed five tracts connecting the ventral tegmental area (VTA) and dorsolateral prefrontal cortex (PFC), ventral lateral PFC, medial orbitofrontal cortex, anterior cingulate cortex (ACC) and nucleus accumbens within meso-cortical and meso-limbic pathways using diffusion weighted imaging. The damage along the five tracts was quantified using the free water (FW) and FW-corrected mean diffusivity indices. Furthermore, we explored the inter-correlations among the six clinical measures and identified their common components using principal component analysis (PCA). Linear regression analyses showed that higher FW values of tracts within meso-cortical pathways were related to these clinical measures in cognition, apathy, and gait (all P -corrected values < 0.05). The PCA showed strong inter-associations among these clinical measures and identified a common component wherein all six clinical measures loaded on. Higher FW values of tracts within meso-cortical pathways were related to the PCA-derived common component (all P -corrected values < 0.05). Moreover, FW values of the VTA-ACC tract showed the strongest contribution to the PCA-derived common component over all other neuroimaging features. In conclusion, our study showed that the three clinical features (cognitive impairment, apathy, and gait dysfunction) of SVD are strongly inter-related and that the damage in meso-cortical pathway could be the common neural basis underlying the three features in SVD. These findings advance our understanding of the mechanisms behind these clinical features of SVD and have the potential to inform novel management and intervention strategies for SVD. [ABSTRACT FROM AUTHOR]

Background: The neurophysiological mechanisms underlying manifestations of bulbar paralysis in acute thyrotoxic myopathy (ATM) and the afflicted brain areas are unclear. Purpose: We used resting-state functional magnetic resonance imaging (rs-fMRI) to evaluate the regional brain activities in patients with ATM. Material and Methods: In total, 16 patients with ATM, 16 patients with hyperthyroidism without ATM, and 16 healthy controls underwent functional MRI scans. By calculating the fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC), we assessed variations in resting-state cerebral activity. The correlation between the resting-state functional indexes and clinical assessments was also explored. Results: Compared to the hyperthyroid patients, patients with ATM had stronger ReHo in the left precentral gyrus, reduced ReHo in the left orbitofrontal gyrus (OFG), and decreased FC in the left precentral gyri, left superior frontal gyrus (SFG), and left middle frontal gyrus (MFG). Patients with ATM showed reduced fALFF and ReHo in the right SFG and decreased ReHo in the bilateral supplementary motor area (SMA). A significantly decreased FC in the left SFG and left MFG, right precentral gyrus, and the orbital part of the right interior frontal gyrus was observed in patients with ATM compared to healthy controls. Additionally, fALFF and ReHo values were positively correlated with serum thyroid-related hormones and antibodies. Conclusion: The findings of rs-fMRI demonstrate that particular brain regions' functional activity was aberrant in individuals with ATM, especially in SFG area. This finding may help with better understanding of underlying pathophysiology of patients with ATM. [ABSTRACT FROM AUTHOR]

Background and Purpose: Neuropathic pain (NP) is a debilitating condition following spinal cord injury (SCI). The role of periaqueductal gray (PAG) in NP development following SCI remains underexplored. Using resting‐state functional MRI (rsfMRI), our study aimed to demonstrate the alterations in functional connectivity (FC) of PAG in NP following SCI. Methods: Ten SCI patients (SCI + NP, n = 7, and SCI − NP, n = 3), alongside 10 healthy controls (HCs), were enrolled. rsfMRI was conducted followed by seed‐to‐voxel analysis using PAG as the seed region and then group‐based analysis comprising three groups (SCI + NP, SCI − NP, and HC). Age and gender were considered as confounding variables. Results: Compared to HCs, SCI + NP demonstrated decreased FC between PAG and right insula, right frontal orbital cortex, right pallidum, dorsal raphe nucleus (DRN), red nuclei (RN), substantia nigra (SN), and ventral posterolateral (VPL) thalamic nuclei. Compared to SCI − NP, SCI + NP demonstrated increased FC between PAG and posterior cingulate cortex (PCC), hippocampus, cerebellar vermis lobules IV and V, and thalamic structures (posterior and lateral pulvinar, the mediodorsal nuclei, and the ventral lateral nuclei). Additionally, decreased FC between the PAG and VPL, geniculate bodies, intralaminar nuclei of thalamus, DRN, RN, SN, and prefrontal cortex was observed in this comparison. Conclusions: Altered FC between PAG and right anterior insula, VPL, DRN, RN, SN, cerebellar vermis lobules IV and V, frontal cortex, and PCC was associated with NP sequelae of SCI. Additionally, SCI was independently associated with decreased FC between PAG and right posterior insula, cerebellar lobules IV and V, and cerebellar vermis lobules III, IV, and V. [ABSTRACT FROM AUTHOR]

Background and Purpose: This study sought to explore dynamic degree centrality (DC) variability in particular regions of the brain in patients with poststroke Broca aphasia (BA) using a resting‐state functional magnetic resonance imaging (rs‐fMRI) approach, comparing differences between Uyghur and Chinese BA patients. Methods: This study investigated two factors, language and BA status, and divided patients into four groups: Uyghur aphasia patients (UA), Uyghur normal control subjects (UN), Chinese aphasia patients (CA), and Chinese normal subjects (CN) who underwent rs‐fMRI analysis. Two‐way analysis of variance (ANOVA) was used to calculate the comprehensive differences in dynamic DC among these four groups. Correlations between DC and language behavior were assessed with partial correlation analyses. Results: Two‐way ANOVA revealed comparable results for the results of pairwise comparisons of dynamic DC variability among the four groups in the right middle frontal gyrus/orbital part (ORBmid.R), right superior frontal gyrus/dorsolateral, and right precuneus (PCUN.R), with results as follows: UA < UN, CA > CN, UA < CA, and UN > CN (p <.05, with the exception of the p‐values for UA and UN in superior frontal gyrus/dorsolateral). In contrast, the opposite results were observed for the right calcarine fissure and surrounding cortex (CAL.R, p <.05). Conclusion: The observed enhancement of dynamic DC variability in ORBmid.R and PCUN.R among Chinese BA patients and in CAL.R in Uyghur BA patients may be attributable to language network restructuring. Overall, these results suggest that BA patients who use different language families may exhibit differences in the network mechanisms that characterize observed impairments of language function. [ABSTRACT FROM AUTHOR]

The massive use of herbicides, particularly glyphosate‐based herbicides (GBHs), raises several worries, notably their neurotoxic effects. Several studies have explored the consequences of developmental exposure. Our work aims to determine the impact of maternal exposure to GBH on behavioral disorders and memory deficits, as well as the involvement of oxidative stress in the hippocampus and prefrontal cortex. In addition, our study explores the neuroprotective properties of melatonin in male and female offspring. Pregnant Wistar rats were injected with GBH 75 mg/kg during gestation and lactation. After weaning, the offspring were treated with melatonin (4 mg/kg) from postnatal days 30–58. Our results show that GBH increases anxiety‐like behavior levels in offspring, as well as depression‐like behavior. GBH also impairs working memory in progeny. While markers of oxidative stress show a disturbance in lipid peroxidation and catalase activity, with a more pronounced effect in females, on the other hand, melatonin considerably attenuated the neurotoxic impact observed in the offspring, with higher efficacy in females. The oxidative stress results confirm the antioxidant power of melatonin to counteract the damaging effects of exposure to environmental contaminants such as glyphosate‐based pesticides. It will then be interesting to further our work to fully understand the sex‐dependent effect of melatonin. [ABSTRACT FROM AUTHOR]

Serotonin is a monoamine neurotransmitter that plays a main role in regulating physiological and cognitive functions. Serotonergic system dysfunction is involved in the etiology of various psychiatric and neurological disorders. Therefore, the present study was designed to investigate the effects of early‐life serotonin depletion on cognitive disorders caused by sleep deprivation. Serotonin was depleted by para‐chlorophenylalanine (PCPA, 100 mg/kg, s.c.) at postnatal days 10–20, followed by sleep deprivation‐induced through the multiple platform apparatus for 24 h at PND 60. After the examination of the novel object recognition and passive avoidance memories, the hippocampi and prefrontal cortex were dissected to examine the brain‐derived neurotrophic factor (BDNF) mRNA expression by PCR. Our findings showed that postnatal serotonin depletion and sleep deprivation impaired the novel object recognition and passive avoidance memories and changed the BDNF levels. In the same way, the serotonin depletion in early life before sleep deprivation exacerbated the harmful effects of sleep deprivation on cognitive function and BDNF levels. It can be claimed that the serotonergic system plays a main role in the modulation of sleep and cognitive functions. [ABSTRACT FROM AUTHOR]

The tendency of falsely remembering events that did not happen in the past increases with age. This is particularly evident in cases in which features presented at study are re-presented at test in a recombined constellation (termed rearranged pairs). Interestingly, older adults also express high confidence in such false memories, a tendency that may indicate reduced metacognitive efficiency. Within an existing cohort study, we aimed at investigating age-related differences in memory metacognitive efficiency (as measured by meta d' ratio) in a sample of 1522 older adults and 397 young adults. The analysis showed an age-related deficit in metacognition which was more pronounced for rearranged pairs than for new pairs. We then explored associations between cortical thickness and memory metacognitive efficiency for rearranged pairs in a subsample of 231 older adults. By using partial least square analysis, we found that a multivariate profile composed by ventromedial prefrontal cortex, insula, and parahippocampal cortex was uniquely associated with between-person differences in memory metacognitive efficiency. These results suggest that the impairment in memory metacognitive efficiency for false alarms is a distinct age-related deficit, above and beyond a general age-related decline in memory discrimination, and that it is associated with brain regions involved in metacognitive processes. [ABSTRACT FROM AUTHOR]

True and false memories recruit a number of shared brain regions; however, they are not completely overlapping. Extensive sex differences have been identified in the brain during true memories and, recently, we identified sex differences in the brain during false memories. In the current fMRI study, we sought to determine whether sex differences existed in the location and extent of overlap between true and false memories. True and false memories activated a number of shared brain regions. Compared to females, males produced a greater number of overlapping brain regions (8 versus 2 activations for males and females, respectively) including the prefrontal cortex, parietal cortex, and early/late visual processing cortices (including V1) in males and prefrontal and parietal cortices in females. Males had significantly higher similarity between true and false memory activation maps, revealed by our novel multi-voxel pattern correlation analysis. Moreover, higher similarity between true and false memory activation maps was associated with higher false memory rates. The current results suggest that true and false memories are more similar in males than females. The significant brain–behavior relationship also suggests that males may be more susceptible to false memory errors due to their highly similar true memory–false memory cortical representations. [ABSTRACT FROM AUTHOR]

Objective To explore the relationship between sociodemographic, clinical, and neurophysiological variables and health-related quality of life (HR-QOL) of patients with phantom limb pain (PLP). Methods This is a cross-sectional analysis of a previous clinical trial. Univariate and multivariate linear and logistic regression analyses were used to model the predictors of HR-QOL. We utilized a sequential modeling approach with increasing adjustment levels, controlling for age and sex, and other relevant clinical variables (time since amputation, level of amputation, and pain). HR-QOL was assessed by the SF-36 Health Survey and its 8 subdomains. Results We analyzed baseline data from 92 patients with lower-limb amputations. They were mostly male (63%), 45.2 ± 15.6 years, with a mean time since amputation of 82.7 ± 122.4 months, and an overall SF-36 score of 55.9 ± 21.5. We found an association between intracortical facilitation (ICF) in the affected hemisphere, gabapentin usage, and HR-QOL. ICF is a predictor of better HRQOL, whereas gabapentin usage was associated with a poorer HR-QOL, with the main model explaining 13.4% of the variance in the outcome. For the SF-36 subdomains, ICF was also a positive predictor for social functioning, bodily pain, and vitality, while medication usage was associated with lower scores in mental health, general health perception, bodily pain, and vitality. Conclusion We found firsthand 2 new independent predictors of HR-QOL in individuals with PLP, namely, the neurophysiological metric ICF and gabapentin usage. These results highlight the role of the motor cortex excitability in the HR-QOL and stress the need for treatments that favor the neuroplastic adaptation after amputation, for which ICF may be used as a possible marker. [ABSTRACT FROM AUTHOR]

Background: Social behaviour is the expression of one of the most generally accepted independent dimensions of personality. Serotonergic neurotransmission has been implicated in typical social response and drugs that promote serotonin (5-hydroxytryptamine (5-HT)) release have prosocial effects. By using the social interaction test, we have previously demonstrated sociability as a temperamental trait in male Wistar rats. Aims: To assess sociability in male rats of the Sprague–Dawley strain and in female rats of both Wistar and Sprague–Dawley strain, and extracellular levels of 5-HT in rats with high and low sociability (high sociability (HS)- and low sociability (LS)-rats). Methods: Social interaction test conducted with different weight-matched partners was used to assess sociability, and in vivo, microdialysis was performed before and after administration of a low dose (2 mg/kg) of parachloroamphetamine (PCA) in the prefrontal cortex, dorsamedial striatum and ventral tegmental area. Results: Similarly to male Wistar rats, female Wistars and Sprague–Dawley rats of both sexes displayed trait-wise sociability. Male Wistar HS-rats had lower extracellular levels of 5-HT in prefrontal cortex at baseline and after administration of PCA, and higher PCA-induced increase of extracellular 5-HT in ventral tegmental area. In dorsomedial striatum, PCA elicited a comparable increase in extracellular dopamine in HS- and LS-rats, but higher release of 5-HT in HS-rats. Comparison of PCA-induced 5-HT release in prefrontal cortex of male and female Sprague–Dawley rats revealed a larger 5-HT response in female HS-rats. Conclusions: 5-HT release potential is higher in rats with high expression of sociability trait, whereas some regionally variable differences may be related to relative contributions of social motivation and anxiety in shaping social behaviour. [ABSTRACT FROM AUTHOR]

Anxiety is a prominent non‐motor symptom of Parkinson's disease (PD). Changes in the B‐spectrum recordings in PD patients of the prefrontal cortex correlate with increased anxiety. Using a rodent model of PD, we reported alterations in glutamate synapses in the striatum and substantia nigra following dopamine (DA) loss. We hypothesize that DA loss will result in increased anxiety‐related behaviours and that this will be associated with alterations in glutamate synapses and transporters within the medial prefrontal cortex (mPFC). Following 4 weeks of progressive 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) administration, there was an increase in anxiety‐related behaviours and a 78% decrease in plasma corticosterone levels versus the vehicle (VEH)‐treated mice. This was associated with a 30% decrease in the density of dendritic spines in Layers Il/Ill, and a 53% decrease in the density of glutamate immuno‐gold labelling within vesicular glutamate transporter 1 (Vglut1)‐labelled nerve terminals and spines, with no change within vesicular glutamate transporter 2 (Vglut2) positive terminals/spines in the MPTP versus VEH groups. Our prior work determined that a decrease in striatal glutamate terminal density was associated with an increase in extracellular glutamate levels. There was an increase in protein expression of Vglut1 (40%), Vglut2 (37%) and glutamate aspartate transporter (GLAST) (225%), and a decrease in glutamate transporter 1 (GLT‐1) (50%) and excitatory amino acid carrier 1 (EAAC1) (51%), in the MPTP versus VEH groups within the mPFC. These data suggest that the decrease in dendritic spines within the mPFC following nigrostriatal DA loss may be due to increased extracellular glutamate levels (decrease in glutamate transporters), leading to an increase in anxiety‐related behaviours. [ABSTRACT FROM AUTHOR]

Freezing of gait (FOG) is a disabling motor symptom prevalent in patients with Parkinson's disease (PD); however, its pathophysiological mechanisms are poorly understood. This study aimed to investigate whole‐brain functional connectivity (FC) pattern alterations in PD patients with FOG. A total of 18 PD patients, 10 with FOG (PD‐FOG) and 8 without FOG (PD‐nFOG), and 10 healthy controls were enrolled. High‐resolution 3D T1‐weighted and resting‐state functional MRI (rs‐fMRI) data were obtained from all participants. The groups' internetwork connectivity differences were explored with rs‐fMRI FC using seed‐based analysis and graph theory. Multiple linear regression analysis estimated the relationship between FC changes and clinical measurements. Rs‐fMRI analysis demonstrated alterations in FC in various brain regions between the three groups. Freezing of Gait Questionnaire severity was correlated with decreased brain functional connection between Vermis12 and the left temporal occipital fusiform cortex (r = −0.82, P <.001). Graph theory topological metrics indicated a decreased clustering coefficient in the right superior temporal gyrus in the PD‐nFOG group. PD‐FOG patients exhibited a compensatory increase in connectivity between the left inferior frontal gyrus language network and the postcentral gyrus compared to PD‐nFOG patients. Further, the decreased connection between Vermis 12 and the left temporal occipital fusiform cortex may serve as a potential neuroimaging biomarker for tracking PD‐FOG and distinguishing between PD subtypes. [ABSTRACT FROM AUTHOR]

Pain catastrophizing is a prominent psychological factor that is strongly correlated with pain. Although the complex properties of pain catastrophizing vary across different pain phases, the contribution of chronic pain to its progression from a general trait to a higher state remains unclear. This study aimed to examine the neural mechanisms and degree to which pain catastrophizing is reinforced in the context of primary dysmenorrhea (PDM), one of the most prevalent gynaecological complaints experienced by women of reproductive age. Altogether, 29 women with moderate‐to‐severe PDM were included in this study. Arterial spin labelling was used to quantify the cerebral blood flow (CBF) in each participant in both the pain‐free and painful phases. The pain catastrophizing scale (PCS) was completed in two phases, and the Short‐Form McGill Pain Questionnaire was completed in the painful phase. Compared with pain catastrophizing in the pain‐free phase (PCSpf), pain catastrophizing in the painful phase (PCSp) is higher and positively correlated with the composite factor of menstrual pain. CBF analysis indicated that the PCSp is positively associated with CBF in the frontal cortex, hippocampus and amygdala. The reinforcement of pain catastrophizing correlates with CBF in the prefrontal cortex. Specifically, the medial prefrontal cortex, which correlates with pain state, plays a crucial role in mediating the reinforcing effect of pain in the PCSp. These results promote the mechanical comprehension of pain catastrophizing management in individuals with chronic pain. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a prevalent mental health condition characterized by persistent feelings of sadness and hopelessness, affecting millions globally. The precise molecular mechanisms underlying MDD remain elusive, necessitating comprehensive investigations. Our study integrates transcriptomic analysis, functional assays, and computational modeling to explore the molecular landscape of MDD, focusing on the DLPFC. We identify key genomic alterations and co-expression modules associated with MDD, highlighting potential therapeutic targets. Functional enrichment and protein–protein interaction analyses emphasize the role of astrocytes in MDD progression. Machine learning is employed to develop a predictive model for MDD risk assessment. Single-cell and spatial transcriptomic analyses provide insights into cell type–specific expression patterns, particularly regarding astrocytes. We have identified significant genomic alterations and co-expression modules associated with MDD in the DLPFC. Key genes involved in neuroactive ligand-receptor interaction pathways, notably in astrocytes, have been highlighted. Additionally, we developed a predictive model for MDD risk assessment based on selected key genes. Single-cell and spatial transcriptomic analyses underscored the role of astrocytes in MDD. Virtual screening of compounds targeting GPR37L1, KCNJ10, and PPP1R3C proteins has identified potential therapeutic candidates. In summary, our comprehensive approach enhances the understanding of MDD's molecular underpinnings and offers promising opportunities for advancing therapeutic interventions, ultimately aiming to alleviate the burden of this debilitating mental health condition. Key messages: Our investigation furnishes insightful revelations concerning the dysregulation of astrocyte-associated processes in MDD. We have pinpointed specific genes, namely KCNJ10, PPP1R3C, and GPR37L1, as potential candidates warranting further exploration and therapeutic intervention. We incorporate a virtual screening of small molecule compounds targeting KCNJ10, PPP1R3C, and GPR37L1, presenting a promising trajectory for drug discovery in MDD. [ABSTRACT FROM AUTHOR]

Cochlear implants (CIs) are the most successful neural prostheses, enabling individuals with severe to profound hearing loss to access sounds and understand speech. While CI has demonstrated success, speech perception outcomes vary largely among CI listeners, with significantly reduced performance in noise. This review paper summarizes prior findings on speech-evoked cortical activities in adult CI listeners using functional near-infrared spectroscopy (fNIRS) to understand (a) speech-evoked cortical processing in CI listeners compared to normal-hearing (NH) individuals, (b) the relationship between these activities and behavioral speech recognition scores, (c) the extent to which current fNIRS-measured speech-evoked cortical activities in CI listeners account for their differences in speech perception, and (d) challenges in using fNIRS for CI research. Compared to NH listeners, CI listeners had diminished speech-evoked activation in the middle temporal gyrus (MTG) and in the superior temporal gyrus (STG), except one study reporting an opposite pattern for STG. NH listeners exhibited higher inferior frontal gyrus (IFG) activity when listening to CI-simulated speech compared to natural speech. Among CI listeners, higher speech recognition scores correlated with lower speech-evoked activation in the STG, higher activation in the left IFG and left fusiform gyrus, with mixed findings in the MTG. fNIRS shows promise for enhancing our understanding of cortical processing of speech in CI listeners, though findings are mixed. Challenges include test-retest reliability, managing noise, replicating natural conditions, optimizing montage design, and standardizing methods to establish a strong predictive relationship between fNIRS-based cortical activities and speech perception in CI listeners. [ABSTRACT FROM AUTHOR]

This study undertook neuropharmacological research on the clinical course of controlled medication discontinuation to guide practitioners who are considering stopping medications for youths with attention-deficit hyperactivity disorder (ADHD). This study analyzed the data for 14 ADHD children (12 male and 2 female) in two datasets: The children prescribed methylphenidate (MPH) were at an initial mean age of 7.5 years (SD = 1.70, range: 6–11) with a mean ADHD-Rating Score (ADHD-RS) of 26.6 (SD = 8.64, range 15–40). The children who discontinued MPH based on clinical judgment were at a mean age of 12.21 years (SD = 2.12, range: 8–15) with a mean ADHD-RS of 15.9 (SD = 6.86, range 5–27). The go/no-go task was used to assess response inhibition, while functional near-infrared spectroscopy (fNIRS) was used to measure cerebral hemodynamics. Oxygenated hemoglobin (Oxy-Hb) values from fNIRS data were analyzed for each subject, focusing on past and current measurements. Baseline was set at 10 s pre-task, with interval means from 4 to 24 s analyzed. One-sample t -tests were used to evaluate brain activity magnitude. The results of the study demonstrate that the children who had discontinued the medication exhibited activation in specific brain regions including the frontopolar cortex and the right ventrolateral prefrontal cortex. Activation (t = 2.363, p = 0.034, Cohen's d = 0.632) was found especially in the right dorsolateral prefrontal cortex during the performance of the go/no-go task. These activated areas were consistent with those observed in a previous study comparing brain activity during a go/no-go task between children with ADHD and healthy children. The present study showed differences in cerebral hemodynamics before and after discontinuation of MPH in ADHD children whose ADHD symptoms did not recur after MPH was discontinued. In the near future, further investigations that include control groups will be conducted to demonstrate the effects of MPH prior to discontinuation based on the changes in cerebral blood flow in the right prefrontal cortex, which is involved in behavioral inhibition, as observed in this study. This and future research will facilitate the development of criteria for discontinuing treatment. [ABSTRACT FROM AUTHOR]

Unitization – the fusion of objects into a single unit through an action/consequence sequence – can mitigate relational memory impairments, but the circumstances under which unitization is effective are unclear. Using transverse patterning (TP), we compared unitization (and its component processes of fusion, motion, and action/consequence) with extended practice on relational learning and transfer in older adults and neuropsychological cases with lesions (to varying extents) in the medial prefrontal cortex (mPFC) or hippocampus/medial temporal lobe (HC/MTL). The latter included a person with bilateral HC lesions primarily within the dentate gyrus. For older adults, TP accuracy increased, and transfer benefits were observed, with extended practice and unitization. Broadly, the lesion cases did not benefit from either extended practice or unitization, suggesting the mPFC and dentate gyrus play important roles in relational memory and in unitization. The results suggest that personalized strategy interventions must align with the cognitive and neural profiles of the user. [ABSTRACT FROM AUTHOR]

Intact executive functions are required for proper performance of cognitive tasks and relies on balance of excitatory and inhibitory (E/I) transmission in the medial prefrontal cortex (mPFC). Hypofrontality is a state of decreased activity in the mPFC and is seen in several neuropsychiatric conditions, including substance use disorders. People who chronically use methamphetamine (meth) develop hypofrontality and concurrent changes in cognitive processing across several domains. Despite the fact that there are sex difference in substance use disorders, few studies have considered sex as a biological variable regarding meth-mediated hypoactivity in mPFC and concurrent cognitive deficits. Hypofrontality along with changes in cognition are emulated in rodent models following repeated meth administration. Here, we used a meth sensitization regimen to study sex differences in a Temporal Order Memory (TOM) task following short (7 days) or prolonged (28 days) periods of abstinence. GABAergic transmission, GABAA receptor (GABAAR) and GABA Transporter (GAT) mRNA expression in the mPFC were evaluated with patch-clamp recordings and RT-qPCR, respectively. Both sexes sensitized to the locomotor activating effects of meth, with the effect persisting in females. After short abstinence, males and females had impaired TOM and increased GABAergic transmission. Female rats recovered from these changes after prolonged abstinence, whereas male rats showed enduring changes. In general, meth appears to elicit an overall decrease in GABAAR expression after short abstinence; whereas GABA transporters are decreased in meth female rats after prolonged abstinence. These results show sex differences in the long-term effects of repeated meth exposure and suggest that females have neuroprotective mechanisms that alleviate some of the meth-mediated cognitive deficits. [ABSTRACT FROM AUTHOR]

The Supplementary Motor Area (SMA), a relatively large brain structure predominantly located along the interhemispheric fissure, is an established target for repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Obsessive-Compulsive Disorder (OCD). We investigated the feasibility, safety, and efficacy of targeting SMA using a double-cone "deep" TMS coil compared to conventional figure-eight coil for treatment of OCD with comorbid Major Depressive Disorder (MDD). Sixty-two patients with treatment-resistant OCD and comorbid MDD participated in the study. All patients received high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) with a figure-eight coil (MagVenture B70), followed by 1 Hz rTMS over the bilateral SMA using either the B70 (N = 25) or double-cone deep coil (MagVenture DB80) (n = 23) for 36 treatment sessions. Weekly clinical assessments were conducted. Subjects overall had significant reductions in OCD and depressive symptom severity at the primary endpoint. Subjects stimulated at SMA with the double-cone deep coil had statistically significantly lesser reductions in overall OCD and depression symptom severity compared to the figure-eight group. The intensity of stimulation at SMA was significantly greater with the double-cone deep than figure-eight coil and e-field modeling showed that it affected broader regions beyond SMA (off-target stimulation). There was no significant difference in reported tolerability between groups. SMA stimulation using either a double-cone deep or conventional figure-of-eight coil was safe and was associated with a significant reduction in comorbid OCD and depression symptoms, but the higher intensities of stimulation with the double-cone deep coil used in this study were significantly less clinically beneficial than figure-eight coil stimulation. [ABSTRACT FROM AUTHOR]

Patients with chronic insomnia exhibit varying degrees of cognitive dysfunction. Functional connectivity of different brain regions contributes to the understanding of underlying cognitive processes in the cerebral cortex. However, this has not yet been studied in patients with chronic insomnia. This study aimed to elucidate the differences between brain activity patterns in patients with chronic insomnia and healthy controls (HCs) using a verbal fluency task (VFT). We recruited 84 patients with chronic insomnia and 81 HCs. Oxy-haemoglobin (Oxy-Hb) concentrations in the brains of the participants were monitored using functional near-infrared spectroscopy (fNIRS) while performing the VFT. During the task period, no significant difference was observed between the VFT results of the two groups; patients with chronic insomnia showed significantly less cortical activation in haemodynamic responses of oxy-Hb at channels and brain regions mainly located in the prefrontal cortex compared to HCs (FDR-corrected p < 0.05). Moreover, the average channel-to-channel connectivity strength of patients in the chronic insomnia group was lower than that of those in the HC group (t = −6.717, p < 0.001). Our study provides neurological evidence for the dynamic detection of executive function in patients with chronic insomnia. Compared to HCs, patients with chronic insomnia exhibit weaker levels of brain activity and reduced task-related functional connectivity. [ABSTRACT FROM AUTHOR]

Schizophrenia is a severe psychiatric disorder associated with brain alterations at rest. Amplitude of low-frequency fluctuations (ALFF) and its fractional version (fALFF) have been widely used to investigate alterations in spontaneous brain activity in schizophrenia. However, results are still inconsistent. Furthermore, while these measurements are similar, they showed some differences, and no meta-analysis has been yet performed to compare them in schizophrenia. Thus, we conducted systematic research in five databases and in the grey literature to find articles investigating fALFF and/or ALFF alterations in schizophrenia. Two separate meta-analyses were performed using the SDM-PSI software to identify fALFF and ALFF alterations separately. Then, a conjunction analysis was conducted to determine congruent results between the two approaches. We found that patients with schizophrenia showed altered fALFF activity in the left insula/putamen, the right paracentral lobule and the left middle occipital gyrus compared to healthy individuals. Patients with schizophrenia exhibited ALFF alterations in the bilateral putamen, the bilateral caudate nucleus, the bilateral inferior frontal gyrus, the right precuneus, the right precentral gyrus, the left postcentral gyrus, the right posterior cingulate gyrus, compared to healthy controls. ALFF increased activity in the left putamen was higher in drug-naïve patients and was correlated with positive symptoms. The conjunction analysis revealed a spatial convergence between fALFF and ALFF studies in the left putamen. This left putamen cluster is part of the associative striatum. Its alteration in schizophrenia provides additional support to the influential aberrant salience hypothesis of psychosis. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a psychiatric disease that may follow traumatic exposure. Current treatments fail in about 30% of patients. Although repeated transcranial magnetic stimulation (rTMS) applied to the prefrontal cortex has been shown to be effective in the treatment of PTSD, the mechanisms need further investigation. Using a PTSD animal model, we verify the beneficial effect of rTMS, and explore the changes it induces on two putative PTSD mechanisms, GABA/glutamate neurotransmission and neuroinflammation. PTSD-like symptoms were elicited in twenty-six mice using a foot-shock conditioning procedure. Fourteen of the 26 were then treated using rTMS (12 were untreated). In the control group (n = 30), 18 were treated with rTMS and 12 were untreated. Animals were sacrificed after re-exposure. The infralimbic (IL) cortex, basolateral amygdala (BLA) and ventral CA1 (vCA1) were isolated using laser microdissection. mRNA was then investigated using PCR array analysis targeting GABA/glutamate and inflammatory pathways. The rTMS treatment significantly decreased the contextual fear memory phenotype. These changes were associated with reduced mRNA expression related to inflammation in the IL cortex and the vCA1, and lowered mRNA-related glutamate neurotransmission and increased GABA neurotransmission in the BLA. Our results suggest that our rTMS treatment was associated with local anti-inflammatory effects and limbic effects, which seemed to counteract PTSD effects. Several of these changes (both stress- and rTMS-induced) have implications for the drug sensitivity of limbic brain areas, and may help in the design of future therapeutic protocols. • rTMS focused on the prefrontal cortex (rTMS-PFC) decreased the fear memory phenotype. • rTMS-PFC was associated with lower infralimbic cortex and ventral CA1 inflammation-related mRNA levels. • rTMS-PFC was associated with higher GABA and lower glutamate neurotransmission-related mRNA in the basolateral amygdala. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic has caused some individuals to experience vicarious traumatization (VT), an adverse psychological reaction to those who are primarily traumatized, which may negatively impact one's mental health and well‐being and has been demonstrated to vary with personal trauma history. The neural mechanism of VT and how past trauma history affects current VT remain largely unknown. This study aimed to identify neurobiological markers that track individual differences in VT and reveal the neural link between childhood cumulative trauma (CCT) and VT. Methods: We used structural and resting‐state functional magnetic resonance imaging before the pandemic to identify prospective brain markers for COVID‐related VT by correlating individuals' VT levels during the pandemic with the gray matter volume (GMV) and seed‐based resting‐state functional connectivity (RSFC) and examined how these brain markers linked CCT to VT in a sample of general young adults (N = 115/100). Results: Whole‐brain GMV–behavior correlation analysis showed that VT was positively associated with GMV in the right dorsolateral prefrontal gyrus (DLPFC). Using the cluster derived from the GMV–behavior correlation analysis as the seed region, we further revealed that the RSFC between the right DLPFC and right precuneus was negatively associated with VT. Importantly, the right DLPFC volume and DLPFC‐precuneus RSFC mediated the effect of CCT on VT. These findings remained unaffected by factors such as family socioeconomic status, other stressful life events, and general mental health. Conclusions: Overall, our study presents structural and functional brain markers for VT and highlights these brain‐based markers as a potential neural mechanism linking CCT to COVID‐related VT, which has implications for treating and preventing the development of trauma‐related mental disorders. [ABSTRACT FROM AUTHOR]

Objective: Studies using proton magnetic resonance spectroscopy reveal substantial inconsistencies in the levels of brain glutamate, glutamine and glutamate + glutamine across schizophrenia spectrum disorders. This systematic review employs qualitative and quantitative methods to analyse the patterns and relationships between glutamatergic metabolites, schizophrenia spectrum disorders and brain regions. Methods: A literature search was conducted using various databases with keywords including glutamate, glutamine, schizophrenia, psychosis and proton magnetic resonance spectroscopy. Inclusion criteria were limited to case-control studies that reported glutamatergic metabolite levels in adult patients with a schizophrenia spectrum disorder diagnosis – i.e. first-episode psychosis, schizophrenia, treatment-resistant schizophrenia and/or ultra-treatment-resistant schizophrenia – using proton magnetic resonance spectroscopy at 3 T or above. Pooled study data were synthesized and analysed. Results: A total of 92 studies met the inclusion criteria, including 2721 healthy controls and 2822 schizophrenia spectrum disorder participants. Glu levels were higher in the basal ganglia, frontal cortex and medial prefrontal of first-episode psychosis participants, contrasting overall lower levels in schizophrenia participants. For Gln, strong differences in metabolite levels were evident in the basal ganglia, dorsolateral prefrontal cortex and frontal cortex, with first-episode psychosis showing significantly higher levels in the basal ganglia. In glutamate + glutamine, higher metabolite levels were found across schizophrenia spectrum disorder groups, particularly in the basal ganglia and dorsolateral prefrontal cortex of treatment-resistant schizophrenia participants. Significant relationships were found between metabolite levels and medication status, clinical measures and methodological variables. Conclusion: The review highlights abnormal glutamatergic metabolite levels throughout schizophrenia spectrum disorders and in specific brain regions. The review underscores the importance of standardized future research assessing glutamatergic metabolites using proton magnetic resonance spectroscopy due to considerable literature heterogeneity. [ABSTRACT FROM AUTHOR]

Adolescent food insecurity is a salient adversity hypothesized to affect neural systems associated with increased impulsive behavior. Family environments shape how adverse experiences influence development. In this study, hypotheses were tested regarding the conjoint effects of food insecurity and family flexibility on impulsivity via alterations in connectivity between regions within the salience and central executive networks. Such alterations are reflected in resting‐state functional connectivity (rsFC) metrics between the anterior insula (AI) and the middle frontal gyrus (MFG). Hypotheses were tested in a longitudinal moderated mediation model with two waves of data from 142 adolescents (Time 1 [T1] Mage = 12.89, SD = 0.85; Time 2 [T2] Mage = 15.01, SD = 1.07). Data on past‐year household food insecurity, family flexibility, and rsFC were obtained at T1. Impulsivity was self‐reported by the adolescent at T1 and T2. Findings revealed that high T1 left‐to‐left rsFC between the AI and MFG was associated with increased impulsivity at T2. The interaction of family flexibility and food insecurity was associated with AI and MFG rsFC. In the context of low family flexibility, food insecurity was linked to high levels of AI and MFG rsFC. Conversely, in the context of optimal family flexibility, food insecurity was associated with low levels of AI and MFG rsFC. Conditional indirect analysis suggests that the links among food insecurity, rsFC, and impulsive behavior depend on family flexibility. Research Highlights: Adolescent food insecurity was associated with anterior insula and middle frontal gyrus connectivity only at certain levels of family flexibility.High family flexibility attenuated the link between food insecurity and neural connectivity, while low levels of family flexibility increased this risk.High left anterior insula and left middle frontal gyrus connectivity was associated with increased impulsivity 1 year later. [ABSTRACT FROM AUTHOR]

Learning safe versus dangerous cues is crucial for survival. During development, parents can influence fear learning by buffering their children's stress response and increasing exploration of potentially aversive stimuli. Rodent findings suggest that these behavioral effects are mediated through parental presence modulation of the amygdala and medial prefrontal cortex (mPFC). Here, we investigated whether similar parental modulation of amygdala and mPFC during fear learning occurs in humans. Using a within‐subjects design, behavioral (final N = 48, 6–17 years, mean = 11.61, SD = 2.84, 60% females/40% males) and neuroimaging data (final N = 39, 6–17 years, mean = 12.03, SD = 2.98, 59% females/41% males) were acquired during a classical fear conditioning task, which included a CS+ followed by an aversive noise (US; 75% reinforcement rate) and a CS−. Conditioning occurred once in physical contact with the participant's parent and once alone (order counterbalanced). Region of interest analyses examined the unconditioned stress response by BOLD activation to the US (vs. implicit baseline) and learning by activation to the CS+ (vs. CS−). Results showed that during US presentation, parental presence reduced the centromedial amygdala activity, suggesting buffering of the unconditioned stress response. In response to learned stimuli, parental presence reduced mPFC activity to the CS+ (relative to the CS−), although this result did not survive multiple comparisons' correction. These preliminary findings indicate that parents modulate amygdala and mPFC activity during exposure to unconditioned and conditioned fear stimuli, potentially providing insight into the neural mechanisms by which parents act as a social buffer during fear learning. Research Highlights: This study used a within‐participant experimental design to investigate how parental presence (vs. absence) affects youth's neural responses in a classical fear conditioning task.Parental presence reduced the youth's centromedial amygdala activation to the unconditioned stimulus (US), suggesting parental buffering of the neural unconditioned response (UR).Parental presence reduced the youth's mPFC activation to a conditioned threat cue (CS+) compared to a safety cue (CS−), suggesting possible parental modulation of fear learning. [ABSTRACT FROM AUTHOR]

Infancy is a sensitive period of development, during which experiences of parental care are particularly important for shaping the developing brain. In a longitudinal study of N = 95 mothers and infants, we examined links between caregiving behavior (maternal sensitivity observed during a mother–infant free‐play) and infants' neural response to emotion (happy, angry, and fearful faces) at 5 and 7 months of age. Neural activity was assessed using functional Near‐Infrared Spectroscopy (fNIRS) in the dorsolateral prefrontal cortex (dlPFC), a region involved in cognitive control and emotion regulation. Maternal sensitivity was positively correlated with infants' neural responses to happy faces in the bilateral dlPFC and was associated with relative increases in such responses from 5 to 7 months. Multilevel analyses revealed caregiving‐related individual differences in infants' neural responses to happy compared to fearful faces in the bilateral dlPFC, as well as other brain regions. We suggest that variability in dlPFC responses to emotion in the developing brain may be one correlate of early experiences of caregiving, with implications for social‐emotional functioning and self‐regulation. Research Highlights: Infancy is a sensitive period of brain development, during which experiences with caregivers are especially important.This study examined links between sensitive maternal care and infants' neural responses to emotion at 5–7 months of age, using functional near‐infrared spectroscopy (fNIRS).Experiences of sensitive care were associated with infants' neural responses to emotion—particularly happy faces—in the dorsolateral prefrontal cortex. [ABSTRACT FROM AUTHOR]

Memory impairment is one of the main characteristics of postoperative cognitive dysfunction. It remains elusive how postoperative pathological changes of the brain link to the memory impairment. The clinical setting of perioperation was mimicked via partial hepatectomy under sevoflurane anaesthesia together with preoperative restraint stress (Hep‐Sev‐stress) in mice. Memory changes were assessed with fear conditioning. The medial prefrontal cortex (mPFC)‐dorsal hippocampus connectivity was evaluated with injecting neurotracer 28 days before surgery. Astrocytic activation was limited via injecting AAV‐GFAP‐hM4Di‐eGFP into the mPFC. Astrocytic and microglial phagocytosis of synapses were visualised with co‐labelling hippocampal neuronal axon terminals with PSD‐95 and S100β or Iba1. Neuroinflammation and oxidative stress status were also detected. Hep‐Sev‐stress impaired the memory consolidation (mean [standard error], 49.91 [2.55]% vs. 35.40 [3.97]% in the contextual memory, p = 0.007; 40.72 [2.78]% vs. 27.77 [2.22]% in cued memory, p = 0.002) and the cued memory retrieval (39.00 [3.08]% vs. 24.11 [2.06]%, p = 0.001) in mice when compared with these in the naïve controls. Hep‐Sev‐stress damaged the connectivity from the dorsal hippocampus to mPFC but not from the mPFC to the dorsal hippocampus and increased the astrocytic but not microglial phagocytosis of hippocampal neuronal axon terminals in the mPFC. The intervention also induced neuroinflammation and oxidative stress in the dorsal hippocampus and the mPFC in a regional‐dependent manner. Limiting astrocyte activation in the mPFC alleviated memory consolidation impairment induced by Hep‐Sev‐stress. Postoperative memory consolidation was impaired due to astrocytic phagocytosis‐induced connectivity injury from the dorsal hippocampus to the medial prefrontal cortex. [ABSTRACT FROM AUTHOR]

The subdivisions of the extended cingulate cortex of the human brain are implicated in a number of high-level behaviors and affected by a range of neuropsychiatric disorders. Its anatomy, function, and response to therapeutics are often studied using non-human animals, including the mouse. However, the similarity of human and mouse frontal cortex, including cingulate areas, is still not fully understood. Some accounts emphasize resemblances between mouse cingulate cortex and human cingulate cortex while others emphasize similarities with human granular prefrontal cortex. We use comparative neuroimaging to study the connectivity of the cingulate cortex in the mouse and human, allowing comparisons between mouse 'gold standard' tracer and imaging data, and, in addition, comparison between the mouse and the human using comparable imaging data. We find overall similarities in organization of the cingulate between species, including anterior and midcingulate areas and a retrosplenial area. However, human cingulate contains subareas with a more fine-grained organization than is apparent in the mouse and it has connections to prefrontal areas not present in the mouse. Results such as these help formally address between-species brain organization and aim to improve the translation from preclinical to human results. [ABSTRACT FROM AUTHOR]

Investigating evolutionary changes in frontal cortex microstructure is crucial to understanding how modifications of neuron and axon distributions contribute to phylogenetic variation in cognition. In the present study, we characterized microstructural components of dorsolateral prefrontal cortex, orbitofrontal cortex, and primary motor cortex from 14 primate species using measurements of neuropil fraction and immunohistochemical markers for fast-spiking inhibitory interneurons, large pyramidal projection neuron subtypes, serotonergic innervation, and dopaminergic innervation. Results revealed that the rate of evolutionary change was similar across these microstructural variables, except for neuropil fraction, which evolves more slowly and displays the strongest correlation with brain size. We also found that neuropil fraction in orbitofrontal cortex layers V–VI was associated with cross-species variation in performance on experimental tasks that measure self-control. These findings provide insight into the evolutionary reorganization of the primate frontal cortex in relation to brain size scaling and its association with cognitive processes. [ABSTRACT FROM AUTHOR]

Similarities and differences in brain structure and function across species are of major interest in systems neuroscience, comparative biology, and brain mapping. Recently, increased emphasis has been placed on tertiary sulci, which are shallow indentations of the cerebral cortex that appear last in gestation, continue to develop after birth, and are largely either human or hominoid specific. While tertiary sulcal morphology in lateral prefrontal cortex (LPFC) has been linked to functional representations and cognition in humans, it is presently unknown if small and shallow LPFC sulci also exist in non-human hominoids. To fill this gap in knowledge, we leveraged two freely available multimodal datasets to address the following main question: Can small and shallow LPFC sulci be defined in chimpanzee cortical surfaces from human predictions of LPFC tertiary sulci? We found that 1–3 components of the posterior middle frontal sulcus (pmfs) in the posterior middle frontal gyrus are identifiable in nearly all chimpanzee hemispheres. In stark contrast to the consistency of the pmfs components, we could only identify components of the paraintermediate frontal sulcus (pimfs) in two chimpanzee hemispheres. Putative LPFC tertiary sulci were relatively smaller and shallower in chimpanzees compared to humans. In both species, two of the pmfs components were deeper in the right compared to the left hemisphere. As these results have direct implications for future studies interested in the functional and cognitive role of LPFC tertiary sulci, we share probabilistic predictions of the three pmfs components to guide the definitions of these sulci in future studies. [ABSTRACT FROM AUTHOR]

• Identified 1169 transcriptionally altered genes (TAGs) linked to major depressive disorder. • Nearly 50% of TAGs exhibited transcript-level alterations, primarily in prefrontal areas. • We identified evidence for a systematic transcript-level alteration in MDD, which follows a sex-specific pattern. Major depressive disorder (MDD) is a leading global cause of disability, being more prevalent in females, possibly due to molecular and neuronal pathway differences between females and males. However, the connection between transcriptional changes and MDD remains unclear. We identified transcriptionally altered genes (TAGs) in MDD through gene and transcript expression analyses, focusing on sex-specific differences. Analyzing 263 brain samples from both sexes, we conducted differential gene expression, differential transcript expression, and differential transcript usage analyses, revealing 1169 unique TAGs, primarily in the prefrontal areas, with nearly half exhibiting transcript-level alterations. Females showed notable RNA splicing and export process disruptions in the orbitofrontal cortex, alongside altered DDX39B gene expression in five of the six brain regions in both sexes. Our findings suggest that disruptions in RNA processing pathways may play a vital role in MDD. [ABSTRACT FROM AUTHOR]

• Age-related SFC changes in specific brain regions are related to cognitive decline. • Elevated SFC of thalamus partially mediates age-related cognitive decline. • Elevated SFC of PFC partially mediates decline in executive function. Normal aging is accompanied by changes in brain structure and function associated with cognitive decline. Structural and functional abnormalities, particularly the prefrontal cortex (PFC) and subcortical regions, contributed to cognitive aging. However, it remains unclear how the synchronized changes in structure and function of individual brain regions affect the cognition in aging. Using 3D T1-weighted structural data and movie watching functional magnetic resonance imaging data in a sample of 422 healthy individuals (ages from 18 to 87 years), we constructed regional structure–function coupling (SFC) of cortical and subcortical regions by quantifying the distribution similarity of gray matter volume (GMV) and amplitude of low-frequency fluctuation (ALFF). Further, we investigated age-related changes in SFC and its relationship with cognition. With aging, increased SFC localized in PFC, thalamus and caudate nucleus, decreased SFC in temporal cortex, lateral occipital cortex and putamen. Moreover, the SFC in the PFC was associated with executive function and thalamus was associated with the fluid intelligence, and partially mediated age-related cognitive decline. Collectively, our results highlight that tighter structure–function synchron of the PFC and thalamus might contribute to age-related cognitive decline, and provide insight into the substrate of the thalamo-prefrontal pathway with cognitive aging. [ABSTRACT FROM AUTHOR]

• Patients with PD with constipation had more serious motor and non-motor symptoms. • Emotional and cognitive impairments are related to constipation in patients with PD. • PD patients with constipation have abnormal brain functional activity & connectivity. • Insula and orbitofrontal cortex are involved in the regulation of constipation in PD. Constipation frequently occurs in patients with Parkinson's disease (PD) and may be related to cognitive and emotional disorders. The aim of this study is to investigate the clinical and brain functional characteristics of patients with PD presenting with constipation. The motor and non-motor symptoms of patients with PD were evaluated, and a resting-state functional magnetic resonance imaging (RS-fMRI) study was conducted based on propensity score matching. Alterations in brain function were analyzed using regional homogeneity (ReHo) and functional connectivity (FC). Compared with patients without constipation (PD-NC group), patients with constipation (PD-C group) had more serious motor and non-motor symptoms (including cognitive and emotional disorders along with visual hallucinations). Further, emotional and cognitive disorders were correlated with the occurrence of constipation in patients with PD. Compared with the PD-NC group, the PD-C group showed a reduced ReHo of the right insula and bilateral orbitofrontal cortex (OFC), increased ReHo of the left postcentral gyrus, and enhanced FC between the right OFC and the left middle temporal gyrus (MTG) and middle occipital gyrus (MOG). Additionally, the activity of the OFC and insula was significantly correlated with the constipation, mood, and cognitive levels of patients with PD. Constipation in patients with PD is closely related to emotional and cognitive impairments, abnormal activity and FC of brain regions such as the right insula and bilateral OFC may play an important role in this. [ABSTRACT FROM AUTHOR]

• 12 studies have examined links between air pollutants and cortical thickness. • PM 2.5 was the most studied pollutant and impactful on decreasing cortical thickness. • Some studies reported both regional increasing and decreasing cortical thickness. • Further research is needed examining life course pollution and cortical thickness. Increasing research has focused on the impact of air pollution on brain health. As the prevalence of air pollution is increasing alongside other environmental harms, the importance of studying the effects of these changes on human health has become more significant. Additionally, gaining insight into how air pollution exposure, measured at different points in the lifespan, can affect brain structure is critical, as this could be a precursor to cognitive decline later in life. The purpose of this review was to synthesize the literature on the association between air pollutant exposure and cortical thickness, a structural change with known associations with later cognition and neurodegenerative disease. After screening, twelve studies were included in this systematic review. Across a majority of studies, results suggest significant associations between increasing air pollution exposure and decreases in cortical thickness, primarily in areas such as prefrontal cortex, precuneus, and temporal regions of the brain. These results did differ somewhat between age groups and different air pollutants, with the most prominent results being found with exposure to PM 2.5 , the smallest particulate matter size included in the review. In the future, it is important to continue studying cortical thickness as it is essential to brain functioning and can be influential in disease progression. Furthermore, conducting more longitudinal studies in which air pollution is measured as a cumulation throughout the lifespan would help elucidate when exposure is most impactful and when brain structural changes become observable. [ABSTRACT FROM AUTHOR]

• A reduced functional connectivity of the olfactory system is observed in PD. • Hyposmia and decreased functional connectivity is also present in MCI. • Males showed increased functional connectivity than females in OFC. • Decreased functional connectivity particularly involves the limbic system. • Functional connectivity of olfactory network can help to identify PD. Olfactory dysfunction is an early sign of such neurodegenerative diseases as Parkinson's (PD) and Alzheimer's (AD), and is often present in Mild Cognitive Impairment (MCI), a precursor of AD. Understanding neuro-temporal relationships, i.e., functional connectivity, between olfactory eloquent structures in such disorders, could shed light on their basic pathophysiology. To this end, we employed region-based analyses using resting-state functional magnetic resonance imaging (rs-fMRI) obtained from cognitively normal (CN), MCI, and PD patients with cognitive impairment (PD-CogImp). Using machine learning (linear and ensemble learning), we determined whether the identified functional patterns could classify abnormal function from normal function. Olfaction, as measured by objective testing, was found to be most strongly associated with diagnostic status, emphasizing the fundamental association of this primary sensory system with these conditions. Consistently lower functional connectivity was observed in the PD-CogImp cohort compared to the CN cohort among all identified brain regions. Differences were also found between PD-CogImp and MCI at the level of the orbitofrontal and cingulate cortices. MCI and CN subjects had different functional connectivity between the posterior orbitofrontal cortex and thalamus. Regardless of study group, males showed significantly higher connectivity than females in connections involving the orbitofrontal cortex. The logistic regression model trained using the top discriminatory features revealed that caudate was the most involved olfaction-related brain structure (accuracy = 0.88, Area under the Receiver operator characteristic curve of 0.90). In aggregate, our study demonstrates that resting functional connectivity among olfactory eloquent structures has potential value in better understanding the pathophysiology of several neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Depression and anxiety are prevalent neuropsychiatric conditions among patients with Parkinson's disease (PD), which may manifest prior to motor symptoms. As levodopa, a prominent treatment for PD motor symptoms, provides few benefits for mood-related abnormalities, tackling non-motor symptoms is particularly important. AdipoRon (Ad), an adiponectin agonist, has demonstrated neuroprotective effects by suppressing neuroinflammatory responses and activating the AMPK/Sirt-1 signaling pathway. This study looked at the potential advantages and underlying mechanisms of intranasal Ad in a rat model of PD induced by 6-hydroxydopamine (6-OHDA). We found that Ad at doses of 1 and 10 µg for 21 days exhibited anxiolytic- and antidepressant effects in the open field (OF) test, elevated plus maze (EPM), sucrose splash test, and forced swimming test in a PD model caused by a unilateral 6-OHDA injection into the medial forebrain bundle (MFB). The Ad also lowered the levels of corticosterone in the blood, decreased inflammasome components (NLRP3, caspase 1, and IL-1β), and increased Sirt-1 protein levels in the prefrontal cortex (PFC) of PD rats. We conclude that Ad ameliorates anxious and depressive-like behaviors in the PD rat model through stimulating the AMPK/Sirt-1 signaling and blocking the NLRP3 inflammasome pathways in the PFC. [ABSTRACT FROM AUTHOR]

Anxiety is a common symptom of several mental health disorders and adversely affects motivated behaviors. Anxiety can emerge from associating risk of future harm while engaged in goal-guided actions. Using a recently developed behavioral paradigm to model this aspect of anxiety, we investigated the role of 2 cortical subregions, the prelimbic medial frontal cortex (PL) and lateral orbitofrontal cortex (lOFC), which have been implicated in anxiety and outcome expectation, in flexible representation of actions associated with harm risk. A seek-take reward-guided instrumental task design was used to train animals (N = 8) to associate the seek action with a variable risk of punishment. After learning, animals underwent extinction training for this association. Fiber photometry was used to measure and compare neuronal activity in the PL and lOFC during learning and extinction. Animals increased action suppression in response to punishment contingencies. This increase dissipated after extinction training. These behavioral changes were associated with region-specific changes in neuronal activity. PL neuronal activity preferentially adapted to the threat of punishment, whereas lOFC activity adapted to safe aspects of the task. Moreover, correlated activity between these regions was suppressed during actions associated with harm risk, suggesting that these regions may guide behavior independently under anxiety. These findings suggest that the PL and lOFC serve distinct but complementary roles in the representation of learned anxiety. This dissociation may provide a mechanism to explain how overlapping cortical systems are implicated in reward-guided action execution during anxiety. [ABSTRACT FROM AUTHOR]

• Prenatal multispecies probiotics shape offspring emotional development. • Enduring effects on adult offspring gut microbiota by prenatal probiotic exposure. • Prenatal probiotics upregulate genes critical for gut and blood–brain barrier function. • IL-10 and the peptidoglycan transporter PepT1 showed sustained upregulation. • Males are more sensitive to prenatal multispecies probiotic exposure than females. Recent research highlights the pivotal role of the maternal gut microbiome during pregnancy in shaping offspring neurodevelopment. In this study, we investigated the impact of maternal intake of a multispecies probiotic formulation during a critical prenatal window (from gestational day 6 until birth) on neurodevelopmental trajectories in mice. Our findings demonstrate significant and persistent benefits in emotional behavior, gut microbiota composition, and expression of tight junction-related genes, particularly in male offspring, who exhibited heightened sensitivity to the probiotic intervention compared to females. Additionally, we observed elevated gene expression levels of the anti-inflammatory cytokine IL-10 and the oxytocin receptor (Oxtr) in the prefrontal cortex (PFC) of exposed juvenile offspring; however, these changes persisted only in the adult male offspring. Furthermore, the sustained increase in the expression of the proton-coupled oligopeptide transporter 1 (PepT1), which is involved in the transport of bacterial peptidoglycan motifs, in the PFC of exposed male offspring suggests a potential mechanistic pathway underlying the observed sex-dependent effects on behavior and gene expression. These results underscore the potential of prenatal multispecies probiotic interventions to promote long-term neurodevelopmental outcomes, with implications for precision microbial reconstitution aimed at promoting healthy neurodevelopment and behavior. [ABSTRACT FROM AUTHOR]

• Low-dose LPS pretreatment prevents mSPS-induced anxiety/fear-like behaviors. • 10-day interval abolishes preventive effects of LPS on anxiety/fear-like behavior. • A second LPS injection produces preventive effects on anxiety/fear-like behavior. • Repeated LPS injection 10 days before mSPS prevents anxiety/fear-like behavior. • Microglia mediate the preventive effect of LPS on anxiety/fear-like behavior. Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder associated with abnormally elevated neuroinflammatory responses. Suppression of neuroinflammation is considered to be effective in ameliorating PTSD-like behaviors in rodents. Since pre-stimulation of microglia prior to stress exposure can prevent neuroinflammation, we hypothesized that pre-stimulation of microglia may prevent PTSD in animals. The results show that a single injection of a classical immune stimulant, lipopolysaccharide (LPS), at 50, 100 or 500, but not 10 μg/kg, one day before stress exposure, prevented the anxiety- and fear-like behaviors induced by modified single prolonged stress (mSPS). The time-dependent analysis shows that a single injection of LPS (100 μg/kg) either one or five, but not ten, days before stress prevented mSPS-induced anxiety- and fear-like behaviors. A second low-dose LPS injection 10 days after the first injection or a repeated LPS injection (4 ×) 10 days before stress induced tolerance to mSPS. Mechanistic studies show that a single injection of LPS one day before stress stimulation prevented mSPS-induced increases in levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6 mRNA in the hippocampus and medial prefrontal cortex. Inhibition of microglia by pretreatment with minocycline or depletion of microglia by PLX3397 abolished the preventive effect of low-dose LPS pre-injection on mSPS-induced anxiety- and fear-like behavior and neuroinflammatory responses. These results suggest that pre-stimulation of microglia may prevent the development of PTSD-like behaviors by attenuating the development of neuroinflammatory responses. This could help to develop new strategies to prevent the damaging effects of harmful stress on the brain. [ABSTRACT FROM AUTHOR]

Chronic insomnia disorder (CID) is commonly associated with mood disorders. The cingulate gyrus (CG) plays a critical role in the pathophysiology of CID and anxiety. However, the specific characteristics of altered brain networks in the CG in CID with anxiety remain unclear. This study aimed to investigate the characteristics of CG functional connectivity (FC) in CID with and without anxiety. Methods: Resting-state functional magnetic resonance imaging was conducted on 92 CID and 36 healthy controls (HC). CID was divided into CID with anxiety (CID-A, N = 37) and CID without anxiety (CID-NA, N = 55) groups based on anxiety scores. Using the Human Brainnetome Atlas, the subregion CG FC network was constructed. Compared with HC, CID showed significantly decreased CG FC with the precuneus, middle frontal gyrus (MFG), and hippocampus, while showing significantly increased CG FC with the middle temporal gyrus (MTG)/superior temporal gyrus (STG). In contrast, CID-A showed significantly decreased CG FC with the salience network (insular, putamen) and default mode network (MTG/STG and inferior parietal lobule), while showing significantly increased CG FC with the thalamus and MFG compared to CID-NA. Further, CID-A and CID-NA could be classified with 84.21 % accuracy by using the CG FCs as features. Among these features, the CG FC with MFG, thalamus, and putamen had the highest contribution weights. This study revealed specific changes in the brain network of the CG subregion in CID-A. Understanding these CG FC alterations can help identify potential biomarkers specific to CID-A, which may be valuable for early detection and differentiation from other CID subtypes. • To explore the cingulate gyrus (CG) subregions FC alteration in CID with anxiety (CID-A). • CID-A shown specific CG FC with default mode network and salience network. • Machine learning with CG FC features classifies CID-A accurately at 84.21 %. • The CG subregional FC alterations may contribute to potential biomarkers for CID-A. [ABSTRACT FROM AUTHOR]