A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex.

The molecular organization of the human neocortex historically has been studied in the context of its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification of transcriptionally defined spatial domains that move beyond classic cytoarchitecture. We used the Visium spatial gene expression platform to generate a data-driven molecular neuroanatomical atlas across the anterior-posterior axis of the human dorsolateral prefrontal cortex. Integration with paired single-nucleus RNA-sequencing data revealed distinct cell type compositions and cell-cell interactions across spatial domains. Using PsychENCODE and publicly available data, we mapped the enrichment of cell types and genes associated with neuropsychiatric disorders to discrete spatial domains.

The Relationship of Anxious Arousal With Treatment of Dysphoria Using Virtual Reality Mindfulness and 2 Accelerated Transcranial Magnetic Stimulation Protocols.

Objective: This secondary analysis investigated the relationship of anxious arousal, as measured by the Tension Anxiety subscale of the Profile of Mood States (TA-POMS), to treatment outcome across diagnoses for each phase of the study. Sequential treatment phases of virtual reality (VR) mindfulness followed by left dorsolateral prefrontal cortex (dlPFC) accelerated transcranial magnetic stimulation (accel-TMS) and then dorsomedial prefrontal cortex (dmPFC) accel-TMS were used to treat dysphoria across diagnoses in an open trial from September 2021 to August 2023.Methods: The change in the TA-POMS subscale was compared to the percent change in primary clinician scale scores using a bivariate analysis. Baseline TA-POMS subscales were compared to treatment response using linear regression models to assess anxious arousal's impact on treatment outcome for the 3 phases. Significance was defined as P < .05, 2-tailed.Results: Twenty-three participants were enrolled in VR mindfulness, 19 in left dlPFC accel-TMS, and 12 in dmPFC accel TMS. Although the change in TA-POMS scores did not significantly correlate with the percent change in primary clinician scale ratings for the VR phase, they did for both the dlPFC (P = .041) and the dmPFC (P = .003) accel-TMS treatment phases. Importantly, baseline anxious arousal levels as measured by TA-POMS were not predictive of treatment outcome in any treatment phase.Conclusion: The outcome of accel-TMS treatment was not adversely affected by anxious arousal and similarly improved along with primary rating scales.Trial Registration: ClinicalTrials.gov identifier: NCT05061745.

A Pilot Study of High-Frequency Transcranial Magnetic Stimulation for Bipolar Depression.

Objective: Repetitive transcranial magnetic stimulation (rTMS) is a standard treatment approach for major depressive disorder. There is growing clinical experience to support the use of high-frequency left-sided rTMS in bipolar depression. This study collected open-label safety and effectiveness data in a sample of patients with bipolar depression.Methods: Thirty-one adults (13 male/ 18 female; mean age: 42.2 [14.3] years) with bipolar (I or II) depression verified by DSM-5 criteria were recruited at Sheppard Pratt and Mayo Clinic between August 2017 and February 2020 for rTMS. Standardized treatment protocols employed 6 weeks of 10-Hz rTMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4-second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥50% or score <10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.Results: The majority of patients with bipolar depression reached response (n = 27; 87.1%) and remission (n = 23; 74.2%). Older age and concurrent treatment with lithium were associated with higher MADRS scores throughout the treatment course (0.1 ± 0.05, P =.05; 4.05 ± 1.27, P = .003, respectively). Concurrent treatment with lamotrigine was associated with lower MADRS scores (-3.48 ± 1.26, P = .01). Treatment with rTMS was safe and well tolerated. There were no completed suicides, induced manic episodes, or other serious adverse events.Conclusion: Although preliminary, the present findings are encouraging regarding the safety and effectiveness of 10-Hz rTMS for bipolar depression.Trial Registration: ClinicalTrials.gov identifier: NCT02640950.

Quantitative proteomics of dorsolateral prefrontal cortex reveals an early pattern of synaptic dysmaturation in children with idiopathic autism.

Autism spectrum disorder (ASD) is a developmental disorder with a rising prevalence and unknown etiology presenting with deficits in cognition and abnormal behavior. We hypothesized that the investigation of the synaptic component of prefrontal cortex may provide proteomic signatures that may identify the biological underpinnings of cognitive deficits in childhood ASD. Subcellular fractions of synaptosomes from prefrontal cortices of age-, brain area-, and postmortem-interval-matched samples from children and adults with idiopathic ASD vs. controls were subjected to HPLC-tandem mass spectrometry. Analysis of data revealed the enrichment of ASD risk genes that participate in slow maturation of the postsynaptic density (PSD) structure and function during early brain development. Proteomic analysis revealed down regulation of PSD-related proteins including AMPA and NMDA receptors, GRM3, DLG4, olfactomedins, Shank1-3, Homer1, CaMK2α, NRXN1, NLGN2, Drebrin1, ARHGAP32, and Dock9 in children with autism (FDR-adjusted P < 0.05). In contrast, PSD-related alterations were less severe or unchanged in adult individuals with ASD. Network analyses revealed glutamate receptor abnormalities. Overall, the proteomic data support the concept that idiopathic autism is a synaptopathy involving PSD-related ASD risk genes. Interruption in evolutionarily conserved slow maturation of the PSD complex in prefrontal cortex may lead to the development of ASD in a susceptible individual.

Prefrontal tDCS modulates risk-taking in male violent offenders.

Detrimental decision-making is a major problem among violent offenders. Non-invasive brain stimulation offers a promising method to directly influence decision-making and has already been shown to modulate risk-taking in non-violent controls. We hypothesize that anodal transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex beneficially modulates the neural and behavioral correlates of risk-taking in a sample of violent offenders. We expect offenders to show more risky decision-making than non-violent controls and that prefrontal tDCS will induce stronger changes in the offender group. In the current study, 22 male violent offenders and 24 male non-violent controls took part in a randomized double-blind sham-controlled cross-over study applying tDCS over the right dorsolateral prefrontal cortex. Subsequently, participants performed the Balloon Analogue Risk Task (BART) during functional magnetic resonance imaging (fMRI). Violent offenders showed significantly less optimal decision-making compared to non-violent controls. Active tDCS increased prefrontal activity and improved decision-making only in violent offenders but not in the control group. Also, in offenders only, prefrontal tDCS influenced functional connectivity between the stimulated area and other brain regions such as the thalamus. These results suggest baseline dependent effects of tDCS and pave the way for treatment options of disadvantageous decision-making behavior in this population.

Sex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus.

Schizophrenia is a complex neuropsychiatric disorder with sexually dimorphic features, including differential symptomatology, drug responsiveness, and male incidence rate. Prior large-scale transcriptome analyses for sex differences in schizophrenia have focused on the prefrontal cortex. Analyzing BrainSeq Consortium data (caudate nucleus: n = 399, dorsolateral prefrontal cortex: n = 377, and hippocampus: n = 394), we identified 831 unique genes that exhibit sex differences across brain regions, enriched for immune-related pathways. We observed X-chromosome dosage reduction in the hippocampus of male individuals with schizophrenia. Our sex interaction model revealed 148 junctions dysregulated in a sex-specific manner in schizophrenia. Sex-specific schizophrenia analysis identified dozens of differentially expressed genes, notably enriched in immune-related pathways. Finally, our sex-interacting expression quantitative trait loci analysis revealed 704 unique genes, nine associated with schizophrenia risk. These findings emphasize the importance of sex-informed analysis of sexually dimorphic traits, inform personalized therapeutic strategies in schizophrenia, and highlight the need for increased female samples for schizophrenia analyses.

Prolonged intermittent theta burst stimulation targeting the left prefrontal cortex and cerebellum does not affect executive functions in healthy individuals.

Repetitive transcranial magnetic stimulation (rTMS) for alleviating negative symptoms and cognitive dysfunction in schizophrenia commonly targets the left dorsolateral prefrontal cortex (LDLPFC). However, the therapeutic effectiveness of rTMS at this site remains inconclusive and increasingly, studies are focusing on cerebellar rTMS. Recently, prolonged intermittent theta-burst stimulation (iTBS) has emerged as a rapid-acting form of rTMS with promising clinical benefits. This study explored the cognitive and neurophysiological effects of prolonged iTBS administered to the LDLPFC and cerebellum in a healthy cohort. 50 healthy participants took part in a cross-over study and received prolonged (1800 pulses) iTBS targeting the LDLPFC, cerebellar vermis, and sham iTBS. Mixed effects repeated measures models examined cognitive and event-related potentials (ERPs) from 2-back (P300, N200) and Stroop (N200, N450) tasks after stimulation. Exploratory non-parametric cluster-based permutation tests compared ERPs between conditions. There were no significant differences between conditions for behavioural and ERP outcomes on the 2-back and Stroop tasks. Exploratory cluster-based permutation tests of ERPs did not identify any significant differences between conditions. We did not find evidence that a single session of prolonged iTBS administered to either the LDLPFC or cerebellum could cause any cognitive or ERP changes compared to sham in a healthy sample.

The Effectiveness of Transcranial Direct Current Stimulation (tDCS) in Binge Eating Disorder (BED)-Review and Insight into the Mechanisms of Action.

INTRODUCTION: Binge eating disorder (BED) is the most common eating disorder among those contributing to the development of obesity, and thus acts as a significant burden on the lives and health of patients. It is characterized by complex neurobiology, which includes changes in brain activity and neurotransmitter secretion. Existing treatments are moderately effective, and so the search for new therapies that are effective and safe is ongoing. AIM AND METHODS: This review examines the use of transcranial direct current stimulation (tDCS) in the treatment of binge eating disorder. Searches were conducted on the PubMed/Medline, Research Gate, and Cochrane databases. RESULTS: Six studies were found that matched the review topic. All of them used the anodal stimulation of the right dorsolateral prefrontal cortex (DLPFC) in BED patients. tDCS proved effective in reducing food cravings, the desire to binge eat, the number of binging episodes, and food intake. It also improved the outcomes of inhibitory control and the treatment of eating disorder psychopathology. The potential mechanisms of action of tDCS in BED are explained, limitations in current research are outlined, and recommendations for future research are provided. CONCLUSIONS: Preliminary evidence suggests that the anodal application of tDCS to the right DLPFC reduces the symptoms of BED. However, caution should be exercised in the broader use of tDCS in this context due to the small number of studies performed and the small number of patients included. Future studies should incorporate neuroimaging and neurophysiological measurements to elucidate the potential mechanisms of action of tDCS in BED.

Cingulate microstimulation induces negative decision-making via reduced top-down influence on primate fronto-cingulo-striatal network.

The dorsolateral prefrontal cortex (dlPFC) is crucial for regulation of emotion that is known to aid prevention of depression. The broader fronto-cingulo-striatal (FCS) network, including cognitive dlPFC and limbic cingulo-striatal regions, has been associated with a negative evaluation bias often seen in depression. The mechanism by which dlPFC regulates the limbic system remains largely unclear. Here we have successfully induced a negative bias in decision-making in female primates performing a conflict decision-making task, by directly microstimulating the subgenual cingulate cortex while simultaneously recording FCS local field potentials (LFPs). The artificially induced negative bias in decision-making was associated with a significant decrease in functional connectivity from cognitive to limbic FCS regions, represented by a reduction in Granger causality in beta-range LFPs from the dlPFC to the other regions. The loss of top-down directional influence from cognitive to limbic regions, we suggest, could underlie negative biases in decision-making as observed in depressive states.

Elucidating the underlying components of metacognitive systematic bias in the human dorsolateral prefrontal cortex and inferior parietal cortex.

Metacognitive systematic bias impairs human learning efficiency, which is characterized by the inconsistency between predicted and actual memory performance. However, the underlying mechanism of metacognitive systematic bias remains unclear in existing studies. In this study, we utilized judgments of learning task in human participants to compare the neural mechanism difference in metacognitive systematic bias. Participants encoded words in fMRI sessions that would be tested later. Immediately after encoding each item, participants predicted how likely they would remember it. Multivariate analyses on fMRI data demonstrated that working memory and uncertainty decisions are represented in patterns of neural activity in metacognitive systematic bias. The available information participants used led to overestimated bias and underestimated bias. Effective connectivity analyses further indicate that information about the metacognitive systematic bias is represented in the dorsolateral prefrontal cortex and inferior parietal cortex. Different neural patterns were found underlying overestimated bias and underestimated bias. Specifically, connectivity regions with the dorsolateral prefrontal cortex, anterior cingulate cortex, and supramarginal gyrus form overestimated bias, while less regional connectivity forms underestimated bias. These findings provide a mechanistic account for the construction of metacognitive systematic bias.

Dopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo.

The polygenic architecture of schizophrenia implicates several molecular pathways involved in synaptic function. However, it is unclear how polygenic risk funnels through these pathways to translate into syndromic illness. Using tensor decomposition, we analyze gene co-expression in the caudate nucleus, hippocampus, and dorsolateral prefrontal cortex of post-mortem brain samples from 358 individuals. We identify a set of genes predominantly expressed in the caudate nucleus and associated with both clinical state and genetic risk for schizophrenia that shows dopaminergic selectivity. A higher polygenic risk score for schizophrenia parsed by this set of genes predicts greater dopamine synthesis in the striatum and greater striatal activation during reward anticipation. These results translate dopamine-linked genetic risk variation into in vivo neurochemical and hemodynamic phenotypes in the striatum that have long been implicated in the pathophysiology of schizophrenia.

Enhancement of phonemic verbal fluency in multilingual young adults by transcranial random noise stimulation.

Several studies have analyzed the effects of transcranial direct current stimulation on verbal fluency tasks in non-clinical populations. Nevertheless, the reported effects on verbal fluency are inconsistent. In addition, the effect of other techniques such as transcranial random noise stimulation (tRNS) on verbal fluency enhancement has yet to be studied in healthy multilingual populations. This study aims to explore the effects of tRNS on verbal fluency in healthy multilingual individuals. Fifty healthy multilingual (Spanish, English and Basque) adults were randomly assigned to a tRNS or sham group. Electrodes were placed on the left dorsolateral prefrontal cortex and left inferior frontal gyrus. All participants performed phonemic and semantic verbal fluency tasks before, during (online assessment) and immediately after (offline assessment) stimulation in three different languages. The results showed significantly better performance by participants who received tRNS in the phonemic verbal fluency tasks in Spanish (in the online and offline assessment) and English (in the offline assessment). No differences between conditions were found in Basque nor semantic verbal fluency. These findings suggests that tRNS on the left prefrontal cortex could help improve phonemic, yet not semantic, fluency in healthy multilingual adults.

Out-of-phase transcranial alternating current stimulation modulates the neurodynamics of inhibitory control.

Transcranial alternating current stimulation (tACS) is an efficient neuromodulation technique that enhances cognitive function in a non-invasive manner. Using functional magnetic resonance imaging, we investigated whether tACS with different phase lags (0° and 180°) between the dorsal anterior cingulate and left dorsolateral prefrontal cortices modulated inhibitory control performance during the Stroop task. We found out-of-phase tACS mediated improvements in task performance, which was neurodynamically reflected as putamen, dorsolateral prefrontal, and primary motor cortical activation as well as prefrontal-based top-down functional connectivity. Our observations uncover the neurophysiological bases of tACS-phase-dependent neuromodulation and provide a feasible non-invasive approach to effectively modulate inhibitory control.

Differential effects of high-definition transcranial direct current stimulation (HD-tDCS) on attentional guidance by working memory in males with substance use disorder according to memory modality.

Information stored in working memory can guide perception selection, and this process is modulated by cognitive control. Although previous studies have demonstrated that neurostimulation over the left dorsolateral prefrontal cortex (lDLPFC) contributes to restore cognitive control among individuals with substance use disorder (SUD), there remains an open question about the potential stimulation effects on memory-driven attention. To address this issue, the present study adopted a combined working memory/attention paradigm while employing high-definition transcranial direct current stimulation (HD-tDCS) to stimulate the lDLPFC. Observers were asked to maintain visual or audiovisual information in memory while executing a search task, while the validity of the memory contents for the subsequent search task could be either invalid or neutral. The results showed a faint memory-driven attentional suppression effect in sham stimulation only under the audiovisual condition. Moreover, anodal HD-tDCS facilitated attentional suppression effect in both the strength and temporal dynamics under the visual-only condition, whereas the effect was impaired or unchanged under the audiovisual condition. Surprisingly, cathodal HD-tDCS selectively improved temporal dynamics of the attentional suppression effect under the audiovisual condition. The present study revealed the differential enhancement of HD-tDCS on cognitive control over visual and audiovisual memory-driven attention among individuals with SUD.

Enhancing ventrolateral prefrontal cortex activation mitigates social pain and modifies subsequent social attitudes: Insights from TMS and fMRI.

Social pain, a multifaceted emotional response triggered by interpersonal rejection or criticism, profoundly impacts mental well-being and social interactions. While prior research has implicated the right ventrolateral prefrontal cortex (rVLPFC) in mitigating social pain, the precise neural mechanisms and downstream effects on subsequent social attitudes remain elusive. This study employed transcranial magnetic stimulation (TMS) integrated with fMRI recordings during a social pain task to elucidate these aspects. Eighty participants underwent either active TMS targeting the rVLPFC (n = 41) or control stimulation at the vertex (n = 39). Our results revealed that TMS-induced rVLPFC facilitation significantly reduced self-reported social pain, confirming the causal role of the rVLPFC in social pain relief. Functional connectivity analyses demonstrated enhanced interactions between the rVLPFC and the dorsolateral prefrontal cortex, emphasizing the collaborative engagement of prefrontal regions in emotion regulation. Significantly, we observed that negative social feedback led to negative social attitudes, whereas rVLPFC activation countered this detrimental effect, showcasing the potential of the rVLPFC as a protective buffer against adverse social interactions. Moreover, our study uncovered the impact role of the hippocampus in subsequent social attitudes, a relationship particularly pronounced during excitatory TMS over the rVLPFC. These findings offer promising avenues for improving mental health within the intricate dynamics of social interactions. By advancing our comprehension of the neural mechanisms underlying social pain relief, this research introduces novel intervention strategies for individuals grappling with social distress. Empowering individuals to modulate rVLPFC activation may facilitate reshaping social attitudes and successful reintegration into communal life.

Evoked oscillatory cortical activity during acute pain: Probing brain in pain by transcranial magnetic stimulation combined with electroencephalogram.

Temporal dynamics of local cortical rhythms during acute pain remain largely unknown. The current study used a novel approach based on transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) to investigate evoked-oscillatory cortical activity during acute pain. Motor (M1) and dorsolateral prefrontal cortex (DLPFC) were probed by TMS, respectively, to record oscillatory power (event-related spectral perturbation and relative spectral power) and phase synchronization (inter-trial coherence) by 63 EEG channels during experimentally induced acute heat pain in 24 healthy participants. TMS-EEG was recorded before, during, and after noxious heat (acute pain condition) and non-noxious warm (Control condition), delivered in a randomized sequence. The main frequency bands (α, ß1, and ß2) of TMS-evoked potentials after M1 and DLPFC stimulation were recorded close to the TMS coil and remotely. Cold and heat pain thresholds were measured before TMS-EEG. Over M1, acute pain decreased α-band oscillatory power locally and α-band phase synchronization remotely in parietal-occipital clusters compared with non-noxious warm (all p < .05). The remote (parietal-occipital) decrease in α-band phase synchronization during acute pain correlated with the cold (p = .001) and heat pain thresholds (p = .023) and to local (M1) α-band oscillatory power decrease (p = .024). Over DLPFC, acute pain only decreased ß1-band power locally compared with non-noxious warm (p = .015). Thus, evoked-oscillatory cortical activity to M1 stimulation is reduced by acute pain in central and parietal-occipital regions and correlated with pain sensitivity, in contrast to DLPFC, which had only local effects. This finding expands the significance of α and ß band oscillations and may have relevance for pain therapies.

The Important Role of the Right Dorsolateral Prefrontal Cortex in Conflict Adaptation: A Combined Voxel-Based Morphometry and Continuous Theta Burst Stimulation Study.

Humans can flexibly adjust their executive control to resolve conflicts. Conflict adaptation and conflict resolution are crucial aspects of conflict processing. Functional neuroimaging studies have associated the dorsolateral prefrontal cortex (DLPFC) with conflict processing, but its causal role remains somewhat controversial. Moreover, the neuroanatomical basis of conflict processing has not been thoroughly examined. In this study, the Stroop task, a well-established measure of conflict, was employed to investigate (1) the neuroanatomical basis of conflict resolution and conflict adaptation with the voxel-based morphometry analysis, (2) the causal role of DLPFC in conflict processing with the application of the continuous theta burst stimulation to DLPFC. The results revealed that the Stroop effect was correlated to the gray matter volume of the precuneus, postcentral gyrus, and cerebellum, and the congruency sequence effect was correlated to the gray matter volume of superior frontal gyrus, postcentral gyrus, and lobule paracentral gyrus. These findings indicate the neuroanatomical basis of conflict resolution and adaptation. In addition, the continuous theta burst stimulation over the right DLPFC resulted in a significant reduction in the Stroop effect of RT after congruent trials compared with vertex stimulation and a significant increase in the Stroop effect of accuracy rate after incongruent trials than congruent trials, demonstrating the causal role of right DLPFC in conflict adaptation. Moreover, the DLPFC stimulation did not affect the Stroop effect of RT and accuracy rate. Overall, our study offers further insights into the neural mechanisms underlying conflict resolution and adaptation.

Brain stimulation over the left DLPFC enhances motivation for effortful rewards in patients with major depressive disorder.

BACKGROUND: Amotivation is a typical feature in major depressive disorder (MDD), which produces reduced willingness to exert effort. The dorsolateral prefrontal cortex (DLPFC) is a crucial structure in goal-directed actions and therefore is a potential target in modulating effortful motivation. However, it remains unclear whether the intervention is effective for patients with MDD. METHODS: We employed transcranial magnetic stimulation (TMS), computational modelling and event-related potentials (ERPs) to reveal the causal relationship between the left DLPFC and motivation for effortful rewards in MDD. Fifty patients underwent both active and sham TMS sessions, each followed by performing an Effort-Expenditure for Rewards Task, during which participants chose and implemented between low-effort/low-reward and high-effort/high-reward options. RESULTS: The patients showed increased willingness to exert effort for rewards during the DLPFC facilitated session, compared with the sham session. They also had a trend in larger P3 amplitude for motivated attention toward chosen options, larger CNV during preparing for effort exertion, and larger SPN during anticipating a high reward. Besides, while behavior indexes for effortful choices were negatively related to depression severity in the sham session, this correlation was weakened in the active stimulation session. CONCLUSIONS: These findings provide behavioral, computational, and neural evidence for the left DLPFC on effortful motivation for rewards. Facilitated DLPFC improves motor preparation and value anticipation after making decisions especially for highly effortful rewards in MDD. Facilitated DLPFC also has a potential function in enhancing motivated attention during cost-benefit trade-off. This neuromodulation effect provides a potential treatment for improving motivation in clinics.

Consistently increased dorsolateral prefrontal cortex activity during the exposure to acute stressors.

Stress has a major impact on our mental health. Nonetheless, it is still not fully understood how the human brain responds to ongoing stressful events. Here, we aimed to determine the cortical dynamics during the exposure to ecologically valid, standardized stressors. To this end, we conducted 3 experiments in which healthy participants underwent the Trier Social Stress Test (experiments 1 and 2) and the Socially Evaluated Cold Pressor Test (experiment 3) or a respective control manipulation, while we measured their cortical activity using functional near-infrared spectroscopy. Increases in salivary cortisol and subjective stress levels confirmed the successful stress induction in all experiments. Results of experiment 1 showed significantly increased cortical activity, in particular in the dorsolateral prefrontal cortex, during the exposure to the Trier Social Stress Test. Experiment 2 replicated this finding and showed further that this stress-related increase in dorsolateral prefrontal cortex activity was transient and limited to the period of the Trier Social Stress Test. Experiment 3 demonstrated the increased dorsolateral prefrontal cortex activity during the Socially Evaluated Cold Pressor Test, suggesting that this increase is generalizable and not specific to the Trier Social Stress Test. Together, these data show consistently that dorsolateral prefrontal cortex activity is not reduced, as commonly assumed, but increased under stress, which may promote coping with the ongoing stressor.

Characteristics of oxyhemoglobin during the verbal fluency task in subthreshold depression: A multi-channel near-infrared spectroscopy study.

OBJECTIVE: Subthreshold depression is an essential precursor and risk factor for major depressive disorder, and its accurate identification and timely intervention are important for reducing the prevalence of major depressive disorder. Therefore, we used functional near-infrared spectroscopic imaging (fNIRS) to explore the characteristics of the brain neural activity of college students with subthreshold depression in the verbal fluency task. METHODS: A total of 72 subthreshold depressed college students (SDs) and 67 healthy college students (HCs) were recruited, and all subjects were subjected to a verbal fluency task (VFT) while a 53-channel fNIRS device was used to collect the subjects' cerebral blood oxygenation signals. RESULTS: The results of the independent samples t-test showed that the mean oxyhemoglobin in the right dorsolateral prefrontal (ch34, ch42, ch45) and Broca's area (ch51, ch53) of SDs was lower than that of HCs. The peak oxygenated hemoglobin of SDs was lower in the right dorsolateral prefrontal (ch34) and Broca's area (ch51, ch53).The brain functional connectivity strength was lower than that of HCs. Correlation analysis showed that the left DLPFC and Broca's area were significantly negatively correlated with the depression level. CONCLUSION: SDs showed abnormally low, inadequate levels of brain activation and weak frontotemporal brain functional connectivity. The right DLPFC has a higher sensitivity for the differentiation of depressive symptoms and is suitable as a biomarker for the presence of depressive symptoms. Dysfunction in Broca's area can be used both as a marker of depressive symptoms and as a biomarker, indicating the severity of depressive symptoms.