Prefrontal Cortex Research Articles

The protective effect of angiotensin II type I receptor blocker (valsartan) on behavioral impairment, NLRP3, BDNF, and oxidative stress in the brain tissue of ovariectomized female rats.

Depression and anxiety are common mental health disorders affecting thoughts, behaviors, and emotions. This study aimed to investigate the effect of the angiotensin II type I receptor blocker (AT1RB), valsartan, on menopause-induced depression and anxiety-like behaviors, and to elucidate possible mechanisms of action by measuring levels of nod-like receptor protein 3 (NLRP3), interleukin-1beta (IL-1β), brain-derived neurotrophic factor (BDNF), and oxidative stress in brain tissue. Thirty-two Wistar albino female rats were randomly divided into four groups (n = 8 per group): Control, AT1RB, OVX, and AT1RB + OVX. Following the bilateral ovariectomy (OVX) protocol, physiological saline was used as valsartan solvent, in a maximum volume of 0.4 mL, and valsartan was administered via intragastric gavage at a dose of 40 mg/kg/day. Depression and anxiety-like behaviors were assessed using the forced swimming test and open field test. Levels of oxidative stress markers, NLRP3, IL-1β, BDNF, and CREB were analyzed in the hippocampus and prefrontal cortex tissues. Behavioral tests indicated that depression and anxiety-like behaviors significantly increased in OVX rats (p < 0.01), while AT1RB treatment significantly reduced these behaviors (p < 0.05). In the hippocampus of OVX rats, oxidative stress (p < 0.01), NLRP3 (p < 0.05), and IL-1β (p < 0.01) levels were elevated, whereas BDNF levels were significantly decreased (p < 0.01). AT1RB treatment significantly improved oxidative stress parameters (p < 0.05) and BDNF levels (p < 0.01) but did not significantly affect the increased levels of NLRP3 and IL-1β in OVX rats. In conclusion, AT1RB has a therapeutic effect on menopause-induced depression and anxiety-like behaviors, likely by reducing oxidative stress and increasing BDNF production in the hippocampus.

The role of frontopolar cortex in adjusting the balance between response execution and action inhibition in anthropoids.

Executive control of behaviour entails keeping a fine balance between response execution and action inhibition. The most anterior part of the prefrontal cortex (frontopolar cortex) is highly developed in anthropoids; however, no previous study has examined its essential (indispensable) role in regulating the interplay between action execution and inhibition. In this cross-species study, we examine the performance of humans and macaque monkeys in the context of a stop-signal task and then assess the consequence of selective and bilateral damage to frontopolar cortex on monkeys’ behaviour. Humans and monkeys showed significant within-session practice-related adjustments in both response execution (increase in response time (RT) and decrease in response variabilities) and action inhibition (enhanced inhibition). Furthermore, both species expressed context-dependent (post-error and post-stop) behavioral adjustments. In post-lesion testing, frontopolar-damaged monkeys had a longer RT and lower percentage of timeout trials, compared to their pre-lesion performance. The practice-related changes in mean RT and in RT variability were significantly heightened in frontopolar-damaged monkeys. They also showed attenuated post-error, but exaggerated post-stop, behavioural adjustments. Importantly, frontopolar damage had no significant effects on monkeys’ inhibition ability. Our findings indicate that frontopolar cortex plays a critical role in allocation of control to response execution, but not action inhibition.

The unique contribution of uncertainty reduction during naturalistic language comprehension

Language comprehension is an incremental process with prediction. Delineating various mental states during such a process is critical to understanding the relationship between human cognition and the properties of language. Entropy reduction, which indicates the dynamic decrease of uncertainty as language input unfolds, has been recognized as effective in predicting neural responses during comprehension. According to the entropy reduction hypothesis (Hale, 2006), entropy reduction is related to the processing difficulty of a word, the effect of which may overlap with other well-documented information-theoretical metrics such as surprisal or next-word entropy. However, the processing difficulty was often confused with the information conveyed by a word, especially lacking neural differentiation. We propose that entropy reduction represents the cognitive neural process of information gain that can be dissociated from processing difficulty. This study characterized various information-theoretical metrics using GPT-2 and identified the unique effects of entropy reduction in predicting fMRI time series acquired during language comprehension. In addition to the effects of surprisal and entropy, entropy reduction was associated with activations in the left inferior frontal gyrus, bilateral ventromedial prefrontal cortex, insula, thalamus, basal ganglia, and middle cingulate cortex. The reduction of uncertainty, rather than its fluctuation, proved to be an effective factor in modeling neural responses. The neural substrates underlying the reduction in uncertainty might imply the brain’s desire for information regardless of processing difficulty.

Transcutaneous auricular vagus nerve stimulation improves cognitive decline by alleviating intradialytic cerebral hypoxia in hemodialysis patients: A fNIRS pilot study

Cognitive impairment is common in hemodialysis patients, possibly due to inadequate cerebral blood flow during hemodialysis. No effective non-pharmacological interventions are available. This study investigates the impact of hemodialysis-induced cerebral hypoxia on cognitive decline in hemodialysis patients and the potential of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-pharmacological intervention. A randomized controlled trial with 36 participants showed that cognitive performance and cerebral oxygenation in the dorsolateral prefrontal cortex (DLPFC) significantly declined in the sham group. In contrast, taVNS improved cognitive function by increasing cerebral oxygenation, with significant correlations to reaction times and MoCA scores. The study suggests that Hemodialysis-induced cerebral hypoxia may contribute to persistent cognitive decline in MHD patients. However, taVNS could be an effective intervention to prevent cognitive impairment in hemodialysis patients by alleviating cerebral hypoxia.

Theta Burst Stimulation Protocols for Schizophrenia

To date, several theta burst stimulation (TBS) protocols, such as intermittent TBS (iTBS), have been proposed; however, previous systematic reviews have revealed inconsistent efficacy findings in individual TBS studies for schizophrenia. To examine which TBS protocols are associated with the most favorable and acceptable outcomes in adults with schizophrenia. The Cochrane Library, PubMed, and Embase databases were searched for studies published before May 22, 2024. The inclusion criteria were as follows: (1) published and unpublished randomized clinical trials (RCTs) of any TBS treatment and (2) RCTs including individuals with schizophrenia spectrum disorders, other psychotic disorders, or both. This study followed the Cochrane standards for data extraction and data quality assessment and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline for reporting. The risk of bias of individual studies was assessed using the second version of the Cochrane risk of bias tool, and the Confidence in Network Meta-Analysis application was used to rate the certainty of evidence for meta-analysis results. At least 2 authors double-checked the literature search, data transfer accuracy, and calculations. The primary outcome of this study was improvement in scores related to negative symptoms. Our frequentist network meta-analysis used a random-effects model. The standardized mean difference (SMD) or odds ratio for continuous or dichotomous variables, respectively, was calculated with 95% CIs. A total of 30 RCTs of 9 TBS protocols, with 1424 participants, were included. Only iTBS over the left dorsolateral prefrontal cortex (L-DLPFC) was associated with reduced negative symptom scores (SMD, -0.89; 95% CI, -1.24 to -0.55), overall symptom scores (SMD, -0.81; 95% CI, -1.15 to -0.48), Positive and Negative Syndrome Scale general subscale scores (SMD, -0.57; 95% CI, -0.89 to -0.25), depressive symptom scores (SMD, -0.70; 95% CI, -1.04 to -0.37), and anxiety symptom scores (SMD, -0.58; 95% CI, -0.92 to -0.24) and improved overall cognitive impairment scores (SMD, -0.52; 95% CI, -0.89 to -0.15) compared with a sham. However, positive symptom score changes, all-cause discontinuation rate, discontinuation rate due to adverse events, headache incidence, and dizziness incidence did not significantly differ between any TBS protocols and sham. In this network meta-analysis, iTBS over the L-DLPFC was associated with improved scores for negative, depressive, anxiety, and cognitive symptoms in individuals with schizophrenia and was well tolerated by the participants. Other forms of TBS were not associated with benefit. Further research is needed to assess the potential role of TBS in the treatment of schizophrenia.

Brains in sync, friends in empathy: interbrain neural mechanisms underlying the impact of interpersonal closeness on mutual empathy.

Many everyday empathetic experiences arise within our social interactions and depend significantly on interpersonal closeness. However, the interbrain processes underlying social-oriented empathy by interpersonal closeness remain unclear. To address this gap, we conducted a dyadic social judgement task with dyads of friends and strangers, where targets received social evaluative feedback and empathizers observed the scenario in different experimental trials. Results showed that dyads of friends exhibited greater affect sharing than strangers when witnessing their partners being accepted or rejected. This was supported by the more pronounced event-related potential similarity in friends during the 340-840 ms post-feedback window, mediating the link between interpersonal closeness and affect sharing. Furthermore, witnessing emotional feedback elicited greater interbrain neural synchronization of brain α-oscillation between the empathizer's left prefrontal cortex and the target's left temporoparietal junction in dyads of friends compared with those of strangers. This empathy-related synchronization was associated with mutual affect sharing within dyads of friends but not within dyads of strangers. Our findings highlight the sensitivity of empathy to interpersonal closeness, which links to sustained attention and detailed evaluation in social scenarios, along with functional communication between brain regions for mentalizing and emotional regulation. These insights have therapeutic potential for improving social functioning and relationship satisfaction.

Efficacy and Safety of Transcranial Direct Current Stimulation as an Add-On Trial Treatment for Acute Bipolar Depression Patients With Suicidal Ideation.

Bipolar depression poses an overwhelming suicide risk. We aimed to examine the efficacy and safety of transcranial direct current stimulation (tDCS) combined with quetiapine in bipolar patients as a suicidal intervention. In a single-center, double-blind, treatment-naive bipolar depression patients with suicidal ideation were randomly assigned to quetiapine in combination with either active (n = 16) or sham (n = 15) tDCS over the left dorsolateral prefrontal cortex for three consecutive weeks. The 30-min, 2-mA tDCS was conducted twice a day on the weekday of the first week and then once a day on the weekdays of the two following weeks. Primary efficacy outcome measure was the change in the Beck Scale for Suicidal Ideation (BSSI). Secondary outcomes included changes on the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Outcome was evaluated on Day 3 and weekend. Safety outcome was based on the reported adverse reactions. Active tDCS was superior to sham tDCS on the BSSI at Day 3 and tended to sustain every weekend during the treatment process, compared to baseline. However, no difference between active and sham in HDRS-17 and MADRS was found. Response and remission rate also supported the antisuicide effect of tDCS, with higher response and remission rate in BSSI, but no antidepressant effect, compared to sham, over time. Regarding safety, active tDCS was well tolerated and all the adverse reactions reported were mild and limited to transient scalp discomfort. The tDCS was effective as an antisuicide treatment for acute bipolar depression patients with suicidal ideation, with minimal side effects reported.

Psychological mechanisms and neural correlates of trait mindfulness in emotion regulation: Testing a novel approach to the monitor and acceptance theory

BackgroundThe ongoing mental health crisis warrants investigations to understand why trait mindfulness is associated with beneficial mental health outcomes. This study examined attention monitoring and acceptance as psychological mechanisms underlying the relationship between trait mindfulness and emotion regulation and connectivity between the dorsolateral prefrontal cortex (dlPFC) and posterior cingulate cortex (PCC) as a potential neural mechanism. MethodsA cross-sectional study was conducted with 501 adult participants (age range: 17–79, M = 31, SD = 11.3) representing the general population. To assess emotion regulation and trait mindfulness, participants completed the Difficulties in Emotion Regulation Scale (DERS) and Five Facets Mindfulness Questionnaire (FFMQ). Resting-state functional MRI was acquired in a subsample of 20 participants to explore the role of dlPFC-PCC functional connectivity. ResultsHigher levels of acceptance, as measured using the Non-judging and Non-reactivity subscales of the FFMQ, were significantly associated with fewer overall emotion regulation difficulties and predicted all emotion regulation subscales. In contrast, higher levels of attention monitoring, measured using the Observe subscale, predicted only three DERS subscales and with mixed effects: higher emotional awareness and clarity, but greater difficulties in goal-directed behaviour. The interaction between monitoring and acceptance was not significant, and no correlation was found between these variables and dlPFC-PCC functional connectivity. ConclusionsThese findings challenge previous theories that argue that attention monitoring is crucial for effective emotion regulation. Instead, we conclude that acceptance is the key psychological mechanism, indicating that the traditional focus on attention monitoring in mindfulness training may be less effective than a primary emphasis on acceptance. This study provides a critical review of past research, highlighting issues with operationalising acceptance, and offers recommendations for future studies and practical implications for developing mindfulness interventions.

Characteristic Changes of Prefrontal and Motor Areas in Patients with Type 2 Diabetes and Major Depressive Disorder During a Motor Task of Tai Chi Chuan: A Functional Near-Infrared Spectroscopy Study.

This cross-sectional study aims to identify the characteristic changes of prefrontal and motor areas during a tai chi chuan task in patients with Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) using wearable functional near-infrared spectroscopy (fNIRS). Three parallel groups (T2DM with DD group, T2DM group, and healthy group) were recruited from December 10, 2022, to May 31, 2023. Participants in three groups conducted a motor task of tai chi chuan designed by Eprime 3.0, and fNIRS was used to monitor the brain activation, functional connectivity (FC), and lateralization of prefrontal and motor areas. Correlation analyses were performed to examine the relationship between depressive symptoms and the function of prefrontal and motor areas. Ninety elder adults (aged ≥ 60), including 30 patients with T2DM and MDD, 30 patients with T2DM, and 30 healthy subjects, were enrolled. In contrast with the patients with T2DM and healthy subjects, the patients with T2DM and MDD had decreased activation and abnormal lateralization in prefrontal and motor areas and decreased FC among supplementary motor area, motor area, and dorsolateral prefrontal cortex (DLPFC). Furthermore, the oxyhemoglobin (HbO2) concentration value of DLPFC in patients with T2DM and MDD was negatively associated with scores of Hamilton Depression Scale-24 (HAMD-24). Patients with T2DM and MDD had characteristic functional changes in prefrontal and motor areas. DLPFC may be a potential target of diagnosis and intervention for patients with T2DM and MDD.

Mapping the electric field of high-definition transcranial electrical stimulation across the lifespan

Transcranial electrical stimulation (tES) is a non-invasive technique widely used in modulating brain activity and behavior, but its effects differ across individuals and are influenced by head anatomy. In this study, we investigated how the electric field (EF) generated by high-definition tES varies across the lifespan among different demographic groups and its relationship with neural responses measured by functional magnetic resonance imaging (fMRI). We employed an MRI-guided finite element method to simulate the EF for the two most common tES montages (i.e., targeting the dorsolateral prefrontal cortex and motor cortex, respectively) in two large cohorts of white and Asian participants aged 12 to 100 years. We found that the EF intensity decreased with age, particularly in individuals under 25 years of age, and was influenced by gender and ethnicity. We identified skull thickness, scalp thickness, and epidural cerebrospinal fluid thickness, as the primary anatomical factors accounting for the inter-individual EF variability. Using a concurrent tES-fMRI approach, we observed a spatial consistency between the simulated EF and the brain activity changes induced by tES in the target region. Finally, we developed an open-source toolbox incorporating age-stratified head models to facilitate efficient EF calculations. These findings characterize and quantify the individual differences in tES-induced EF, offering a reference for implementing personalized neuromodulation strategies.

Improvements in Sleep Quality in Patients With Major Depressive and Generalized Anxiety Disorders Treated With Individualized, Parcel-Guided Transcranial Magnetic Stimulation.

Poor quality sleep has often been cited as a cause of lowered quality of life in patients with affective disorders such as major depressive disorder (MDD) and generalized anxiety disorder (GAD). As sleep and affective disorders are affected by multi-network interactions, we hypothesize that the modulation of the central executive network (CEN), salience, and default mode networks (DMNs) through individualized repetitive transcranial magnetic stimulation (rTMS) may improve sleep and quality of life. A retrospective analysis from 2020 to 2023 was conducted in patients with affective disorders at Cingulum Health. Multiple targets were selected based on anomalies detected from individual, functional connectivity networks from a machine-learning connectivity software. rTMS was conducted with accelerated continuous or intermittent theta burst stimulation (TBS) based on the anomaly detected. Pittsburgh Sleep Quality Index (PSQI), EuroQol (EQ5D), Beck's Depression Inventory (BDI), and the General Anxiety Disorder-7 (GAD-7) questionnaires were administered prior to, after, and at follow-up of rTMS. Twenty-seven patients were identified, and the most common diagnoses were MDD (41%) or MDD with GAD (41%). All patients had at least one rTMS target in the CEN. The most common target (19 patients) was L8Av in the dorsolateral prefrontal cortex (dlPFC). Patients experienced significant improvements in sleep, quality of life, depressive, and anxiety symptoms after rTMS and during follow-up. Improvements in sleep correlated with quality of life at follow-up. This study suggests that personalized, parcel-guided rTMS is safe and may provide sustained improvements in sleep, quality of life, and affective symptoms for patients with affective disorders.

The presence of drum and bass modulates responses in the auditory dorsal pathway and mirror-related regions to pop songs

In pop music, drum and bass components are crucial for generating the desire to move one’s body, primarily due to their role in delivering salient metrical cues. This study explored how the presence of drum and bass influences neural responses to unfamiliar pop songs. Using AI-based algorithms, we isolated the drum and bass components from the musical excerpts, creating two additional versions: one that included only the drum and bass (excluding vocals and other instruments), and another that excluded the drum and bass (consisting solely of vocals and other instruments). Twenty-five participants were subjected to fMRI scans while listening to these musical stimuli. Analysis of fMRI data indicated that the removal of drum and bass led to increased activity in the auditory dorsal pathway, suggesting that the absence of these metrical cues demands greater cognitive effort to process the beats. In contrast, the version featuring only drum and bass elicited stronger activation in frontal regions associated with mirror properties, including the right ventral premotor cortex (extending into the inferior frontal gyrus) and left dorsolateral prefrontal cortex, compared to the original version. Overall, this study contributed insights into the foundational role of drum and bass in imparting metrical salience to pop songs, enriching our understanding of listeners’ sensorimotor processing of musical genres that prominently feature these two elements.

Personalised transcranial magnetic stimulation for treatment-resistant depression, depression with comorbid anxiety and negative symptoms of schizophrenia: a narrative review.

Transcranial magnetic stimulation (TMS) is a promising intervention for treatment-resistant psychiatric disorders. However, conventional TMS typically utilises a one-size-fits-all approach when determining stimulation targets. Recent retrospective brain circuit-based analyses using lesion network mapping have suggested that a left dorsal lateral prefrontal cortex target has a higher efficacy for alleviating depression symptoms, a dorsomedial prefrontal cortex target is more effective for anxiety symptoms, and a rostromedial prefrontal cortex target is effective for schizophrenia-associated psychiatric symptoms. Nonetheless, symptom-specific brain circuit targeting has not been tested prospectively. We conducted a narrative review of selected literature to investigate individualised targeting for TMS and discuss potential future directions to elucidate the efficacy of this approach.

Structural alterations in a rumination-related network in patients with major depressive disorder

Rumination is a common symptom in major depressive disorder (MDD). Previous work has connected individual differences in rumination to structural properties in various brain regions. Some of these, such as the dorsolateral prefrontal cortex (dlPFC), have also been highlighted as being altered in MDD, suggesting a connection between structural changes and ruminative symptoms. Although informative, such localised relations have limitations in the context of a network view of the brain. To further investigate rumination-related structural changes in depression, and to situate these within potential functional networks, we acquired T1-weighted structural MRI data from patients with MDD (n=32) and controls (n=69). Rumination was measured with the Rumination Response Scale. Surface-based, whole-brain analysis of cortical grey-matter identified group differences in the dlPFC that were, however, not related to rumination. Instead, rumination was correlated with grey-matter properties in the right precuneus. Using normative functional connectivity analysis on an independent sample (n = 100), we show these two regions to be interconnected. Further developing a network-based perspective, it was shown that the rumination-related precuneus region is connected with networks associated with processes such as executive function, autobiographical memory, and visual perception. Notably, these processes have been connected to rumination. These results suggest that rumination in depression may be linked to focal structural changes. The effects of these focal changes on rumination may then be connected to their influence on distributed functional networks.

Contextual memory bias in emotional events: neurobiological correlates and depression risk

BackgroundContextual memory loss of emotional events plays a critical role in depression psychopathology. Individuals with depression, clinical or subclinical, exhibit enhanced and impaired memory for emotionally negative stimuli and context in an event, respectively. This suggests that contextual encoding may fail because of attentional interference caused by concurrent negative stimuli, possibly leading to contextual memory loss as a depression risk. Amygdala–prefrontal connectivity and cortisol may underlie the mechanism; however, the relationships remain unknown. MethodsOne hundred twenty participants, including 34 with subclinical depression, underwent behavioral tasks, functional magnetic resonance imaging (fMRI) scans, and saliva collection. Encoding and 24h later recollection performance of visuoperceptual/spatial/temporal context in a series of events, where fearful (vs. neutral) faces appeared, were measured via contextual memory tasks. Overgeneral autobiographical memory (OGM), a more remote form of contextual memory loss, was also assessed via the Autobiographical Memory Test. Amygdala connectivity was measured by fMRI during attentional interference by fearful (vs. neutral) faces to differentiate selective attention from encoding. Basal cortisol levels were assayed through saliva collected at encoding during the visit day and across 2 consecutive days in the following week (12 time points in total). We explored whether contextual memory encoding failure would explain depressive symptoms through OGM under possible moderation of amygdala connectivity and cortisol. ResultsIn individuals with subclinical depression compared to those without, fearful faces disturbed memory encoding of the visuoperceptual context rather than 24h later recollection, while neutral faces in their temporal proximity contrastingly augmented it. The more the contextual memory encoding bias (fearful vs. neutral) intensified, the more the amygdala’s functional connectivity with the ventromedial prefrontal cortex (vmPFC) weakened. Higher total cortisol output was correlated with poorer 24-h later recollection of the temporal context, although at a trend level. Moderated mediation effects of the amygdala-vmPFC connectivity and cortisol were non-significant; however, contextual encoding bias explained depressive symptoms through negatively valenced OGM. ConclusionsNegative stimuli appearing in an event might impair memory encoding of the visuoperceptual context under attentional interference, represented as weakened amygdala-vmPFC connectivity implicated in emotion-related attentional dysregulation. Conversely, negative stimuli might enhance temporally proximal visuoperceptual encoding after their disappearance. Contextual encoding bias could explain the overgeneralization (or lower coherence) of autobiographical memory and increase the risk of depression. The possible role of cortisol in recollecting the context of emotional events warrants further investigation.

Depicting Primate-Like Granular Dorsolateral Prefrontal Cortex in the Chinese Tree Shrew.

It remains unknown whether the Chinese tree shrew, regarded as the closest sister of primate, has evolved a dorsolateral prefrontal cortex (dlPFC) comparable with primates that is characterized by a fourth layer (L4) enriched with granular cells and reciprocal connections with the mediodorsal nucleus (MD). Here, we reported that following AAV-hSyn-EGFP expression in the MD neurons, the fluorescence micro-optical sectioning tomography revealed their projection trajectories and targeted brain areas, such as the hippocampus, the corpus striatum, and the dlPFC. Cre-dependent transsynaptic viral tracing identified the MD projection terminals that targeted the L4 of the dlPFC, in which the presence of granular cells was confirmed via cytoarchitectural studies by using the Nissl, Golgi, and vGlut2 stainings. Additionally, the L5/6 of the dlPFC projected back to the MD. These results suggest that the tree shrew has evolved a primate-like dlPFC which can serve as an alternative for studying cognition-related functions of the dlPFC.

Cell Type-Specific Profiles and Developmental Trajectories of Transcriptomes in Primate Prefrontal Layer 3 Pyramidal Neurons: Implications for Schizophrenia.

In schizophrenia, impaired working memory is associated with transcriptome alterations in layer 3 pyramidal neurons (L3PNs) in the dorsolateral prefrontal cortex (DLPFC). Distinct subtypes of L3PNs that send axonal projections to the DLPFC in the opposite hemisphere (callosal projection [CP] neurons) or the parietal cortex in the same hemisphere (ipsilateral projection [IP] neurons) play critical roles in working memory. However, how the transcriptomes of these L3PN subtypes might shift during late postnatal development when working memory impairments emerge in individuals later diagnosed with schizophrenia is not known. The aim of this study was to characterize and compare the transcriptome profiles of CP and IP L3PNs across developmental transitions from prepuberty to adulthood in macaque monkeys. The authors used retrograde labeling to identify CP and IP L3PNs in the DLPFC of prepubertal, postpubertal, and adult macaque monkeys, and used laser microdissection to capture these neurons for RNA sequencing. At all three ages, CP and IP L3PNs had distinct transcriptomes, with the number of genes differentially expressed between neuronal subtypes increasing with age. For IP L3PNs, age-related shifts in gene expression were most prominent between prepubertal and postpubertal animals, whereas for CP L3PNs such shifts were most prominent between postpubertal and adult animals. These findings demonstrate the presence of cell type-specific profiles and developmental trajectories of the transcriptomes of PPC-projecting IP and DLPFC-projecting CP L3PNs in monkey DLPFC. The evidence that IP L3PNs reach a mature transcriptome earlier than CP L3PNs suggests that these two subtypes differentially contribute to the maturation of working memory performance across late postnatal development and that they may be differentially vulnerable to the disease process of schizophrenia at specific stages of postnatal development.

Contribution of resting-state functional connectivity of the subgenual anterior cingulate to prediction of antidepressant efficacy in patients with major depressive disorder

This study investigated how resting-state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC) predicts antidepressant response in patients with major depressive disorder (MDD). Eighty-seven medication-free MDD patients underwent baseline resting-state functional MRI scans. After 12 weeks of escitalopram treatment, patients were classified into remission depression (RD, n = 42) and nonremission depression (NRD, n = 45) groups. We conducted two analyses: a voxel-wise rsFC analysis using sgACC as a seed to identify group differences, and a prediction model based on the sgACC rsFC map to predict treatment efficacy. Haufe transformation was used to interpret the predictive rsFC features. The RD group showed significantly higher rsFC between the sgACC and regions in the fronto-parietal network (FPN), including the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal lobule (IPL), compared to the NRD group. These sgACC rsFC measures correlated positively with symptom improvement. Baseline sgACC rsFC also significantly predicted treatment response after 12 weeks, with a mean accuracy of 72.64% (p < 0.001), mean area under the curve of 0.74 (p < 0.001), mean specificity of 0.82, and mean sensitivity of 0.70 in 10-fold cross-validation. The predictive voxels were mainly within the FPN. The rsFC between the sgACC and FPN is a valuable predictor of antidepressant response in MDD patients. These findings enhance our understanding of the neurobiological mechanisms underlying treatment response and could help inform personalized treatment strategies for MDD.

The Alpha-7 Nicotinic Receptor Positive Allosteric Modulator PNU120596 Attenuates Lipopolysaccharide-Induced Depressive-Like Behaviors and Cognitive Impairment by Regulating the PPAR-α Signaling Pathway in Mice.

The brain α7 nicotinic acetylcholine receptor (α7 nAChR) has a critical role in the pathophysiology of Major Depressive Disorder (MDD) involving neuroinflammation. The α7 nAChR stimulation has been shown to modulate the anti-inflammatory effects of nuclear peroxisome proliferator-activated receptor-α (PPAR-α) via its endogenous ligands in the brain. The present study determined the effects of α7 nAChR modulator PNU120596 on PPAR-α, an inhibitor of κB (IκB) and nuclear factor-κB (NF-κB) expression and interleukin-1β (IL-1β) level in the hippocampus and prefrontal cortex (PFC) in an inflammatory mouse model of MDD induced by lipopolysaccharide (LPS). We also evaluated the combined effects of PNU120596 and GW6471, a PPAR-α antagonist, on depressive-like and cognitive deficit-like behaviors in mice. Male C57BL/6J mice were treated with PNU120596, followed by systemic LPS (1 mg/kg, i.p.) administration. The effects of PNU120596 on the mRNA expression of PPAR-α and IκB were assessed in the hippocampus and PFC using qRT-PCR following LPS administration. Similarly, the effects of PNU120596 on the immunoreactivity of PPAR-α and NF-κB were measured in the hippocampus and PFC using an immunofluorescence assay. Furthermore, the effects of PNU120596 on pro-inflammatory cytokine IL-1β levels were measured in the hippocampus and PFC using ELISA. The combined effects of PNU120596 and GW6471 were also assessed against LPS-induced depressive-like and cognitive deficit-like behaviors using the Tail Suspension Test (TST), Forced Swim Test (FST), and Y-maze test. PNU120596 (4 mg/kg) significantly prevented LPS-induced dysregulation of PPAR-α, IκB, p-NF-κB p65, and IL-1β in the hippocampus and PFC. Pretreatment with PNU120596 showed significant antidepressant-like effects by reducing immobility time in the TST and FST. Similarly, pretreatment with PNU120596 significantly reduced cognitive deficit-like behavior in the Y-maze test. The antidepressant and pro-cognitive-like effects of PNU120596 were reversed by PPAR-α antagonist GW6471 (2 mg/kg). These results suggest that PNU120596 prevented LPS-induced MDD and cognitivelike behavior by regulating α7 nAChR/PPAR-α signaling pathway in the hippocampus and PFC.

Comparative analysis of electroencephalogram (EEG) data gathered from the frontal region with other brain regions affected by attention deficit hyperactivity disorder (ADHD) through multiresolution analysis and machine learning techniques

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by repeated patterns of hyperactivity, impulsivity, and inattention that limit daily functioning and development. Electroencephalography (EEG) anomalies correspond to changes in brain connection and activity. The authors propose utilizing empirical mode decomposition (EMD) and discrete wavelet transform (DWT) for feature extraction and machine learning (ML) algorithms to categorize ADHD and control subjects. For this study, the authors considered freely accessible ADHD data obtained from the IEEE data site. Studies have demonstrated a range of EEG anomalies in ADHD patients, such as variations in power spectra, coherence patterns, and event-related potentials (ERPs). Some of the studies claimed that the brain’s prefrontal cortex and frontal regions collaborate in intricate networks, and disorders in either of them exacerbate the symptoms of ADHD. , Based on the research that claimed the brain’s prefrontal cortex and frontal regions collaborate in intricate networks, and disorders in either of them exacerbate the symptoms of ADHD, the proposed study examines the optimal position of EEG electrode for identifying ADHD and in addition to monitoring accuracy on frontal/ prefrontal and other regions of brain our study also investigates the position groupings that have the highest effect on accurateness in identification of ADHD. The results demonstrate that the dataset classified with AdaBoost provided values for accuracy, precision, specificity, sensitivity, and F1-score as 1.00, 0.70, 0.70, 0.75, and 0.71, respectively, whereas using random forest (RF) it is 0.98, 0.64, 0.60, 0.81, and 0.71, respectively, in detecting ADHD. After detailed analysis, it is observed that the most accurate results included all electrodes. The authors believe the processes can detect various neurodevelopmental problems in children utilizing EEG signals.