Prefrontal Cortex Regions Research Articles

Integration of Single-Cell and Spatial Transcriptomic Data Reveals Spatial Architecture and Potential Biomarkers in Alzheimer's Disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the gradual loss of neurons and the accumulation of amyloid plaques and neurofibrillary tangles. Despite advancements in the understanding of AD's pathophysiology, the cellular organization and interactions in the prefrontal cortex (PFC) remain elusive. Eight single-cell RNA sequencing (scRNA-seq) datasets from both normal controls and individuals with AD were harmonized. Stringent preprocessing protocols were implemented to uphold dataset integrity. Unsupervised clustering and annotation revealed 22 distinct cell clusters corresponding to 19 unique cell types. The spatial architecture of the PFC region was constructed using the CARD tool. Further analyses encompassed trajectory examination of Oligodendrocyte subtypes, evaluation of regulon activity scores, and spot clustering within white matter regions (WM). Differential expression analysis and functional enrichment assays unveiled molecular signatures linked to AD progression and were validated using microarray data sourced from neurodegenerative disorder patients. Our investigation employs scRNA-seq and spatial transcriptomics to uncover the cellular atlas and spatial architecture of the human PFC in AD. Moreover, our results indicate that Oligodendrocytes are more prevalent in AD patients, showcasing diverse subtypes and spatial organization within WM regions. Each subtype appears to be associated with distinct biological processes and transcriptional regulators, shedding light on their involvement in AD pathology. Notably, the Oligodendrocyte_C6 subtype is linked to neurological damage in AD patients, characterized by heightened expression of genes involved in cell-cell connections, cell membrane stability, and myelination. Additionally, 12 target genes regulated by NFIA were identified, which are upregulated in AD patients and associated with disease progression. Elevated PLXDC2 expression in peripheral blood was also identified, suggesting its potential as a non-invasive biomarker for early AD detection. Our study provides novel insights into the role of Oligodendrocytes in AD and highlights the potential of PLXDC2 as a blood biomarker for non-invasive diagnosis and monitoring of AD patients.

Diminished negative emotion regulation through affect labeling and reappraisal: insights from functional near infrared spectroscopy on lateral prefrontal cortex activation

BackgroundReappraisal, an emotion regulation strategy, includes reinterpretation and affect labeling involving verbalizing emotions. In general, reappraisal is supported by lateral prefrontal cortical regions, which are also known to underlie cognitive regulation. Other research has shown that affect labeling combined with reappraisal of negative emotions increases lateral prefrontal cortex activity more than reappraisal alone does, suggesting that affect labeling facilitates emotional regulation. However, the influence of affect labeling on the efficacy of reappraisal in reducing subjective negative emotions has not been determined.MethodsIn the experiment, 35 participants (mean age = 28.2 years (SD = 9.63); 12 women and 23 men) viewed vignettes that aroused negative emotion. Then, they rated subjective negative emotions as baseline values. Following the baseline rating, the task branched into four conditions, combining affect labeling and emotion regulation factors. In the affect-labeling factor, participants selected emotional labels consistent with their own emotions or not. Regarding the emotion regulation factor, participants engaged in reappraisal to regulate their negative emotions. Throughout the experiment, the intensity of negative emotions was measured three times, mirroring the baseline measurement. Oxyhemoglobin (OxyHb) signal values in prefrontal cortex regions during tasks were measured by functional near-infrared spectroscopy.ResultsDifferences between the subjective negative emotion ratings at baseline and after reappraisal indicated that reappraisal significantly reduced negative emotion with and without affect labeling (t (1173.05) = 29.97, p < 0.001), and the combination of affect labeling and reappraisal was less effective in regulating negative emotions at the subjective level than reappraisal without affect labeling (t (1172.03) = 3.15, p < 0.01). Additionally, there was an increase in OxyHb signal in the bilateral dorsolateral prefrontal and right ventral prefrontal cortices while participants performed reappraisal with affect labeling.ConclusionOur findings suggest that affect labeling, when performed prior to cognitive reappraisal, may influence the process of negative emotion regulation in complex ways. The interaction between affect labeling and reappraisal appears to modulate prefrontal cortex activity, potentially reflecting changes in cognitive processing during emotion regulation attempts. These results highlight the need for further investigation into the intricate relationship between different emotion regulation strategies.

Executive functions and theory of mind development in preschoolers: Insights from NIRS data

Numerous studies have highlighted the importance of executive functions (EFs) in the development of Theory of Mind (ToM) in preschoolers. However, research focusing on young children at the neural level has been limited. This study examined the relationship between EFs and ToM in twenty-nine healthy Japanese preschoolers aged 5–7 years, focusing on neural responses during EF and ToM tasks using near-infrared spectroscopy (NIRS) to monitor prefrontal cortex (PFC) activity. The study utilized EF tasks and the Sally-Anne scenario to assess false- and true-belief understanding, aiming to provide a comprehensive analysis of ToM capabilities. Results indicated that despite advanced EF capabilities and a ceiling effect across all EF tasks, there were no significant correlations between EF performance or verbal ability and ToM task performance. NIRS data revealed no PFC activation during the Stroop task. However, activation was observed in the left and right lateral PFC in the control false belief condition, the left lateral PFC in the false belief condition, and across all PFC regions in the true belief condition during ToM tasks. Significant relationships were found between behavioral performance in ToM tasks and neural activity in key brain regions. The study also identified a complex relationship between false and true belief reasoning, suggesting a nuanced developmental trajectory for ToM. These findings underscore the crucial role of early childhood in the development of ToM and the complex interplay between cognitive functions and neural efficiency in understanding others' mental states.

Decrease in walking ability with increased functional connectivity between multiple brain areas in Parkinson's disease: a functional near-infrared spectroscopy study.

Gait disturbances significantly impact the mobility and quality of life of individuals with Parkinson's disease (PD). This study aims to delve into the cortical mechanisms underlying gait disorders in PD, specifically focusing on the prefrontal cortex (PFC), premotor cortex (PMC), and primary somatosensory cortex (PSC). To compare the functional connectivity of the PFC, PMC, and PSC regions during walking between individuals with PD and healthy controls. The study included 30 individuals with PD (mean age 62.40 ± 7.16 years) and 22 healthy older adults (mean age 60.95 ± 6.34 years). All participants were requested to walk back and forth at a comfortable pace for 30 s over a 10-meter course three times. A mobile functional near-infrared spectroscopy (fNIRS) system was employed to evaluate the oxyhemoglobin concentration change (∆HbO2). To assess the interactions between the PFC, PMC, and PSC, the connectivity strength between different fNIRS channels was computed. Individuals with PD in the off-state exhibited significantly decreased walking speed and shorter stride length compared to the healthy controls. For six brain regions including the left (L) and right (R) PFC, PMC, and PSC, no significant differences in functional connectivity within each region were found between the PD and control groups. However, when it comes to the functional connectivity between every two regions, the PD group exhibited stronger functional connectivity than the control group in the LPFC-LPMC, LPFC-RPMC, LPFC-LPSC, RPFC-LPMC, RPFC-LPSC, LPMC-LPSC, LPMC-RPSC, and RPMC-RPSC. Positive correlations were found between gait performance (speed and stride length) and functional connectivity within the RPMC as well as between the RPMC and the RPSC. Individuals with PD exhibit notable gait disturbances and increased functional connectivity in brain regions responsible for sensorimotor integration and motor function in their off-state. Strengthening the functional connectivity within the RPMC and between the RPMC and the RPSC could be a potential target for future treatments of gait impairments in PD.

Ventral Striatum is Preferentially Correlated with the Salience Network Including Regions in Dorsolateral Prefrontal Cortex.

The ventral striatum (VS) receives input from the cerebral cortex and is modulated by midbrain dopaminergic projections in support of processing reward and motivation. Here we explored the organization of cortical regions linked to the human VS using within-individual functional connectivity MRI in intensively scanned participants. In two initial participants (scanned 31 sessions each), seed regions in the VS were preferentially correlated with distributed cortical regions that are part of the Salience (SAL) network. The VS seed region recapitulated SAL network topography in each individual including anterior and posterior midline regions, anterior insula, and dorsolateral prefrontal cortex (DLPFC) - a topography that was distinct from a nearby striatal seed region. The region of DLPFC linked to the VS is positioned adjacent to regions associated with domain-flexible cognitive control. The full pattern was replicated in independent data from the same two individuals and generalized to 15 novel participants (scanned 8 or more sessions each). These results suggest that the VS forms a cortico-basal ganglia loop as part of the SAL network. The DLPFC is a neuromodulatory target to treat major depressive disorder. The present results raise the possibility that the DLPFC may be an effective neuromodulatory target because of its preferential coupling to the VS and suggests a path toward further personalization.

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.

Research on brain functional network property analysis and recognition methods targeting brain fatigue

At present, researches on brain fatigue recognition are still in the stage of single task and simple brain region network features, while researches on high-order brain functional network features and brain region state mechanisms during fatigue in multi-task scenarios are still insufficient, making it difficult to meet the needs of fatigue recognition under complex conditions. Therefore, this study utilized functional near-infrared spectroscopy (fNIRS) technology to explore the correlation and differences in the low-order and high-order brain functional network attributes of three task induced mental fatigue, and to explore the brain regions that have a major impact on mental fatigue. Self-training algorithms were used to identify the three levels of brain fatigue. The results showed that during the fatigue development, the overall connection strength of the endothelial cell metabolic activity and neural activity frequency bands of the low-order brain functional network first decreased and then increased, while the myogenic activity and heart rate activity frequency bands showed the opposite pattern. Network topology analysis indicated that from no fatigue to mild fatigue, the clustering coefficient of endothelial cell metabolic activity and myogenic activity frequency bands significantly decreased, while the characteristic path length of myogenic activity significantly increased; when experiencing severe fatigue, the small-world attribute of the neural frequency band significantly weakened. However, each frequency band maintained its small-world attribute, reflecting the self-optimization and adaptability of the network during the fatigue process. During mild fatigue, neuronal activity bands’ node degree, cluster coefficient, and efficiency rose in high-order brain networks, while low-order networks showed no significant changes. As fatigue progressed, the myogenic activity bands of high-order network properties dominated, but neural bands gained prominence in mild fatigue, approaching the level of myogenic bands in severe fatigue, indicating that brain fatigue orchestrated a shift from myogenic to neural dominance in frequency bands. In addition, during the process of fatigue, the four network attributes of the high-order network cluster composed of low-order nodes related to the prefrontal cortex region, left anterior motor region, motor assist region, and left frontal lobe eye movement region significantly increased, indicating that these brain regions had a significant impact on brain fatigue status. The accuracy of using both high-order and low-order features to identify fatigue levels reached 88.095%, indicating that the combined network features of both high-order and low-order fNIRS signals could effectively detect multi-level mental fatigue, providing innovative ideas for fatigue warning.

The Role of the Rat Prefrontal Cortex and Sex Differences in Decision-Making.

The prefrontal cortex is critical for decision-making across species, with its activity linked to choosing between options. Drift Diffusion Models (DDMs) are commonly employed to understand the neural computations underlying this behavior. Studies exploring the specific roles of regions of the rodent prefrontal cortex in controlling the decision process are limited. This study explored the role of the prelimbic cortex (PLC) in decision-making using a two-alternative forced-choice task. Rats first learned to report the location of a lateralized visual stimulus. The brightness of the stimulus indicated its reward value. Then, the rats learned to make choices between pairs of stimuli. Sex differences in learning were observed, with females responding faster and more selectively to high-value stimuli than males. DDM analysis found that males had decreased decision thresholds during initial learning, whereas females maintained a consistently higher drift rate. Pharmacological manipulations revealed that PLC inactivation reduced the decision threshold for all rats, indicating that less information was needed to make a choice in the absence of normal PLC processing. Mu opioid receptor stimulation of the PLC had the opposite effect, raising the decision threshold and reducing bias in the decision process towards high-value stimuli. These effects were observed without any impact on the rats' choice preferences. Our findings suggest that PLC has an inhibitory role in the decision process and regulates the amount of evidence that is required to make a choice. That is, PLC activity controls "when", but not "how", to act.Significance Statement This study reports causal evidence for a part of the rat prefrontal cortex, the prelimbic cortex, in controlling the amount of information needed to make a choice. Results were based on reversible inactivation using the GABA-A agonist muscimol and by stimulation of mu opioid receptors using intra-cortical infusions of the selective mu agonist DAMGO. We also found evidence for a sex difference in learning and performing a visually guided two-alternative forced-choice task. Drift Diffusion Models found that females had stable decision processes throughout learning, and showed a persistent bias against the lower value option. By contrast, males exhibited changes in their decision processes, notably reducing the amount of information needed to make choice over the period of early choice learning.

Exploring the late maturation of an intrinsic episodic memory network: A resting-state fMRI study

Previous research suggests that episodic memory relies on functional neural networks,which are present even in the absence of an explicit task. The regions that integrate.these networks and the developmental changes in intrinsic functional connectivity.remain elusive. In the present study, we outlined an intrinsic episodic memory network.(iEMN) based on a systematic selection of functional connectivity studies, and.inspected network differences in resting-state fMRI between adolescents (13–17 years.old) and adults (23–27 years old) from the publicly available NKI-Rockland Sample.Through a review of brain regions commonly associated with episodic memory.networks, we identified a potential iEMN composed by 14 bilateral ROIs, distributed.across temporal, frontal and parietal lobes. Within this network, we found an increase.in resting-state connectivity from adolescents to adults between the right temporal pole.and two regions in the right lateral prefrontal cortex. We argue that the coordination of.these brain regions, connecting areas of semantic processing and areas of controlled.retrieval, arises as an important feature towards the full maturation of the episodic.memory system. The findings add to evidence suggesting that adolescence is a key.period in memory development and highlights the role of intrinsic functional.connectivity in such development.

Environmental enrichment and sex, but not n-acetylcysteine, alter extended-access amphetamine self-administration and cue-seeking

There are no approved therapeutics for psychostimulant use and recurrence of psychostimulant use. However, in preclinical rodent models environmental enrichment can decrease psychostimulant self-administration of low unit doses and cue-induced amphetamine seeking. We have previously demonstrated that glutamate-dependent therapeutics are able to alter amphetamine seeking to amphetamine-associated cues only in enriched rats. In the current experiment, we will determine if enrichment can attenuate responding and cue-induced amphetamine seeking during extended access to a high dose of intravenous amphetamine. We will also determine if N-acetylcysteine (NAC), a glutamate dependent therapeutic, can attenuate amphetamine seeking in differentially reared rats. Female and male Sprague-Dawley rats were reared in enriched, isolated, or standard conditions from postnatal day 21–51. Rats were trained to self-administer intravenous amphetamine (0.1 mg/kg/infusion) during twelve 6-hour sessions. During the abstinence period, NAC (100 mg/kg) or saline was administered daily. Following a cue-induced amphetamine-seeking test, astrocyte densities within regions of the medial prefrontal cortex (mPFC) and nucleus accumbens (ACb) were quantified using immunohistochemistry. Environmental enrichment decreased responding for amphetamine and during the cue-induced amphetamine-seeking test. NAC did not attenuate cue-induced amphetamine seeking or alter astrocyte density. Across all groups, female rats self-administered less amphetamine but responded more during cue-induced amphetamine seeking than male rats. While amphetamine increased astrocyte densities within the ACb and mPFC, it did not alter mPFC astrocyte densities in female rats. The results suggest that enrichment can attenuate responding during extended access to a high dose of amphetamine and the associated cues. Sex alters amphetamine-induced changes to astrocyte densities in a regionally specific matter.

Disturbances of thalamus and prefrontal cortex contribute to cognitive aging: A structure-function coupling analysis based on KL divergence

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.

The uniqueness of human vulnerability to brain aging in great ape evolution.

Aging is associated with progressive gray matter loss in the brain. This spatially specific, morphological change over the life span in humans is also found in chimpanzees, and the comparison between these great ape species provides a unique evolutionary perspective on human brain aging. Here, we present a data-driven, comparative framework to explore the relationship between gray matter atrophy with age and recent cerebral expansion in the phylogeny of chimpanzees and humans. In humans, we show a positive relationship between cerebral aging and cortical expansion, whereas no such relationship was found in chimpanzees. This human-specific association between strong aging effects and large relative cortical expansion is particularly present in higher-order cognitive regions of the ventral prefrontal cortex and supports the "last-in-first-out" hypothesis for brain maturation in recent evolutionary development of human faculties.

Neuritin Controls Axonal Branching in Serotonin Neurons: A Possible Mediator Involved in the Regulation of Depressive and Anxiety Behaviors via FGF Signaling.

Abnormal neuronal morphological features, such as dendrite branching, axonal branching, and spine density, are thought to contribute to the symptoms of depression and anxiety. However, the role and molecular mechanisms of aberrant neuronal morphology in the regulation of mood disorders remain poorly characterized. Here, we show that neuritin, an activity-dependent protein, regulates the axonal morphology of serotonin neurons. Male neuritin knock-out (KO) mice harbored impaired axonal branches of serotonin neurons in the medial prefrontal cortex and basolateral region of the amygdala (BLA), and male neuritin KO mice exhibited depressive and anxiety-like behaviors. We also observed that the expression of neuritin was decreased by unpredictable chronic stress in the male mouse brain and that decreased expression of neuritin was associated with reduced axonal branching of serotonin neurons in the brain and with depressive and anxiety behaviors in mice. Furthermore, the stress-mediated impairments in axonal branching and depressive behaviors were reversed by the overexpression of neuritin in the BLA. The ability of neuritin to increase axonal branching in serotonin neurons involves fibroblast growth factor (FGF) signaling, and neuritin contributes to FGF-2-mediated axonal branching regulation in vitro. Finally, the oral administration of an FGF inhibitor reduced the axonal branching of serotonin neurons in the brain and caused depressive and anxiety behaviors in male mice. Our results support the involvement of neuritin in models of stress-induced depression and suggest that neuronal morphological plasticity may play a role in controlling animal behavior.

Pretreatment with 4-methylumbilliferon improves anxiety-like behaviors and memory impairment in stressed rats via modulation of neuronal cell death and oxidative stress

This work was done to investigate the ameliorating impact of 4-methylumbilliferon (4-MU) on spatial learning and memory dysfunction and restraint stress (STR)-induced anxiety-like behaviors in male Wistar rats and the underlying mechanisms. Thirty-two animals were assigned into 4 cohorts: control, 4-MU, STR, and STR+4-MU. Animals were exposed to STR for 4 h per day for 14 consecutive days or kept in normal conditions (healthy animals without exposure to stress). 4-MU (25 mg/kg) was intraperitoneally administered once daily to STR rats before restraint stress for 14 consecutive days. The behavioral tests were performed through Morris water maze tests and elevated-plus maze to examine learning/memory function, and anxiety levels, respectively. The levels of the antioxidant defense biomarkers (GPX, SOD) and MDA as an oxidant molecule in the brain tissues were measured using commercial ELISA kits. Neuronal loss or density of neurons was evaluated using Nissl staining. STR exposure could cause significant alterations in the levels of the antioxidant defense biomarkers (MDA, GPX, and SOD) in the prefrontal cortex and hippocampus, induce anxiety, and impair spatial learning and memory function. Treatment with 4-MU markedly reduced anxiety levels and improved spatial learning and memory dysfunction via restoring the antioxidant defense biomarkers to normal values and reducing MDA levels. Moreover, more intact cells with normal morphologies were detected in STR-induced animals treated with 4-MU. 4-MU could attenuate the STR-induced anxiety-like behaviors and spatial learning and memory dysfunction by reducing oxidative damage and neuronal loss in the prefrontal cortex and hippocampus region. Taken together, our findings provide new insights regarding the potential therapeutic effects of 4-MU against neurobehavioral disorders induced by STR.

Neural mechanisms of inhibitory control in preadolescent irritability: Insights from the ABCD study

ObjectiveElevated pediatric irritability is a transdiagnostic symptom that predicts multiple mental health problems in adolescence and adulthood. Altered top-down regulatory networks, such as inhibitory control networks that suppress an impulse in favor of goal-directed behavior, are thought to contribute to high levels of youth irritability. Nevertheless, little work has examined links between youth irritability and neural processes supporting inhibitory control in large diverse samples, nor have they focused on the key period ramping up to adolescence (i.e., preadolescence). MethodFunctional MRI data from 5380 preadolescents (age M=9.97 years, SD=0.62) in the baseline Adolescent Brain and Cognitive Development (ABCD) Study were analyzed. Parents reported on their preadolescent’s irritability. The stop signal task (SST) was leveraged to probe successful and failed inhibitory control. Activation and functional connectivity with amygdala, ventral striatum, and prefrontal seed regions were calculated during the SST and used in whole brain and region of interest (ROI) group-level analyses evaluating irritability effects. ResultsPreadolescents with higher levels of irritability displayed decreases in functional connectivity among amygdala, ventral striatum, and prefrontal cortex regions during both successful and failed inhibitory control conditions. These results remained after adjusting for co-occurring anxiety, depression, and attention-deficit/hyperactivity symptoms. ConclusionsFindings suggest neural aberrations in inhibitory control play a role in the pathophysiology of preadolescent irritability and associations are not merely due to co-occurring symptoms. Neural mechanisms of inhibitory control associated with irritability may provide novel intervention targets.

Fast depressive symptoms improvement in bipolar I disorder after Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT): A two-site feasibility and safety open-label trial

BackgroundAlthough there are a few first-line treatment options for bipolar depression, none are rapid-acting. A new rTMS protocol, Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT®), has been shown to have a rapid antidepressant effect in major depressive disorder (MDD). We examined the preliminary safety, tolerability, and efficacy of SAINT for the treatment of depression in a small sample of persons with treatment-resistant bipolar I disorder. MethodsParticipants with treatment-resistant bipolar I disorder currently experiencing moderate to severe depression were treated with open-label SAINT. Resting-state functional MRI (fMRI) was used to generate individualized treatment targets for each participant based on the region of the left dorsolateral prefrontal cortex most anticorrelated with the subgenual anterior cingulate cortex. Participants were treated with 10 iTBS sessions daily, with 50-min intersession intervals, for up to 5 consecutive days. The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to immediate follow-up after treatment. ResultsWe treated 10 participants and found a mean reduction of 16.9 in MADRS scores, with a 50 % response rate and 40 % remission rate immediately following treatment. 60 % of participants met remission criteria within the 1-month period following treatment. No serious adverse events, manic episodes, or cognitive side effects were observed. LimitationsOur study has a limited sample size and larger samples are needed to confirm safety and efficacy. ConclusionsSAINT has shown preliminary feasibility, safety, tolerability, and efficacy in treating treatment-resistant bipolar I depression. Double-blinded sham-controlled trials with larger samples are needed to confirm safety and efficacy.

Transcriptomic changes in oligodendrocytes and precursor cells associate with clinical outcomes of Parkinson’s disease

Several prior studies have proposed the involvement of various brain regions and cell types in Parkinson’s disease (PD) pathology. Here, we performed snRNA-seq on the prefrontal cortex and anterior cingulate regions from a small cohort of post-mortem control and PD brain tissue. We found a significant association of oligodendrocytes (ODCs) and oligodendrocyte precursor cells (OPCs) with PD-linked risk loci and report several dysregulated genes and pathways, including regulation of tau-protein kinase activity, regulation of inclusion body assembly and protein processing involved in protein targeting to mitochondria. In an independent PD cohort with clinical measures (681 cases and 549 controls), polygenic risk scores derived from the dysregulated genes significantly predicted Montreal Cognitive Assessment (MoCA)-, and Beck Depression Inventory-II (BDI-II)-scores but not motor impairment (UPDRS-III). We extended our analysis of clinical outcome prediction by incorporating differentially expressed genes from three separate datasets that were previously published by different laboratories. In the first dataset from the anterior cingulate cortex, we identified an association between ODCs and BDI-II. In the second dataset obtained from the substantia nigra (SN), OPCs displayed an association with UPDRS-III. In the third dataset from the SN region, a distinct subtype of OPCs, labeled OPC_ADM, exhibited an association with UPDRS-III. Intriguingly, the OPC_ADM cluster also demonstrated a significant increase in PD samples. These results suggest that by expanding our focus to glial cells, we can uncover region-specific molecular pathways associated with PD symptoms.

Exploring role of prefrontal cortex region of brain in children having ADHD with machine learning: Implications and insights

Objective Attention deficit hyperactivity disorder (ADHD), is a general neurodevelopmental syndrome. This affects both adults and children, causing issues like hyperactivity, inattention, and impulsivity. Diagnosis, typically reliant on patient narratives and questionnaires, can sometimes be inaccurate, leading to distress. We propose utilizing empirical mode decomposition (EMD) for feature extraction and a machine learning (ML) algorithm to categorize ADHD and control. Method Publicly available Kaggle dataset is used for research. The EMD technique decomposes an electroencephalogram (EEG) waveform to 12 intrinsic mode functions (IMFs). Thirty-one statistical parameters are generated over the first 6 IMFs to create an input feature vector for the deep belief network (DBN) classifier. Principal component analysis (PCA) is utilized to reduce dimension. Findings Experimental results are compared on prefrontal cortex channels Fp1 and Fp2. After an in-depth evaluation of all metrics, it is observed that, in patients with ADHD, the prefrontal cortex regulates attention, behavior, and emotion. Our findings align with established neuroscience. The critical functions of the brain, such as organization, planning, attention, and decision making, are performed by the frontal lobe. Novelty Our work provides a novel approach to understanding the disorder’s underlying neurobiological mechanisms. It has the potential to deepen our understanding of the condition, improve diagnostic accuracy, personalize treatment methods, and, ultimately, improve outcomes for those affected.

Unraveling the Prefrontal Cortex-Basolateral Amygdala Pathway's Role on Schizophrenia's Cognitive Impairments: A Multimodal Study in Patients and Mouse Models.

This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques. This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant cognitive deficits, which were addressed through stereotaxic injections of an adeno-associated viral vector to unveil the neural connection between the mPFC and BLA. Significant disparities in brain volume and neural activity, particularly in the dorsolateral prefrontal cortex (DLPFC) and BLA regions, were found between SCZ patients and healthy controls. Additionally, we observed correlations indicating that reduced volumes of the DLPFC and BLA were associated with lower cognitive function scores. Activation of the mPFC-BLA pathway notably improved cognitive performance in the SCZ model mice, with the targeting of excitatory or inhibitory neurons alone failing to replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences in excitatory and inhibitory neurons in the BLA of SCZ model mice. Notably, genes differentially expressed in the BLA of these model mice were also found in the blood exosomes of SCZ patients. Our research provides a comprehensive understanding of the role of the PFC-BLA pathway in SCZ, underscoring its significance in cognitive impairment and offering novel diagnostic and therapeutic avenues. Additionally, our research highlights the potential of blood exosomal mRNAs as noninvasive biomarkers for SCZ diagnosis, underscoring the clinical feasibility and utility of this method.

Teach a man to fish: Hyper-brain evidence on scaffolding strategy enhancing creativity acquisition and transfer

Creativity is an indispensable competency in today's innovation-driven society. Yet, the influences of instructional strategy, a key determinant of educational outcomes, on the creativity-fostering process remains an unresolved mystery. We proposed that instructional strategy affects creativity cultivation and further investigated the intricate neural mechanisms underlying this relationship. In a naturalistic laboratory setting, 66 instructor-learner dyads were randomized into three groups (scaffolding, explanation, and control), with divergent thinking instructions separately. Functional near-infrared spectroscopy (fNIRS) hyperscanning simultaneously collected brain signals in the prefrontal cortex and temporal-parietal junction regions. Results indicated that learners instructed with a scaffolding strategy demonstrated superior creative performance both in acquisition (direct learning) and transfer (use in a novel context) of creativity skills, compared to pretest levels. In contrast, the control and explanation groups did not exhibit such effects. Notably, we also observed remarkable interbrain neural synchronization (INS) between instructors and learners in the left superior frontal cortex in the scaffolding group, but not in the explanation or control groups. Furthermore, INS positively predicted enhancements in creativity performance (acquisition and transfer), indicating that it is a crucial neural mechanism in the creativity-fostering process. These findings reveal that scaffolding facilitates the acquisition and transfer of creativity and deepen our understanding of the neural mechanisms underlying the process of creativity-fostering. The current study provides valuable insights for implementing teaching strategies to fostering creativity.