Frontal Cortex Research Articles

Morphological patterns and spatial probability maps of the inferior frontal sulcus in the human brain.

The inferior frontal sulcus (ifs) is a prominent sulcus on the lateral frontal cortex, separating the middle frontal gyrus from the inferior frontal gyrus. The morphology of the ifs can be difficult to distinguish from adjacent sulci, which are often misidentified as continuations of the ifs. The morphological variability of the ifs and its relationship to surrounding sulci were examined in 40 healthy human subjects (i.e., 80 hemispheres). The sulci were identified and labeled on the native cortical surface meshes of individual subjects, permitting proper intra-sulcal assessment. Two main morphological patterns of the ifs were identified across hemispheres: in Type I, the ifs was a single continuous sulcus, and in Type II, the ifs was discontinuous and appeared in two segments. The morphology of the ifs could be further subdivided into nine subtypes based on the presence of anterior and posterior sulcal extensions. The ifs was often observed to connect, either superficially or completely, with surrounding sulci, and seldom appeared as an independent sulcus. The spatial variability of the ifs and its various morphological configurations were quantified in the form of surface spatial probability maps which are made publicly available in the standard fsaverage space. These maps demonstrated that the ifs generally occupied a consistent position across hemispheres and across individuals. The normalized mean sulcal depths associated with the main morphological types were also computed. The present study provides the first detailed description of the ifs as a sulcal complex composed of segments and extensions that can be clearly differentiated from adjacent sulci. These descriptions, together with the spatial probability maps, are critical for the accurate identification of the ifs in anatomical and functional neuroimaging studies investigating the structural characteristics and functional organization of this region in the human brain.

Newborn's neural representation of instrumental and vocal music as revealed by fMRI: A dynamic effective brain connectivity study.

Music is ubiquitous, both in its instrumental and vocal forms. While speech perception at birth has been at the core of an extensive corpus of research, the origins of the ability to discriminate instrumental or vocal melodies is still not well investigated. In previous studies comparing vocal and musical perception, the vocal stimuli were mainly related to speaking, including language, and not to the non-language singing voice. In the present study, to better compare a melodic instrumental line with the voice, we used singing as a comparison stimulus, to reduce the dissimilarities between the two stimuli as much as possible, separating language perception from vocal musical perception. In the present study, 45 newborns were scanned, 10 full-term born infants and 35 preterm infants at term-equivalent age (mean gestational age at test = 40.17 weeks, SD = 0.44) using functional magnetic resonance imaging while listening to five melodies played by a musical instrument (flute) or sung by a female voice. To examine the dynamic task-based effective connectivity, we employed a psychophysiological interaction of co-activation patterns (PPI-CAPs) analysis, using the auditory cortices as seed region, to investigate moment-to-moment changes in task-driven modulation of cortical activity during an fMRI task. Our findings reveal condition-specific, dynamically occurring patterns of co-activation (PPI-CAPs). During the vocal condition, the auditory cortex co-activates with the sensorimotor and salience networks, while during the instrumental condition, it co-activates with the visual cortex and the superior frontal cortex. Our results show that the vocal stimulus elicits sensorimotor aspects of the auditory perception and is processed as a more salient stimulus while the instrumental condition activated higher-order cognitive and visuo-spatial networks. Common neural signatures for both auditory stimuli were found in the precuneus and posterior cingulate gyrus. Finally, this study adds knowledge on the dynamic brain connectivity underlying the newborns capability of early and specialized auditory processing, highlighting the relevance of dynamic approaches to study brain function in newborn populations.

Transcranial photobiomodulation for neurodevelopmental disorders: a narrative review.

Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Down syndrome (DS) significantly impact social, communicative, and behavioral functioning. Transcranial photobiomodulation (t-PBM) with near-infrared light is a promising non-invasive neurostimulation technique for neuropsychiatric disorders, including NDDs. This narrative review aimed to examine the preclinical and clinical evidence of photobiomodulation (PBM) in treating NDDs. A comprehensive search across six databases was conducted, using a combination of MeSH terms and title/abstract keywords: "photobiomodulation", "PBM", "neurodevelopmental disorders", "NDD", and others. Studies applying PBM to diagnosed NDD cases or animal models replicating NDDs were included. Protocols, reviews, studies published in languages other than English, and studies not evaluating clinical or cognitive outcomes were excluded. Nine studies were identified, including one preclinical and eight clinical studies (five on ASD, two on ADHD, and one on DS). The reviewed studies encompassed various t-PBM parameters (wavelengths: 635-905nm) and targeted primarily frontal cortex areas. t-PBM showed efficacy in improving disruptive behavior, social communication, cognitive rigidity, sleep quality, and attention in ASD; in enhancing attention in ADHD; and in improving motor skills and verbal fluency in DS. Minimal adverse effects were reported. Proposed mechanisms involve enhanced mitochondrial function, modulated oxidative stress, and reduced neuroinflammation. t-PBM emerges as a promising intervention for NDDs, with potential therapeutic effects across ASD, ADHD, and DS. These findings underscore the need for further research, including larger-scale, randomized sham-controlled clinical trials with comprehensive biomarker analyses, to optimize treatment parameters and understand the underlying mechanisms associated with the effects of t-PBM.

Frontoparietal Response to Working Memory Load Mediates the Association between Sleep Duration and Cognitive Function in Children.

Lack of sleep has been found to be associated with cognitive impairment in children, yet the neural mechanism underlying this relationship remains poorly understood. To address this issue, this study utilized the data from the Adolescent Brain Cognitive Development (ABCD) study (n = 4930, aged 9-10), involving their sleep assessments, cognitive measures, and functional magnetic resonance imaging (fMRI) during an emotional n-back task. Using partial correlations analysis, we found that the out-of-scanner cognitive performance was positively correlated with sleep duration. Additionally, the activation of regions of interest (ROIs) in frontal and parietal cortices for the 2-back versus 0-back contrast was positively correlated with both sleep duration and cognitive performance. Mediation analysis revealed that this activation significantly mediated the relationship between sleep duration and cognitive function at both individual ROI level and network level. After performing analyses separately for different sexes, it was revealed that the mediation effect of the task-related activation was present in girls (n = 2546). These findings suggest that short sleep duration may lead to deficit in cognitive function of children, particularly in girls, through the modulation of frontoparietal activation during working memory load.

Thyroid hormone T4 mitigates traumatic brain injury in mice by dynamically remodeling cell type specific genes, pathways, and networks in hippocampus and frontal cortex

The complex pathology of mild traumatic brain injury (mTBI) is a main contributor to the difficulties in achieving a successful therapeutic regimen. Thyroxine (T4) administration has been shown to prevent the cognitive impairments induced by mTBI in mice but the mechanism is poorly understood. To understand the underlying mechanism, we carried out a single cell transcriptomic study to investigate the spatiotemporal effects of T4 on individual cell types in the hippocampus and frontal cortex at three post-injury stages in a mouse model of mTBI. We found that T4 treatment altered the proportions and transcriptomes of numerous cell types across tissues and timepoints, particularly oligodendrocytes, astrocytes, and microglia, which are crucial for injury repair. T4 also reversed the expression of mTBI-affected genes such as Ttr, mt-Rnr2, Ggn12, Malat1, Gnaq, and Myo3a, as well as numerous pathways such as cell/energy/iron metabolism, immune response, nervous system, and cytoskeleton-related pathways. Cell-type specific network modeling revealed that T4 mitigated select mTBI-perturbed dynamic shifts in subnetworks related to cell cycle, stress response, and RNA processing in oligodendrocytes. Cross cell-type ligand-receptor networks revealed the roles of App, Hmgb1, Fn1, and Tnf in mTBI, with the latter two ligands having been previously identified as TBI network hubs. mTBI and/or T4 signature genes were enriched for human genome-wide association study (GWAS) candidate genes for cognitive, psychiatric and neurodegenerative disorders related to mTBI. Our systems-level single cell analysis elucidated the temporal and spatial dynamic reprogramming of cell-type specific genes, pathways, and networks, as well as cell-cell communications as the mechanisms through which T4 mitigates cognitive dysfunction induced by mTBI.

RNA editing regulates glutamatergic synapses in the frontal cortex of a molecular subtype of Amyotrophic Lateral Sclerosis

BackgroundAmyotrophic Lateral Sclerosis (ALS) is a highly heterogenous neurodegenerative disorder that primarily affects upper and lower motor neurons, affecting additional cell types and brain regions. Underlying molecular mechanisms are still elusive, in part due to disease heterogeneity. Molecular disease subtyping through integrative analyses including RNA editing profiling is a novel approach for identification of molecular networks involved in pathogenesis.MethodsWe aimed to highlight the role of RNA editing in ALS, focusing on the frontal cortex and the prevalent molecular disease subtype (ALS-Ox), previously determined by transcriptomic profile stratification. We established global RNA editing (editome) and gene expression (transcriptome) profiles in control and ALS-Ox cases, utilizing publicly available RNA-seq data (GSE153960) and an in-house analysis pipeline. Functional annotation and pathway analyses identified molecular processes affected by RNA editing alterations. Pearson correlation analyses assessed RNA editing effects on expression. Similar analyses on additional ALS-Ox and control samples (GSE124439) were performed for verification. Targeted re-sequencing and qRT-PCR analysis targeting CACNA1C, were performed using frontal cortex tissue from ALS and control samples (n = 3 samples/group).ResultsWe identified reduced global RNA editing in the frontal cortex of ALS-Ox cases. Differentially edited transcripts are enriched in synapses, particularly in the glutamatergic synapse pathway. Bioinformatic analyses on additional ALS-Ox and control RNA-seq data verified these findings. We identified increased recoding at the Q621R site in the GRIK2 transcript and determined positive correlations between RNA editing and gene expression alterations in ionotropic receptor subunits GRIA2, GRIA3 and the CACNA1C transcript, which encodes the pore forming subunit of a post-synaptic L-type calcium channel. Experimental data verified RNA editing alterations and editing-expression correlation in CACNA1C, highlighting CACNA1C as a target for further study.ConclusionsWe provide evidence on the involvement of RNA editing in the frontal cortex of an ALS molecular subtype, highlighting a modulatory role mediated though recoding and gene expression regulation on glutamatergic synapse related transcripts. We report RNA editing effects in disease-related transcripts and validated editing alterations in CACNA1C. Our study provides targets for further functional studies that could shed light in underlying disease mechanisms enabling novel therapeutic approaches.

Dissociable functional responses along the posterior-anterior gradient of the frontal and parietal cortices revealed by parametric working memory and training.

While the storage capacity is limited, accumulating studies have indicated that working memory (WM) can be improved by cognitive training. However, understanding how exactly the brain copes with limited WM capacity and how cognitive training optimizes the brain remains inconclusive. Given the hierarchical functional organization of WM, we hypothesized that the activation profiles along the posterior-anterior gradient of the frontal and parietal cortices characterize WM load and training effects. To test this hypothesis, we recruited 51 healthy volunteers and adopted a parametric WM paradigm and training method. In contrast to exclusively strengthening the activation of posterior areas, a broader range of activation concurrently occurred in the anterior areas to cope with increased memory load for all subjects at baseline. Moreover, there was an imbalance in the responses of the posterior and anterior areas to the same increment of 1 item at different load levels. Although a general decrease in activation after adaptive training, the changes in the posterior and anterior areas were distinct at different memory loads. Particularly, we found that the activation gradient between the posterior and anterior areas was significantly increased at load 4-back after adaptive training, and the changes were correlated with improvement in WM performance. Together, our results demonstrate a shift in the predominant role of posterior and anterior areas in the frontal and parietal cortices when approaching WM capacity limits. Additionally, the training-induced performance improvement likely benefits from the elevated neural efficiency reflected in the increased activation gradient between the posterior and anterior areas.

Insights into Brominated Flame Retardant Neurotoxicity: Mechanisms of Hippocampal Neural Cell Death and Brain Region-Specific Transcriptomic Shifts in Mice.

Brominated Flame Retardants (BFRs) reduce flammability in a wide range of products including electronics, carpets, and paint, but leach into the environment to result in continuous, population-level exposure. Epidemiology studies have correlated BFR exposure with neurological problems, including alterations in learning and memory. This study investigated the molecular mechanisms mediating BFR-induced cell death in hippocampal cells and clarified the impact of HBCD exposure on gene transcription in the hippocampus, dorsal striatum, and frontal cortex of male mice. Exposure of hippocampus derived HT-22 cells to various flame retardants, including tetrabromobisphenol-A (TBBPA, current use), hexabromocyclododecane (HBCD, phasing out), or 2,2',4,4'-tetrabromodiphenyl ether (BDE-47, phased out) resulted in time, concentration, and chemical-dependent cellular and nuclear morphology alterations, alterations in cell cycle and increases in annexin V staining. All three BFRs increased p53 and p21 expression; however, inhibition of p53 nuclear translocation using pifthrin-α did not decrease cell death. Transcriptomic analysis upon low (10 nM) and cytotoxic (10 μM) BFR exposure indicated that HBCD and BDE-47 altered genes mediating autophagy-related pathways. Further evaluation showed BFR exposure increased LC3-II conversion and autophagosome formation, and co-exposure with the autophagy inhibitor 3-methyladenine (3-MA) attenuated cytotoxicity. Transcriptomic assessment of select brain regions from subchronically HBCD-exposed male mice demonstrated alteration of genes mediating vesicular transport, with greater impact on the frontal cortex and dorsal striatum compared to the dorsal and ventral hippocampus. Immunoblot analysis demonstrated no increases in cell death or autophagy markers, but did demonstrate increases in the SNARE binding complex SNAP29, specifically in the dorsal hippocampus. These data demonstrate that BFRs can induce chemical-dependent autophagy in neural cells in vitro and provide evidence that BFRs induce region-specific transcriptomic and protein expression in the brain suggestive of change in vesicular trafficking.

Postoperative EEG abnormalities in relation to neurodevelopmental outcomes after pediatric cardiac surgery.

We had reported that postoperative EEG background including sleep-wake cycle (SWC) and discharge (seizures, spikes/sharp waves) abnormalities were significantly correlated with adverse early outcomes in children after cardiac surgery. We aimed to analyze the relations between these EEG abnormalities and neurodevelopmental outcomes at about2 years after cardiac surgery. We enrolled 121 patients undergoing cardiac surgery at 3.3 months (0.03 ~ 28 months). EEG abnormalities described above during the first postoperative 48 h were evaluated. Griffiths Mental Development Scales-Chinese was used to evaluate the quotients of overall development and 5 subscales of the child's locomotor, language, personal-social, eye-hand coordination and performance skills at 16 ~ 31 months of age. EEG background abnormalities occurred in 59/121 (48.8%) patients and 33 (55.9%) unrecovered to normal by 48 h. Abnormal SWC occurred in 15 (12.4%) patients and 7 (5.8%) unrecovered to normal by 48 h. EEG seizures occurred in 11 (9.1%) patients with frontal lobe seizures in 4. Spikes/sharp waves occurred in 100 (82.6%). EEG background abnormalities, number of spikes/sharp waves and frontal lobe seizures were significantly associated with neurodevelopmental impairment at about 1 ~ 2 year after surgery (Ps ≤ 0.05). Most parameters of EEG abnormalities were significantly associated with neurodevelopmental impairment after cardiac surgery. Neurodevelopmental impairment in children with congenital heart disease remain poorly understood. Previous studies had reported that either EEG seizures or background abnormalities were associated with worse neurodevelopmental outcomes. Our present study showed that all the EEG background and discharge abnormalities including EEG background, seizures and spikes/sharp waves in the early postoperative period were significantly associated with neurodevelopmental impairment at about 1 ~ 2 years after cardiac surgery. Comprehensive evaluation of early postoperative EEG may provide further insights about postoperative brain injury, its relation with neurodevelopmental impairment, and guide to improve clinical management.

DNA methylation patterns in the frontal lobe white matter of multiple system atrophy, Parkinson’s disease, and progressive supranuclear palsy: a cross-comparative investigation

Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by neuronal loss and gliosis, with oligodendroglial cytoplasmic inclusions (GCIs) containing α-synuclein being the primary pathological hallmark. Clinical presentations of MSA overlap with other parkinsonian disorders, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP), posing challenges in early diagnosis. Numerous studies have reported alterations in DNA methylation in neurodegenerative diseases, with candidate loci being identified in various parkinsonian disorders including MSA, PD, and PSP. Although MSA and PSP present with substantial white matter pathology, alterations in white matter have also been reported in PD. However, studies comparing the DNA methylation architectures of white matter in these diseases are lacking. We therefore aimed to investigate genome-wide DNA methylation patterns in the frontal lobe white matter of individuals with MSA (n = 17), PD (n = 17), and PSP (n = 16) along with controls (n = 15) using the Illumina EPIC array, to identify shared and disease-specific DNA methylation alterations. Genome-wide DNA methylation profiling of frontal lobe white matter in the three parkinsonian disorders revealed substantial commonalities in DNA methylation alterations in MSA, PD, and PSP. We further used weighted gene correlation network analysis to identify disease-associated co-methylation signatures and identified dysregulation in processes relating to Wnt signaling, signal transduction, endoplasmic reticulum stress, mitochondrial processes, RNA interference, and endosomal transport to be shared between these parkinsonian disorders. Our overall analysis points toward more similarities in DNA methylation patterns between MSA and PD, both synucleinopathies, compared to that between MSA and PD with PSP, which is a tauopathy. Our results also highlight several shared DNA methylation changes and pathways indicative of converging molecular mechanisms in the white matter contributing toward neurodegeneration in all three parkinsonian disorders.

Dissociable representations of decision variables within subdivisions of macaque orbitofrontal and ventrolateral frontal cortex.

Ventral frontal cortex (VFC) in macaques is involved in many affective and cognitive processes and has a key role in flexibly guiding reward-based decision-making. VFC is composed of a set of anatomically distinct subdivisions that are within the orbitofrontal cortex, ventrolateral prefrontal cortex, and anterior insula. In part, because prior studies have lacked the resolution to test for differences, it is unclear if neural representations related to decision-making are dissociable across these subdivisions. Here we recorded the activity of thousands of neurons within eight anatomically defined subregions of VFC in male macaque monkeys performing a two-choice probabilistic task for different fruit juices outcomes. We found substantial variation in the encoding of decision variables across these eight subdivisions. Notably, ventrolateral subdivision 12l was unique relative to the other areas that we recorded from as the activity of single neurons integrated multiple attributes when monkeys evaluated the different choice options. Activity within 12o, by contrast, more closely represented reward probability and whether reward was received on a given trial. Orbitofrontal area 11m/l contained more specific representations of the quality of the outcome that could be earned later on. We also found that reward delivery encoding was highly distributed across all VFC subregions, while the properties of the reward, such as its flavor, were more strongly represented in areas 11m/l and 13m. Taken together, our work reveals the diversity of encoding within the various anatomically distinct subdivisions of VFC in primates.Significance statement Ventral frontal cortex (VFC) is essential for flexible decision-making and is composed of many anatomically defined subdivisions. How neural representations related to decision-making vary or not between these subdivisions is unclear. Here we recorded single neuron activity from eight anatomically distinct subdivisions of VFC while macaques made choices between stimuli based on the probability of receiving different flavored fruit juices. We report that neural representations across these subdivisions were dissociable. Area 12l exhibiting the most integrated representations of decision variables at the level of single neurons. By contrast, activity in area 12o was closely related to reward probability whereas activity in area 11m/l and 13m represented juice flavor. Thus, neural representations are distinct across anatomically separable parts of VFC.

Loneliness and Resting-State Functional Brain Connectivity Among Older Adults: A Proportional Correlation.

Loneliness reportedly increases the risk of dementia, especially Alzheimer's disease (AD). The authors' previous study demonstrated associations between loneliness and structural abnormalities observed in early-stage AD. The present study examined associations between the brain's functional characteristics and loneliness among older adults with concerns about cognitive decline. This single-center study included 43 participants (13 with amnestic mild cognitive impairment and 30 with normal cognition). Participants were assessed with the revised University of California Los Angeles (UCLA) Loneliness Scale and underwent resting-state functional MRI. Functional images were preprocessed with the CONN toolbox. The selected seeds were within brain regions reportedly associated with loneliness. One-sample general linear model analysis was performed to examine regressions of UCLA Loneliness Scale scores and functional connectivity between the seeds and regions of interest. The revised UCLA Loneliness Scale scores were positively correlated with functional connectivity between the right hippocampus and left lateral parietal lobe and were negatively correlated with functional connectivity between the left amygdala and left frontal operculum and between the left amygdala and right supramarginal gyrus. Analyses were adjusted for age, sex, and education and scores on the Mini-Mental State Examination and Clinical Dementia Rating scale. Loneliness was associated with abnormal function of the hippocampus, parts of the parietal lobe and frontal cortex, and the amygdala. These findings may suggest a possible correlation between loneliness and neurological changes associated with dementia.

Socioemotional Dysfunction From Temporal Lobe Involvement in Frontotemporal Dementia: A Preliminary Report.

Socioemotional changes, rather than cognitive impairments, are the feature that defines behavioral variant frontotemporal dementia (bvFTD). Investigators have attributed the socioemotional changes in bvFTD and other dementias to frontal lobe dysfunction; however, recent work implies a further contribution from right anterior temporal disease. The authors evaluated relationships between regional brain atrophy and socioemotional changes in both bvFTD and early-onset Alzheimer's disease (EOAD). This study explored the neuroanatomical correlations of performance on the Socioemotional Dysfunction Scale (SDS), an instrument previously shown to document socioemotional changes in bvFTD, among 13 patients with bvFTD not preselected for anterior temporal involvement and 16 age-matched patients with early-onset Alzheimer's disease (EOAD). SDS scores were correlated with volumes of regions of interest assessed with tensor-based morphometric analysis of MRI images. As expected, the bvFTD group had significantly higher SDS scores overall and smaller frontal regions compared with the EOAD group, which in turn had smaller volumes in temporoparietal regions. SDS scores significantly correlated with lateral anterior temporal lobe (ATL) atrophy, and a regression analysis that controlled for diagnosis indicated that SDS scores predicted lateral ATL volume. Within the bvFTD group, higher SDS scores were associated with smaller lateral and right ATL regions, as well as a smaller orbitofrontal cortex. Within the EOAD group, higher SDS scores were associated with a smaller right parietal cortex. This study confirms that, in addition to orbitofrontal disease, there is a prominent right and lateral ATL origin of socioemotional changes in bvFTD and further suggests that right parietal involvement contributes to socioemotional changes in EOAD.

Use of cortical hemodynamic responses in digital therapeutics for upper limb rehabilitation in patients with stroke

BackgroundStroke causes long-term disabilities, highlighting the need for innovative rehabilitation strategies for reducing residual impairments. This study explored the potential of functional near-infrared spectroscopy (fNIRS) for monitoring cortical activation during rehabilitation using digital therapeutics.MethodsThis cross-sectional study included 18 patients with chronic stroke, of whom 13 were men. The mean age of the patients was 67.0 ± 7.1 years. Motor function was evaluated through various tests, including the Fugl–Meyer assessment for upper extremity (FMA-UE), grip and pinch strength test, and box and block test. All the patients completed the digital rehabilitation program (MotoCog®, Cybermedic Co., Ltd., Republic of Korea) while being monitored using fNIRS (NIRScout®, NIRx Inc., Germany). Statistical parametric mapping (SPM) was employed to analyze the cortical activation patterns from the fNIRS data. Furthermore, the K-nearest neighbor (K-NN) algorithm was used to analyze task performance and fNIRS data to classify the severity of motor impairment.ResultsThe participants showed diverse task performances in the digital rehabilitation program, demonstrating distinct patterns of cortical activation that correlated with different motor function levels. Significant activation was observed in the ipsilesional primary motor area (M1), primary somatosensory area (S1), and contralateral prefrontal cortex. The activation patterns varied according to the FMA-UE scores. Positive correlations were observed between the FMA-UE scores and SPM t-values in the ipsilesional M1, whereas negative correlations were observed in the ipsilesional S1, frontal lobe, and parietal lobe. The incorporation of cortical hemodynamic responses with task scores in a digital rehabilitation program substantially improves the accuracy of the K-NN algorithm in classifying upper limb functional levels in patients with stroke. The accuracy for tasks, such as the gas stove-operation task, increased from 44.4% using only task scores to 83.3% when these scores were combined with oxy-Hb t-values from the ipsilesional M1.ConclusionsThe results advocated the development of tailored digital rehabilitation strategies by combining the behavioral and cerebral hemodynamic data of patients with stroke. This approach aligns with the evolving paradigm of personalized rehabilitation in stroke recovery, highlighting the need for further extensive research to optimize rehabilitation outcomes.

Alterations in electroencephalographic functional connectivity in individuals with major depressive disorder: a resting-state electroencephalogram study.

Major depressive disorder (MDD) is the leading cause of disability among all mental illnesses with increasing prevalence. The diagnosis of MDD is susceptible to interference by several factors, which has led to a trend of exploring objective biomarkers. Electroencephalography (EEG) is a non-invasive procedure that is being gradually applied to detect and diagnose MDD through some features such as functional connectivity (FC). In this research, we analyzed the resting-state EEG of patients with MDD and healthy controls (HCs) in both eyes-open (EO) and eyes-closed (EC) conditions. The phase locking value (PLV) method was utilized to explore the connection and synchronization of neuronal activities spatiotemporally between different brain regions. We compared the PLV between participants with MDD and HCs in five frequency bands (theta, 4-8 Hz; alpha, 8-12 Hz; beta1, 12-16 Hz; beta2, 16-24 Hz; and beta3, 24-40 Hz) and further analyzed the correlation between the PLV of connections with significant differences and the severity of depression (via the scores of 17-item Hamilton Depression Rating Scale, HDRS-17). During the EO period, lower PLVs were found in the right temporal-left midline occipital cortex (RT-LMOC; theta, alpha, beta1, and beta2) and posterior parietal-right temporal cortex (PP-RT; beta1 and beta2) in the MDD group compared with the HC group, while PLVs were higher in the MDD group in LT-LMOC (beta2). During the EC period, for the MDD group, lower theta and beta (beta1, beta2, and beta3) PLVs were found in PP-RT, as well as lower theta, alpha, and beta (beta1, beta2, and beta3) PLVs in RT-LMOC. Additionally, in the left midline frontal cortex-right temporal cortex (LMFC-RT) and posterior parietal cortex-right temporal cortex (PP-RMOC), higher PLVs were observed in beta2. There were no significant correlations between PLVs and HDRS-17 scores when connections with significantly different PLVs (all p > 0.05) were checked. Our study confirmed the presence of differences in FC between patients with MDD and healthy individuals. Lower PLVs in the connection of the right temporal-left occipital cortex were mostly observed, whereas an increase in PLVs was observed in patients with MDD in the connections of the left temporal with occipital lobe (EO), the circuits of the frontal-temporal lobe, and the parietal-occipital lobe. The trends in FC involved in this study were not correlated with the level of depression. The study was limited due to the lack of further analysis of confounding factors and follow-up data. Future studies with large-sampled and long-term designs are needed to further explore the distinguishable features of EEG FC in individuals with MDD.

Alterations in Neural Activation During Facial Emotion Processing in Adolescent Male Participants With Klinefelter Syndrome.

Klinefelter syndrome (KS) is the most common sex-chromosome aneuploidy (47,XXY), affecting 1 in 500 male participants. The phenotype of male participants with KS includes both physical features, such as tall stature and testicular insufficiency, and behavioral alterations, including difficulties in social functioning, anxiety, and depression. Studies examining underlying neural alterations associated with the behavioral phenotype, however, are sparse. We aimed to address this gap in knowledge using functional magnetic resonance imaging in conjunction with an emotion processing paradigm. Functional magnetic resonance imaging was conducted on 38 children and adolescents with KS (Mage = 12.85, SD = 2.45) and 47 typical developing (control) boys (Mage = 12.04, SD = 1.82) as they completed a facial emotion processing task. Group differences in activation occurring during the processing of angry versus neutral faces were examined while controlling for age. The results indicated that relative to typically developing boys, boys with KS exhibited anomalous increases in activation of frontal, temporal, and occipital cortices. Within the KS group, secondary analyses indicated that greater activation in these regions was associated with more internalizing symptoms (e.g., anxiety, depression, withdrawn behaviors) and greater social impairments (e.g., social cognition, social communication, social motivation, social communication and interaction, functional communication). The findings from this study indicate a possible neural correlation for difficulties in social and emotional function in KS and add to a growing body of research aimed at increasing our understanding of neural biomarkers in this condition. Future studies that examine the influence of testosterone-replacement therapy on these differences are warranted.

Decision-making shapes dynamic inter-areal communication within macaque ventral frontal cortex.

Macaque ventral frontal cortex is comprised of a set of anatomically heterogeneous and highly interconnected areas. Collectively these areas have been implicated in many higher-level affective and cognitive processes, most notably the adaptive control of decision-making. Despite this appreciation, little is known about how subdivisions of ventral frontal cortex dynamically interact with each other during decision-making. Here we assessed functional interactions between areas by analyzing the activity of thousands of single neurons recorded from eight anatomically defined subdivisions of ventral frontal cortex in macaques performing a visually guided two-choice probabilistic task for different fruit juices. We found that the onset of stimuli and reward delivery globally increased communication between all parts of ventral frontal cortex. Inter-areal communication was, however, temporally specific, occurred through unique activity subspaces between areas, and depended on the encoding of decision variables. In particular, areas 12l and 12o showed the highest connectivity with other areas while being more likely to receive information from other parts of ventral frontal cortex than to send it. This pattern of functional connectivity suggests a role for these two areas in integrating diverse sources of information during decision processes. Taken together, our work reveals the specific patterns of interareal communication between anatomically connected subdivisions of ventral frontal cortex that are dynamically engaged during decision-making.

Anatomy and Microsurgical Relevance of the Outer Arachnoid Envelope around the Olfactory Bulb Based on Endoscopic Cadaveric Observations.

There is high risk of injury to the olfactory tract and olfactory bulb during surgery of the anterior cranial fossa. The goal of this study was to describe the outer arachnoid envelope around the olfactory bulb, which plays a significant role in approach-related injury of the nerve. A total of 20 fresh human cadaveric heads were examined. Five cadaveric heads were used to describe a gross overview of the topographic anatomy of the outer arachnoid cover of the olfactory bulb. In 15 cadaveric heads, endoscopic surgical approaches were performed to examine the in situ undisrupted anatomy of the outer arachnoid around the olfactory bulb. Four cadaveric heads were used for the lateral subfrontal approach, 5 heads for the medial subfrontal approach, 3 heads for the median subfrontal approach, and 3 heads for the anterior interhemispheric approach. The outer arachnoid membrane of the frontal lobe attaches the olfactory bulb strongly to the above lying olfactory sulcus. Only the most rostral portion of the olfactory bulb became slightly detached from the frontal lobe. The outer arachnoid forms a decent protrusion around the tip of the olfactory bulbs. The fila olfactoria have their own outer arachnoid cover as a continuation of the same layer of the olfactory bulb. The effect of brain retraction and manipulation forces on the olfactory bulb and the role of the arachnoid membranes located here were visually analyzed and described in detail through the four different neurosurgical approaches we performed. The results of our observations provide important anatomical details for preserving the sense of smell during neurosurgical procedures.

White matter and cortical gray matter microstructural abnormalities in new daily persistent headache: a NODDI study.

New daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH. This study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson's correlation analysis between the NODDI indicators and clinical characteristics. Compared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction. Our research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH.

White matter and cortical gray matter microstructural abnormalities in new daily persistent headache: a NODDI study

BackgroundNew daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH.MethodsThis study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson’s correlation analysis between the NODDI indicators and clinical characteristics.ResultsCompared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction.ConclusionsOur research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH.