Cortical Brain Function Research Articles

Brain functional gradients are related to cortical folding gradient.

Cortical folding is closely linked to brain functions, with gyri acting more like local functional "hubs" to integrate information than sulci do. However, understanding how anatomical constraints relate to complex functions remains fragmented. One possible reason is that the relationship is estimated on brain mosaics divided by brain functions and cortical folding patterns. The boundaries of these hypothetical hard-segmented mosaics could be subject to the selection of functional/morphological features and as well as the thresholds. In contrast, functional gradient and folding gradient could provide a more feasible and unitless platform to mitigate the uncertainty introduced by boundary definition. Based on the MRI datasets, we used cortical surface curvature as the folding gradient and related it to the functional connectivity transition gradient. We found that, at the local scale, the functional gradient exhibits different function transition patterns between convex/concave cortices, with positive/negative curvatures, respectively. At the global scale, a cortex with more positive curvature could provide more function transition efficiency and play a more dominant role in more abstractive functional networks. These results reveal a novel relation between cortical morphology and brain functions, providing new clues to how anatomical constraint is related to the rise of an efficient brain function architecture.

Mapping neural correlates of biological motion perception in autistic children using high-density diffuse optical tomography

BackgroundAutism spectrum disorder (ASD), a neurodevelopmental disorder defined by social communication deficits plus repetitive behaviors and restricted interests, currently affects 1/36 children in the general population. Recent advances in functional brain imaging show promise to provide useful biomarkers of ASD diagnostic likelihood, behavioral trait severity, and even response to therapeutic intervention. However, current gold-standard neuroimaging methods (e.g., functional magnetic resonance imaging, fMRI) are limited in naturalistic studies of brain function underlying ASD-associated behaviors due to the constrained imaging environment. Compared to fMRI, high-density diffuse optical tomography (HD-DOT), a non-invasive and minimally constraining optical neuroimaging modality, can overcome these limitations. Herein, we aimed to establish HD-DOT to evaluate brain function in autistic and non-autistic school-age children as they performed a biological motion perception task previously shown to yield results related to both ASD diagnosis and behavioral traits.MethodsWe used HD-DOT to image brain function in 46 ASD school-age participants and 49 non-autistic individuals (NAI) as they viewed dynamic point-light displays of coherent biological and scrambled motion. We assessed group-level cortical brain function with statistical parametric mapping. Additionally, we tested for brain-behavior associations with dimensional metrics of autism traits, as measured with the Social Responsiveness Scale-2, with hierarchical regression models.ResultsWe found that NAI participants presented stronger brain activity contrast (coherent > scrambled) than ASD children in cortical regions related to visual, motor, and social processing. Additionally, regression models revealed multiple cortical regions in autistic participants where brain function is significantly associated with dimensional measures of ASD traits.LimitationsOptical imaging methods are limited in depth sensitivity and so cannot measure brain activity within deep subcortical regions. However, the field of view of this HD-DOT system includes multiple brain regions previously implicated in both task-based and task-free studies on autism.ConclusionsThis study demonstrates that HD-DOT is sensitive to brain function that both differentiates between NAI and ASD groups and correlates with dimensional measures of ASD traits. These findings establish HD-DOT as an effective tool for investigating brain function in autistic and non-autistic children. Moreover, this study established neural correlates related to biological motion perception and its association with dimensional measures of ASD traits.

Scalp Acupuncture Synchronizing Dual Task Gait for Enhancing Prefrontal Cortex Response.

Studies have shown that motor-cognitive dual task can greatly improve motor/cognitive function. However, the therapeutic effect of motor-cognitive dual task is still limited. How to improve dual-task performance is the key to solving this problem. Scalp acupuncture is a non-drug intervention method of traditional Chinese medicine to treat brain-derived diseases by acupuncturing the corresponding projection area of cerebral cortex function on the scalp. Studies have shown that scalp acupuncture helps improve neuronal damage and cognitive dysfunction and plays a neuroprotective function in central nervous system diseases. However, no relevant studies have discussed the synergistic gain effect of motor-cognitive dual task and scalp acupuncture. Therefore, this protocol aims to demonstrate the standardized operation of scalp acupuncture synchronizing motor-cognitive dual task and motor-cognitive dual task and compares the differences between these two tasks in healthy subjects through a randomized cross-over trial. This protocol initially revealed the possible influence mechanism of scalp acupuncture synchronizing motor-cognitive dual task on cognitive performance, gait control, and cortical brain function, which can provide new ideas and a theoretical basis for clinical exploration of new and effective non-drug treatment of integrated Chinese and Western medicine.

Anterior cingulate cortex-related functional hyperconnectivity underlies sensory hypersensitivity in Grin2b-mutant mice

Sensory abnormalities are observed in ~90% of individuals with autism spectrum disorders (ASD), but the underlying mechanisms are poorly understood. GluN2B, an NMDA receptor subunit that regulates long-term depression and circuit refinement during brain development, has been strongly implicated in ASD, but whether GRIN2B mutations lead to sensory abnormalities remains unclear. Here, we report that Grin2b-mutant mice show behavioral sensory hypersensitivity and brain hyperconnectivity associated with the anterior cingulate cortex (ACC). Grin2b-mutant mice with a patient-derived C456Y mutation (Grin2bC456Y/+) show sensory hypersensitivity to mechanical, thermal, and electrical stimuli through supraspinal mechanisms. c-fos and functional magnetic resonance imaging indicate that the ACC is hyperactive and hyperconnected with other brain regions under baseline and stimulation conditions. ACC pyramidal neurons show increased excitatory synaptic transmission. Chemogenetic inhibition of ACC pyramidal neurons normalizes ACC hyperconnectivity and sensory hypersensitivity. These results suggest that GluN2B critically regulates ASD-related cortical connectivity and sensory brain functions.

Negative association between neurovascular coupling and cortical gray matter volume during the lifespan.

Recent studies have established the moment-to-moment turnover of the blood-oxygen-level-dependent signal (TBOLD) at resting state as a key measure of local cortical brain function. Here, we sought to extend that line of research by evaluating TBOLD in 70 cortical areas with respect to corresponding brain volume, age, and sex across the lifespan in 1,344 healthy participants including 633 from the Human Connectome Project (HCP)-Development cohort (294 males and 339 females, age range 8-21 yr) and 711 healthy participants from HCP-Aging cohort (316 males and 395 females, 36-90 yr old). In both groups, we found that 1) TBOLD increased with age, 2) volume decreased with age, and 3) TBOLD and volume were highly significantly negatively correlated, independent of age. The inverse association between TBOLD and volume was documented in nearly all 70 brain areas and for both sexes, with slightly stronger associations documented for males. The strong correspondence between TBOLD and volume across age and sex suggests a common influence such as chronic neuroinflammation contributing to reduced cortical volume and increased TBOLD across the lifespan.NEW & NOTEWORTHY We report a significant negative association between resting functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) signal turnover (TBOLD) and cortical gray matter volume across the lifespan, such that TBOLD increased whereas volume decreased. We attribute this association to a hypothesized chronic, low-grade neuroinflammation, probably induced by various neurotropic pathogens, including human herpes viruses known to be dormant in the brain in a latent state and reactivated by stress, fever, and various environmental exposures, such as ultraviolet light.

Use of Quantitative Electroencephalography to Inform Age- and Sex-Related Differences in NMDA Receptor Function Following MK-801 Administration.

Sex- and age-related differences in symptom prevalence and severity have been widely reported in patients with schizophrenia, yet the underlying mechanisms contributing to these differences are not well understood. N-methyl-D-aspartate (NMDA) receptor hypofunction contributes to schizophrenia pathology, and preclinical models often use NMDA receptor antagonists, including MK-801, to model all symptom clusters. Quantitative electroencephalography (qEEG) represents a translational approach to measure neuronal activity, identify targetable biomarkers in neuropsychiatric disorders and evaluate possible treatments. Abnormalities in gamma power have been reported in patients with schizophrenia and correspond to psychosis and cognitive impairment. Further, as gamma power reflects cortical glutamate and GABA signaling, it is highly sensitive to changes in NMDA receptor function, and NMDA receptor antagonists aberrantly increase gamma power in rodents and humans. To evaluate the role of sex and age on NMDA receptor function, MK-801 (0.03-0.3 mg/kg, SC) was administered to 3- and 9-month-old male and female Sprague-Dawley rats that were implanted with wireless EEG transmitters to measure cortical brain function. MK-801-induced elevations in gamma power were observed in 3-month-old male and female and 9-month-old male rats. In contrast, 9-month-old female rats demonstrated blunted maximal elevations across a wide dose range. Importantly, MK-801-induced hyperlocomotor effects, a common behavioral screen used to examine antipsychotic-like activity, were similar across all groups. Overall, sex-by-age-related differences in gamma power support using qEEG as a translational tool to evaluate pathological progression and predict treatment response across a heterogeneous population.

Gene knockout of RNA binding motif 5 in the brain alters RIMS2 protein homeostasis in the cerebellum and Hippocampus and exacerbates behavioral deficits after a TBI in mice

RNA binding motif 5 (RBM5) is a tumor suppressor in cancer but its role in the brain is unclear. We used conditional gene knockout (KO) mice to test if RBM5 inhibition in the brain affects chronic cortical brain tissue survival or function after a controlled cortical impact (CCI) traumatic brain injury (TBI). RBM5 KO decreased baseline contralateral hemispheric volume (p < 0.0001) and exacerbated ipsilateral tissue loss at 21 d after CCI in male mice vs. wild type (WT) (p = 0.0019). CCI injury, but not RBM5 KO, impaired beam balance performance (0-5d post-injury) and swim speed on the Morris Water Maze (MWM) (19-20d) (p < 0.0001). RBM5 KO was associated with mild learning impairment in female mice (p = 0.0426), reflected as a modest increase in escape latency early in training (14-18d post-injury). However, KO did not affect spatial memory at 19d post-injury in male or in female mice but it was impaired by CCI in females (p = 0.0061). RBM5 KO was associated with impaired visual function in male mice on the visible platform test at 20d post-injury (p = 0.0256). To explore signaling disturbances in KOs related to behavior, we first cross-referenced known brain-specific RBM5-regulated gene targets with genes in the curated RetNet database that impact vision. We then performed a secondary literature search on RBM5-regulated genes with a putative role in hippocampal function. Regulating synaptic membrane exocytosis 2 (RIMS) 2 was identified as a gene of interest because it regulates both vision and hippocampal function. Immunoprecipitation and western blot confirmed protein expression of a novel ~170 kDa RIMS2 variant in the cerebellum, and in the hippocampus, it was significantly increased in KO vs WT (p < 0.0001), and in a sex-dependent manner (p = 0.0390). Furthermore, male KOs had decreased total canonical RIMS2 levels in the cerebellum (p = 0.0027) and hippocampus (p < 0.0001), whereas female KOs had increased total RIMS1 levels in the cerebellum (p = 0.0389). In summary, RBM5 modulates brain function in mammals. Future work is needed to test if RBM5 dependent regulation of RIMS2 splicing effects vision and cognition, and to verify potential sex differences on behavior in a larger cohort of mice.

Retraction: To Study the Effect of Anterior Palatal Surface Modifications of Complete Denture on Speech Intelligibility Oral Perception and Cortical Brain Function Activity: An In Vivo Study.

[This retracts the article DOI: 10.7759/cureus.33595.].

To Study the Effect of Anterior Palatal Surface Modifications of Complete Denture on Speech Intelligibility Oral Perception and Cortical Brain Function Activity: An In Vivo Study.

The classic maxillary full denture covers the whole palate,preventing the tongue from touching the denture base tissues itself.Thus, it has deleterious effects on cortical brain function and the ability to understand spoken language. This study aimed to determinethe effect of anterior palatal surface modifications of the complete denture on speech intelligibility oral perception and cortical brain function activity. This study compared the speech clarity, oral discernment, and cortical mind capability activity of complete denture wearers in three study groups: a)complete denture wearers with a small opening (SO) in the maxillary front palatal base; b) complete denture patients who wear regular complete denture; c) complete denture patients who did not wear complete denture; and d) complete denture patients who wear a functionally contoured modified palate(FCMP). Patients with no teeth at all underwent four phases of testing to assess their cognitive abilities and speech quality (pitch and volume). In the first phase, partial dentures were used. During phase 2, a conventional full denture was inserted.In the third phase, a palatal base denture was functionally altered. In phase 4, dentures with a little aperture at the front of the palatal base were used. Results:The values of pitch and intensity of sound in category A with FCMP modification I were 180.76 ± 24.12 and 73.27 ± 9.74,respectively. On the other hand, the values of pitch and intensity of sound in category B with FCMP modification I were 185.41 ± 27.29and 73.91 ± 8.31, respectively. The values of pitch and intensity of sound in category A with SO modification II were 188.52 ± 21.11 and 76.13 ± 5.21, respectively. On the other hand, the values of pitch and intensity of sound in category B with SO modification II were 194.59 ± 24.02and 75.21 ± 6.12, respectively. The findings for values of pitch and intensity were statistically significant among the four phases (p < 0.001). The highest speech intelligibility and cortical brain function were observed in phase 4 in both categories A and B, with the highest scores by experts of 3.21 and 3.42, respectively. Conclusion:Based on the findings of this in vivo investigation, it can be concluded that using modified dentures (modification types I and II) following denture installation improves speech intelligibility, oral perception, and cortical brain function activity.

Heart Transplantation after Circulatory Death: It Is Time to Redefine Death According to Irreversible Cessation of the Circulation and Reconcile It with Irreversible Cessation of Brain Function

In this article, we examine whether organ procurement of the heart and transplantation contravenes the dead donor rule and Australian legislative definitions of death as an irreversible cessation of the circulation. We contend that this practice upholds a long-held belief that donors of any organs after cessation of the circulation are not actually dead at the time of procurement – principally because of insufficient time lapse between cessation of the circulation and procurement of organs. Moreover, the fact that the transplanted heart functions in a recipient proves the donor’s circulation had never actually ceased irreversibly. Nonetheless, we suggest that this practice may be legitimised by amending legislation to redefine death as an irreversible cessation of brain function preceded by cessation of the circulation and requiring medical proof that the donor’s cortical brain function has ceased function before organ procurement.

Heritability of brain neurovascular coupling.

The moment-to-moment variation of neurovascular coupling in the brain was determined by computing the moment-to-moment turnover of the blood-oxygen-level-dependent signal (TBOLD) at resting state. Here we show that 1) TBOLD is heritable, 2) its heritability estimates are highly correlated between left and right hemispheres, and 3) the degree of its heritability is determined, in part, by the anatomical proximity of the brain areas involved. We also show that the regional distribution of TBOLD in the cortex is significantly associated with that of the vesicular acetylcholine transporter. These findings establish that TBOLD as a key heritable measure of local cortical brain function captured by neurovascular coupling.NEW & NOTEWORTHY Here we show that the sample-to-sample turnover of the resting state fMRI blood-oxygen-level-dependent turnover (TBOLD) is heritable, the left and right hemisphere TBOLD heritabilities are highly correlated, and TBOLD heritability varies among cortical areas. Moreover, we documented that TBOLD is associated with the regional cortical distribution of the vesicular acetylcholine transporter.

Persistent Postural-Perceptual Dizziness (PPPD) from Brain Imaging to Behaviour and Perception.

Persistent postural-perceptual dizziness (PPPD) is a common cause of chronic dizziness associated with significant morbidity, and perhaps constitutes the commonest cause of chronic dizziness across outpatient neurology settings. Patients present with altered perception of balance control, resulting in measurable changes in balance function, such as stiffening of postural muscles and increased body sway. Observed risk factors include pre-morbid anxiety and neuroticism and increased visual dependence. Following a balance-perturbing insult (such as vestibular dysfunction), patients with PPPD adopt adaptive strategies that become chronically maladaptive and impair longer-term postural behaviour. In this article, we explore the relationship between behavioural postural changes, perceptual abnormalities, and imaging correlates of such dysfunction. We argue that understanding the pathophysiological mechanisms of PPPD necessitates an integrated methodological approach that is able to concurrently measure behaviour, perception, and cortical and subcortical brain function.

EP156: Pilot study of functional near-infrared spectroscopy of cortical brain function during an auditory and visual N-back task in Klinefelter syndrome

47,XXY (Klinefelter syndrome) is a sex chromosomal aneuploidy, occurring in approximately 1:660 live male births, that results in an extra X chromosome. Most notably, the neurodevelopmental presentation of 47,XXY is associated with deficits in speech and language processing, motor delays, and reading disorders, with language processing and neurodevelopmental impairments. Previous literature has reported structural brain differences in individuals with 47,XXY. Specifically, thinner cortex structure in the temporal and frontal lobes has been reported, including decreased caudate volumes, typically believed to be the origin of speech and language dysfunction associated with this disorder.

Surface-Based Amplitude of Low-Frequency Fluctuation Alterations in Patients With Tinnitus Before and After Sound Therapy: A Resting-State Functional Magnetic Resonance Imaging Study.

This study aimed to investigate abnormal tinnitus activity by evaluating brain surface-based amplitude of low-frequency fluctuation (ALFF) changes detected by resting-state functional magnetic resonance imaging (RS-fMRI) in patients with idiopathic tinnitus before and after 24 weeks of sound therapy. We hypothesized that sound therapy could gradually return cortical local brain function to a relatively normal range. In this prospective observational study, we recruited thirty-three tinnitus patients who had undergone 24 weeks of sound therapy and 26 matched healthy controls (HCs). For the two groups of subjects, we analyzed the spontaneous neural activity of tinnitus patients by cortical ALFF and detected its correlation with clinical indicators of tinnitus. Patients’ Tinnitus Handicap Inventory (THI) scores were assessed to determine the severity of their tinnitus before and after treatment. Two-way mixed model analysis of variance and Pearson’s correlation analysis were used in the statistical analysis. Student–Newman–Keuls tests were used in the post hoc analysis. Interaction effects between the two groups and between the two scans revealing local neural activity as assessed by ALFF were observed in the bilateral dorsal stream visual cortex (DSVC), bilateral posterior cingulate cortex (PCC), bilateral anterior cingulate and medial prefrontal cortex (ACC and MPC), left temporo-parieto-occipital junction (TPOJ), left orbital and polar frontal cortex (OPFC), left paracentral lobular and mid cingulate cortex (PCL and MCC), right insular and frontal opercular cortex (IFOC), and left early visual cortex (EVC). Importantly, local functional activity in the left TPOJ and right PCC in the patient group was significantly lower than that in the HCs at baseline and was increased to relatively normal levels after treatment. The 24-week sound therapy tinnitus group demonstrated significantly higher ALFF in the left TPOJ and right PCC than in the tinnitus baseline group. Also, compared with the HC baseline group and the 24-week HC group, the 24-week sound therapy tinnitus group demonstrated slightly lower or higher ALFF in the left TPOJ and right PCC, and there were no differences between the 24-week sound therapy tinnitus and HC groups. Decreased THI scores and ALFF changes in the abovementioned brain regions were not correlated. Taken together, surface-based RS-fMRI can provide more subtle local functional activity to explain the mechanism of tinnitus treatment, and long-term sound therapy had a normalizing effect on tinnitus patients.

Changes in Brain Functional Network Connectivity in Adult Moyamoya Diseases.

The online version contains supplementary material available at (10.1007/s11571-021-09666-1).

Role of axonal fibers in the cortical folding patterns: A tale of variability and regularity

Cortical folding is one of the most complex processes that occur during the normal development of the human brain. Despite variability in folding patterns of different individuals, there are a few specific types of preserved folding patterns within individuals or across species. The origin and formation mechanism of variable or regular folding patterns in the human brain yet remains to be thoroughly explored. This study aims to delineate how the interplay between the differential tangential growth of cerebral cortex and axonal fiber tension induces and regulates the folding patterns in a developing human brain. To achieve this aim, an image-based multiscale mechanical model on the basis of the embedded nonlinear finite element method is employed to investigate a set of growth and folding scenarios. Our results show that the differential growth between cortical and subcortical layers is the main inducer of cortical folding. In addition, the gyrification of the cortex pulls the areas with a high density of stiff axonal fiber bundles towards gyri rather than sulci; therefore, axonal fiber bundles induce symmetry breaking, and regulate the folding patterns. In particular, spatial distribution of axonal fiber bundles is the determinant factor to control the locations of gyri and sulci. In conclusion, we propose that neural wiring might be the main regulator of folding patterns responsible for the formation of regular cortical folding patterns. This study provides a deeper understanding of cortical folding and its morphogenesis which are the key to interpreting normal brain development and growth. Statement of SignificanceThere is a vital need to discover the role of axonal fibers of the brain’s connectivity on the formation and modulation of folding patterns in the developing human brain. The lack of knowledge of the physical interplay between cortical folding and neural wiring is a critical barrier to the fundamental understanding of the relationship between cortical folding, brain connectivity, and brain function in different neurodevelopmental stages. This study by using image-based multiscale mechanical models investigates the role of the differential tangential growth of cerebral cortex and axonal fibers in the formation and regulation of the folding patterns in the developing human brain. This is the first study to explain why despite variation in folding patterns, there are some specific types of regular shapes within individuals or across species and why axonal fibers connected to gyri in the human brain are typically denser than those connected to sulci. The study has a positive impact on the deeper understanding of cortical folding and its morphogenesis that is the key to interpreting the normal development of the human brain during the early stages of growth.

Resilience, Psychological Characteristics, and Resting-state Brain Cortical Activity in Athletes and Non-athletes

Background: Athletes might build long-term resilience due to their need to adapt constantly to stressful situations. Further, physical activity is a powerful tool for stress-release, and controlling anxiety and depressive symptoms which might induce resilience by enhancing coping skills. Objective: This study aimed to compare the resilience, psychological characteristics, and the resting-state brain cortical activity of athletes and non-athletes. The secondary goal was to identify which variables could predict the resilience score. Methods: Ninety participants were divided into three groups, athlete (n=30), physically active (n=30) and sedentary (n=30), and asked to fill out the international physical activity questionnaire – short version (IPAQ), the resilience scale, the Beck depression inventory (BDI) and the trait and state anxiety inventory (STAI). Moreover, resting-state brain cortical activity was recorded by using an EEG to compute the standardized low-resolution brain electromagnetic tomography (sLORETA) analyses. Results: Significant differences between groups were observed in terms of resilience (X2=8.52; p=0.014) and physical activity level (X 2=76.07; p&lt;0.001), with the athletes presenting higher values. Lower anxiety and depression, and higher physical activity levels were associated with higher resilience scores (R2=0.45; p=0.02). The results of sLORETA showed higher activity for sedentary individuals compared to athletes in frontal areas (Broadmann Area-BA 6, BA 8, BA 9), as well as when compared to physically active individuals in the superior frontal gyrus (BA 9). Additionally, physically active individuals presented less activity than athletes in the inferior occipital gyrus (BA 18). Conclusion: The results suggest that the physically active and athlete groups may have built a more resilient profile (compared to sedentary), have similar anxiety and depressive symptoms, and present a divergent resting-state brain cortical activity from the sedentary group, mainly in prefrontal areas. These findings suggest that regular physical activity and sports should be encouraged to aid in enhancing resilience and resting-state brain cortical function, and consequently, improving mental health.

Sex and oestrogen receptor β have modest effects on gene expression in the mouse brain posterior cortex.

IntroductionSex differences in brain cortical function affect cognition, behaviour and susceptibility to neural diseases, but the molecular basis of sexual dimorphism in cortical function is still largely unknown. Oestrogen and oestrogen receptors (ERs), specifically ERβ, the most abundant ER in the cortex, may play a role in determining sex differences in gene expression, which could underlie functional sex differences. However, further investigation is needed to address brain region specificity of the effects of sex and ERβ on gene expression. The goal of this study was to investigate sex differences in gene expression in the mouse posterior cortex, where sex differences in transcription have never been examined, and to determine how genetic ablation of ERβ affects transcription.MethodsIn this study, we performed unbiased transcriptomics on RNA from the posterior cortex of adult wild‐type and ERβ knockout mice (n = 4/sex/genotype). We used unbiased clustering to analyse whole‐transcriptome changes between the groups. We also performed differential expression analysis on the data using DESeq2 to identify specific changes in gene expression.ResultsWe found only 27 significantly differentially expressed genes (DEGs) in wild‐type (WT) males vs females, of which 17 were autosomal genes. Interestingly, in ERβKO males vs females all the autosomal DEGs were lost. Gene Ontology analysis of the subset of DEGs with sex differences only in the WT cortex revealed a significant enrichment of genes annotated with the function ‘cation channel activity’. Moreover, within each sex we found only a few DEGs in ERβKO vs WT mice (8 and 5 in males and females, respectively).ConclusionsOverall, our results suggest that in the adult mouse posterior cortex there are surprisingly few sex differences in gene expression, and those that exist are mainly related to cation channel activity. Additionally, they indicate that brain region‐specific functional effects of ERβ may be largely post‐transcriptional.

Prenatal sevoflurane exposure causes neuronal excitatory/inhibitory imbalance in the prefrontal cortex and neurofunctional abnormality in rats

The balance of excitatory and inhibitory neurons in the central nervous system is critical for maintaining brain function and sevoflurane, a general anesthetic and an GABA receptor modulator, may change the balance of excitatory and inhibitory neurons in the cortex during early brain development. Herein, we investigated whether prenatal sevoflurane exposure (PSE) disturbs cortical neuronal development and brain function. Pregnant rats at the gestational day 14.5 were subjected to sevoflurane exposure at 3.0% for 3 h and their offspring were studied thereafter. We found a significant increase of parvalbumin-positive neurons, vesicular GABA transporter (VGAT) and GAD67 expression, and GABA neurotransmitter, and a significant decrease of vesicular glutamate transporter 1 (VGLUT1) expression and glutamate in the medial prefrontal cortex (mPFC) of offspring. Pyramidal neurons showed atrophy with shorter dendrites, less branches and lower spine density visualized by Golgi stain and a decrease of excitability with the increased miniature inhibitory postsynaptic current (mIPSC) frequency and amplitude, the decreased miniature excitatory postsynaptic current (mEPSC) frequency and excitation/inhibition (E/I) ratio using whole-cell recording in offspring. There was a significant increase of inhibitory synapse in the mPFC detected by electron microscopy. Furthermore, PSE animals showed hypo-excitatory phenotype including depression-like behaviors and learning deficits. Thus, our studies provide novel evidence that PSE causes the persisted imbalance of excitatory and inhibitory neurons in the mPFC, and this is very likely the mechanisms of the sevoflurane-induced brain functional abnormalities.

Cerebellar and prefrontal-cortical engagement during higher-order rule learning in older adulthood

To date most aging research has focused on cortical systems and networks, ignoring the cerebellum which has been implicated in both cognitive and motor function. Critically, older adults (OA) show marked differences in cerebellar volume and functional networks, suggesting it may play a key role in the behavioral differences observed in advanced age. OA may be less able to recruit cerebellar resources due to network and structural differences. Here, 26 young adults (YA) and 25 OA performed a second-order learning task, known to activate the cerebellum in the fMRI environment. Behavioral results indicated that YA performed significantly better and learned more quickly compared to OA. Functional imaging detailed robust parietal and cerebellar activity during learning (compared to control) blocks within each group. OA showed increased activity (relative to YA) in the left inferior parietal lobe in response to instruction cues during learning (compared to control); whereas, YA showed increased activity (relative to OA) in the left anterior cingulate to feedback cues during learning, potentially explaining age-related performance differences. Visual interpretation of effect size maps showed more bilateral posterior cerebellar activation in OA compared to YA during learning blocks, but early learning showed widespread cerebellar activation in YA compared to OA. There were qualitatively large age-related differences in cerebellar recruitment in terms of effect sizes, yet no statistical difference. These findings serve to further elucidate age-related differences and similarities in cerebellar and cortical brain function and implicate the cerebellum and its networks as regions of interest in aging research.