Prefrontal Cortex Function Research Articles

COVID-19 Exacerbates Neurovascular Uncoupling and Contributes to Endothelial Dysfunction in Patients with Mild Cognitive Impairment

Mild cognitive impairment (MCI) affects nearly 20% of older adults worldwide, with no targetable interventions for prevention. COVID-19 adversely affects cognition, with >70% of older adults with Long COVID presenting with cognitive complaints. Neurovascular coupling (NVC), an essential mechanism of cognitive function, declines with aging and is further attenuated in neurocognitive disorders. The effect of COVID-19 on NVC responses has yet to be addressed in older adults who are vulnerable to dementia progression. Participants with MCI and a history of COVID-19 (COV+, N = 31) and MCI participants with no history of infection (COV− N = 11) participated in this cross-sectional study to determine if COVID-19 affects cerebrocortical NVC responses and vascular function. Functional near-infrared spectroscopy was used to measure cerebrocortical NVC responses, and endothelial function was assessed via insonation of the brachial artery during a flow-mediated dilation protocol. NVC responses were elicited by the working memory n-back paradigm. NVC in the left dorsolateral prefrontal cortex and endothelial function was decreased in the COV+ group compared to the COV− group. These data provide mechanistic insight into how COVID-19 may exacerbate long-term cognitive sequela seen in older adults, highlighting the urgent need for further research and clinical trials to explore novel therapeutic interventions aimed at preserving/restoring NVC.

Surgery-induced neuroinflammatory transcriptional programs in medial prefrontal cortex of mice during early phase of perioperative neurocognitive disorders.

Patients receiving anesthesia and surgery may experience cognitive dysfunction, memory deficits, and mental disturbances, which are referred to as perioperative neurocognitive disorders (PND). The function of the medial prefrontal cortex (mPFC) is disrupted during early phase of PND. To gain insight into the mechanisms of PND, we collected mouse mPFC tissues 6 h post-surgery and performed RNA sequencing analysis. In total, 178 differentially expressed genes (DEGs) were identified, including 105 upregulated and 73 downregulated genes. Bioinformatic analysis highlighted the significant enrichment of these DEGs in several immune-related biological processes and signaling pathways, suggesting that pronounced neuroinflammatory transcriptional programming in the mPFC was evoked during early phase of PND. Interleukin-6 level increased in both serum and mPFC, while the mRNA levels of Il-6, Tnf-α, and Il-1β remained unchanged. Taken together, our findings suggest that a distinct and acute neuroinflammatory response in the mPFC is evoked after peripheral surgery, which might play a key role in the development of PND.

Prefrontal serotonin depletion delays reversal learning and increases theta synchronization of the infralimbic-prelimbic-orbitofrontal prefrontal cortex circuit.

Prefrontal serotonin plays a role in the expression of flexible behavior during reversal learning tasks as its depletion delays reversal learning. However, the mechanisms by which serotonin modulates the prefrontal cortex functions during reversal learning remain unclear. Nevertheless, serotonin has been shown to modulate theta activity during spatial learning and memory. We evaluated the effects of prefrontal serotonin depletion on theta activity in the prefrontal infralimbic, prelimbic, and orbitofrontal (IL, PL, and OFC) subregions of male rats during a spatial reversal learning task in an aquatic T-maze. Prefrontal serotonin depletion delayed spatial reversal learning and increased theta activity power in the PL and OFC. Furthermore, animals with serotonin depletion had increased functional coupling between the OFC and the IL and PL cortices compared with the control group. These results indicate that serotonin regulates reversal learning through modulation of prefrontal theta activity by tuning both the power and functional synchronization of the prefrontal subregions.

Relationship Between Cognitive Estimation, Executive Functions, and Theory of Mind in Patients With Prefrontal Cortex Damage.

Conflicting evidence has arisen from the few studies that have examined the role of the prefrontal cortex and executive control functions in theory of mind (ToM). Moreover, the involvement of other cognitive domains in the ability to infer mental states is still under debate. This study aims to examine, in addition to the potential contribution of executive functions, the role of cognitive estimation in ToM abilities, given that cognitive estimation processes are strongly associated with some aspects of executive control functions. The cognitive estimation task, along with a set of neuropsychological tasks assessing executive functions, was administered to 30 patients with prefrontal cortex damage and 30 control subjects matched by gender, age, and education level. Patients with prefrontal cortex damage were impaired in all measures of executive functions, cognitive estimation, and theory of mind compared with control subjects. Regression analysis showed a significant interaction between executive measures and cognitive estimation in predicting ToM performance for patients with prefrontal cortex damage. Additionally, voxel-based lesion analysis identified a partially common bilaterally distributed prefrontal network involved in all three domains, centered within the ventral and dorsomedial areas with extension to the dorsolateral prefrontal cortex. Our findings highlight that, apart from executive functions, cognitive estimation plays a crucial role in the ability to interpret others' cognitive and emotional states in both patients with prefrontal cortex damage and control subjects.

Mu and Delta Opioid Receptors Modulate Inhibition within the Prefrontal Cortex Through Dissociable Cellular and Molecular Mechanisms.

The endogenous opioid system regulates behaviors that rely on prefrontal cortex (PFC) function. Previous studies have described Mu and Delta opioid receptor expression within cortical GABAergic interneurons, but a detailed understanding of how opioids regulate different interneuron subtypes and cortical microcircuits has not been reported. We use whole-cell patch-clamp electrophysiology, genetically engineered mice, and optogenetics to assess MOR and DOR regulation of PFC inhibitory transmission, demonstrating that MOR and DOR inhibition of interneurons display qualitative and quantitative variation across GABAergic circuits within mouse prelimbic PFC.

Hubungan Penggunaan Gadget Terhadap Potensi Gangguan Pemusatan Perhatian Dan Hiperaktivitas Pada Anak Prasekolah Dipaud Bougenville Cawang

This study examines the relationship between gadget use and the potential for Attention Deficit and Hyperactivity Disorders (GPPH) in preschool children. The American Academy of Pediatrics recommends gadget use for preschoolers for no more than 1 hour per day. Gadget addiction can affect a child's brain development because excessive production of the hormone dopamine disrupts the maturity of the prefrontal cortex function, namely controlling emotions, self-control, responsibility, decision making and other moral values. Excessive use of gadgets can also cause problems such as ADHD. The intensity of gadget use was measured using a gadget usage habits questionnaire and GPPH using the Abbreviated Conners Rating Scale (ACRS). This study used a cross-sectional design with 27 respondents in PAUD Bougenville, Cawang with a percentage of 100%, and as many as 29.6% had normal results with a total of 8 children and as many as 70.4% had potential ADHD results with a total of 19 people. Based on the Kendall Tau test, the p-value was 0.005 < 0.05. The results of the correlation test between the gadget intensity variable and the potential for GPPH show that between the variables there is a correlation coefficient (R) of 1,000. This can mean that there is a perfect correlation between the two variables with a strong and significant level of relationship because of the sig value. less than 0.05. It is concluded that there is a significant relationship between gadget use and the risk of attention deficit hyperactivity disorder in preschool children

Progress towards understanding risk factor mechanisms in the development of autism spectrum disorders.

Autism spectrum disorders (ASD) are a heterogenous set of syndromes characterised by social impairment and cognitive symptoms. Currently, there are limited treatment options available to help people with ASD manage their symptoms. Understanding the biological mechanisms that result in ASD diagnosis and symptomatology is an essential step in developing new interventional strategies. Human genetic studies have identified common gene variants of small effect and rare risk genes and copy number variants (CNVs) that substantially increase the risk of developing ASD. Reverse translational studies using rodent models based on these genetic variants provide new insight into the biological basis of ASD. Here we review recent findings from three ASD associated CNV mouse models (16p11.2, 2p16.3 and 22q11.2 deletion) that show behavioural and cognitive phenotypes relevant to ASD. These models have identified disturbed excitation-inhibition neurotransmitter balance, evidenced by dysfunctional glutamate and GABA signalling, as a key aetiological mechanism. These models also provide emerging evidence for serotoninergic neurotransmitter system dysfunction, although more work is needed to clarify the nature of this. At the brain network level, prefrontal cortex (PFC) dysfunctional connectivity is also evident across these models, supporting disturbed PFC function as a key nexus in ASD aetiology. Overall, published data highlight the utility and valuable insight gained into ASD aetiology from preclinical CNV mouse models. These have identified key aetiological mechanisms that represent putative novel therapeutic targets for the treatment of ASD symptoms, making them useful translational models for future drug discovery, development and validation.

Complex housing in adulthood state-dependently affects the excitation-inhibition balance in the infralimbic prefrontal cortex of male C57Bl/6 mice

The prefrontal cortex (PFC) plays an important role in social behavior and is sensitive to stressful circumstances. Challenging life conditions might change PFC function and put individuals at risk for maladaptive social behavior. The excitation-inhibition (EI) balance of prefrontal neurons appears to play a crucial role in this process. Here, we examined how a challenging life condition in C57BL/6JolaHsd mice, i.e. group-housing 6 mice in a complex environment for 10 days in adulthood, changes the EI-balance of infralimbic prefrontal neurons in layer 2/3, compared to standard pair-housing. Slices were prepared from “undisturbed” mice, i.e. the first mouse taken from the cage, or mice taken ∼15 min later, who were mildly aroused after removal of the first mouse. We observed a housing-condition by arousal-state interaction, with in the complex housing group an elevated EI-balance in undisturbed and reduced EI-balance in mildly aroused animals, while no differences were observed in standard housed animals. The change was explained by a shift in mIPSC and mEPSC frequency, while amplitudes remained unaffected. Female mice showed no housing-by-state interaction, but a main effect of housing was found for mIPSCs, with a higher frequency in complex- versus standard-housed females. No effects were observed in males who were complex-housed from a young age onwards. Explorative investigations support a potential mediating role of corticosterone in housing effects on the EI-balance of males. We argue that taking the arousal state of individuals into account is necessary to better understand the consequences of exposure to challenging life conditions for prefrontal function.

Effects of social dominance and acute social stress on morphology of microglia and structural integrity of the medial prefrontal cortex

Chronic stress increases activity of the brain’s innate immune system and impairs function of the medial prefrontal cortex (mPFC). However, whether acute stress triggers similar neuroimmune mechanisms is poorly understood. Across four studies, we used a Syrian hamster model to investigate whether acute stress drives changes in mPFC microglia in a time-, subregion-, and social status-dependent manner. We found that acute social defeat increased expression of ionized calcium binding adapter molecule 1 (Iba1) in the infralimbic (IL) and prelimbic (PL) and altered the morphology Iba1+ cells 1, 2, and 7 days after social defeat. We also investigated whether acute defeat induced tissue degeneration and reductions of synaptic plasticity 2 days post-defeat. We found that while social defeat increased deposition of cellular debris and reduced synaptophysin immunoreactivity in the PL and IL, treatment with minocycline protected against these cellular changes. Finally, we tested whether a reduced conditioned defeat response in dominant compared to subordinate hamsters was associated with changes in microglia reactivity in the IL and PL. We found that while subordinate hamsters and those without an established dominance relationships showed defeat-induced changes in morphology of Iba1+ cells and cellular degeneration, dominant hamsters showed resistance to these effects of social defeat. Taken together, these findings indicate that acute social defeat alters microglial morphology, increases markers of tissue degradation, and impairs structural integrity in the IL and PL, and that experience winning competitive interactions can specifically protect the IL and reduce stress vulnerability.

Distinct roles of prefrontal cortex neurons in set shifting.

Cognitive flexibility, the ability to adjust behavioral strategies in response to changing environmental contingencies, requires adaptive processing of internal states and contextual cues to guide goal-oriented behavior, and is dependent on prefrontal cortex (PFC) functions. However, the neurophysiological underpinning of how the PFC supports cognitive flexibility is not well understood and has been under active investigation. We recorded spiking activity from single PFC neurons in mice performing the attentional set-shifting task, where mice learned to associate different contextually relevant sensory stimuli to reward. We identified subgroups of PFC neurons encoding task context, choice and trial outcome. Putative fast-spiking neurons were more involved in representing outcome and choice than putative regular-spiking neurons. Regression model further revealed that task context and trial outcome modulated the activity of choice-encoding neurons in rule-dependent and cell type-dependent manners. Together, our data provide new evidence to elucidate PFC's role in cognitive flexibility, suggesting differential cell type-specific engagement during set shifting, and that both contextual rule representation and trial outcome monitoring underlie PFC's unique capacity to support flexible behavioral switching.

Bridging the gap: Prenatal nutrition, myelination, and schizophrenia etiopathogenesis

Schizophrenia (SZ) is a complex mental illness characterized by disturbances in thinking, emotionality, and behavior, significantly impacting the quality of life for individuals affected and those around them. The etiology of SZ involves intricate interactions between genetic and environmental factors, although the precise mechanisms remain incompletely understood. Genetic predisposition, neurotransmitter dysregulation (particularly involving dopamine and serotonin), and structural brain abnormalities, including impaired prefrontal cortex function, have been implicated in SZ development. However, increasing evidence reveals the role of environmental factors, such as nutrition, during critical periods like pregnancy and lactation. Epidemiological studies suggest that early malnutrition significantly increases the risk of SZ symptoms manifesting in late adolescence, a crucial period coinciding with peak myelination and brain maturation. Prenatal undernutrition may disrupt myelin formation, rendering individuals more susceptible to SZ pathology. This review explores the potential relationship between prenatal undernutrition, myelin alterations, and susceptibility to SZ. By delineating the etiopathogenesis, examining genetic and environmental factors associated with SZ, and reviewing the relationship between SZ and myelination disorders, alongside the impact of malnutrition on myelination, we aim to examine how malnutrition might be linked to SZ by altering myelination processes, which contribute to increasing the understanding of SZ etiology and help identify targets for intervention and management.

Preschoolers' deception related to prefrontal cortex activation: An fNIRS study

Deception is an essential part of children's moral development. Previous developmental studies have shown that children start to deceive at the age of 3 years, and as age increased to 5 years, almost all children were able to deceive for their own benefit. Although behavioral studies have indicated that the emergence and development of deception are related to cognitive abilities, their neural correlates remain poorly understood. Therefore, the present study examined the neural correlates underlying deception in preschool-aged children (N = 89, 44 % boys, age 3.13 to 5.96 years, Han Chinese) using functional near-infrared spectroscopy. A modified hide-and-seek paradigm was applied to elicit deceptive and truth-telling behaviors. The results showed that activation of bilateral dorsolateral prefrontal cortex was positively associated with the tendency to deceive an opponent in a competitive game in the 3-year-olds. In addition, 3-year-olds who showed a high tendency to deceive showed the same brain activation in the frontopolar area as 5-year-olds did when engaged in deception, whereas no such effect was found in 3-year-olds who never engaged in deception. These findings underscore the link between preschoolers’ deception and prefrontal cortex function.

Adolescent Thalamoprefrontal Inhibition Leads to Changes in Intrinsic Prefrontal Network Connectivity.

Adolescent inhibition of thalamocortical projections from postnatal days P20 to 50 leads to long-lasting deficits in prefrontal cortex function and cognition in the adult mouse. While this suggests a role of thalamic activity in prefrontal cortex maturation, it is unclear how inhibition of these projections affects prefrontal circuitry during adolescence. Here, we used chemogenetic tools to inhibit thalamoprefrontal projections in male/female mice from P20 to P35 and measured synaptic inputs to prefrontal pyramidal neurons by layer (either II/III or V/VI) and projection target (mediodorsal thalamus (MD), nucleus accumbens (NAc), or callosal prefrontal projections) 24 h later using slice physiology. We found a decrease in the frequency of excitatory and inhibitory currents in layer II/III NAc and layer V/VI MD-projecting neurons while layer V/VI NAc-projecting neurons showed an increase in the amplitude of excitatory and inhibitory currents. Regarding cortical projections, the frequency of inhibitory but not excitatory currents was enhanced in contralateral mPFC-projecting neurons. Notably, despite these complex changes in individual levels of excitation and inhibition, the overall balance between excitation and inhibition in each cell was only altered in the contralateral mPFC projections. This finding suggests homeostatic regulation occurs within subcortically but not intracortical callosal-projecting neurons. Increased inhibition of intraprefrontal connectivity may therefore be particularly important for prefrontal cortex circuit maturation. Finally, we observed cognitive deficits in the adult mouse using this narrowed window of thalamocortical inhibition.

Effects of an online mindfulness-based intervention on brain haemodynamics: a pilot randomized controlled trial using functional near-infrared spectroscopy.

Although many neuroimaging studies have evaluated changes in the prefrontal cortex during mindfulness-based interventions, most of these studies were cross-sectional studies of skilled participants or involved pre-post comparisons before and after a single session. While functional near-infrared spectroscopy is a useful tool to capture changes in the hemodynamic response of the prefrontal cortex during continuous mindfulness-based intervention, its ability to detect the accumulated effects of continuous mindfulness-based intervention is currently unclear. We investigated whether a 12-wk online mindfulness-based intervention changed the hemodynamic response of the prefrontal cortex during a verbal fluency task. Eighty-two healthy university students were randomly allocated to a 12-wk online mindfulness-based intervention group or a wait-list control group. The integral values of oxygenated hemoglobin measured using functional near-infrared spectroscopy before and after the intervention were compared to the values in the wait-list group. The intervention condition showed significantly greater functional near-infrared spectroscopy signal activation than the control condition; however, the effect sizes before and after the intervention were small. Thus, continuous mindfulness-based intervention could alter prefrontal cortex function, and functional near-infrared spectroscopy could be useful for measuring the accumulated effects of continuous mindfulness-based interventions. With a better understanding of the association between mindfulness and functional near-infrared spectroscopy signals, functional near-infrared spectroscopy can be used for biofeedback analyses.

The metacontrol of event segmentation-A neurophysiological and behavioral perspective.

During our everyday life, the constant flow of information is divided into discrete events, a process conceptualized in Event Segmentation Theory (EST). How people perform event segmentation and the resulting granularity of encapsulated segments likely depends on their metacontrol style. Yet, the underlying neural mechanisms remain undetermined. The current study examines how the metacontrol style affects event segmentation through the analysis of EEG data using multivariate pattern analysis (MVPA) and source localization analysis. We instructed two groups of healthy participants to either segment a movie as fine-grained as possible (fine-grain group) or provided no such instruction (free-segmentation group). The fine-grain group showed more segments and a higher likelihood to set event boundaries upon scene changes, which supports the notion that cognitive control influences segmentation granularity. On a neural level, representational dynamics were decodable 400 ms prior to the decision to close a segment and open a new one, and especially fronto-polar regions (BA10) were associated with this representational dynamic. Groups differed in their use of this representational dynamics to guide behavior and there was a higher sensitivity to incoming information in the Fine-grain group. Moreover, a higher likelihood to set event boundaries was reflected by activity increases in the insular cortex suggesting an increased monitoring of potentially relevant upcoming events. The study connects the EST with the metacontrol framework and relates these to overarching neural concepts of prefrontal cortex function.

Prefrontal Cortex Oxygenation During Exercise in Older Adults with Motoric Cognitive Risk Syndrome.

Motoric cognitive risk syndrome (MCR) is a pre-dementia syndrome characterized by subjective memory complaints and gait impairments that may be related to lower prefrontal cortex (PFC) function. Acute bouts of aerobic exercise are shown to improve PFC function, however, the acute effects of exercise on PFC oxygenation have not yet been examined in MCR. This study aims to characterize the PFC oxygenation responses during acute exercise in older adults with MCR. Nineteen older adults with MCR performed a submaximal cycling exercise protocol. Functional near-infrared spectroscopy (fNIRS) is used to measure concentrations of oxygenated (OxyHb) and deoxygenated (DeoxyHb) hemoglobin from the PFC. There is a trend for increased OxyHb concentrations and decreased DeooxyHb concentrations during exercise. Exercise also induced significant increases in ratings of perceived exertion (RPEs) and heart rate. A significant, positive correlation between PFC OxyHb and RPEs during the cycling exercise are also observed. The findings reveal that PFC oxygenation increases during exercise in an intensity-dependent manner and the subjective perception of exertion is associated with the magnitude of PFC oxygenation. These results suggest that moderate-intensity cycling exercise may have beneficial effects on increasing cerebral blood flow in the PFC of older adults with MCR.

Cerebellar contribution to cognitive deficits and prefrontal cortex dysfunction in Spinocerebellar Ataxia Type 1 (SCA1).

The cerebellum role in cognition and its functional bi-directional connectivity with prefrontal cortex (PFC) is well recognized. However, how chronic cerebellar dysfunction affects PFC function and cognition remains less understood. Spinocerebellar ataxia type 1 (SCA1), is an inherited, fatal neurodegenerative disease caused by an abnormal expansion of glutamine (Q) encoding CAG repeats in the gene Ataxin-1 (ATXN1) and characterized by severe loss of Purkinje cells (PCs) in the cerebellum. Patients with SCA1 suffer from movement and balance deficits, cognitive decline and premature lethality. Cognitive deficits significantly impact patients quality of life, yet how exactly cerebellar degeneration contributes to cognitive deficits and PFC dysfunction in SCA1 is unknown. We have previously demonstrated that expression of mutant ATXN1 only in cerebellar Purkinje cells (PCs) is sufficient to cause cognitive deficits in a transgenic ATXN1[82Q] mouse line. To understand how cerebellar dysfunction impacts the PFC, we examined neuronal activity, synaptic density, and gene expression changes in the PFC of ATXN1[82Q] mice. Remarkably, we found decreased neuronal activity, reduced synaptic density, and altered expression of immediate early genes and pathways involved in glucose metabolism, inflammation and amphetamine in the PFC of ATXN1[82Q] mice. Furthermore, we characterized cellular and molecular PFC dysfunction in a novel conditional knock-in SCA1 line, f-ATXN1146Q mice, expressing floxed human expanded ATXN1 throughout the brain. Intriguingly, we found an increased number of neurons, increased synaptic density and large gene expression alterations in the PFC of f-ATXN1146Q mice. Finally, to precisely determine the role of cerebellar dysfunction in cognitive deficits and PFC dysfunction in SCA1, we crossed f-ATXN1146Q mice with Pcp2-Cre mice expressing Cre recombinase in PCs to delete expanded ATXN1 only in PCs. Surprisingly, we have found that deleting expanded ATXN1 in PCs exacerbated cognitive deficits and PFC dysfunction in these mice. Our findings demonstrate that circumscribed cerebellar dysfunction is sufficient to impact PFC activity and synaptic connectivity impairing cognition. However, when multiple brain regions are impacted in disease, cerebellar dysfunction may ameliorate PFC pathology and cognitive performance.

Drinker driver flyer diver.

Blood alcohol concentrations above defined levels are detrimental to cognitive performance. Empirical and published evidence suggest that nitrogen narcosis is analogous to alcohol intoxication with both impairing prefrontal cortex function. Nitrogen narcosis is also known to have been a factor in fatal accidents. To examine the effects of nitrogen narcosis, a recent publication used the Iowa Gambling Task tool, to simulate dynamic real-life risky decision-making behaviour. If the reported outcomes are corroborated in larger rigorously designed studies it is likely to provide further evidence that divers may well experience the negative effects of a 'narcotic agent', even at relatively shallow depths. These deleterious effects may occur regardless of diving experience, aptitude or professional status. In 1872, English law made it an offence to be 'drunk' whilst in charge of horses, carriages, cattle and steam engines. Understanding the danger was easy, establishing who is 'drunk' in the eyes of the court required a legal definition. Driving above a 'legal limit' for alcohol was made illegal in the United Kingdom in 1967. The limit was set at 80 milligrams of alcohol per 100 millilitres of blood. It took just short of one hundred years to get from first introducing a restriction to specific activities, whilst under the influence of alcohol, to having a clear and well-defined enforceable law. The question surely is whether our modern society will tolerate another century before legally defining safe parameters for nitrogen narcosis?

Cerebral cortex functional reorganization in preschool children with congenital sensorineural hearing loss: a resting-state fMRI study.

How cortical functional reorganization occurs after hearing loss in preschool children with congenital sensorineural hearing loss (CSNHL) is poorly understood. Therefore, we used resting-state functional MRI (rs-fMRI) to explore the characteristics of cortical reorganization in these patents. Sixty-three preschool children with CSNHL and 32 healthy controls (HCs) were recruited, and the Categories of Auditory Performance (CAP) scores were determined at the 6-month follow-up after cochlear implantation (CI). First, rs-fMRI data were preprocessed, and amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were calculated. Second, whole-brain functional connectivity (FC) analysis was performed using bilateral primary auditory cortex as seed points. Finally, Spearman correlation analysis was performed between the differential ALFF, ReHo and FC values and the CAP score. ALFF analysis showed that preschool children with CSNHL had lower ALFF values in the bilateral prefrontal cortex and superior temporal gyrus than HCs, but higher ALFF values in the bilateral thalamus and calcarine gyrus. And correlation analysis showed that some abnormal brain regions were weak negatively correlated with CAP score (p < 0.05). The ReHo values in the bilateral superior temporal gyrus, part of the prefrontal cortex and left insular gyrus were lower, whereas ReHo values in the bilateral thalamus, right caudate nucleus and right precentral gyrus were higher, in children with CSNHL than HCs. However, there was no correlation between ReHo values and the CAP scores (p < 0.05). Using primary auditory cortex (PAC) as seed-based FC further analysis revealed enhanced FC in the visual cortex, proprioceptive cortex and motor cortex. And there were weak negative correlations between the FC values in the bilateral superior temporal gyrus, occipital lobe, left postcentral gyrus and right thalamus were weakly negatively correlated and the CAP score (p < 0.05). After auditory deprivation in preschool children with CSNHL, the local functions of auditory cortex, visual cortex, prefrontal cortex and somatic motor cortex are changed, and the prefrontal cortex plays a regulatory role in this process. There is functional reorganization or compensation between children's hearing and these areas, which may not be conducive to auditory language recovery after CI in deaf children.

Loss of protein tyrosine phosphatase receptor delta PTPRD increases the number of cortical neurons, impairs synaptic function and induces autistic-like behaviors in adult mice

BackgroundThe brain cortex is responsible for many higher-level cognitive functions. Disruptions during cortical development have long-lasting consequences on brain function and are associated with the etiology of brain disorders. We previously found that the protein tyrosine phosphatase receptor delta Ptprd, which is genetically associated with several human neurodevelopmental disorders, is essential to cortical brain development. Loss of Ptprd expression induced an aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRβ in neural precursor cells. However, whether these alterations have long-lasting consequences in adulthood remains unknown.ResultsHere, we found that in Ptprd+/- or Ptprd-/- mice, the developmental increase of excitatory neurons persists through adulthood, affecting excitatory synaptic function in the medial prefrontal cortex. Likewise, heterozygosity or homozygosity for Ptprd also induced an increase of inhibitory cortical GABAergic neurons and impaired inhibitory synaptic transmission. Lastly, Ptprd+/- or Ptprd-/- mice displayed autistic-like behaviors and no learning and memory impairments or anxiety.ConclusionsThese results indicate that loss of Ptprd has long-lasting effects on cortical neuron number and synaptic function that may aberrantly impact ASD-like behaviors.