Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working...Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working memory,and emotional regulation,is notably impaired in this condition.This review consolidates current insights into the role of PFC dysfunction in schizophrenia,with a focus on its implications for therapeutic strategies.The neuroanatomical and neurobiological foundations of PFC dysfunction are explored,emphasizing structural abnormalities,functional dysconnectivity,and microcircuit disruptions that contribute to cognitive deficits and impaired decision-making.Clinical implications are discussed,particularly the correlation between PFC dysfunction and the severity and progression of schizophrenia symptoms.Additionally,pharmacological and non-pharmacological approaches aimed at modulating PFC activity are reviewed as potential therapeutic options.In conclusion,a deeper understanding of PFC dysfunction is pivotal for developing targeted treatments,and ongoing research offers promising avenues for enhancing outcomes for individuals affected by this debilitating disorder.展开更多
Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods...Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods:The PTSD mouse model was subjected to single prolonged stress and shock(SPS&S),and the animals received 15 min sessions of EA at Shenmen acupoint(HT7).Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear.Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex(PFC).Additionally,the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.Results:Mice subjected to SPS&S presented increased anxiety-and fear-like behaviors.Lcn2 expression in the PFC was significantly upregulated following SPS&S,leading to increased expression of the proinflammatory cytokines tumor necrosis factor-a and interleukin-6 and suppression of PFC neuronal activity.However,EA at HT7 inhibited Lcn2 release,reducing neuroinflammation and hypoexcitability in the PFC.Lcn2 overexpression mitigated the effects of EA at HT7,resulting in anxiety-and fear-like behaviors.Conclusion:EA at HT7 can ameliorate PTSD-associated anxiety and fear,and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC.展开更多
While multiple step saccades(MSS)are occasionally reported in the healthy population,they are more evident in patients with Parkinson’s disease(PD).Therefore,MSS has been suggested as a biological marker for the diag...While multiple step saccades(MSS)are occasionally reported in the healthy population,they are more evident in patients with Parkinson’s disease(PD).Therefore,MSS has been suggested as a biological marker for the diagnosis of PD.However,the lack of clarity on the neural mechanism underlying the generation of MSS largely impedes their application in the clinic.We have proposed recently that MSS are triggered by the discrepancy between desired and executed saccades.Accordingly,brain regions involved in saccadic planning and execution might play a role in the generation of MSS.To test this hypothesis,we explored the role of the prefrontal(PFC)and posterior parietal cortex(PPC)in generating MSS by conducting two experiments:electroencephalographic recording and single-pulse transcranial magnetic stimulation in the PFC or PPC of humans while participants were performing a gap saccade task.We found that the PFC and PPC are involved in the generation of MSS.展开更多
Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivi...Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivity of basolateral amygdala(BLA)pyramidal neurons(PNs)in Shank3 InsG3680 knock-in(InsG3680+/+)mice is involved in the development of anxiety.Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs.Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+mice.Further study found that the diminished control of the BLA by medial prefrontal cortex(mPFC)and optogenetic activation of the mPFC-BLA pathway also had a rescue effect,which increased the feedforward inhibition of the BLA.Taken together,our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+mice.展开更多
Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive ...Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.展开更多
The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation.This stereoelectroencephalography(SEEG)study investigated how the dorsolateral prefrontal corte...The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation.This stereoelectroencephalography(SEEG)study investigated how the dorsolateral prefrontal cortex(DLPFC)interacts with the hippocampus in the online processing of sequential information.Twenty patients with epilepsy(eight women,age 27.6±8.2 years)completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus.Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise(random trials)than to maintain ordered lines(ordered trials)before recalling the orientation of a particular line.First,the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC(3–10 Hz).In particular,the hippocampal theta power increase correlated with the memory precision of line orientation.Second,theta phase coherences between the DLPFC and hippocampus were enhanced for ordering,especially for more precisely memorized lines.Third,the theta band DLPFC→hippocampus influence was selectively enhanced for ordering,especially for more precisely memorized lines.This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.展开更多
Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiet...Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.展开更多
BACKGROUND Cases of depression among adolescents are gradually increasing.The study of the physiological basis of cognitive function from a biochemical perspective has therefore been garnering increasing attention.Dep...BACKGROUND Cases of depression among adolescents are gradually increasing.The study of the physiological basis of cognitive function from a biochemical perspective has therefore been garnering increasing attention.Depression has been hypothesized to be associated with the brain biochemical metabolism of the anterior cingulate gyrus,frontal lobe white matter,and the thalamus.AIM To explore the application of proton magnetic resonance spectroscopy(1H-MRS)in the metabolic alterations in the prefrontal white matter(PWM)and gray matter(GM)in adolescents with depression.METHODS 1H-MRS was performed for semi-quantitative analysis of the biochemical metabolites N-acetylaspartate(NAA),choline(Cho)complexes,creatine(Cr),and myoinositol(mI)in bilateral PWM,anterior cingulate GM,and thalami of 31 adolescent patients with depression(research group)and 35 healthy adolescents(control group),and the NAA/Cr,Cho/Cr,and mI/Cr ratios were calculated.Meanwhile,Hamilton Depression Scale(HAMD)and Wechsler Memory Scale were used to assess the degree of depression and memory function in all adolescents.The correlation of brain metabolite levels with scale scores was also analyzed.RESULTS The research group had markedly higher HAMD-24 scores and lower memory quotient(MQ)compared with the control group(P<0.05).Adolescents with depression were found to have lower bilateral PWM NAA/Cr and Cho/Cr ratios compared with healthy adolescents(P<0.05).The mI/Cr ratios were found to be similar in both groups(P>0.05).The bilateral anterior cingulate GM NAA/Cr,Cho/Cr,and mI/Cr also did not demonstrate marked differences(P>0.05).No statistical inter-group difference was determined in NAA/Cr of the bilateral thalami(P>0.05),while bilateral thalamic Cho/Cr and mI/Cr were reduced in teenagers with depression compared with healthy adolescents(P<0.05).A significant negative correlation was observed between the HAMD-24 scores in adolescents with depression with bilateral PWM NAA/Cr and Cho/Cr and were inversely linked to bilateral thalamic Cho/Cr and mI/Cr(P<0.05).In adolescents with depressions,MQ positively correlated with right PWH NAA/Cr,left PWH Cho/Cr,and bilateral thalamic Cho/Cr and mI/Cr.CONCLUSION PWM and thalamic metabolic abnormalities might influence teen depression,and the reduction in bilateral PWM NAA/Cr and Cho/Cr could be related to the neuropathology of adolescents with depression suffering from memory impairment.There exists a possibility of dysfunction of nerve cell membrane phospholipids in the thalami of adolescent patients with depression.展开更多
Social behaviors are fundamental and intricate functions in both humans and animals,governed by the interplay of social cognition and emotions.A noteworthy feature of several neuropsychiatric disorders,including autis...Social behaviors are fundamental and intricate functions in both humans and animals,governed by the interplay of social cognition and emotions.A noteworthy feature of several neuropsychiatric disorders,including autism spectrum disorder(ASD)and schizophrenia(SCZ),is a pronounced deficit in social functioning.Despite a burgeoning body of research on social behaviors,the precise neural circuit mechanisms underpinning these phenomena remain to be elucidated.In this paper,we review the pivotal role of the prefrontal cortex(PFC)in modulating social behaviors,as well as its functional alteration in social disorders in ASD or SCZ.We posit that PFC dysfunction may represent a critical hub in the pathogenesis of psychiatric disorders characterized by shared social deficits.Furthermore,we delve into the intricate connectivity of the medial PFC(mPFC)with other cortical areas and subcortical brain regions in rodents,which exerts a profound influence on social behaviors.Notably,a substantial body of evidence underscores the role of N-methyl-D-aspartate receptors(NMDARs)and the proper functioning of parvalbumin-positive interneurons within the mPFC for social regulation.Our overarching goal is to furnish a comprehensive understanding of these intricate circuits and thereby contribute to the enhancement of both research endeavors and clinical practices concerning social behavior deficits.展开更多
The high-order cognitive and executive functions are necessary for an individual to survive.The densely bidirectional innervations between the medial prefrontal cortex(mPFC)and the mediodorsal thalamus(MD)play a vital...The high-order cognitive and executive functions are necessary for an individual to survive.The densely bidirectional innervations between the medial prefrontal cortex(mPFC)and the mediodorsal thalamus(MD)play a vital role in regulating high-order functions.Pyramidal neurons in mPFC have been classified into several subclasses according to their morphological and electrophysi-ological properties,but the properties of the input-specific pyramidal neurons in mPFC remain poorly understood.The present study aimed to profile the morphological and electrophysiological properties of mPFC pyramidal neurons innervated by MD.In the past,the studies for characterizing the morphological and electrophysiological properties of neurons mainly relied on the electrophysiological recording of a large number of neurons and their morphologic reconstructions.But,it is a low efficient method for characterizing the circuit-specific neurons.The present study combined the advantages of traditional morphological and electrophysiological methods with machine learning to address the shortcomings of the past method,to establish a classification model for the morphological and electrophysiological properties of mPFC pyramidal neurons,and to achieve more accurate and efficient identification of the properties from a small size sample of neurons.We labeled MD-innervated pyramidal neurons of mPFC using the trans-synaptic neural circuitry tracing method and obtained their morphological properties using whole-cell patch-clamp recording and morphologic reconstructions.The results showed that the classification model established in the present study could predict the electrophysiological properties of MD-innervated pyramidal neurons based on their morphology.MD-innervated pyramidal neurons exhibit larger basal dendritic length but lower apical dendrite complexity compared to non-MD-innervated neurons in the mPFC.The morphological characteristics of the two subtypes(ET-1 and ET-2)of mPFC pyramidal neurons innervated by MD are different,with the apical dendrites of ET-1 neurons being longer and more complex than those of ET-2 neurons.These results suggest that the electrophysiological properties of MD-innervated pyramidal neurons within mPFC correlate with their morphological properties,indicating that the different roles of these two subclasses in local circuits within PFC,as well as in PFC-cortical/subcortical brain region circuits.展开更多
Nicotine addiction is a concern worldwide.Most mechanistic investigations are on nicotine substance dependence properties based on its pharmacological effects.However,no effective therapeutic treatment has been establ...Nicotine addiction is a concern worldwide.Most mechanistic investigations are on nicotine substance dependence properties based on its pharmacological effects.However,no effective therapeutic treatment has been established.Nicotine addiction is reinforced by environments or habits.We demonstrate the neurobiological basis of the behavioural aspect of nicotine addiction.We utilized the conditioned place preference to establish nicotine-associated behavioural preferences(NABP)in rats.Brain-wide neuroimaging analysis revealed that the medial prefrontal cortex(mPFC)was activated and contributed to NABP.Chemogenetic manipulation ofµ-opioid receptor positive(MOR+)neurons in the mPFC or the excitatory outflow to the nucleus accumbens shell(NAcShell)modulated the NABP.Electrophysiological recording confirmed that the MOR+neurons directly regulate the mPFC-NAcShell circuit via GABAA receptors.Thus,the MOR+neurons in the mPFC modulate the formation of behavioural aspects of nicotine addiction via direct excitatory innervation to the NAcShell,which may provide new insight for the development of effective therapeutic strategies.展开更多
The relation between evolution of spatial working memory function and of morphology of the dorsolateral prefrontal cortex among the rhesus monkey (Macaca mulatta), the slow loris (Nycticebus coucang) and the tree shre...The relation between evolution of spatial working memory function and of morphology of the dorsolateral prefrontal cortex among the rhesus monkey (Macaca mulatta), the slow loris (Nycticebus coucang) and the tree shrew (Tupaia belangen chinensis) were reported in present paper. The results read as follows: In the DR performance with training, the rhesus monkeys and slow lorises could reach a criterion of 90% correct response at 1.1 ± 3.2 seconds, and 3.8±0.4 seconds delay interval, respectively, by 1000 training trails. The tree shrews failed to reach the criterion of 90% correct response even at 0 seconds delay interval by 1000 training trails. If a delay interval was tested in one session (30 trails) only, doing the DR performamce without training, the rhesus monkeys reached a correct of 80% or higher in each session at 0, 1, 2, 3, 4, and 5 seconds delay, respectively. The percent correct in each session of the slow lorises showed no differences from the rhesus monkeys at 0, 1, 2, 3, and 4 seconds delay. However, when the delay interval was increased to 5 seconds, the percent correct of the DR performance declined to 70% or lower in the slow lorises. In the tree shrews the percent correct in each session reached to 70% or lower at 0, 1, 2, 3, 4, and 5 seconds delay interval, respectively. The morphological studies revealed that the size of the prefrontal cortex increased, and the structure got complex in the course of the evolution in primates. It is suggested that the relation of evolution between the spatial working memory function and anatomy in the prefrontal cortex might be significant among the three species, both the development of morphology and that of the spatial working memory function in the dorsolateral prefrontal cortex are later than other regions of cerebral cortex in phylogenetic evolution course.展开更多
Objective The ventral part of the medial prefrontal cortex（mPFC）plays an important role in initiation and control of voluntary movement,mood and cognition.However,after the degeneration of the nigrostriatal pathway,...Objective The ventral part of the medial prefrontal cortex（mPFC）plays an important role in initiation and control of voluntary movement,mood and cognition.However,after the degeneration of the nigrostriatal pathway,the neuronal activity of the ventral mPFC and the role of serotonin1A（5-hydroxytryptamine,5-HT1A）receptors in the firing of the neurons are still unknown.The present study is to investigate the change of neuronal activity in the ventral mPFC and the effect of systemic administration of the selective 5-HT1Areceptor antagonist WAY-100635 on the activity of the neurons in normal and 6-hydroxydopamine（6-OHDA）-lesioned rats.Methods Single unit responses were recorded extracellularly with glass microelectrodes from ventral mPFC neurons in normal rats and 6-OHDA unilaterally lesiond rats in vivo.Results 6-OHDA lesion of the substantia nigra pars compacta（SNc）significantly increased the firing rate with no change in the firing pattern of neurons of the ventral mPFC in rats.Systemic administration of WAY-100635（0.1 mg/kg,i.v.）did not change the mean firing rate and firing pattern of ventral mPFC neurons in normal rats.In contrast,WAY-100635 signifi- cantly decreased the mean firing rate of the neurons in rats with 6-OHDA lesion of the SNc.Conclusion These data suggest that the degeneration of the nigrostriatal pathway results in an increase of neuronal activity of ventral mPFC and dysfunction of 5-HT1Areceptor.展开更多
This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with n...This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with non-aphasic ischemic stroke aged -〉 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited. Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex, along with its subdivisions： anterior cingulate cortex, orbitofrontal cortex and dorsolateral prefrontal cortex. The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke. At 3 months poststroke, left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only （partial coefficient = 0.453, P = 0.045）, after controlling for age, education, diabetes, neurological deficit, white matter lesions volume, as well as the location and volume of infarcts. At 15 months poststroke, there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test （partial coefficient = 0.661, P = 0.001） and between the left prefrontal cortex volume and Verbal Fluency Test （partial coefficient = 0.573, P = 0.004） in female patients after the same adjustments. These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke. Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke.展开更多
Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus ner...Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation （frequency, 30 Hz, current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes）. In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1 （OXIR） antagonist SB334867 and received vagus nerve stimulation. Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group, consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expres- sion reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1R expression were decreased, compared with that of the stim- ulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OXIR expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.展开更多
Schizophrenia is hypothesized to arise from disrupted brain connectivity. This ＂dysconnectivity hypothesis＂ has generated interest in discovering whether there is anatomical and functional dysconnectivity between th...Schizophrenia is hypothesized to arise from disrupted brain connectivity. This ＂dysconnectivity hypothesis＂ has generated interest in discovering whether there is anatomical and functional dysconnectivity between the prefrontal cortex （PFC） and other brain regions, and how this dysconnectivity is linked to the impaired cognitive functions and aberrant behaviors of schizophrenia. Critical advances in neuroimaging technologies, including diffusion tensor imaging （DTI） and functional magnetic resonance imaging （fMRI）, make it possible to explore these issues. DTI affords the possibility to explore anatomical connectivity in the human brain in vivo and fMRI can be used to make inferences about functional connections between brain regions. In this review, we present major advances in the understanding of PFC anatomical and functional dysconnectivity and their implications in schizophrenia. We then briefly discuss future prospects that need to be explored in order to move beyond simple mapping of connectivity changes to elucidate the neuronal mechanisms underlying schizophrenia.展开更多
People with schizophrenia exhibit impaired social cognitive functions, particularly emotion regulation. Abnormal activations of the ventral medial prefrontal cortex （vMPFC） during emotional tasks have been demonstra...People with schizophrenia exhibit impaired social cognitive functions, particularly emotion regulation. Abnormal activations of the ventral medial prefrontal cortex （vMPFC） during emotional tasks have been demonstrated in schizophrenia, suggesting its important role in emotion processing in patients. We used the resting-state functional connectivity approach, setting a functionally relevant region, the vMPFC, as a seed region to examine the intrinsic functional interactions and communication between the vMPFC and other brain regions in schizophrenic patients. We found hypo-connectivity between the vMPFC and the medial frontal cortex, right middle temporal lobe （MTL）, right hippocampus, parahippocampal cortex （PHC） and amygdala. Further, there was a decreased strength of the negative connectivity （or anticorrelation） between the vMPFC and the bilateral dorsal lateral prefrontal cortex （DLPFC） and pre-supplementary motor areas. Among these connectivity alterations, reduced vMPFC-DLPFC connectivity was positively correlated with positive symptoms on the Positive and Negative Syndrome Scale, while vMPFC-right MTL/PHC/amygdala functional connectivity was positively correlated with the performance of emotional regulation in patients. These findings imply that communication and coordination throughout the brain networks are disrupted in schizophrenia. The emotional correlates of vMPFC connectivity suggest a role of the hypo-connectivity between these regions in the neuropathology of abnormal social cognition in chronic schizophrenia.展开更多
The short allele of the serotonin-transporter gene is associated with higher risk for anxiety and depression in Caucasians, but this association is still unclear in Asians. Here, we addressed this issue using behavior...The short allele of the serotonin-transporter gene is associated with higher risk for anxiety and depression in Caucasians, but this association is still unclear in Asians. Here, we addressed this issue using behavioral and multi-modal MRI approaches in a large group of healthy Han Chinese participants （n = 233）. In contrast to findings in Caucasians, we found that long-allele （L） carriers had higher anxiety scores. In another group （n = 64） experiencing significant levels of depression or anxiety, the L-allele frequency was also significantly higher. In healthy participants, L-carriers had reduced functional and anatomical connectivity between the amygdala and prefrontal cortex （PFC）, which was correlated with anxiety or depression scores. Our findings demonstrated that in Chinese Han participants, in contrast to Caucasians, the L-allele confers vulnerability to anxiety or depression and weakens top-down emotional control between the PFC and amygdala. Therefore, ethnic background should be taken into account in gene-related studies and their potential clinical applications.展开更多
The ability to recall and recognize facts we experienced in the past is based on a complex mechanism in which several cerebral regions are implicated. Neuroimaging and lesion studies agree in identifying the frontal l...The ability to recall and recognize facts we experienced in the past is based on a complex mechanism in which several cerebral regions are implicated. Neuroimaging and lesion studies agree in identifying the frontal lobe as a crucial structure for memory processes, and in particular for working memory and episodic memory and their relationships. Furthermore, with the introduction of transcranial magnetic stimulation （TMS） a new way was proposed to investigate the relationships between brain correlates, memory functions and behavior. The aim of this review is to present the main findings that have emerged from experiments which used the TMS technique for memory analysis. They mainly focused on the role of the dorsolateral prefrontal cortex in memory process. Furthermore, we present state-of-the-art evidence supporting a possible use of TMS in the clinic. Specifically we focus on the treatment of memory deficits in depression and anxiety disorders.展开更多
Previous studies have demonstrated that doublecortin-positive immature neurons exist pre- dominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very...Previous studies have demonstrated that doublecortin-positive immature neurons exist pre- dominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine （a marker of cell prolifera- tion）, c-Fos （a marker of cell viability） and NeuN （a marker of mature neurons）. Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs.展开更多
文摘Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working memory,and emotional regulation,is notably impaired in this condition.This review consolidates current insights into the role of PFC dysfunction in schizophrenia,with a focus on its implications for therapeutic strategies.The neuroanatomical and neurobiological foundations of PFC dysfunction are explored,emphasizing structural abnormalities,functional dysconnectivity,and microcircuit disruptions that contribute to cognitive deficits and impaired decision-making.Clinical implications are discussed,particularly the correlation between PFC dysfunction and the severity and progression of schizophrenia symptoms.Additionally,pharmacological and non-pharmacological approaches aimed at modulating PFC activity are reviewed as potential therapeutic options.In conclusion,a deeper understanding of PFC dysfunction is pivotal for developing targeted treatments,and ongoing research offers promising avenues for enhancing outcomes for individuals affected by this debilitating disorder.
基金supported by the Anhui Provincial Department of Education Outstanding Young Teachers Cultivation Key Project(No.YQZD2023046)the Anhui University of Traditional Chinese Medicine School Talent Support Program Project(Nos.DT2400000222 and DT2100000545)。
文摘Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods:The PTSD mouse model was subjected to single prolonged stress and shock(SPS&S),and the animals received 15 min sessions of EA at Shenmen acupoint(HT7).Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear.Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex(PFC).Additionally,the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.Results:Mice subjected to SPS&S presented increased anxiety-and fear-like behaviors.Lcn2 expression in the PFC was significantly upregulated following SPS&S,leading to increased expression of the proinflammatory cytokines tumor necrosis factor-a and interleukin-6 and suppression of PFC neuronal activity.However,EA at HT7 inhibited Lcn2 release,reducing neuroinflammation and hypoexcitability in the PFC.Lcn2 overexpression mitigated the effects of EA at HT7,resulting in anxiety-and fear-like behaviors.Conclusion:EA at HT7 can ameliorate PTSD-associated anxiety and fear,and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC.
基金supported by North Sichuan Medical College(CBY23-QDA14)the National Natural Science Foundation of China(32030045 and 82071454)+4 种基金Nanchong Federation of Social Science Associations(NC24C145)the Sichuan Science and Technology Program(2024NSFSC2017,2024ZYD0086)the Sichuan Students'Platform for Innovation Training Program(S202410634035)the Health Commission of Sichuan Province(24WSXT044)funded by the Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning(CNLYB2403).
文摘While multiple step saccades(MSS)are occasionally reported in the healthy population,they are more evident in patients with Parkinson’s disease(PD).Therefore,MSS has been suggested as a biological marker for the diagnosis of PD.However,the lack of clarity on the neural mechanism underlying the generation of MSS largely impedes their application in the clinic.We have proposed recently that MSS are triggered by the discrepancy between desired and executed saccades.Accordingly,brain regions involved in saccadic planning and execution might play a role in the generation of MSS.To test this hypothesis,we explored the role of the prefrontal(PFC)and posterior parietal cortex(PPC)in generating MSS by conducting two experiments:electroencephalographic recording and single-pulse transcranial magnetic stimulation in the PFC or PPC of humans while participants were performing a gap saccade task.We found that the PFC and PPC are involved in the generation of MSS.
基金supported by grants from the National Natural Science Foundation of China(31970902,U22A20306,and 3192010300)the Municipal Administration of Hospitals Incubating Program(PZ2023009)+1 种基金the Key-Area R&D Program of Guangdong Province(2019B030335001)the Autism Research Special Fund of Zhejiang Foundation for Disabled Persons(2022003).
文摘Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivity of basolateral amygdala(BLA)pyramidal neurons(PNs)in Shank3 InsG3680 knock-in(InsG3680+/+)mice is involved in the development of anxiety.Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs.Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+mice.Further study found that the diminished control of the BLA by medial prefrontal cortex(mPFC)and optogenetic activation of the mPFC-BLA pathway also had a rescue effect,which increased the feedforward inhibition of the BLA.Taken together,our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+mice.
基金supported by the National Natural Science Foundation of China,No.82101263Jiangsu Province Science Foundation for Youths,No.BK20210903Research Foundation for Talented Scholars of Xuzhou Medical University,No.RC20552114(all to CT)。
文摘Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.
基金supported by the STI2030-Major Project(2021ZD0203600)with additional support from the Shanghai Municipal Science and Technology Commission(2018SHZDZX05 and 2018ZR1406500)+3 种基金the Shanghai Pujiang Program(19PJ1407500)the Shanghai Jiao Tong University Medical and Engineering Cross Research Fund(YG2019QNA31)the Shanghai Municipal Health Commission Clinical Study Special Fund(20194Y0067)the Ruijin Hospital Guangci Excellence Youth Training Program(GCQN-2019-B10).
文摘The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation.This stereoelectroencephalography(SEEG)study investigated how the dorsolateral prefrontal cortex(DLPFC)interacts with the hippocampus in the online processing of sequential information.Twenty patients with epilepsy(eight women,age 27.6±8.2 years)completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus.Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise(random trials)than to maintain ordered lines(ordered trials)before recalling the orientation of a particular line.First,the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC(3–10 Hz).In particular,the hippocampal theta power increase correlated with the memory precision of line orientation.Second,theta phase coherences between the DLPFC and hippocampus were enhanced for ordering,especially for more precisely memorized lines.Third,the theta band DLPFC→hippocampus influence was selectively enhanced for ordering,especially for more precisely memorized lines.This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.
基金supported by the National Natural Science Foundation of ChinaNos.32170950(to LY),31970915(to LY),31871170(to CL)+4 种基金the Natural Science Foundation of Guangdong Province for Major Cultivation ProjectNo.2018B030336001(to LY)the Natural Science Foundation of Guangdong Province,Nos.2021A1515010804(to CL),2023A1515010899(to CL)the Guangdong Grant‘Key Technologies for Treatment of Brain Disorders’No.2018B030332001(to CL)。
文摘Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.
基金Supported by the General Scientific Research Project of Zhejiang Provincial Department of Education,No.Y202248840 and No.Y201942374。
文摘BACKGROUND Cases of depression among adolescents are gradually increasing.The study of the physiological basis of cognitive function from a biochemical perspective has therefore been garnering increasing attention.Depression has been hypothesized to be associated with the brain biochemical metabolism of the anterior cingulate gyrus,frontal lobe white matter,and the thalamus.AIM To explore the application of proton magnetic resonance spectroscopy(1H-MRS)in the metabolic alterations in the prefrontal white matter(PWM)and gray matter(GM)in adolescents with depression.METHODS 1H-MRS was performed for semi-quantitative analysis of the biochemical metabolites N-acetylaspartate(NAA),choline(Cho)complexes,creatine(Cr),and myoinositol(mI)in bilateral PWM,anterior cingulate GM,and thalami of 31 adolescent patients with depression(research group)and 35 healthy adolescents(control group),and the NAA/Cr,Cho/Cr,and mI/Cr ratios were calculated.Meanwhile,Hamilton Depression Scale(HAMD)and Wechsler Memory Scale were used to assess the degree of depression and memory function in all adolescents.The correlation of brain metabolite levels with scale scores was also analyzed.RESULTS The research group had markedly higher HAMD-24 scores and lower memory quotient(MQ)compared with the control group(P<0.05).Adolescents with depression were found to have lower bilateral PWM NAA/Cr and Cho/Cr ratios compared with healthy adolescents(P<0.05).The mI/Cr ratios were found to be similar in both groups(P>0.05).The bilateral anterior cingulate GM NAA/Cr,Cho/Cr,and mI/Cr also did not demonstrate marked differences(P>0.05).No statistical inter-group difference was determined in NAA/Cr of the bilateral thalami(P>0.05),while bilateral thalamic Cho/Cr and mI/Cr were reduced in teenagers with depression compared with healthy adolescents(P<0.05).A significant negative correlation was observed between the HAMD-24 scores in adolescents with depression with bilateral PWM NAA/Cr and Cho/Cr and were inversely linked to bilateral thalamic Cho/Cr and mI/Cr(P<0.05).In adolescents with depressions,MQ positively correlated with right PWH NAA/Cr,left PWH Cho/Cr,and bilateral thalamic Cho/Cr and mI/Cr.CONCLUSION PWM and thalamic metabolic abnormalities might influence teen depression,and the reduction in bilateral PWM NAA/Cr and Cho/Cr could be related to the neuropathology of adolescents with depression suffering from memory impairment.There exists a possibility of dysfunction of nerve cell membrane phospholipids in the thalami of adolescent patients with depression.
基金supported by the National Natural Science Foundation of China(Nos.81801355,U22A20306,and 3192010300)the Autism Research Special Fund of Zhejiang Foundation for Disabled Persons(Nos.2022001 and 2023002)+1 种基金the Research and Development Program of Guangdong Province(No.2019B030335001)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2023-PT310-01)。
文摘Social behaviors are fundamental and intricate functions in both humans and animals,governed by the interplay of social cognition and emotions.A noteworthy feature of several neuropsychiatric disorders,including autism spectrum disorder(ASD)and schizophrenia(SCZ),is a pronounced deficit in social functioning.Despite a burgeoning body of research on social behaviors,the precise neural circuit mechanisms underpinning these phenomena remain to be elucidated.In this paper,we review the pivotal role of the prefrontal cortex(PFC)in modulating social behaviors,as well as its functional alteration in social disorders in ASD or SCZ.We posit that PFC dysfunction may represent a critical hub in the pathogenesis of psychiatric disorders characterized by shared social deficits.Furthermore,we delve into the intricate connectivity of the medial PFC(mPFC)with other cortical areas and subcortical brain regions in rodents,which exerts a profound influence on social behaviors.Notably,a substantial body of evidence underscores the role of N-methyl-D-aspartate receptors(NMDARs)and the proper functioning of parvalbumin-positive interneurons within the mPFC for social regulation.Our overarching goal is to furnish a comprehensive understanding of these intricate circuits and thereby contribute to the enhancement of both research endeavors and clinical practices concerning social behavior deficits.
基金supported by the National Natural Science Foundation of China(No.31571098,32071026)Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01),ZJ Lab.and Shanghai Center for Brain Science and Brain-Inspired Technology。
文摘The high-order cognitive and executive functions are necessary for an individual to survive.The densely bidirectional innervations between the medial prefrontal cortex(mPFC)and the mediodorsal thalamus(MD)play a vital role in regulating high-order functions.Pyramidal neurons in mPFC have been classified into several subclasses according to their morphological and electrophysi-ological properties,but the properties of the input-specific pyramidal neurons in mPFC remain poorly understood.The present study aimed to profile the morphological and electrophysiological properties of mPFC pyramidal neurons innervated by MD.In the past,the studies for characterizing the morphological and electrophysiological properties of neurons mainly relied on the electrophysiological recording of a large number of neurons and their morphologic reconstructions.But,it is a low efficient method for characterizing the circuit-specific neurons.The present study combined the advantages of traditional morphological and electrophysiological methods with machine learning to address the shortcomings of the past method,to establish a classification model for the morphological and electrophysiological properties of mPFC pyramidal neurons,and to achieve more accurate and efficient identification of the properties from a small size sample of neurons.We labeled MD-innervated pyramidal neurons of mPFC using the trans-synaptic neural circuitry tracing method and obtained their morphological properties using whole-cell patch-clamp recording and morphologic reconstructions.The results showed that the classification model established in the present study could predict the electrophysiological properties of MD-innervated pyramidal neurons based on their morphology.MD-innervated pyramidal neurons exhibit larger basal dendritic length but lower apical dendrite complexity compared to non-MD-innervated neurons in the mPFC.The morphological characteristics of the two subtypes(ET-1 and ET-2)of mPFC pyramidal neurons innervated by MD are different,with the apical dendrites of ET-1 neurons being longer and more complex than those of ET-2 neurons.These results suggest that the electrophysiological properties of MD-innervated pyramidal neurons within mPFC correlate with their morphological properties,indicating that the different roles of these two subclasses in local circuits within PFC,as well as in PFC-cortical/subcortical brain region circuits.
基金supported by JSPS KAKENHI(24659574,26112003,and 15K14328),and JP 16H06276(AdAMS).
文摘Nicotine addiction is a concern worldwide.Most mechanistic investigations are on nicotine substance dependence properties based on its pharmacological effects.However,no effective therapeutic treatment has been established.Nicotine addiction is reinforced by environments or habits.We demonstrate the neurobiological basis of the behavioural aspect of nicotine addiction.We utilized the conditioned place preference to establish nicotine-associated behavioural preferences(NABP)in rats.Brain-wide neuroimaging analysis revealed that the medial prefrontal cortex(mPFC)was activated and contributed to NABP.Chemogenetic manipulation ofµ-opioid receptor positive(MOR+)neurons in the mPFC or the excitatory outflow to the nucleus accumbens shell(NAcShell)modulated the NABP.Electrophysiological recording confirmed that the MOR+neurons directly regulate the mPFC-NAcShell circuit via GABAA receptors.Thus,the MOR+neurons in the mPFC modulate the formation of behavioural aspects of nicotine addiction via direct excitatory innervation to the NAcShell,which may provide new insight for the development of effective therapeutic strategies.
文摘The relation between evolution of spatial working memory function and of morphology of the dorsolateral prefrontal cortex among the rhesus monkey (Macaca mulatta), the slow loris (Nycticebus coucang) and the tree shrew (Tupaia belangen chinensis) were reported in present paper. The results read as follows: In the DR performance with training, the rhesus monkeys and slow lorises could reach a criterion of 90% correct response at 1.1 ± 3.2 seconds, and 3.8±0.4 seconds delay interval, respectively, by 1000 training trails. The tree shrews failed to reach the criterion of 90% correct response even at 0 seconds delay interval by 1000 training trails. If a delay interval was tested in one session (30 trails) only, doing the DR performamce without training, the rhesus monkeys reached a correct of 80% or higher in each session at 0, 1, 2, 3, 4, and 5 seconds delay, respectively. The percent correct in each session of the slow lorises showed no differences from the rhesus monkeys at 0, 1, 2, 3, and 4 seconds delay. However, when the delay interval was increased to 5 seconds, the percent correct of the DR performance declined to 70% or lower in the slow lorises. In the tree shrews the percent correct in each session reached to 70% or lower at 0, 1, 2, 3, 4, and 5 seconds delay interval, respectively. The morphological studies revealed that the size of the prefrontal cortex increased, and the structure got complex in the course of the evolution in primates. It is suggested that the relation of evolution between the spatial working memory function and anatomy in the prefrontal cortex might be significant among the three species, both the development of morphology and that of the spatial working memory function in the dorsolateral prefrontal cortex are later than other regions of cerebral cortex in phylogenetic evolution course.
基金the National Natural Science Foundation of China（No.30370464） ；the Science and Technological Program of Shaanxi Province,China（No.2005K13-G6）
文摘Objective The ventral part of the medial prefrontal cortex（mPFC）plays an important role in initiation and control of voluntary movement,mood and cognition.However,after the degeneration of the nigrostriatal pathway,the neuronal activity of the ventral mPFC and the role of serotonin1A（5-hydroxytryptamine,5-HT1A）receptors in the firing of the neurons are still unknown.The present study is to investigate the change of neuronal activity in the ventral mPFC and the effect of systemic administration of the selective 5-HT1Areceptor antagonist WAY-100635 on the activity of the neurons in normal and 6-hydroxydopamine（6-OHDA）-lesioned rats.Methods Single unit responses were recorded extracellularly with glass microelectrodes from ventral mPFC neurons in normal rats and 6-OHDA unilaterally lesiond rats in vivo.Results 6-OHDA lesion of the substantia nigra pars compacta（SNc）significantly increased the firing rate with no change in the firing pattern of neurons of the ventral mPFC in rats.Systemic administration of WAY-100635（0.1 mg/kg,i.v.）did not change the mean firing rate and firing pattern of ventral mPFC neurons in normal rats.In contrast,WAY-100635 signifi- cantly decreased the mean firing rate of the neurons in rats with 6-OHDA lesion of the SNc.Conclusion These data suggest that the degeneration of the nigrostriatal pathway results in an increase of neuronal activity of ventral mPFC and dysfunction of 5-HT1Areceptor.
基金supported by the Research Grants Council of the Hong Kong SAR,No. 452906
文摘This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with non-aphasic ischemic stroke aged -〉 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited. Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex, along with its subdivisions： anterior cingulate cortex, orbitofrontal cortex and dorsolateral prefrontal cortex. The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke. At 3 months poststroke, left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only （partial coefficient = 0.453, P = 0.045）, after controlling for age, education, diabetes, neurological deficit, white matter lesions volume, as well as the location and volume of infarcts. At 15 months poststroke, there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test （partial coefficient = 0.661, P = 0.001） and between the left prefrontal cortex volume and Verbal Fluency Test （partial coefficient = 0.573, P = 0.004） in female patients after the same adjustments. These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke. Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke.
基金supported by the Natural Science Foundation of China,No.81260295the Graduate Student Innovation Fund of Jiangxi Province of China,No.YC2015-S090
文摘Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation （frequency, 30 Hz, current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes）. In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1 （OXIR） antagonist SB334867 and received vagus nerve stimulation. Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group, consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expres- sion reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1R expression were decreased, compared with that of the stim- ulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OXIR expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.
基金supported by the National Basic Research Development Program (973 Program) of China (2011CB707800)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB02030300)the National Natural Science Foundation of China (91132301 and 81371476)
文摘Schizophrenia is hypothesized to arise from disrupted brain connectivity. This ＂dysconnectivity hypothesis＂ has generated interest in discovering whether there is anatomical and functional dysconnectivity between the prefrontal cortex （PFC） and other brain regions, and how this dysconnectivity is linked to the impaired cognitive functions and aberrant behaviors of schizophrenia. Critical advances in neuroimaging technologies, including diffusion tensor imaging （DTI） and functional magnetic resonance imaging （fMRI）, make it possible to explore these issues. DTI affords the possibility to explore anatomical connectivity in the human brain in vivo and fMRI can be used to make inferences about functional connections between brain regions. In this review, we present major advances in the understanding of PFC anatomical and functional dysconnectivity and their implications in schizophrenia. We then briefly discuss future prospects that need to be explored in order to move beyond simple mapping of connectivity changes to elucidate the neuronal mechanisms underlying schizophrenia.
基金supported by grants from the Beijing Municipal Science & Technology Commission(D0906001040191,D101107047810005,D101100050010051)the Beijing Natural Science Foundation(7102086)+3 种基金the Fund for Capital Medical Development and Research(2007-3059)the National Natural Science Foundation of China(81171409)Startup Foundation for Distinguished Research Professors of the Institute for Psychology(Y0CX492S03)Fund for Outstanding Talents in Beijing(2012D003034000003)
文摘People with schizophrenia exhibit impaired social cognitive functions, particularly emotion regulation. Abnormal activations of the ventral medial prefrontal cortex （vMPFC） during emotional tasks have been demonstrated in schizophrenia, suggesting its important role in emotion processing in patients. We used the resting-state functional connectivity approach, setting a functionally relevant region, the vMPFC, as a seed region to examine the intrinsic functional interactions and communication between the vMPFC and other brain regions in schizophrenic patients. We found hypo-connectivity between the vMPFC and the medial frontal cortex, right middle temporal lobe （MTL）, right hippocampus, parahippocampal cortex （PHC） and amygdala. Further, there was a decreased strength of the negative connectivity （or anticorrelation） between the vMPFC and the bilateral dorsal lateral prefrontal cortex （DLPFC） and pre-supplementary motor areas. Among these connectivity alterations, reduced vMPFC-DLPFC connectivity was positively correlated with positive symptoms on the Positive and Negative Syndrome Scale, while vMPFC-right MTL/PHC/amygdala functional connectivity was positively correlated with the performance of emotional regulation in patients. These findings imply that communication and coordination throughout the brain networks are disrupted in schizophrenia. The emotional correlates of vMPFC connectivity suggest a role of the hypo-connectivity between these regions in the neuropathology of abnormal social cognition in chronic schizophrenia.
基金supported by the National Key Basic Research and Development Program(973)(2011CB707800)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB02030300)+1 种基金the Natural Science Foundation of China(91132301and81000582)the Beijing Nova Program(2010B06)
文摘The short allele of the serotonin-transporter gene is associated with higher risk for anxiety and depression in Caucasians, but this association is still unclear in Asians. Here, we addressed this issue using behavioral and multi-modal MRI approaches in a large group of healthy Han Chinese participants （n = 233）. In contrast to findings in Caucasians, we found that long-allele （L） carriers had higher anxiety scores. In another group （n = 64） experiencing significant levels of depression or anxiety, the L-allele frequency was also significantly higher. In healthy participants, L-carriers had reduced functional and anatomical connectivity between the amygdala and prefrontal cortex （PFC）, which was correlated with anxiety or depression scores. Our findings demonstrated that in Chinese Han participants, in contrast to Caucasians, the L-allele confers vulnerability to anxiety or depression and weakens top-down emotional control between the PFC and amygdala. Therefore, ethnic background should be taken into account in gene-related studies and their potential clinical applications.
文摘The ability to recall and recognize facts we experienced in the past is based on a complex mechanism in which several cerebral regions are implicated. Neuroimaging and lesion studies agree in identifying the frontal lobe as a crucial structure for memory processes, and in particular for working memory and episodic memory and their relationships. Furthermore, with the introduction of transcranial magnetic stimulation （TMS） a new way was proposed to investigate the relationships between brain correlates, memory functions and behavior. The aim of this review is to present the main findings that have emerged from experiments which used the TMS technique for memory analysis. They mainly focused on the role of the dorsolateral prefrontal cortex in memory process. Furthermore, we present state-of-the-art evidence supporting a possible use of TMS in the clinic. Specifically we focus on the treatment of memory deficits in depression and anxiety disorders.
基金the National Natural Science Foundation of China,No.30900773the Natural Science Foundation of Hunan Province in China,No.11JJ2020Young Teachers Training Program of University of Hunan Province
文摘Previous studies have demonstrated that doublecortin-positive immature neurons exist pre- dominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine （a marker of cell prolifera- tion）, c-Fos （a marker of cell viability） and NeuN （a marker of mature neurons）. Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs.
