Convergent evidence from multimodal imaging reveals amygdala abnormalities in schizophrenic patients and their first-degree relatives

Background

Shared neuropathological features between schizophrenic patients and their first-degree relatives have potential as indicators of genetic vulnerability to schizophrenia. We sought to explore genetic influences on brain morphology and function in schizophrenic patients and their relatives.

Methods

Using a multimodal imaging strategy, we studied 33 schizophrenic patients, 55 of their unaffected parents, 30 healthy controls for patients, and 29 healthy controls for parents with voxel-based morphometry of structural MRI scans and functional connectivity analysis of resting-state functional MRI data.

Results

Schizophrenic patients showed widespread gray matter reductions in the bilateral frontal cortices, bilateral insulae, bilateral occipital cortices, left amygdala and right thalamus, whereas their parents showed more localized reductions in the left amygdala, left thalamus and right orbitofrontal cortex. Patients and their parents shared gray matter loss in the left amygdala. Further investigation of the resting-state functional connectivity of the amygdala in the patients showed abnormal functional connectivity with the bilateral orbitofrontal cortices, bilateral precunei, bilateral dorsolateral frontal cortices and right insula. Their parents showed slightly less, but similar changes in the pattern in the amygdala connectivity. Co-occurrences of abnormal connectivity of the left amygdala with the left orbitofrontal cortex, right dorsolateral frontal cortex and right precuneus were observed in schizophrenic patients and their parents.

Conclusions

Our findings suggest a potential genetic influence on structural and functional abnormalities of the amygdala in schizophrenia. Such information could help future efforts to identify the endophenotypes that characterize the complex disorder of schizophrenia.     

Cerebral Inefficient Activation in Schizophrenia Patients and Their Unaffected Parents during the N-Back Working Memory Task: A Family fMRI Study

Background

It has been suggested that working memory deficits is a core feature of symptomatology of schizophrenia, which can be detected in patients and their unaffected relatives. The impairment of working memory has been found related to the abnormal activity of human brain regions in many functional magnetic resonance imaging (fMRI) studies. This study investigated how brain region activation was altered in schizophrenia and how it was inherited independently from performance deficits.

Method

The authors used fMRI method during N-back task to assess working memory related cortical activation in four groups (N = 20 in each group, matching task performance, age, gender and education): schizophrenic patients, their unaffected biological parents, young healthy controls for the patients and older healthy controls for their parents.

Results

Compared to healthy controls, patients showed an exaggerated response in the right dorsolateral prefrontal cortex (brodmann area [BA] 46) and bilateral ventrolateral prefrontal cortex, and had reduced activation in bilateral dorsolateral prefrontal cortex (BA 9). In the conjunction analysis, the effect of genetic risk (parents versus older control) shared significantly overlapped activation with effect of disease (patients versus young control) in the right middle frontal gyrus (BA 46) and left inferior parietal gyrus (BA 40).

Conclusions

Physiological inefficiency of dorsal prefrontal cortex and compensation involvement of ventral prefrontal cortex in working memory function may one physiological characteristics of schizophrenia. And relatively inefficient activation in dorsolateral prefrontal cortex probably can be a promising intermediate phenotype for schizophrenia.     

带状疱疹后遗神经痛患者脑基础活动改变的功能核磁共振研究

带状疱疹后遗神经痛(postherpetic neuralgia,PHN)是临床上一种慢性顽固性神经病理性疼痛,然而,对于其潜在的中枢机制还知之甚少.为了进一步探讨带状疱疹后遗神经痛患者的相关脑区活动,利用功能核磁共振成像低频振幅振荡(ALFF)技术观察带状疱疹后遗神经痛患者的基础脑区活动.8名带状疱疹后遗神经痛患者与8名性别、年龄相匹配的健康者行静息态功能磁共振(f MRI)成像扫描,用SPM8中的多重回归分析,在控制被试年龄、性别、教育年限的影响下,将每个体素的ALFF值同每个被试的病程、视觉模拟评分(visual analog scale,VAS)进行相关分析.与健康志愿者相比,PHN组与VAS评分相关的ALFF值增高的脑区有:右侧小脑后叶、前额叶背外侧区域(BA11/46/47)、右侧顶叶(BA40)、右侧舌回(BA17/18/19);与VAS评分相关的ALFF值降低的脑区有:右侧颞中回(BA21)、左侧舌回(BA17/18)、右侧小脑前叶、左侧后扣带回(BA30/19)和右侧中央前回(BA3/4/6);PHN组与病程相关的ALFF值增高的脑区有:右侧小脑后叶、前额叶背外侧区域(BA9/10/11/47)、左侧颞上回(BA38)、右侧顶叶和右侧舌回(BA17/18/19);与病程相关ALFF值降低的脑区有:左侧海马旁回(BA28)、右侧小脑前叶、左侧扣带回(BA24)、右侧颞上回(BA13)、左侧中央前回和右侧顶下小叶(BA39/40).研究结果提示,涉及疼痛的情绪、警觉行为、注意的脑区在带状疱疹后遗痛慢性疼痛的产生和维持中发挥重要作用.     

Regional Brain Structural Abnormality in Meal-Related Functional Dyspepsia Patients: A Voxel-Based Morphometry Study

Background and Aims

Brain dysfunction in functional dyspepsia (FD) has been identified by multiple neuroimaging studies. This study aims to investigate the regional gray matter density (GMD) changes in meal-related FD patients and their correlations with clinical variables, and to explore the possible influence of the emotional state on FD patients’s brain structures.

Methods

Fifty meal-related FD patients and forty healthy subjects (HS) were included and underwent a structural magnetic resonance imaging scan. Voxel-based morphometry analysis was employed to identify the cerebral structure alterations in meal-related FD patients. Regional GMD changes'' correlations with the symptoms and their durations, respectively, have been analyzed.

Results

Compared to the HS, the meal-related FD patients showed a decreased GMD in the bilateral precentral gyrus, medial prefrontal cortex (MPFC), anterior cingulate cortex (ACC) and midcingulate cortex (MCC), left orbitofrontal cortex (OFC) and right insula (p<0.05, FWE Corrected, Cluster size>50). After controlling for anxiety and depression, the meal-related FD patients showed a decreased GMD in the bilateral middle frontal gyrus, left MCC, right precentral gyrus and insula (p<0.05, FWE Corrected, Cluster size>50). Before controlling psychological factors, the GMD decreases in the ACC were negatively associated with the symptom scores of the Nepean Dyspepsia Index (NDI) (r = −0.354, p = 0.048, Bonferroni correction) and the duration of FD (r = −0.398, p = 0.02, Bonferroni correction) respectively.

Conclusions

The regional GMD of meal-related FD patients, especially in the regions of the homeostatic afferent processing network significantly differed from that of the HS, and the psychological factors might be one of the essential factors significantly affecting the regional brain structure of meal-related FD patients.     

The Neuroanatomical Basis of Panic Disorder and Social Phobia in Schizophrenia: A Voxel Based Morphometric Study

ObjectiveIt is known that there is a high prevalence of certain anxiety disorders among schizophrenic patients, especially panic disorder and social phobia. However, the neural underpinnings of the comorbidity of such anxiety disorders and schizophrenia remain unclear. Our study aims to determine the neuroanatomical basis of the co-occurrence of schizophrenia with panic disorder and social phobia.MethodsVoxel-based morphometry was used in order to examine brain structure and to measure between-group differences, comparing magnetic resonance images of 20 anxious patients, 20 schizophrenic patients, 20 schizophrenic patients with comorbid anxiety, and 20 healthy control subjects.ResultsCompared to the schizophrenic patients, we observed smaller grey-matter volume (GMV) decreases in the dorsolateral prefrontal cortex and precentral gyrus in the schizophrenic-anxiety group. Additionally, the schizophrenic group showed significantly reduced GMV in the dorsolateral prefrontal cortex, precentral gyrus, orbitofrontal cortex, temporal gyrus and angular/inferior parietal gyrus when compared to the control group.ConclusionsOur findings suggest that the comorbidity of schizophrenia with panic disorder and social phobia might be characterized by specific neuroanatomical and clinical alterations that may be related to maladaptive emotion regulation related to anxiety. Even thought our findings need to be replicated, our study suggests that the identification of neural abnormalities involved in anxiety, schizophrenia and schizophrenia-anxiety may lead to an improved diagnosis and management of these conditions.     

Effects of VRK2 (rs2312147) on White Matter Connectivity in Patients with Schizophrenia

Recent genome-wide association studies of schizophrenia reported a novel risk variant, rs2312147 at vaccinia-related kinase 2 gene (VRK2), in multiple Asian and European samples. However, its effect on the brain structure in schizophrenia is little known. We analyzed the brain structure of 36 schizophrenia patients and 18 healthy subjects with regard to rs2312147 genotype groups. Brain magnetic resonance scans for gray matter (GM) and white matter (WM) analysis, and genotype analysis for VRK2 rs2312147, were conducted. The Positive and Negative Syndrome Scale and the Digit Symbol Test were assessed for schizophrenia patients. There was no significant difference in either GM volume or WM connectivity with regard to rs2312147 genotype in healthy subjects. In contrast, we found significant differences in the WM connectivity between rs2312147 CC and CT/TT genotype groups of schizophrenia patients. The related brain areas included the splenium of corpus callosum, the left occipital lobe WM, the internal capsule (left anterior limb and right retrolenticular part), the bilateral temporal lobe WM, the left fornix/stria terminalis, the left cingulate gyrus WM, and the left parietal lobe WM. Voxelwise correlation analysis revealed that the Digit Symbol Test scores (age corrected) correlated with the fractional anisotropy in WM tracts that previously showed significant group differences between the CT/TT and CC genotypes in the rs2312147 CT/TT genotype group, while no significant correlation was found in the CC genotype group. Our data may provide evidence for the effect of VRK2 on WM connectivity in patients with schizophrenia.     

Resting-State Functional Connectivity Bias of Middle Temporal Gyrus and Caudate with Altered Gray Matter Volume in Major Depression

Magnetic resonance imaging (MRI) studies have indicated that the structure deficits and resting-state functional connectivity (FC) imbalances in cortico-limbic circuitry might underline the pathophysiology of MDD. Using structure and functional MRI, our aim is to investigate gray matter abnormalities in patients with treatment-resistant depression (TRD) and treatment-responsive depression (TSD), and test whether the altered gray matter is associated with altered FC. Voxel-based morphometry was used to investigate the regions with gray matter abnormality and FC analysis was further conducted between each gray matter abnormal region and the remaining voxels in the brain. Using one-way analysis of variance, we found significant gray matter abnormalities in the right middle temporal cortex (MTG) and bilateral caudate among the TRD, TSD and healthy controls. For the FC of the right MTG, we found that both the patients with TRD and TSD showed altered connectivity mainly in the default-mode network (DMN). For the FC of the right caudate, both patient groups showed altered connectivity in the frontal regions. Our results revealed the gray matter reduction of right MTG and bilateral caudate, and disrupted functional connection to widely distributed circuitry in DMN and frontal regions, respectively. These results suggest that the abnormal DMN and reward circuit activity might be biomarkers of depression trait.     

Subthalamic Nucleus Stimulation Affects Theory of Mind Network: A PET Study in Parkinson's Disease

Background

There appears to be an overlap between the limbic system, which is modulated by subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson''s disease (PD), and the brain network that mediates theory of mind (ToM). Accordingly, the aim of the present study was to investigate the effects of STN DBS on ToM of PD patients and to correlate ToM modifications with changes in glucose metabolism.

Methodology/Principal Findings

To this end, we conducted ¹⁸FDG-PET scans in 13 PD patients in pre- and post-STN DBS conditions and correlated changes in their glucose metabolism with modified performances on the Eyes test, a visual ToM task requiring them to describe thoughts or feelings conveyed by photographs of the eye region. Postoperative PD performances on this emotion recognition task were significantly worse than either preoperative PD performances or those of healthy controls (HC), whereas there was no significant difference between preoperative PD and HC. Conversely, PD patients in the postoperative condition performed within the normal range on the gender attribution task included in the Eyes test. As far as the metabolic results are concerned, there were correlations between decreased cerebral glucose metabolism and impaired ToM in several cortical areas: the bilateral cingulate gyrus (BA 31), right middle frontal gyrus (BA 8, 9 and 10), left middle frontal gyrus (BA 6), temporal lobe (fusiform gyrus, BA 20), bilateral parietal lobe (right BA 3 and right and left BA 7) and bilateral occipital lobe (BA 19). There were also correlations between increased cerebral glucose metabolism and impaired ToM in the left superior temporal gyrus (BA 22), left inferior frontal gyrus (BA 13 and BA 47) and right inferior frontal gyrus (BA 47). All these structures overlap with the brain network that mediates ToM.

Conclusion/Significance

These results seem to confirm that STN DBS hinders the ability to infer the mental states of others and modulates a distributed network known to subtend ToM.     

Impact of the genome wide supported NRGN gene on anterior cingulate morphology in schizophrenia

Background

The rs12807809 single-nucleotide polymorphism in NRGN is a genetic risk variant with genome-wide significance for schizophrenia. The frequency of the T allele of rs12807809 is higher in individuals with schizophrenia than in those without the disorder. Reduced immunoreactivity of NRGN, which is expressed exclusively in the brain, has been observed in Brodmann areas (BA) 9 and 32 of the prefrontal cortex in postmortem brains from patients with schizophrenia compared with those in controls.

Methods

Genotype effects of rs12807809 were investigated on gray matter (GM) and white matter (WM) volumes using magnetic resonance imaging (MRI) with a voxel-based morphometry (VBM) technique in a sample of 99 Japanese patients with schizophrenia and 263 healthy controls.

Results

Although significant genotype-diagnosis interaction either on GM or WM volume was not observed, there was a trend of genotype-diagnosis interaction on GM volume in the left anterior cingulate cortex (ACC). Thus, the effects of NRGN genotype on GM volume of patients with schizophrenia and healthy controls were separately investigated. In patients with schizophrenia, carriers of the risk T allele had a smaller GM volume in the left ACC (BA32) than did carriers of the non-risk C allele. Significant genotype effect on other regions of the GM or WM was not observed for either the patients or controls.

Conclusions

Our findings suggest that the genome-wide associated genetic risk variant in the NRGN gene may be related to a small GM volume in the ACC in the left hemisphere in patients with schizophrenia.     

A Functional Magnetic Resonance Imaging (fMRI) Study of Cue-Induced Smoking Craving in Virtual Environments

Smokers who are exposed to smoking-related cues show cardiovascular reactivity and smoking craving compared with their responses to neutral cues, and increased cue reactivity predicts decreased likelihood of successful cessation. Several brain imaging studies suggested four candidate brain regions that might differ in gray matter volumes and densities between smokers and nonsmokers. However, in these studies, smokers were only exposed to smoking-related objects. In our pilot study utilizing a virtual reality (VR) technique, virtual environments (VEs) were more immersive and evoked smoking craving more effectively than traditionally used methods. In this study, we sought to test whether smokers could experience cue-induced smoking craving inside the MRI scanner by using the VR system. The smoking cue reactivity scenario was based in part on our preliminary task and consisted of 2D and 3D (or VE) conditions. The group mean of participants had increased activity in the prefrontal cortex (PFC), left anterior cingulate gyrus (ACC), left supplementary motor area, left uncus, right inferior temporal gyrus, right lingual gyrus, and right precuneus in the 2D condition. Areas of differential activation in the 3D condition were as follows: left superior temporal gyrus, right superior frontal gyrus, and left inferior occipital gyrus in the 3D condition. This finding is consistent with those of previous studies of nicotine craving showing PFC and ACC activation. However, in the 3D condition, the PFC including the superior frontal gyrus as well as the superior temporal gyrus, inferior occipital gyrus, and cerebellum were activated. Therefore, in the 3D condition, participants seemed to have more attention, visual balance, and coordinating movement than in the 2D condition.     

The Impact of Genome-Wide Supported Schizophrenia Risk Variants in the Neurogranin Gene on Brain Structure and Function

The neural mechanisms underlying genetic risk for schizophrenia, a highly heritable psychiatric condition, are still under investigation. New schizophrenia risk genes discovered through genome-wide association studies (GWAS), such as neurogranin (NRGN), can be used to identify these mechanisms. In this study we examined the association of two common NRGN risk single nucleotide polymorphisms (SNPs) with functional and structural brain-based intermediate phenotypes for schizophrenia. We obtained structural, functional MRI and genotype data of 92 schizophrenia patients and 114 healthy volunteers from the multisite Mind Clinical Imaging Consortium study. Two schizophrenia-associated NRGN SNPs (rs12807809 and rs12541) were tested for association with working memory-elicited dorsolateral prefrontal cortex (DLPFC) activity and surface-wide cortical thickness. NRGN rs12541 risk allele homozygotes (TT) displayed increased working memory-related activity in several brain regions, including the left DLPFC, left insula, left somatosensory cortex and the cingulate cortex, when compared to non-risk allele carriers. NRGN rs12807809 non-risk allele (C) carriers showed reduced cortical gray matter thickness compared to risk allele homozygotes (TT) in an area comprising the right pericalcarine gyrus, the right cuneus, and the right lingual gyrus. Our study highlights the effects of schizophrenia risk variants in the NRGN gene on functional and structural brain-based intermediate phenotypes for schizophrenia. These results support recent GWAS findings and further implicate NRGN in the pathophysiology of schizophrenia by suggesting that genetic NRGN risk variants contribute to subtle changes in neural functioning and anatomy that can be quantified with neuroimaging methods.     

精神分裂症患者暴力行为与全脑皮质厚度、甲状腺功能和Th17相关炎症因子的相关性分析

目的:探讨精神分裂症患者暴力行为与全脑皮质厚度、甲状腺功能和辅助性T细胞17(Th17)相关炎症因子的相关性。方法:选择常德市康复医院2020年1月~2021年4月收治的精神分裂症患者82例为研究对象。采用修订版外显攻击行为量表(MOAS)评分将患者分成暴力组(n=37)与无暴力组(n=45)。比较两组全脑皮质厚度、甲状腺功能、Th17相关炎症因子水平,利用Pearson相关系数分析MOAS评分与全脑皮质厚度、甲状腺功能指标和Th17相关炎症因子的相关性。结果:暴力组左侧枕中回、顶上回、顶下角回、顶下缘上回、枕极以及右侧枕上回、顶上回、顶下角回、顶下缘上回皮质厚度低于无暴力组(P<0.05)。暴力组血清游离三碘甲状腺原氨酸(FT₃)、总甲状腺激素(TT₄)、游离甲状腺素(FT₄)、总三碘甲状腺原氨酸(TT₃)、促甲状腺激素(TSH)、白介素-17(IL-17)、白介素-23(IL-23)、转化生长因子-β1(TGF-β1)水平高于无暴力组(P<0.05)。Pearson相关性分析结果显示,精神分裂症患者MOAS评分与左侧枕中回、顶上回、顶下角回、顶下缘上回、枕极以及右侧枕上回、顶上回、顶下角回、顶下缘上回皮质厚度呈负相关,与血清FT₃、TT₄、FT₄、TT₃、TSH、IL-17、IL-23、TGF-β1水平呈正相关(P<0.05)。结论:有暴力行为的精神分裂症患者伴有明显的全脑皮质厚度降低与甲状腺功能指标、Th17相关炎症因子水平升高,这可能对此类患者暴力行为的防治有一定参考意义。     

Regional Abnormality of Grey Matter in Schizophrenia: Effect from the Illness or Treatment?

Both schizophrenia and antipsychotic treatment are known to modulate brain morphology. However, it is difficult to establish whether observed structural brain abnormalities are due to disease or the effects of treatment. The aim of this study was to investigate the effects of illness and antipsychotic treatment on brain structures in antipsychotic-naïve first-episode schizophrenia based on a longitudinal short-term design. Twenty antipsychotic-naïve subjects with first-episode schizophrenia and twenty-four age- and sex-matched healthy controls underwent 3T MRI scans. Voxel-based morphometry (VBM) was used to examine the brain structural abnormality in patients compared to healthy controls. Nine patients were included in the follow-up examination after 8 weeks of treatment. Tensor-based morphometry (TBM) was used to identify longitudinal brain structural changes. We observed significantly reduced grey matter volume in the right superior temporal gyrus in antipsychotic-naïve patients with schizophrenia compared with healthy controls. After 8 weeks of treatment, patients showed significantly increased grey matter volume primarily in the bilateral prefrontal cortex, insula, right thalamus, left superior occipital cortex and the bilateral cerebellum. In addition, a greater enlargement of the prefrontal cortex is associated with the improvement in negative symptoms, and a more enlarged thalamus is associated with greater improvement in positive symptoms. Our results suggest the following: (1) the abnormality in the right superior temporal gyrus is present in the early stages of schizophrenia, possibly representing the core region related to schizophrenia; and (2) atypical antipsychotics could modulate brain morphology involving the thalamus, cortical grey matter and cerebellum. In addition, examination of the prefrontal cortex and thalamus might facilitate an efficient response to atypical antipsychotics in terms of symptom improvement.     

Female Adolescents with Severe Substance and Conduct Problems Have Substantially Less Brain Gray Matter Volume

ObjectiveStructural neuroimaging studies have demonstrated lower regional gray matter volume in adolescents with severe substance and conduct problems. These research studies, including ours, have generally focused on male-only or mixed-sex samples of adolescents with conduct and/or substance problems. Here we compare gray matter volume between female adolescents with severe substance and conduct problems and female healthy controls of similar ages. Hypotheses: Female adolescents with severe substance and conduct problems will show significantly less gray matter volume in frontal regions critical to inhibition (i.e. dorsolateral prefrontal cortex and ventrolateral prefrontal cortex), conflict processing (i.e., anterior cingulate), valuation of expected outcomes (i.e., medial orbitofrontal cortex) and the dopamine reward system (i.e. striatum).MethodsWe conducted whole-brain voxel-based morphometric comparison of structural MR images of 22 patients (14-18 years) with severe substance and conduct problems and 21 controls of similar age using statistical parametric mapping (SPM) and voxel-based morphometric (VBM8) toolbox. We tested group differences in regional gray matter volume with analyses of covariance, adjusting for age and IQ at p<0.05, corrected for multiple comparisons at whole-brain cluster-level threshold.ResultsFemale adolescents with severe substance and conduct problems compared to controls showed significantly less gray matter volume in right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, medial orbitofrontal cortex, anterior cingulate, bilateral somatosensory cortex, left supramarginal gyrus, and bilateral angular gyrus. Considering the entire brain, patients had 9.5% less overall gray matter volume compared to controls.ConclusionsFemale adolescents with severe substance and conduct problems in comparison to similarly aged female healthy controls showed substantially lower gray matter volume in brain regions involved in inhibition, conflict processing, valuation of outcomes, decision-making, reward, risk-taking, and rule-breaking antisocial behavior.     

Different Regional Gray Matter Loss in Recent Onset PTSD and Non PTSD after a Single Prolonged Trauma Exposure

Objective

Gray matter loss in the limbic structures was found in recent onset post traumatic stress disorder (PTSD) patients. In the present study, we measured regional gray matter volume in trauma survivors to verify the hypothesis that stress may cause different regional gray matter loss in trauma survivors with and without recent onset PTSD.

Method

High resolution T1-weighted magnetic resonance imaging (MRI) were obtained from coal mine flood disaster survivors with (n = 10) and without (n = 10) recent onset PTSD and 20 no trauma exposed normal controls. The voxel-based morphometry (VBM) method was used to measure the regional gray matter volume in three groups, the correlations of PTSD symptom severities with the gray matter volume in trauma survivors were also analyzed by multiple regression.

Results

Compared with normal controls, recent onset PTSD patients had smaller gray matter volume in left dorsal anterior cingulate cortex (ACC), and non PTSD subjects had smaller gray matter volume in the right pulvinar and left pallidum. The gray matter volume of the trauma survivors correlated negatively with CAPS scores in the right frontal lobe, left anterior and middle cingulate cortex, bilateral cuneus cortex, right middle occipital lobe, while in the recent onset PTSD, the gray matter volume correlated negatively with CAPS scores in bilateral superior medial frontal lobe and right ACC.

Conclusion

The present study identified gray matter loss in different regions in recent onset PTSD and non PTSD after a single prolonged trauma exposure. The gray matter volume of left dorsal ACC associated with the development of PTSD, while the gray matter volume of right pulvinar and left pallidum associated with the response to the severe stress. The atrophy of the frontal and limbic cortices predicts the symptom severities of the PTSD.     

Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep (primarily stages 2 and 3) showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than waking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep.     

Amplitude asymmetry of hemifield pattern reversal VEPs in healthy subjects

The amplitudes of transient and steady-state visual evoked potentials (VEPs) were measured during hemifield stimulation of the left eye in 10 healthy adults. Pattern reversal of a checkerboard was produced at 4 stimulation frequencies: 1, 5, 10 and 15 Hz. The amplitudes of pattern VEPs were evaluated using the paired t test to determine significant differences between right and left hemifields. The transient VEP amplitudes from midoccipital, midparietal, ipsilateral occipital and contralateral occipital electrodes were significantly greater with right hemifield stimulation. The steady-state VEP amplitudes from the midoccipital electrode during 15 Hz stimulation were significantly greater with right hemifield stimulation. Our neurophysiological data may be compatible with neuroanatomical asymmetries of the occipital lobes in humans.     

Investigation of changes in the activity and function of dry eye-associated brain regions using the amplitude of low-frequency fluctuations method

Objective: The local characteristics of spontaneous brain activity in patients with dry eye (DE) and its relationship with clinical characteristics were evaluated using the amplitude of low-frequency fluctuations (ALFF) method.Methods: A total of 27 patients with DE (10 males and 17 females) and 28 healthy controls (HCs) (10 males and 18 females) were recruited, matched according to sex, age, weight and height, classified into the DE and HC groups, and examined using functional magnetic resonance imaging (fMRI) scans. Spontaneous brain activity changes were recorded using ALFF technology. Data were recorded and plotted on the receiver operating characteristic (ROC) curve, reflecting changes in activity in different brain areas. Finally, Pearson correlation analysis was used to calculate the potential relationship between spontaneous brain activity abnormalities in multiple brain regions and clinical features in patients with DE. GraphPad Prism 8 (GraphPad Software, Inc.) was used to analyze the linear correlation between the Hospital Anxiety and Depression Scale and ALFF value.Results: Compared with HCs, the ALFF values of patients with DE were decreased in the right middle frontal gyrus (MFG)/right inferior orbitofrontal cortex (OFC), left triangle inferior frontal gyrus, left MFG, and right superior frontal gyrus. In contrast, the ALFF value of patients with DE was increased in the left calcarine.Conclusion: There are significant fluctuations in the ALFF value of specific brain regions in patients with DE versus HCs. This corroborates previous evidence showing that the symptoms of ocular surface damage in patients with DE are related to dysfunction in specific brain areas.     

Does Shape Discrimination by the Mouth Activate the Parietal and Occipital Lobes? – Near-Infrared Spectroscopy Study

A cross-modal association between somatosensory tactile sensation and parietal and occipital activities during Braille reading was initially discovered in tests with blind subjects, with sighted and blindfolded healthy subjects used as controls. However, the neural background of oral stereognosis remains unclear. In the present study, we investigated whether the parietal and occipital cortices are activated during shape discrimination by the mouth using functional near-infrared spectroscopy (fNIRS). Following presentation of the test piece shape, a sham discrimination trial without the test pieces induced posterior parietal lobe (BA7), extrastriate cortex (BA18, BA19), and striate cortex (BA17) activation as compared with the rest session, while shape discrimination of the test pieces markedly activated those areas as compared with the rest session. Furthermore, shape discrimination of the test pieces specifically activated the posterior parietal cortex (precuneus/BA7), extrastriate cortex (BA18, 19), and striate cortex (BA17), as compared with sham sessions without a test piece. We concluded that oral tactile sensation is recognized through tactile/visual cross-modal substrates in the parietal and occipital cortices during shape discrimination by the mouth.     

rTMS of the Left Dorsolateral Prefrontal Cortex Modulates Dopamine Release in the Ipsilateral Anterior Cingulate Cortex and Orbitofrontal Cortex

Background

Brain dopamine is implicated in the regulation of movement, attention, reward and learning and plays an important role in Parkinson''s disease, schizophrenia and drug addiction. Animal experiments have demonstrated that brain stimulation is able to induce significant dopaminergic changes in extrastriatal areas. Given the up-growing interest of non-invasive brain stimulation as potential tool for treatment of neurological and psychiatric disorders, it would be critical to investigate dopaminergic functional interactions in the prefrontal cortex and more in particular the effect of dorsolateral prefrontal cortex (DLPFC) (areas 9/46) stimulation on prefrontal dopamine (DA).

Methodology/Principal Findings

Healthy volunteers were studied with a high-affinity DA D2-receptor radioligand, [¹¹C]FLB 457-PET following 10 Hz repetitive transcranial magnetic stimulation (rTMS) of the left and right DLPFC. rTMS on the left DLPFC induced a significant reduction in [¹¹C]FLB 457 binding potential (BP) in the ipsilateral subgenual anterior cingulate cortex (ACC) (BA 25/12), pregenual ACC (BA 32) and medial orbitofrontal cortex (BA 11). There were no significant changes in [¹¹C]FLB 457 BP following right DLPFC rTMS.

Conclusions/Significance

To our knowledge, this is the first study to provide evidence of extrastriatal DA modulation following acute rTMS of DLPFC with its effect limited to the specific areas of medial prefrontal cortex. [¹¹C]FLB 457-PET combined with rTMS may allow to explore the neurochemical functions of specific cortical neural networks and help to identify the neurobiological effects of TMS for the treatment of different neurological and psychiatric diseases.