Anterior Cingulate Cortex In Patients Research Articles

In Vivo Assessment of Astrocyte Reactivity in Patients with Progressive Supranuclear Palsy.

Although astrocytic pathology is a pathological hallmark of progressive supranuclear palsy (PSP), its pathophysiological role remains unclear. This study aimed to assess astrocyte reactivity in vivo in patients with PSP. Furthermore, we investigated alterations in brain lactate levels and their relationship with astrocyte reactivity. We included 30 patients with PSP-Richardson syndrome and 30 healthy controls; in patients, tau deposition was confirmed through 18F-florzolotau positron emission tomography. Myo-inositol, an astroglial marker, and lactate were quantified in the anterior cingulate cortex through magnetic resonance spectroscopy. We measured plasma biomarkers, including glial fibrillary acidic protein as another astrocytic marker. The anterior cingulate cortex was histologically assessed in postmortem samples of another 3 patients with PSP with comparable disease durations. The levels of myo-inositol and plasma glial fibrillary acidic protein were significantly higher in patients than those in healthy controls (p < 0.05); these increases were significantly associated with PSP rating scale and cognitive function scores (p < 0.05). The lactate level was high in patients, and correlated significantly with high myo-inositol levels. Histological analysis of the anterior cingulate cortex in patients revealed reactive astrocytes, despite mild tau deposition, and no marked synaptic loss. We discovered high levels of astrocyte biomarkers in patients with PSP, suggesting astrocyte reactivity. The association between myo-inositol and lactate levels suggests a link between reactive astrocytes and brain energy metabolism changes. Our results indicate that astrocyte reactivity in the anterior cingulate cortex precedes pronounced tau pathology and neurodegenerative processes in that region, and affects brain function in PSP. ANN NEUROL 2024.

Gender-related alterations of serum trace elements and neurometabolism in the anterior cingulate cortex of patients with major depressive disorder

BackgroundIt is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. Methods109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. ResultsIn individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N-acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. ConclusionsOur findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC.

Loss, gain and choice difficulty in gambling patients: Neural and behavioural processes.

Impaired decision-making is often displayed by individuals suffering from gambling disorder (GD). Since there are a variety of different phenomena influencing decision-making, we focused in this study on the effects of GD on neural and behavioural processes related to loss aversion and choice difficulty. Behavioural responses as well as brain images of 23 patients with GD and 20 controls were recorded while they completed a mixed gambles task, where they had to decide to either accept or reject gambles with different amounts of potential gain and loss. We found no behavioural loss aversion in either group and no group differences regarding loss and gain-related choice behaviour, but there was a weaker relation between choice difficulty and decision time in patients with GD. Similarly, we observed no group differences in processing of losses or gains, but choice difficulty was weaker associated with brain activity in the right anterior insula and anterior cingulate cortex in patients with GD. Our results showed for the first time the effects of GD on neural processes related to choice difficulty. In addition, our findings on choice difficulty give new insights on the psychopathology of GD and on neural processes related to impaired decision-making in GD.

Histamine-3 Receptor Availability and Glutamate Levels in the Brain: A PET-1H-MRS Study of Patients With Schizophrenia and Healthy Controls.

The histamine-3 receptor (H3R) may have a role in cognitive processes through its action as a presynaptic heteroreceptor inhibiting the release of glutamate in the brain. To explore this, we examined anterior cingulate cortex (ACC) and striatum H3R availability in patients with schizophrenia and characterized their relationships with glutamate levels in corresponding brain regions. We employed a cross-sectional study, recruiting 12 patients with schizophrenia and 12 healthy volunteers. Participants underwent positron emission tomography using the H3R-specific radio ligand [11C]MK-8278, followed by proton magnetic resonance spectroscopy to measure glutamate levels, recorded as Glu and Glx. Based on existing literature, the ACC and striatum were selected as regions of interest. We found significant inverse relationships between tracer uptake and Glu (r = -0.66, P = .02) and Glx (r = -0.62, P = .04) levels in the ACC of patients, which were absent in healthy volunteers (Glu: r = -0.19, P = .56, Glx: r = 0.10, P = .75). We also found a significant difference in striatal (F1,20 = 6.00, P = .02) and ACC (F1,19 = 4.75, P = .04) Glx levels between groups. These results provide evidence of a regionally specific relationship between H3Rs and glutamate levels, which builds on existing preclinical literature. Our findings add to a growing literature indicating H3Rs may be a promising treatment target in schizophrenia, particularly for cognitive impairment, which has been associated with altered glutamate signaling.

Distinct resting-state functional connectivity of the anterior cingulate cortex subregions in first-episode schizophrenia.

The anterior cingulate cortex (ACC) is a heterogeneous region of the brain's limbic system that regulates cognitive and emotional processing, and is frequently implicated in schizophrenia. This study aims to characterize resting-state functional connectivity (rsFC) profiles of three subregions of ACC in patients with first-episode schizophrenia and healthy controls. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were collected from 60 first-episode schizophrenia (FES) patients and 60 healthy controls (HC), and the subgenual ACC (sgACC), pregenual ACC (pgACC), and dorsal ACC (dACC) were selected as seed regions from the newest automated anatomical labeling atlas 3 (AAL3). Seed-based rsFC maps for each ACC subregion were generated and compared between the two groups. The results revealed that compared to the HC group, the FES group showed higher rsFC between the pgACC and bilateral lateral orbitofrontal cortex (lOFC), and lower rsFC between the dACC and right posterior OFC (pOFC), the medial prefrontal gyrus (MPFC), and the precuneus cortex (PCu). These findings point to a selective functional dysconnectivity of pgACC and dACC in schizophrenia and provide more accurate information about the functional role of the ACC in this disorder.

Synaptic Terminal Density Early in the Course of Schizophrenia: An In Vivo UCB-J Positron Emission Tomographic Imaging Study of SV2A

BackgroundThe synaptic hypothesis is an influential theory of the pathoetiology of schizophrenia (SCZ), which is supported by the finding that there is lower uptake of the synaptic terminal density marker [11C]UCB-J in patients with chronic SCZ than in control participants. However, it is unclear whether these differences are present early in the illness. To address this, we investigated [11C]UCB-J volume of distribution (VT) in antipsychotic-naïve/free patients with SCZ who were recruited from first-episode services compared with healthy volunteers. MethodsForty-two volunteers (SCZ n = 21, healthy volunteers n = 21) underwent [11C]UCB-J positron emission tomography to index [11C]UCB-J VT and distribution volume ratio in the anterior cingulate, frontal, and dorsolateral prefrontal cortices; the temporal, parietal and occipital lobes; and the hippocampus, thalamus, and amygdala. Symptom severity was assessed in the SCZ group using the Positive and Negative Syndrome Scale. ResultsWe found no significant effects of group on [11C]UCB-J VT or distribution volume ratio in most regions of interest (effect sizes from d = 0.0–0.7, p > .05), with two exceptions: we found lower distribution volume ratio in the temporal lobe (d = 0.7, uncorrected p < .05) and lower VT/fp in the anterior cingulate cortex in patients (d = 0.7, uncorrected p < .05). The Positive and Negative Syndrome Scale total score was negatively associated with [11C]UCB-J VT in the hippocampus in the SCZ group (r = −0.48, p = .03). ConclusionsThese findings indicate that large differences in synaptic terminal density are not present early in SCZ, although there may be more subtle effects. When taken together with previous evidence of lower [11C]UCB-J VT in patients with chronic illness, this may indicate synaptic density changes during the course of SCZ.

1H-MRS of the anterior cingulate cortex in obsessive-compulsive disorder: metabolic abnormalities in pgACC - controlled study

IntroductionObsessive-compulsive disorder (OCD) is connected with increased activity in cortico-striatal-thalamic-cortical (CSTC) loop. The anterior cingulate cortex (ACC) is a part of this loop and plays a role in error detection and monitoring and processing of conflicting information, core OCD clinical signs. This area also contains a high density of Von Economo neurons. Biochemistry in this area is closely connected with the pathophysiology of OCD.ObjectivesDecreased concentrations of total N-acetylaspartate (tNAA) have been reported in ACC in patients with OCD compared to healthy controls (HC), with increase after successful treatment. Findings by other metabolites: choline-containing compounds (tCho), total creatine (tCr) and myo-inositol are not consistent. Differences in levels of tNAA, tCho, tCr would correlate with the severity of symptoms measured by Y-BOCS. In the comparison in the subgroup of patients with/ without medication, there will be differences in levels of metabolites.Methods54 patients diagnosed with OCD according to ICD-10 and DSM-IV criteria, and 54 HC matched for age and sex were included in the study. They underwent MRI and MR Spectroscopy on a 3T Magnetom Prisma scanner (Siemens, Germany) equipped with a 64-channel volume head coil (Fig. 2). After spectral quality control, 28 OCD and 28 HC subjects were included in the statistical analysis. OCD subjects were interviewed using the Y-BOCS to evaluate the severity of the symptoms. Patients enrolled in the study were without medication at least 5 days before MRI or on a stable dosage of SSRI antidepressants. To assess the intergroup differences Wilcoxon Rank Sum test or Kruskal-Wallis test was used as appropriate. The correlation between metabolite levels and clinical characteristics was assessed by Spearman’s rank correlation coefficient. The statistics were calculated using R, version 4.1.1.ResultsWe found no differences in levels of tNAA in ACC in OCD vs. HC (p=0,21; see Tab.1, Fig.1). We found significantly increased level of tCho, tCr and Ins in OCD vs. HC (p=0,03; p=0,004 resp.; p=0,017 resp.). tCr levels corelated negatively with YBOCS compulsions subscale (p=0,046; cor=-0,38). tCho levels showed a trend to negative correlation with Y-BOCS compulsions subscale (p=0,067; cor=-0,35). Analysis on the subgroup with (13 subjects, 46,43 %) and without (13 subjects, 46,43 %) stable SSRI medication did not reveal significant differences.Image:Image 2:ConclusionsOur study found difference in ACC by OCD patients compared to HC, mainly increased tCho, tCr and Ins. Also, the study shows a significant correlation between the severity of compulsions and tCr levels. We can see this trend also in the correlation of the tCho and Y-BOCS compulsions subscale. Similar tNAA level by OCD and HC groups could indicates correctly adjusted medication or stable state by enrolled patients.Disclosure of InterestNone Declared

Glutamatergic Neurometabolite Levels in Bipolar Disorder: A Systematic Review and Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies

BackgroundThe glutamatergic system is thought to play an important role in the pathophysiology of bipolar disorder (BD). While there has been an increase in proton magnetic resonance spectroscopy studies examining this neurotransmission system, the results are inconsistent. Possible reasons for the inconsistency, including clinical features such as mood state and childhood versus adulthood age, were not addressed in previous meta-analyses. MethodsThis systematic review and meta-analysis of proton magnetic resonance spectroscopy studies of BD included 40 studies, with 1135 patients with BD and 964 healthy control (HC) subjects. ResultsGlutamate plus glutamine and glutamine levels in the anterior cingulate cortex of patients with BD were significantly elevated compared with those of HC subjects (standardized mean difference = 0.42, 0.48, respectively). Subgroup analyses showed that adult BD patients had significantly higher levels of glutamate plus glutamine than adult HC subjects, but this was not the case in pediatric patients. For mood states, anterior cingulate cortex glutamate plus glutamine levels were higher in patients with bipolar depression than those in HC subjects. ConclusionsOur results imply that glutamatergic dysfunction in the anterior cingulate cortex may be implicated in the pathophysiology of BD, which is most evident in adult BD patients and patients with bipolar depression.

Metabolite changes in prefrontal lobes and the anterior cingulate cortex correlate with processing speed and executive function in Parkinson disease patients.

BackgroundProcessing speed and executive function can be impaired in patients with Parkinson disease (PD). However, the neural factors related to the slowdown in processing speed and dysexecutive function in PD are not completely understood. The objective of this study is to investigate the metabolic changes of the frontal and anterior cingulate cortex (ACC) through the use of 1H magnetic resonance spectroscopy and to explore the association between cognitive function and metabolic ratios.MethodsIn this retrospective case-control study, we conducted neuropsychological assessments of executive function and information processing speed in healthy controls (HCs) and in patients with PD. Chemical information was obtained for the of N-acetyl-aspartate (NAA):creatine (Cr) ratio and the choline-containing compounds (Cho):Cr ratio within the bilateral prefrontal cortex and ACC. Using hierarchical multiple regression analysis, we analyzed the relationship between cognitive function and metabolic ratios in the bilateral prefrontal lobe and ACC in patients with PD.ResultsIn all, 59 patients with PD and 30 HCs were recruited. Patients with PD showed worse performance in executive function and processing speed compared with HCs (P<0.001). In patients with PD, the Cho:Cr ratios in the ACC (Z=2.20, P=0.028) and the right prefrontal cortex (t=2.16, P=0.034) were significantly increased. The hierarchical multiple regressions in patients with PD showed that the NAA:Cr ratio in the ACC correlated with the Stroop A completion times (P<0.05) and that the NAA:Cr ratio of the right prefrontal cortex correlated with the scores of the Wechsler Adult Intelligence Scale (WAIS)-Digit symbol test (P<0.05).ConclusionsInformation processing speed and executive function are impaired in patients with PD. Neuronal integrity and membrane turnover in the ACC and the right prefrontal cortex may be important factors in the slowdown of the information processing speed in patients with PD.

The behavioral variant of Alzheimer\u2019s disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex

BackgroundThe neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer’s disease (bvAD) remain unclear. A selective loss of Von Economo neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric diseases. Here, we assessed whether these specific neuronal populations show a selective loss in bvAD.MethodsVENs and GABA receptor subunit theta (GABRQ)-immunoreactive pyramidal neurons of the anterior cingulate cortex (ACC) were quantified in post-mortem tissue of patients with bvAD (n = 9) and compared to typical AD (tAD, n = 6), bvFTD due to frontotemporal lobar degeneration based on TDP-43 pathology (FTLD, n = 18) and controls (n = 13) using ANCOVAs adjusted for age and Bonferroni corrected. In addition, ratios of VENs and GABRQ-immunoreactive (GABRQ-ir) pyramidal neurons over all Layer 5 neurons were compared between groups to correct for overall Layer 5 neuronal loss.ResultsThe number of VENs or GABRQ-ir neurons did not differ significantly between bvAD (VENs: 26.0 ± 15.3, GABRQ-ir pyramidal: 260.4 ± 87.1) and tAD (VENs: 32.0 ± 18.1, p = 1.00, GABRQ-ir pyramidal: 349.8 ± 109.6, p = 0.38) and controls (VENs: 33.5 ± 20.3, p = 1.00, GABRQ-ir pyramidal: 339.4 ± 95.9, p = 0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.5 ± 82.658, p = 0.01) and no significant differences in number of VENs (bvFTD: 10.9 ± 13.8, p = 0.13). Results were similar when assessing the number of VENs and GABRQ-ir relative to all neurons of Layer 5.DiscussionVENs and phylogenetically related neurons did not show a selective loss in the ACC in patients with bvAD. Our results suggest that, unlike in bvFTD, the clinical presentation in bvAD may not be related to the loss of VENs and related neurons in the ACC.

Prof K C Dube Poster Award

BACKGROUNDRecent studies have shown altered N-Acetyl Aspartate (NAA) levels in the anterior cingulate cortex (ACC). Magnetic Resonance Spectroscopy (MRS) is a non-invasive method to examine the brain metabolites. In adult patients, most of the studies reported abnormalities in terms of decreased NAA levels in the ACC. Schizophrenia patients also show impaired performance on neurocognitive measures. These impairments are also seen in first episode patients.AIMS and OBJECTIVESThe purpose of the current study was to investigate the levels of NAA in the ACC along with neurocognitive deficits in patients of first episode schizophrenia, and if 6 weeks of usual treatment was able to produce any changes in the same.METHODOLOGY20 drug free or drug naïve patients of first episode schizophrenia and 10 healthy controls were taken. Single-voxel 1H-MRS was performed using the PRESS sequence with number of scans (NS) of 160, TR of 1500 ms and TE of 80 ms. Neurocognitive test was performed using Wisconsin Card Sorting test (WCST) and Montreal Cognitive Assessment (MoCA). Tests were repeated after 6 weeks of treatment. Statistical analysis was performed by SPSS 25.RESULTSThe peak height of NAA in the ACC and performance of the patients on the WCST and MoCA showed significant difference compared to healthy controls at baseline. The peak height of NAA in the ACC showed significant improvement after 6 weeks of treatment. Correlation studies showed significant positive correlation between MoCA total score and NAA height at baseline.DISCUSSION and CONCLUSIONThe study findings provide evidence in support of cognitive dysfunction in first episode schizophrenia, which is associated with neuronal loss, as evidenced by lower NAA peaks in the ACC in patients. The improvement in the metabolite levels after 6 weeks of antipsychotic treatment demonstrates neuroplastic effects of drug therapy.

Neural Changes in Borderline Personality Disorder After Dialectical Behavior Therapy–A Review

The biological component of the biosocial theory of emotion regulation stipulates that borderline personality disorder (BPD) arises from biological vulnerabilities to heightened emotional reactivity. Comprehensive reviews have consistently implicated abnormalities in the amygdala, anterior cingulate cortex, and hippocampus in the neurobiology of BPD. While Dialectical Behavior Therapy (DBT) is the leading evidence-based psychotherapy for the treatment of BPD, there remains a paucity of literature examining changes in the neurobiology of BPD following DBT treatment. Nine studies were identified that examined neurobiological changes in BPD after the completion of DBT. Results indicated that there was significant deactivation of amygdala activity as well as the anterior cingulate cortex in patients with BPD after DBT treatment. As well, several studies found after DBT treatment, BPD patients had a decreased activity in the inferior frontal gyrus in response to arousing stimuli and increased activity in response to inhibitory control. Future research on the neurobiological change after DBT treatment can help clarify biological mechanisms of change in BPD.

Altered cerebellum functional network on newly diagnosed drug-naïve Parkinson's disease patients with anxiety.

IntroductionDamage to the cerebellar functional network may underlie anxiety symptoms in patients with Parkinson’s disease (PD). Herein we investigated the regional homogeneity (ReHo) and functional connectivity (FC) patterns of cerebellar and clinical correlates in PD patients with anxiety and explored their clinical significance.MethodsWe enrolled 50 newly diagnosed drug-naïve PD patients and 30 normal controls (NCs). Twenty-six PD patients with anxiety symptoms (PD-A) and 24 PD patients without anxiety symptoms (PD-NA) were sorted into groups based on the Hamilton Anxiety Scale (HAMA). All included participants underwent rest-state functional magnetic resonance imaging (rs-fMRI) scanning. Cerebellar FC based on the seed-based method was used to investigate regional and whole brain function in PD-A, PD-NA, and NCs, and the relationship between the abnormal brain function and anxiety symptoms in PD patients was also detected.ResultsCompared with the PD-NA group and the NCs, the ReHo value of the PD-A group was significantly decreased in the left medial frontal gyrus and increased in the left cerebellum. Further, left-cerebellum-based FC patterns were used to detect the decreased FC in the right cerebellum, while FC was increased in the right caudate nucleus, and the right anterior cingulate cortex (ACC) in the PD-A group was compared with that in the PD-NA group. Further, the altered FC between the left cerebellum and the right cerebellum was significantly associated with anxiety symptoms in the PD-A group.ConclusionThe present study found abnormal regional cerebellum function as well as disruptions in the connectivity network within the cerebellum, caudate, and ACC in patients with PD-A. In addition, the FC between the left cerebellum and the right cerebellum was associated with anxiety symptoms in patients with PD. The present study indicated that cerebellar functional damage may be associated with anxiety symptoms in PD patients.

Brain glutamate concentration in men with early psychosis: a magnetic resonance spectroscopy case\u2013control study at 7\u2009T

Abnormalities in glutamate neurotransmission are linked to psychotic symptoms and cognitive dysfunction in schizophrenia. magnetic resonance spectroscopy (MRS) provides an acceptable means of measuring glutamate in the human brain but findings from patient studies at conventional magnetic field strength show considerable heterogeneity. Ultra-high-field MRS offers greater precision in glutamate measurement, particularly in delineation of glutamate from its precursor and metabolite, glutamine. This study aimed to use high-field (7 T) MRS to measure concentrations of glutamate and glutamine in three brain regions, anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and putamen (PUT), in young men with early psychosis. MRS was performed in 17 male participants with early psychosis and 18 healthy age-matched controls. Neurometabolite levels were calculated with unsuppressed water signal as the reference and corrected for individual grey matter, white matter and cerebrospinal fluid concentration. Cognitive function was measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Compared to controls, patients with early psychosis had lower concentrations of glutamate and glutamine in ACC. No differences were apparent in the DLPFC and PUT. In patients with early psychosis, there was a highly significant correlation between glutamate concentration in ACC and performance on the BACS, though the numbers available for this analysis were small. Our finding of lower glutamate levels in ACC in patients with schizophrenia is consistent with a recent meta-analysis of 7 T studies and suggests that this abnormality is present in both patients with early psychosis and those with longer-established illness. The possible link between ACC glutamate and cognitive performance requires replication in larger studies.

Proinflammatory Cytokines Predict Brain Metabolite Concentrations in the Anterior Cingulate Cortex of Patients With Bipolar Disorder.

Bipolar disorder (BD) is a severe psychiatric illness characterized by abnormalities in the immune/inflammatory function and in brain metabolism. Evidences suggest that inflammation may affect the levels of brain metabolites as measured by single-proton magnetic resonance spectroscopy (1H-MRS). The aim of the study was to investigate whether a wide panel of inflammatory markers (i.e., cytokines, chemokines, and growth factors) can predict brain metabolite concentrations of glutamate, myo-inositol, N-acetylaspartate, and glutathione in a sample of 63 bipolar patients and 49 healthy controls. Three cytokines influenced brain metabolite concentrations: IL-9 positively predicts glutamate, IL-1β positively predicts Myo-inositol, and CCL5 positively predicts N-acetylaspartate concentrations. Furthermore, patients showed higher concentrations of glutamate, Myo-inositol, and glutathione and lower concentrations of N-acetylaspartate in respect to healthy controls. Our results confirm that inflammation in BD alters brain metabolism, through mechanisms possibly including the production of reactive oxygen species and glia activation.

Grey matter abnormalities in first-episode mania: A systematic review and meta-analysis of voxel-based morphometry studies.

It has been proposed that different stages of bipolar disorder may be underpinned by distinct neurobiological substrates. However, structural neuroimaging studies in early stages of the illness are limited by small sample sizes yielding inconsistent findings. The purpose of this systematic review and meta-analysis, therefore, was to identify regional grey matter volume (GMV) changes that are consistently associated with first episode of mania (FEM). Following PRISMA guidelines, we conducted a systematic search of the literature to identify Voxel-Based Morphometry (VBM) studies in FEM patients compared with healthy individuals. We then conducted a voxel-wise meta-analysis using Seed-based d-Mapping technique. Finally, we performed univariate meta-regression analyses to explore the potential effects of moderator variables including age, gender, and percentage of lithium users on GMV alterations. We identified 15 VBM studies and included 12 studies in the meta-analysis. Four studies found no regional differences in GM volumes while other 11 studies reported volume changes in frontal and temporal regions as well as anterior cingulate cortex (ACC), cerebellum and basal ganglia. The meta-analysis revealed a single cluster of GMV reduction in bilateral pregenual ACC in patients with FEM compared to healthy individuals (P<.001). The Egger's test showed no evidence of publication bias at peak voxel level (P=.447). Meta-regression analyses revealed no significant effects of moderators evaluated. Structural brain changes are evident in the early stages of bipolar disorder. GMV reduction in bilateral pregenual ACC is the most consistent finding in VBM studies of FEM.

Neurochemicals of limbic system and thalamofrontal cortical network: Are they different between patients with idiopathic generalized epilepsy and psychogenic nonepileptic seizure?

ObjectiveThalamofrontal cortical network and limbic system are proposed to be involved in psychogenic nonepileptic seizure (PNES) and idiopathic generalized epilepsy (IGE). This study aimed to investigate neurochemical changes in prefrontal cortex, thalamus, and limbic circuits in patients with PNES and IGE. We also analyzed the interaction between cognitive functions and neurochemical changes in both groups. MethodsHydrogen proton magnetic resonance spectroscopy (1H-MRS) was used to measure N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), glutamate–glutamine (Glx), and myo-inositol (MI). The voxels were placed on the bilateral dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), anterior cingulate cortex (ACC), and thalamus. Attention and inhibitory control, as well as general intelligence status, were investigated using the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT) and the Wechsler Adult Intelligence Scale (WAIS), respectively, in patients with PNES and IGE, as well as healthy volunteers. ResultsThe 1H-MRS showed a decreased ratio of NAA/Cr in the right and left thalamus, right DMPFC, and right ACC in patients with IGE and PNES. Furthermore, a decrease of the NAA/Cr ratio in the left DMPFC and an increase of NAA/Cr ratio in the right DLPFC were observed in patients with PNES compared with the controls. The patient groups had a decreased ratio of Cho/Cr in right ACC compared with the healthy subjects. Moreover, the NAA/Cr ratio in the left thalamus and left DMPFC was correlated with seizure frequency in patient groups. Reduced NAA/Cr ratio in the right ACC and left DLPFC were also correlated with poor IVA-CPT scores. ConclusionThis study highlighted the dysfunction in prefrontal-thalamic–limbic circuits and impairment in neurocognition in patients with PNES and IGE.

Autonomic modulation networks in schizophrenia: The relationship between heart rate variability and functional and structural connectivity in the brain

Heart rate variability (HRV), a measurement of autonomic nervous system (ANS) activity, has been found reduced in schizophrenia. The anterior cingulate cortex (ACC), which is important in regulating the ANS, is structurally and functionally affected in schizophrenia. We investigate the relationship between HRV and functional and structural connectivity of the ACC in patients with schizophrenia and healthy controls. Ten patients with a diagnosis of schizophrenia and ten healthy controls were recruited. Heart rate was monitored in a naturalistic out-of-clinic setting. Magnetic resonance imaging (MRI) was performed, including resting-state functional MRI and diffusion tensor imaging. Patients with schizophrenia had significantly lower HRV compared to controls. A positive correlation between ACC connectivity with the bilateral cerebellum and HRV was found in the patients. HRV was also positively correlated with amplitude of low frequency fluctuations (ALFF) in the cerebellum, and with axial diffusivity in the middle cerebellar peduncle, in the patients. There was a significant negative relationship between antipsychotic medication dosage, HRV and all neuroimaging measures related to HRV. We conclude that ACC connectivity seems to be affected in schizophrenia, both structurally and functionally, and that the ACC-cerebellum connectivity, as well as cerebellar function, is associated with ANS regulation in patients with schizophrenia.

Dynamics of Activity in the Anterior Cingulate Cortex on Development of Obsessive-Compulsive Disorder: a Combined PET and FMRI Study

Impairment of the cerebral error detection mechanism is believed to be one of the causes of obsessive-compulsive disorder (OCD) and the anterior cingulate cortex (ACC) is the key element supporting this mechanism. However, neuroimaging data on the functional activity of the ACC in patients with OCD in the state of operational rest* and during activity are extremely diverse. An earlier explanation of this fact was the hypothesis that changes in ACC activity depend on the nature of the OCD present. With the aim of testing this hypothesis experimentally, the present studies performed combined PET-fMRI studies of the functional activity of the ACC in patients with OCD in the state of operational rest and on performance of activity presumptively involving the error detection mechanism. This activity was modeled using a Go/NoGo test with two tasks with different levels of difficulty. The ACC in patients in the state of operational rest showed glucose hypermetabolism, which decreased with increases in disease duration. The functional activity of the ACC during performance of actions was decreased in patients with OCD as compared with a group of healthy subjects. In addition, ACC activity on performance of the simpler task was found to increase with the course of illness; conversely, performance of the more difficult task decreased activity. Thus, the data obtained here support the hypothesis. Glucose hypermetabolism in the state of operational rest at the initial stages of illness was replaced by hypometabolism, probably because the ACC stopped carrying out its normal functions, which were compensated for by redistribution of the function among other relatively intact structures. This may lead to distortion of the functional specialization of the ACC, where the functional activity of the ACC in conditions of enhanced cognitive load decreased with increases in the duration of illness, while activity increased in conditions of relatively simple cognitive loading.

Prefrontal Regulation of Threat-Elicited Behaviors: A Pathway to Translation.

Regions of the prefrontal and cingulate cortices play important roles in the regulation of behaviors elicited by threat. Dissecting out their differential involvement will greatly increase our understanding of the varied etiology of symptoms of anxiety. I review evidence for altered activity within the major divisions of the prefrontal cortex, including orbitofrontal, ventrolateral, dorsolateral, and ventromedial sectors, along with the anterior cingulate cortex in patients with clinical anxiety. This review is integrated with a discussion of current knowledge about the causal role of these different prefrontal and cingulate regions in threat-elicited behaviors from experimental studies in rodents and monkeys. I highlight commonalities and inconsistencies between species and discuss the current state of our translational success in relating findings across species. Finally, I identify key issues that, if addressed, may improve that success in the future.