Bilateral Medial Frontal Cortex Research Articles

IMMU-04. THE ROLE OF CHECK POINT INHIBITORS IN PEDIATRIC PRIMARY DIFFUSE LEPTOMENINGEAL MELANOMATOSIS: REPORT OF TWO CASES

Abstract BACKGROUND Primary diffuse leptomeningeal melanomatosis (PDLM), a subtype of malignant melanomas of CNS, is rare, especially in children. PDLM is defined by diffuse invasiveness of the leptomeninges with or without nodules. Clinical manifestations of PDLM are nonspecific, mimicking the diagnosis of meningitis. As PDLM is neither sensitive to chemotherapy nor radiotherapy, the prognosis is extremely poor. Recently, some new therapeutic aspects like immunotherapy, especially immune check point inhibitors (ICI) are emerging. Cases report: First case: A 13 years old boy presented with 4 months of weakness, dysphasia and vomiting. MRI demonstrated diffuse leptomeningeal enhancement of the brain and spine. Brain biopsy confirmed the diagnosis of PDLM, with low PDL1 stains in immunohistochemistry, without targetable alterations on NGS. PET FDG normal. Treatment with ICI (Nivolumab 1 mg/kg/dose and Ipilimumab 3 mg/kg/dose, 4 courses every 21 days) was started. He developed severe complications after the 1st course (ICI enterocolitis, pancreatitis) and progressive disease after 2 courses. Craniospinal radiotherapy was delivered at a dose of 30 Gy. The disease continued to progress; the patient died nine months after diagnosis. Second case: A 7-year-old boy presented with diplopia, headache and vomiting. MRI demonstrated a cranial leptomeningeal enhancement and hypo-intense T1 and hyper-intense T2 signal at bilateral medial frontal cortex area. PET FDG normal. Brain biopsy confirmed the diagnosis of PDLM, with TMB 1.9, NRAS mutation and wild type BRAF by NGS. He started combination of ICI therapy. Three weeks after 1st course of Ipilimumab-Nivolumab he was admitted to PICU with prolonged status epilepticus. MRI demonstrated progression of leptomeningeal disease. Trametinib was deferred by parents and the child succumbed a year from diagnosis. CONCLUSIONS We report two cases of pediatric patients with PDLM treated unsuccessfully by immune check point inhibitors, emphasizing the diagnostic and therapeutic challenges in such a rare disease.

Association Between Serum NT-proBNP and Gray Matter Atrophy Patterns in an Older Japanese Population: The Hisayama Study.

Several population-based studies have reported that higher serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are associated with brain morphological changes. However, no population-based studies have examined the relationship between serum NT-proBNP and various regional brain volumes in detail. We here analyzed the brain MRI data of 1201 community-dwelling Japanese aged ≥65 years. Regional gray matter volumes (GMV) and intracranial volume (ICV) were estimated by applying voxel-based morphometry (VBM) methods. The associations of serum NT-proBNP with regional GMV/ICV were examined by analysis of covariance. The regional gray matter atrophy patterns associated with elevated serum NT-proBNP levels were investigated using VBM without a priori regions of interest. The multivariable-adjusted means of the frontal, temporal, hippocampal, parahippocampal, and entorhinal GMV/ICV decreased significantly with elevated serum NT-proBNP levels (all p for trend and q values of false discovery rate correction < .05). In VBM, elevated serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral entorhinal areas, bilateral fusiform gyri, left middle temporal gyrus, left inferior temporal gyrus, right central operculum, right posterior orbital gyrus, bilateral middle frontal gyri, anterior cingulate gyrus and bilateral medial frontal cortices. In a sensitivity analysis excluding 254 participants with mild cognitive impairment or dementia, serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral fusiform gyri, and left middle frontal gyrus. Our data suggest that elevated serum NT-proBNP levels are associated with gray matter atrophy in brain regions that play an important role in cognitive function.

Volumetric brain assessment of long-term head and neck cancer survivors

BackgroundRadiation therapy (RT) for locally advanced head and neck cancer (HNC) often exposes subcortical brain structures to radiation. We performed this study to assess region-specific brain volumetrics in a population of long term HNC survivors. Methods and MaterialsForty HNC survivors were enrolled at a mean of 6.4 years from completion of RT. Patients underwent a research MRI protocol that included a 3D T1- weighted whole-brain scan on a 3 Tesla MRI scanner. Voxel based morphometry was performed using the Computational Anatomy Toolbox with the Neuromorphometrics atlas. Healthy controls from the Human Connectome Project were used as a comparison cohort. Study participants also completed a comprehensive neurocognitive assessment. ResultsThe final study cohort consisted of 38 participants after excluding 2 participants due to image quality. HNC survivors displayed widespread reduction in gray matter (GM) brain region volumes that included bilateral medial frontal cortex, temporal lobe, hippocampus, supplemental motor area, and cerebellum. Greater radiation exposure was associated with reduced GM volume in the left ventral diencephalon (r = -0.512, p = 0.003). Associations between cognition and regional GM volumes were identified for motor coordination and bilateral cerebellum (left, r = 0.444, p = 0.009; right, r = 0.372, p = 0.030), confrontation naming and left amygdala (r = 0.382, p = 0.026), verbal memory and bilateral thalamus (left, r = 0.435, p = 0.010; right, r = 0.424, p = 0.012), right amygdala (r = 0.339, p = 0.050), and right putamen (r = 0.364, p = 0.034). ConclusionsReductions in GM were observed within this cohort of primarily non-nasopharyngeal HNC survivors as compared to a control sample. GM volumes were associated with performance in multiple cognitive domains. Results of this exploratory study support the need for investigation of anatomic brain changes as an important translational corollary to cognitive problems among HNC survivors.

Effects of rTMS Intervention on Functional Neuroimaging Activities in Adolescents with Major Depressive Disorder Measured Using Resting-State fMRI.

Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) is commonly used for the clinical treatment of major depressive disorder (MDD). The neuroimaging biomarkers and mechanisms of rTMS are still not completely understood. This study aimed to explore the functional neuroimaging changes induced by rTMS in adolescents with MDD. A total of ten sessions of rTMS were administrated to the L-DLPFC in thirteen adolescents with MDD once a day for two weeks. All of them were scanned using resting-state functional magnetic resonance imaging at baseline and after rTMS treatment. The regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and the subgenual anterior cingulate cortex (sgACC)-based functional connectivity (FC) were computed as neuroimaging indicators. The correlation between changes in the sgACC-based FC and the improvement in depressive symptoms was also analyzed. After rTMS treatment, ReHo and ALFF were significantly increased in the L-DLPFC, the left medial prefrontal cortex, bilateral medial orbital frontal cortex, and the left ACC. ReHo and ALFF decreased mainly in the left middle occipital gyrus, the right middle cingulate cortex (MCC), bilateral calcarine, the left cuneus, and the left superior occipital gyrus. Furthermore, the FCs between the left sgACC and the L-DLPFC, the right IFGoper, the left MCC, the left precuneus, bilateral post-central gyrus, the left supplementary motor area, and the left superior marginal gyrus were enhanced after rTMS treatment. Moreover, the changes in the left sgACC-left MCC FC were associated with an improvement in depressive symptoms in early improvers. This study showed that rTMS treatment in adolescents with MDD causes changes in brain activities and sgACC-based FC, which may provide basic neural biomarkers for rTMS clinical trials.

Comparison of quantitative FDG-PET and MRI in anti-LGI1 autoimmune encephalitis

ObjectivesAnti-leucine glioma-inactivated protein 1 (anti-LGI1) autoimmune encephalitis (AE) presents as subacute memory loss, behavioral changes, and seizures. Diagnosis and treatment delays can result in long term sequelae, including cognitive impairment. 18F-FDG PET/CT may be more sensitive than MRI in patients with AE. Our objective was to determine if anti-LGI1 is associated with a distinct pattern of FDG uptake and whether this pattern persists following treatment.MethodsNineteen18F-FDG PET/CT brain scans (13 pre-treatment, 6 convalescent phase) for 13 patients with anti-LGI1 were studied using NeuroQ™ and CortexID™. The sensitivity of the PET images was compared to MRI. The Z scores of 47 brain regions between the pre-treatment and next available follow-up images during convalescence were compared.ResultsAll 18F-FDG PET/CT scans demonstrated abnormal FDG uptake, while only 6 (42.9%) pre-treatment brain MRIs were abnormal. The pre-treatment scans demonstrated hypermetabolism in the bilateral medial temporal cortices, basal ganglia, brain stem, and cerebellum and hypometabolism in bilateral medial and mid frontal, cingulate, and parietotemporal cortices. Overall, the brain uptake during convalescence showed improvement of the Z scores towards 0 or normalization of previous hypometabolic activity in medial frontal cortex, inferior frontal cortex, Broca’s region, parietotemporal cortex, and posterior cingulate cortex and previous hypermetabolic activity in medial temporal cortices, caudate, midbrain, pons and cerebellum.ConclusionsBrain FDG uptake was more commonly abnormal than MRI in the pre-treatment phase of anti-LGI1, and patterns of dysmetabolism differed in the pre-treatment and convalescent phases. These findings may expedite the diagnosis, treatment, and monitoring of anti-LGI1 patients.

A Cross-Sectional Study: Structural and Related Functional Connectivity Changes in the Brain: Stigmata of Adverse Parenting in Patients with Major Depressive Disorder?

Background: There is a high correlation between the risk of major depressive disorder (MDD) and adverse childhood experiences (ACEs) such as adverse parenting (AP). While there appears to be an association between ACEs and changes in brain structure and function, there have yet to be multimodal neuroimaging studies of associations between parenting style and brain developmental changes in MDD patients. To explore the effect of AP on brain structure and function. Methods: In this cross-sectional study, 125 MDD outpatients were included in the study and divided into the AP group and the optimal parenting (OP) group. Participants completed self-rating scales to assess depressive severity, symptoms, and their parents' styles. They also completed magnetic resonance imaging within one week of filling out the instruments. The differences between groups of gender, educational level, and medications were analyzed using the chi-squared test and those of age, duration of illness, and scores on scales using the independent samples t-test. Differences in gray matter volume (GMV) and resting-state functional connectivity (RS-FC) were assessed between groups. Results: AP was associated with a significant increase in GMV in the right superior parietal lobule (SPL) and FC between the right SPL and the bilateral medial superior frontal cortex in MDD patients. Limitations: The cross-cultural characteristics of AP will result in the lack of generalizability of the findings. Conclusions: The results support the hypothesis that AP during childhood may imprint the brain and affect depressive symptoms in adulthood. Parents should pay attention to the parenting style and avoid a style that lacks warmth.

Altered neuromagnetic activity in default mode network in childhood absence epilepsy.

The electrophysiological characterization of resting state oscillatory functional connectivity within the default mode network (DMN) during interictal periods in childhood absence epilepsy (CAE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in CAE. Using a cross-sectional design, we analyzed MEG data from 33 children newly diagnosed with CAE and 26 controls matched for age and sex. The spectral power and functional connectivity of the DMN were estimated using minimum norm estimation combined with the Welch technique and corrected amplitude envelope correlation. Default mode network showed stronger activation in the delta band during the ictal period, however, the relative spectral power in other bands was significantly lower than that in the interictal period (p corrected < 0.05 for DMN regions, except bilateral medial frontal cortex, left medial temporal lobe, left posterior cingulate cortex in the theta band, and the bilateral precuneus in the alpha band). It should be noted that the significant power peak in the alpha band was lost compared with the interictal data. Compared with controls, the interictal relative spectral power of DMN regions (except bilateral precuneus) in CAE patients was significantly increased in the delta band (p corrected < 0.01), whereas the values of all DMN regions in the beta-gamma 2 band were significantly decreased (p corrected < 0.01). In the higher frequency band (alpha-gamma1), especially in the beta and gamma1 band, the ictal node strength of DMN regions except the left precuneus was significantly higher than that in the interictal periods (p corrected < 0.01), and the node strength of the right inferior parietal lobe increased most significantly in the beta band (Ictal: 3.8712 vs. Interictal: 0.7503, p corrected < 0.01). Compared with the controls, the interictal node strength of DMN increased in all frequency bands, especially the right medial frontal cortex in the beta band (Controls: 0.1510 vs. Interictal: 3.527, p corrected < 0.01). Comparing relative node strength between groups, the right precuneus in CAE children decreased significantly (β: Controls: 0.1009 vs. Interictal: 0.0475; γ 1: Controls:0.1149 vs. Interictal:0.0587, p corrected < 0.01) such that it was no longer the central hub. These findings indicated DMN abnormalities in CAE patients, even in interictal periods without interictal epileptic discharges. Abnormal functional connectivity in CAE may reflect abnormal anatomo-functional architectural integration in DMN, as a result of cognitive mental impairment and unconsciousness during absence seizure. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction, and prognosis in CAE patients.

Higher betweenness and degree centrality in the frontal and cerebellum cortex of Meige's syndrome patients than hemifacial spasm patients.

Meige's syndrome and hemifacial spasm (HFS) are two different forms of dystonic movement disorder, but their difference in terms of resting state functional connectivity (rsFC) remains unclear. The present study applied resting state fMRI on the patients and quantified their functional connectivity with graph theoretical measures, including the degree centrality and the betweenness centrality. Fifteen Meige's syndrome patients and 19 HFS patients matched in age and gender were recruited and their MRI data were collected. To analyze the rsFC, we adopted the Anatomical Automatic Labeling (AAL) template, a brain atlas system including 90 regions of interest (ROIs) covering all the brain regions of cerebral cortex. For each participant, the time-course of each ROI was extracted, and the corresponding degree centrality and betweenness centrality of each ROI were computed. These measures were then compared between the Meige's syndrome patients and the HFS patients. Meige's syndrome patients showed higher betweenness centrality and degree centrality of bilateral superior medial frontal cortex, the left cerebellum cortex, etc. than the HFS patients. Our results suggest that the rsFC pattern in Meige's syndrome patients might become more centralized toward the prefrontal and vestibular cerebellar systems, indicating less flexibility in their functional connections. These results preliminarily revealed the characteristic abnormality in the functional connection of Meige's patients and may help to explore better treatment.

Sarcopenia and decline in appendicular skeletal muscle mass are associated with hypoperfusion in key hubs of central autonomic network on 3DSRT in older adults with progression of normal cognition to Alzheimer's disease.

Although sarcopenia is common in patients with Alzheimer's disease (AD), the neural substrates involved remain unclear. We investigated the relationship between sarcopenia, as well as its definition components, and regional cerebral blood flow (rCBF) in older adults with progression of normal cognition to AD. 99m Tc-ethyl-cysteinate-dimer single-photon emission computed tomography was carried out in 95 older adults with progression of normal cognition to AD (40 men and 55 women, mean ± SD age 80.9 ± 6.8 years). The associations of rCBF determined by 3-D stereotactic region of interest template software, with sarcopenia and its definition components, slower gait speed, weaker grip strength, and decline in appendicular skeletal muscle mass index (ASMI) were analyzed. Logistic regression analysis adjusted by age, sex, mini-mental state examination score and education showed that sarcopenia as well as ASMI less than the cut-off (men 7.0 kg/m2 , women 5.7kg/m2 ) were associated with significantly reduced rCBF in the key hub of the central autonomic network, including the insula, anterior cingulate cortex, subcallosal area, rectal gyrus, hypothalamus, amygdala and caudate head. Sarcopenia and ASMI decline were associated with hypoperfusion in the aforementioned cortical hubs of the central autonomic network in men, but with hypoperfusion of the hypothalamus in women. Linear regression analysis showed significant correlations of ASMI/cut-off with rCBF in the bilateral medial frontal cortex, as well as rCBF in the aforementioned key hubs. Hypoperfusion in key hubs of central autonomic network is implicated in the emergence of sarcopenia, probably through ASMI decline in vulnerable older adults. Geriatr Gerontol Int 2023; 23: 16-24.

Association between resting-state functional connectivity of amygdala subregions and peripheral pro-inflammation cytokines levels in bipolar disorder.

The pathophysiological mechanisms of bipolar disorder (BD) are not completely known, and systemic inflammation and immune dysregulation are considered as risk factors. Previous neuroimaging studies have proved metabolic, structural and functional abnormalities of the amygdala in BD, suggesting the vital role of amygdala in BD patients. This study aimed to test the underlying neural mechanism of inflammation-induced functional connectivity (FC) in the amygdala subregions of BD patients. Resting-state functional MRI (rs-fMRI) was used to delineate the amygdala FC from two pairs of amygdala seed regions (the bilateral lateral and medial amygdala) in 51 unmedicated BD patients and 69 healthy controls (HCs). The levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were measured in the serum. The correlation between abnormal levels of pro-inflammatory cytokines and FC values were calculated in BD patients. The BD group exhibited decreased FC between the right medial amygdala and bilateral medial frontal cortex (MFC), and decreased FC between the left medial amygdala and the left temporal pole (TP), right orbital inferior frontal gyrus compared with HCs. The BD patients had higher levels of TNF-α than HCs. Correlation analysis showed negative correlation between the TNF-α level and abnormal FC of the right medial amygdala-bilateral MFC; and negative correlation between TNF-α levels and abnormal FC of the left medial amygdala-left TP in BD group. These findings suggest that dysfunctional and immune dysregulation between the amygdala and the frontotemporal circuitry might play a critical role in the pathogenesis of BD.

Alterations in metamemory capacity and neural correlates in a subtype of subjective cognitive decline

BackgroundsSubjective cognitive decline (SCD), one of the important clinical indicators for preclinical Alzheimer's disease (AD), is primarily defined as self-perceived cognitive decline without objective evidence for cognitive impairment. However, the accuracy of their self-evaluation of cognition is unclear. This study sought to investigate the capacity for self-evaluation of own cognitive performance in SCD by applying an objective metamemory paradigm. Methods147 individuals with SCD were classified into four subgroups by their subjective feeling of worse performance than peers or not (P+/-) and whether they have objectively slight cognitive impairment compared to normative data (S+/-). Metamemory scores, the amplitude of the low-frequency fluctuation (ALFF), fractional low-frequency fluctuation amplitude (fALFF), and cortical thickness were compared among four subgroups. Partial correlations between neuropsychological scores and neuroimaging measures were examined, controlling for age, sex, and education years. ResultsSCD S+P- showed the worst performance in short-term delayed recall and the worst metamemory performance, indicated by the highest value in the degree of confidence of short-term delayed recall (DOC-N4) and long-term cued recall (DOC-N6) and the worst value in relative accuracy of judgments of short-term delayed recall (ROJ-N4). ALFF values in the bilateral superior medial frontal and olfactory cortices and the left superior orbitofrontal gyrus cortex were significantly higher in SCD P- compared with SCD P+ groups (all P < 0.05, FWE-corrected, cluster-wise level). A significant S × P interaction effect in the left hippocampus and middle cingulate cortex was found for the fALFF signals (all P < 0.05, FWE-corrected, cluster-wise level). Significant interaction and main effects on cortical thickness were reported. The parahippocampal and posterior cingulate cortices were significantly decreased in SCD S+P- (all P < 0.05). ConclusionSCD S+P- showed the worst episodic memory performance, altered metamemory capacity (overconfidence and less accuracy of judgment), and altered neuroimaging measures, though they had feelings of similar performance with peers. Our results indicate that metamemory capacity is affected in a subtype of SCD with reduced cortical thickness and intensity of regional spontaneous activity in key areas for metamemory processing.

Suicidal behaviour: What's the brain up to?

BackgroundIndividuals with suicidal behaviours are increasingly recognized as having impairments in brain metabolism. However, these are not well delineated. AimTo evaluate regional cerebral glucose metabolism (rCMglu) in subjects with suicidal behaviours and assess differences in rCMglu between depressed and non-depressed suicidal subjects. MethodsThirty-three subjects with suicidal behaviours were assessed using Columbia Suicide Severity Rating scale (CSSRS) and Beck's Depression Inventory (BDI). Brain metabolism was assessed using [18F]Fluoro,Deoxy-Glucose Positron Emission Tomography (FDG-PET). ResultsOf 33 subjects, eighteen had depression. FDG-PET findings revealed that in comparison to mean asymptomatic controls, subjects had decreased rCMglu in right inferior frontal, left Broca's, left inferiolateral andsuperiolateral temporal, right inferior parietal and left posterior cingulate cortex. Increased rCMglu was seen in bilateral superior and medial frontal, right inferiolateral and posteriomedial temporal cortex, and midbrain. CSSRS total intensity inversely correlated with rCMglu in medial frontal cortex, left Broca's and superiolateral temporal cortex and directly correlated with rCMglu in right cerebellum. There was no significant difference in rCMglu between depressed and non depressed group. ConclusionsSignificant differences exist in rCMglu of suicidal individuals, chiefly in frontal and temporal regions. Understanding these would help us identify individuals more at risk for suicidal behaviours.

Disrupted Regional Homogeneity in Major Depressive Disorder With Gastrointestinal Symptoms at Rest.

Background: Gastrointestinal (GI) symptoms are prominent in patients with major depressive disorder (MDD). Previous studies have reported brain structural and functional changes in both MDD and digestive system diseases but it remains unclear whether MDD patients with GI symptoms have brain imaging changes.Methods: We recruited 35 MDD patients with GI symptoms, 17 MDD patients without GI symptoms and 28 age-, gender-, and education-matched healthy controls. All participants were scanned by resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with regional homogeneity (ReHo).Results: The GI group showed higher total HRSD-17 scores, anxiety/somatization, weight loss, and sleep disturbance scores compared to the non-GI group. We found increased ReHo in the right inferior parietal gyrus (IPL), bilateral supplementary motor area (SMA), bilateral cerebellum Crus II, left inferior frontal gyrus (IFG), and bilateral superior medial frontal cortex (SMFC) and decreased ReHo in the right posterior cingulate cortex (PCC), bilateral cuneus, and left middle occipital gyrus (MOG) in patients with GI symptoms relative to the HCs. The GI group showed higher ReHo values in the bilateral precuneus than the non-GI group.Conclusion: MDD patients with GI symptoms showed a greater severity of symptoms than MDD patients without GI symptoms, particularly in terms of anxiety/somatization, weight loss, and sleep disturbances. Increased activity in the default-mode network might be associated with GI symptoms in MDD patients.

Support vector machine-based classification of schizophrenia patients and healthy controls using structural magnetic resonance imaging from two independent sites.

Structural brain alterations have been repeatedly reported in schizophrenia; however, the pathophysiology of its alterations remains unclear. Multivariate pattern recognition analysis such as support vector machines can classify patients and healthy controls by detecting subtle and spatially distributed patterns of structural alterations. We aimed to use a support vector machine to distinguish patients with schizophrenia from control participants on the basis of structural magnetic resonance imaging data and delineate the patterns of structural alterations that significantly contributed to the classification performance. We used independent datasets from different sites with different magnetic resonance imaging scanners, protocols and clinical characteristics of the patient group to achieve a more accurate estimate of the classification performance of support vector machines. We developed a support vector machine classifier using the dataset from one site (101 participants) and evaluated the performance of the trained support vector machine using a dataset from the other site (97 participants) and vice versa. We assessed the performance of the trained support vector machines in each support vector machine classifier. Both support vector machine classifiers attained a classification accuracy of >70% with two independent datasets indicating a consistently high performance of support vector machines even when used to classify data from different sites, scanners and different acquisition protocols. The regions contributing to the classification accuracy included the bilateral medial frontal cortex, superior temporal cortex, insula, occipital cortex, cerebellum, and thalamus, which have been reported to be related to the pathogenesis of schizophrenia. These results indicated that the support vector machine could detect subtle structural brain alterations and might aid our understanding of the pathophysiology of these changes in schizophrenia, which could be one of the diagnostic findings of schizophrenia.

Nigrostriatal Degeneration in the Cognitive Part of the Striatum in Parkinson Disease Is Associated With Frontomedial Hypometabolism.

The present study investigated possible associations between cortical dysfunction/degeneration as measured by F-FDG PET and nigrostriatal degeneration according to the specific I-FP-CIT binding ratio (SBR) in striatal subregions defined by striato-cortical anatomical connectivity in Parkinson disease (PD) patients. The study included 41 patients (61.4 ± 12.8 years) with PD-typical reduction of striatal FP-CIT SBR and no sign of atypical parkinsonian syndrome on FDG PET. FP-CIT SBR was determined separately in the cognitive (composite of executive and limbic) and sensorimotor part of the striatum according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Scaled FDG uptake was tested voxelwise for correlation with FP-CIT SBR (familywise error corrected P < 0.05). A large cluster (17.6 mL) of significant correlation of scaled FDG uptake with FP-CIT SBR in the cognitive part of the striatum, corrected for SBR in the sensorimotor part, was detected in the bilateral medial frontal cortex and the anterior cingulate cortex (partial correlation coefficient R = 0.767); small clusters were detected in ipsilateral caudate and ipsilateral thalamus. There was a small contralateral occipital cluster (3.0 mL) of significant correlation between FDG uptake and sensorimotor SBR corrected for cognitive SBR (R = 0.709). The correlation between nigrostriatal degeneration in the cognitive striatum and reduced cerebral glucose metabolism in the medial parts of the frontal cortex including the anterior cingulate suggests that nigrostriatal degeneration is specifically involved in the pathogenesis of cognitive deficits associated with medial frontal dysfunction such as impaired inhibitory control.

The Stroop effect: An activation likelihood estimation meta-analysis in healthy young adults

Age plays a significant role in executive control processes in the Stroop task. This study aims to draw together the Stroop tasks to determine the role of the frontal cortex in cognitive control among healthy young adults using activation likelihood estimation. Forty-six studies were selected according to the fMRI neuroimaging tools, Stroop experimental tasks, young participants’ age. The results showed that the contrast of incongruent conditions and congruent conditions revealed 7 significant clusters, including the right cingulate cortex, left dorsolateral prefrontal cortex, bilateral inferior frontal gyrus, right superior frontal gyrus and temporal cortex. In addition, the contrast comparing incongruent conditions with neutral conditions activated a network including the right inferior frontal gyrus, left dorsolateral prefrontal cortex, bilateral medial frontal cortex, left insular cortex and bilateral inferior parietal lobule and precuneus. In this study, we found that the brain areas for executive performance had a higher concordance in the frontal cortex among healthy young adults than temporal-parietal network.

Hippocampal atrophy and functional connectivity disruption in cirrhotic patients with minimal hepatic encephalopathy.

The hippocampus is a crucial pathological node for minimal hepatic encephalopathy (MHE) and it is associated with various cognitive impairments. Investigations on alterations involving hippocampal morphology and functional connectivity (FC) in MHE are limited. This study aimed to simultaneously evaluate hippocampal volume and FC alterations and their association with cognitive decline in MHE. Twenty-two cirrhotic patients with MHE, 31 cirrhotic patients without MHE (NHE), and 43 healthy controls underwent high-resolution T1-weighted imaging, resting-state functional magnetic resonance imaging, and cognition assessment based on Psychometric Hepatic Encephalopathy Score (PHES). The structural images were preprocessed using a voxel-based morphometry method, during which hippocampal volume was measured. The hippocampal connectivity network was identified using seed-based correlation analysis. Hippocampal volume and FC strength were compared across the three groups and correlated against the PHES results of the cirrhotic patients. Compared to the controls, MHE patients exhibited a significantly lower bilateral hippocampal volume. A slight decrease in hippocampal volume was obtained from NHE to MHE, but it did not reach statistically significance. In addition, the average FC strength of the bilateral hippocampal connectivity network was significantly lower in the MHE patients. In particular, the MHE patients showed a decrease in FC involving the left hippocampus to bilateral posterior cingulate gyrus and left angular gyrus. The MHE patients also showed FC reduction between the right hippocampus and bilateral medial frontal cortex. A progressive reduction in hippocampal FC from NHE to MHE was also observed. The bilateral hippocampal FC strength (but not hippocampal volume) was positively correlated with the PHES results of the cirrhotic patients. Our assessment of MHE patients revealed decreased hippocampal volume, which suggests regional atrophy, and reduced hippocampal connectivity with regions that are primarily involved in the default-mode network, thereby suggesting a functional disconnection syndrome. These alterations reveal the mechanisms underlying cognitive deterioration with disease progression.

Common and distinct patterns of grey matter alterations in borderline personality disorder and bipolar disorder: voxel-based meta-analysis.

Whether borderline personality disorder (BPD) and bipolar disorder are the same or different disorders lacks consistency.AimsTo detect whether grey matter volume (GMV) and grey matter density (GMD) alterations show any similarities or differences between BPD and bipolar disorder. Web-based publication databases were searched to conduct a meta-analysis of all voxel-based studies that compared BPD or bipolar disorder with healthy controls. We included 13 BPD studies (395 patients with BPD and 415 healthy controls) and 47 bipolar disorder studies (2111 patients with bipolar disorder and 3261 healthy controls). Peak coordinates from clusters with significant group differences were extracted. Effect-size signed differential mapping meta-analysis was performed to analyse peak coordinates of clusters and thresholds (P &lt; 0.005, uncorrected). Conjunction analyses identified regions in which disorders showed common patterns of volumetric alteration. Correlation analyses were also performed. Patients with BPD showed decreased GMV and GMD in the bilateral medial prefrontal cortex network (mPFC), bilateral amygdala and right parahippocampal gyrus; patients with bipolar disorder showed decreased GMV and GMD in the bilateral medial orbital frontal cortex (mOFC), right insula and right thalamus, and increased GMV and GMD in the right putamen. Multi-modal analysis indicated smaller volumes in both disorders in clusters in the right medial orbital frontal cortex. Decreased bilateral mPFC in BPD was partly mediated by patient age. Increased GMV and GMD of the right putamen was positively correlated with Young Mania Rating Scale scores in bipolar disorder. Our results show different patterns of GMV and GMD alteration and do not support the hypothesis that bipolar disorder and BPD are on the same affective spectrum.Declaration of interestNone.

Sex-Related Reserve Hypothesis in Alzheimer’s Disease: Changes in Cortical Thickness with a Five-Year Longitudinal Follow-Up

Sex effects on the progression of Alzheimer's disease (AD) have received less attention than other demographic factors, including onset age and education. The aim of this study was to investigate whether sex affected cortical thinning in the disease progression of AD. We prospectively recruited 36 patients with early-stage AD and 14 people with normal cognition. All subjects were assessed with magnetic resonance imaging at baseline, Year 1, Year 3, and Year 5. We performed cortical thickness analyses using surface-based morphometry on magnetic resonance imaging. Women with AD showed more rapid cortical thinning in the left dorsolateral frontal cortex, left superior temporal gyrus, bilateral temporo-parietal association cortices, bilateral anterior cingulate gyri, bilateral medial frontal cortices, and bilateral occipital cortices over 5 years than men with AD, even though there was no difference in cortical thickness at baseline. In contrast, there were no regions of significantly more rapid atrophy in men with AD. Our findings suggest that women deteriorate faster than men in the progression of AD.

Aberrant default mode network in amnestic mild cognitive impairment: a meta-analysis of independent component analysis studies.

Independent component analysis (ICA) is one of the most popular and valid methods to investigate the default mode network (DMN), an intrinsic network which attracts particular attention in amnestic mild cognitive impairment (aMCI). However, previous studies present inconsistent results regarding the topographical organization of the DMN in aMCI. Therefore, we conducted a quantitative, voxel-wise meta-analysis of resting-state ICA studies using Seed-based d Mapping to establish the most consistent pattern of DMN functional connectivity alterations in aMCI. Twenty studies, comprising 23 independent datasets involving 535 patients and 586 healthy controls, met the inclusion criteria. Patients with aMCI exhibited reliably lower DMN functional connectivity than the healthy controls in the bilateral precuneus/posterior cingulate cortices and medial temporal lobes, which are implicated in episodic memory deficits. Moreover, an exploratory meta-regression analysis revealed that greater severity of global cognitive impairment in the patient groups was associated with stronger functional connectivity in the bilateral medial frontal cortices (including the anterior cingulate cortices), left angular gyrus, and right temporal pole extending to the middle temporal gyrus, likely reflecting a compensatory mechanism for maintaining cognitive efficiency. This meta-analysis identifies a consistent pattern of aberrant DMN functional connectivity in aMCI, which facilitates understanding of the neurobiological substrates of this disease.