Left Hippocampus Research Articles

Deep Learning-Based Pediatric Brain Region Segmentation and Volumetric Analysis for General Growth Pattern in Healthy Children.

To establish a quantitative reference for brain structural changes in children with neurological disorders, we employed deep learning technique to brain region segmentation and volumetric analysis within a cohort of healthy children. In this study, we recruited 312 participants aged 1.5 to 14.5years (210 boys and 102 girls), dividing them into five age groups. High-resolution structural T1-weighted images were obtained, and an established toolkit utilizing deep learning algorithms was employed for brain region segmentation. For each age group, the volumes of gray matter and white matter, along with the thickness and surface area of the cortex, were calculated and compared between boys and girls. The results indicated that the volumes of gray matter and white matter in both bilateral cerebral hemispheres, as well as the total brain volume, increased with age. Furthermore, the volumes of the left and right hippocampus, amygdala, and thalamus also demonstrated an increase as age progressed. Conversely, cortical thickness and surface area decreased with age. Our findings provide a quantitative reference for understanding brain structural changes in children with neurological disorders.

Connectivity Changes Following Episodic Future Thinking in Alcohol Use Disorder.

Introduction: Recent addiction and obesity-related research suggests that episodic future thinking (EFT) can serve as a promising intervention to promote healthy decision-making. We used data from a pilot study to investigate the acute neural effects of EFT in alcohol use disorder (AUD). Because of the limitations of those data, we additionally used data from a previously published functional MRI (fMRI) study in which participants had not received any intervention for their AUD. Methods: In an out-of-scanner, guided interview, participants (n = 24; median age = 37.3 years; median AUDIT = 22.5) generated scenarios and cues about their future (EFT intervention, n = 15) or recent past (control episodic thinking [CET] control intervention, n = 9). Then, they performed both resting-state and task-based (delay discounting [DD]) fMRI. We used nodes from the default mode network and salience networks as well as the hippocampus to perform seed-based analyses of the resting-state data. The results then guided psychophysiological interaction analyses in the DD task. In addition, we used data from a larger, previously reported study as a "no intervention" group of AUD participants (n = 50; median age = 43.3; median Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol dependence score = 7) to reproduce and aid in interpreting our key findings. Results: EFT, but not CET, participants showed statistically improved DD rates-a behavioral marker for addiction. Resting-state analyses of the left hippocampus revealed connectivity differences in the frontal poles. The directionality of this difference suggested that EFT may reduce a hypo-connectivity relationship between these regions in AUD. We also found resting-state connectivity differences between the salience network and the right dorsolateral prefrontal cortex (R DLPFC), which then led us to discover R-to-L DLPFC psychophysiological interaction differences during DD. Moreover, the resting-state salience-to-DLPFC functional connectivity showed an inverse relationship to DD rate while hyperconnectivity between left and right DLPFC reflected slower reaction times during DD trials. Discussion: These findings suggest that previously noted benefits of EFT such as the improved DD replicated here might coincide with changes in neural connectivity patterns in AUD. The alterations in connectivity highlight potential mechanisms underlying the effectiveness of EFT in improving decision-making in AUD. Understanding these neural effects may contribute to the further development of targeted interventions for AUD and related disorders.

Pediatric Neural Changes to Physical and Emotional Pain After Intensive Interdisciplinary Pain Treatment: A Pilot Study.

Brain areas activated during pain can contribute to enhancing or reducing the pain experience, showing a potential connection between chronic pain and the neural response to pain in adolescents and youth. This study examined changes in brain activation associated with experiencing physical pain and observing physical and emotional pain in others by using functional magnetic resonance imaging (fMRI) before and after intensive interdisciplinary pain treatment (IIPT). Eighteen youths (age 14 to 18) with widespread chronic pain completed fMRI testing before and after IIPT to assess changes in brain activation in response to physical and emotional pain. Broadly, brain activation changes were observed in frontal, somatosensory, and limbic regions. These changes may suggest improvements in descending pain modulation via thalamus and caudate, and the different pattern of brain activation after treatment suggests potentially better discrimination between physical and emotional pain. Brain activation changes were also correlated with improvements in clinical outcomes of catastrophizing (reduced activation in right caudate, right mid-cingulate, and postcentral gyrus) and pain-related disability (increased activation in precentral gyrus, left hippocampus, right middle occipital cortex, and left superior frontal gyrus). These changes could indicate that reduced brain protective responses to pain were associated with treatment-related improvements. This pilot study highlights the need for larger trials designed to better understand the brain mechanisms involved in pediatric widespread pain treatment.

Curved multiplanar reformatting allows the accurate histological delineation of hippocampal subfields.

Hippocampal subfields perform specific roles in normal cognitive functioning and have distinct vulnerabilities in neurological disorders. However, measurement of subfields with MRI is technically difficult in the head and tail of the hippocampus. Recent studies have utilized curved multiplanar reconstruction (CMPR) to improve subfield visualization in the head and tail, but this method has not yet been applied to histological data. We utilized BigBrain data, an open-source database of serially sectioned histological data for our analyses. The left hippocampus was segmented according to histological criteria by two raters in order to evaluate intra- and inter-rater reliability of histology-based segmentation throughout the long axis. Segmentation according to our previous protocol for the hippocampal body was then compared to these histological measurements to evaluate for histological validity. Agreement between segmentations was evaluated using Dice similarity coefficients (DSCs). Intra-rater reliability (DSCs) of histological segmentation was excellent for all subfields: CA1 (0.8599), CA2 (0.7586), CA3/CA4/DG (0.8907), SLM (0.9123), subiculum (0.8149). Similarly, inter-rater reliability analysis demonstrated excellent agreement (DSCs) for all subfield locations: CA1 (0.8203), CA2 (0.7253), CA3/CA4/DG (0.8439), SLM (0.8700), subiculum (0.7794). Finally, histological accuracy (DSCs) for our previous protocol was excellent for all subfields: CA1 (0.8821), CA2 (0.8810), CA3/CA4/DG (0.9802), SLM (0.9879), subiculum (0.8774). When subfields in the hippocampus head, body, and tail were analyzed independently, DSCs also showed excellent agreement. CMPR allows reliable subfield segmentation based on histological criteria throughout the hippocampal head, body, and tail. Our previous protocol for the hippocampal body can be applied to provide histologically valid subfield measurements throughout the entire hippocampal long axis.

Different stimulation targets of rTMS modulate specific triple-network and hippocampal-cortex functional connectivity

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is widely applied to treat Alzheimer's disease (AD). Various treatment targets are currently being explored in clinical research. However, target diversity can result in considerable heterogeneity. ObjectiveThis study aimed to investigate whether different rTMS targets can enhance cognitive domains by modulating functional connectivity (FC) of the hippocampus (HIP) and triple network, which comprises the salience network (SN), central executive network (CEN), and default mode network (DMN). MethodsWe enrolled 63 patients with AD, of whom 48 and 15 underwent rTMS targeting the left dorsolateral prefrontal cortex (dlPFC) and the bilateral angular gyrus (ANG), respectively. We examined the network-level FC differences within the triple-network before and after treatment. Additionally, we utilized HIP as a seed for voxel-level analysis. We compared the similarities and differences in the effects of dlPFC and ANG rTMS. ResultsrTMS targeting the dlPFC primarily influenced the FC of the CEN, whereas rTMS targeting the ANG primarily influenced the SN and DMN. Moreover, the right temporal lobe within the DMN exhibited reduced FC with the left HIP following both therapies. The results of least absolute shrinkage and selection operator (LASSO) analysis indicated that hippocampal-cortex FC played a dominant role in the therapeutic effect. The observed FC changes significantly correlated with improvements in multiple cognitive scales. ConclusionrTMS targeting different regions affected the FC of specific networks. Both stimulation targets modulate the FC of hippocampal-cortex to influence therapeutic outcomes. Classification of patients based on damaged networks can further inform subsequent treatment strategies.

Automated Fiber Quantification Analysis Identifies Tract-specific Microstructural Alterations in Brain in Intermittent exotropia

BackgroundGrowing evidence of neuroimaging has indicated brain microstructural abnormalities in comitant strabismus. Nonetheless, few studies have investigated neuropathological alterations in patients with intermittent exotropia (IXT). This study aimed at examining the characteristics of brain microstructure along major fiber tracts in IXT patients using an automated fiber quantification analysis. MethodsA total of 25 patients with IXT as well as 25 healthy participants matched for age and gender finished the diffusion tensor imaging scanning and the ophthalmic examination. Automated fiber quantification analysis of 20 major fiber tracts was carried out for IXT patients and healthy subjects, respectively. Diffusion metrics of 100 equidistant nodes resampled along each tract were measured for every subject and compared between two groups. Effect size analysis was performed to identify the most affected fiber tracts in IXT. ResultsWidely declined mean diffusivity was noted in IXT along major tracts containing bilateral thalamic radiations, bilateral corticospinal fasciculi, bilateral cingulum cingulate, left inferior fronto-occipital fasciculus, right arcuate fasciculus and superior longitudinal fasciculus. Local reduction in fractional anisotropy was observed in IXT along left cingulum hippocampus, right inferior longitudinal fasciculus and right uncinate fasciculus, in contrast to the regionally increased fractional anisotropy along bilateral thalamic radiation, left corticospinal tract and left arcuate fasciculus. Among the tracts with significantly changed diffusion metrics in IXT, right inferior longitudinal fasciculus was the most affected one in fractional anisotropy while left thalamic radiation was the most influenced one in mean diffusivity. ConclusionsAbnormalities in microstructural properties along visual-related fiber tracts are likely to contribute to difficulties in visual information processing in IXT patients, which could serve as the neural basis of underlying pathological mechanism of IXT.

Augmenting mindfulness training through neurofeedback: a pilot study of the pre-post changes on resting-state functional connectivity in typically developing adolescents.

Mindfulness training has been shown to promote positive mental health outcomes and related changes in neural networks such as the default mode network, which has a central node in the posterior cingulate cortex (PCC). Previous work from our group reported on the impact of a novel, neurofeedback augmented mindfulness training (NAMT) task on regulation of PCC hemodynamic activity in typically developing adolescents. The present pilot study aimed to expand on this finding by examining the pre-post changes of the NAMT task on resting-state functional connectivity of the PCC. Thirty-one typically developing adolescents (14.77 ± 1.23 years; 45% female) underwent a resting-state functional magnetic resonance imaging scan both before and after completing the NAMT task. A linear mixed effects model was used to assess for changes in functional connectivity of the PCC across the two resting-state runs. Data did not support the hypothesized decrease in connectivity between the PCC seed and other DMN regions from pre- to post-NAMT task. However, we observed a significant increase in functional connectivity between the PCC and a cluster encompassing the left hippocampus and amygdala following completion of the NAMT task (run 1 Fisher's Z = 0.16; run 2 Fisher's Z = 0.26). Although preliminary, this finding suggests NAMT has the potential to strengthen connectivity between default mode and salience regions. We speculate that such changed connectivity may facilitate enhanced self-referential and emotional processing in adolescents. https://clinicaltrials.gov/, identifier NCT04053582.

Subsegmentation of the hippocampus in subgroups of migraine with aura patients: advanced structural neuroimaging study

BackgroundThis study investigated for a possible contributing role of hippocampus in the different clinical phenotypic manifestations of migraine aura.MethodsHerein, patients were categorized as those with pure visual aura (MwAv), those who reported additional somatosensory and dysphasic symptoms (MwAvsd), and healthy controls (HCs). Neuroimaging data obtained using FreeSurfer-based segmentation of hippocampal subfields were compared between HCs and patients with migraine with aura, as well as between HCs and those with MwAv and MwAvsd. The average migraine aura complexity score (MACS) was calculated for each patient to investigate the correlation between hippocampal subfield volume and migraine aura complexity.ResultsHerein, 46 patients with migraine with aura (28 MwAvsd and 18 MwAv) and 31 HCs were included. There were no significant differences in the hippocampal subfields between HCs and patients with migraine with aura. The average MACS negatively correlated with the volumes of the left and right hippocampi, Cornu Ammonis (CA) 1, CA3, CA4, molecular layer, left granule cell layer of the dentate gyrus, hippocampal fissure, and hippocampus-amygdala transition area. The MwAvsd subgroup had significantly smaller whole hippocampal volumes in both hemispheres, as well as in both subicula, compared with the MwAv subgroup and HCs. In addition, the left molecular layer, right CA1, and hippocampal fissures were significantly smaller in the MwAvsd group than in the MwAv subgroup and HCs.ConclusionsSmaller left and right hippocampal volumes, particularly of the subiculum/CA1 area, may play an important role in the pathophysiology of somatosensory and dysphasic symptoms in migraine with aura.

Genetic architectures of the human hippocampus and those involved in neuropsychiatric traits

BackgroundThe hippocampus, with its complex subfields, is linked to numerous neuropsychiatric traits. While most research has focused on its global structure or a few specific subfields, a comprehensive analysis of hippocampal substructures and their genetic correlations across a wide range of neuropsychiatric traits remains underexplored. Given the hippocampus’s high heritability, considering hippocampal and subfield volumes (HASV) as endophenotypes for neuropsychiatric conditions is essential.MethodsWe analyzed MRI-derived volumetric data of hippocampal and subfield structures from 41,525 UK Biobank participants. Genome-wide association studies (GWAS) on 24 HASV traits were conducted, followed by genetic correlation, overlap, and Mendelian randomization (MR) analyses with 10 common neuropsychiatric traits. Polygenic risk scores (PRS) based on HASV traits were also evaluated for predicting these traits.ResultsOur analysis identified 352 independent genetic variants surpassing a significance threshold of 2.1 × 10−9 within the 24 HASV traits, located across 93 chromosomal regions. Notably, the regions 12q14.3, 17q21.31, 12q24.22, 6q21, 9q33.1, 6q25.1, and 2q24.2 were found to influence multiple HASVs. Gene set analysis revealed enrichment of neural differentiation and signaling pathways, as well as protein binding and degradation. Of 240 HASV-neuropsychiatric trait pairs, 75 demonstrated significant genetic correlations (P < 0.05/240), revealing 433 pleiotropic loci. Particularly, genes like ACBD4, ARHGAP27, KANSL1, MAPT, ARL17A, and ARL17B were involved in over 50 HASV-neuropsychiatric pairs. Leveraging Mendelian randomization analysis, we further confirmed that atrophy in the left hippocampus, right hippocampus, right hippocampal body, and right CA1-3 region were associated with an increased risk of developing Parkinson’s disease (PD). Furthermore, PRS for all four HASVs were significantly linked to a higher risk of Parkinson’s disease (PD), with the highest hazard ratio (HR) of 1.30 (95% CI 1.18–1.43, P = 6.15 × 10⁻⁸) for right hippocampal volume.ConclusionsThese findings highlight the extensive distribution of pleiotropic genetic determinants between HASVs and neuropsychiatric traits. Moreover, they suggest a significant potential for effectively managing and intervening in these diseases during their early stages.

White matter alterations associated with chronic cannabis use disorder: a structural network and fixel-based analysis

Cannabis use disorder (CUD) is associated with adverse mental health effects, as well as social and cognitive impairment. Given prevalence rates of CUD are increasing, there is considerable efforts, and need, to identify prognostic markers which may aid in minimising any harm associated with this condition. Previous neuroimaging studies have revealed changes in white matter (WM) organization in people with CUD, though, the findings are mixed. In this study, we applied MRI-based analysis techniques that offer complimentary mechanistic insights, i.e., a connectome approach and fixel-based analysis (FBA) to investigate properties of individual WM fibre populations and their microstructure across the entire brain, providing a highly sensitive approach to detect subtle changes and overcome limitations of previous diffusion models. We compared 56 individuals with CUD (median age 25 years) to a sample of 38 healthy individuals (median age 31.5 years). Compared to controls, those with CUD had significantly increased structural connectivity strength (FDR corrected) across 9 edges between the right parietal cortex and several cortical and subcortical regions, including left orbitofrontal, left temporal pole, and left hippocampus and putamen. Utilizing FBA, WM density was significantly higher in those with CUD (FWE-corrected) across the splenium of the corpus callosum, and lower in the bilateral cingulum and right cerebellum. We observed significant correlation between cannabis use over the past month and connectivity strength of the frontoparietal edge, and between age of regular use and WM density of the bilateral cingulum and right cerebellum. Our findings enhance the understanding of WM architecture alterations associated with CUD.

Abnormal changes in neuropsychological function, brain structure and cerebral perfusion in patients with unruptured intracranial aneurysms.

Patients with unruptured intracranial aneurysms (UIAs) often experience emotional changes and cognitive impairments. However, the specific mechanisms underlying these impairments are still not fully understood. In the present study, voxel-based morphometry (VBM) and surface-based morphometry (SBM) were employed to investigate structural alterations in 49 patients diagnosed with UIAs compared with 50 healthy controls. Additionally, this study aimed to analyze the correlations among cortical morphological indices, cerebral blood perfusion values and neuropsychological test results. Compared with control group, UIA patients exhibited increased gray matter volume in the right anterior orbitofrontal cortex and decreased gray matter volume in the left thalamus pulvinar and hippocampus. Furthermore, the fractal dimension was lower in the right postcentral gyrus and entorhinal cortex. The cerebral perfusion values in the abnormal brain regions demonstrated a downward trend, which was associated with a reduction in gray matter volume in the left thalamus pulvinar and hippocampus, elevated anxiety levels and impaired executive function. UIA patients are prone to cognitive impairment and emotional dysregulation, which are accompanied by subtle changes in local gray matter volume and decreases in fractal dimension and cerebral blood flow. These findings provide new insights into the potential mechanisms underlying the cognitive impairment observed in UIA patients.

COVID-19 related cognitive, structural and functional brain changes among Italian adolescents and young adults: a multimodal longitudinal case-control study

Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting-state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in ECdelta (i.e., the difference in EC values pre- and post-COVID-19) and Volumetricdelta (i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that ECdelta significantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in Volumetricdelta between groups (p = 0.041). The reduced ECdelta in the left amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.

Altered Subcortical Brain Volume and Cortical Thickness Related to Insulin Resistance in Type 2 Diabetes Mellitus.

The objective of this study is to examine the alterations in subcortical brain volume and cortical thickness among individuals diagnosed with Type 2 diabetes mellitus (T2DM) through the application of morphometry techniques and, additionally, to investigate the potential association between these modifications and insulin resistance (IR). The present cross-sectional study comprised a total of 121 participants (n=48 with healthy controls [HCs] and n=73 with T2DM) who were recruited and underwent a battery of cognitive testing and structural magnetic resonance imaging (MRI). FreeSurfer was used to process the MRI data. Analysis of covariance compared discrepancies in cortical thickness and subcortical brain volume between T2DM and HCs, adjusting for the potential confounding effects of gender, age, education, and body mass index (BMI). Exploratory partial correlations investigated links between IR and brain structure in T2DM participants. Compared with HCs, individuals with T2DM demonstrated a cortical thickness decrease in the right caudal middle frontal gyrus, right pars opercularis, left precentral gyrus, and bilateral superior frontal gyrus. Furthermore, this study for T2DM found that the severity of IR was inversely related to the volume of the left putamen and left hippocampus, as well as the thickness of the left pars orbitalis, left pericalcarine, right entorhinal area, and right rostral anterior cingulate gyrus. The evidence for structural brain changes in T2DM was observed, and alterations in cortical thickness were concentrated in the frontal lobes. Correlations between IR and frontal cortical thinning may serve as a potential neuroimaging marker of T2DM and lead to various diabetes-related brain complications.

Depressive symptoms are linked to age-specific neuroanatomical and cognitive variations

Depression is a heterogeneous disorder, both in terms of patient symptomatology and in patient sociodemographic factors. Here, we examine the contribution of age to this heterogeneity, by characterizing the associations of depressive symptoms with cognitive performance and brain structure across the lifespan. We analyzed data from the Cambridge Centre for Aging Neuroscience (Cam-CAN) cohort (N = 2591, age 18–99). A subset of this cohort (N = 647) underwent structural MRI. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale. Cognitive assessments were performed using The Addenbrooke's Cognitive Examination Revised. Generalized linear models were employed to examine the relationship between depressive symptoms and cognitive performance. Statistical parametric mapping explored age-dependent associations between depressive symptoms and grey matter volume. Cognitive performance was associated with a significant age by depression by cognitive domain interaction, indicating that older individuals with more depressive symptoms had a lower cognitive performance, particularly in the fluency domain. Structural MRI revealed preferential depression-related reduction in grey matter volume in the left and right hippocampi in older adults. By contrast, in younger adults, depressive symptoms were more strongly associated with grey matter volume reduction in the left superior frontal gyrus and left middle frontal gyrus. Collectively, these findings indicate that the associations of depression with cognitive performance and brain structure are age-dependent, suggesting that the pathophysiological mechanisms underlying depression may differ between young and older adults. Recognizing these differences will support the development of better diagnostic tools and therapeutic interventions for depression across the lifespan.

MRI textural plasticity in limbic gray matter associated with clinical response to electroconvulsive therapy for psychosis.

Electroconvulsive therapy (ECT) is effective against treatment-resistant psychosis, but its mechanisms remain unclear. Conventional volumetry studies have revealed plasticity in limbic structures following ECT but with inconsistent clinical relevance, as they potentially overlook subtle histological alterations. Our study analyzed microstructural changes in limbic structures after ECT using MRI texture analysis and demonstrated a correlation with clinical response. 36 schizophrenia or schizoaffective patients treated with ECT and medication, 27 patients treated with medication only, and 70 healthy controls (HCs) were included in this study. Structural MRI data were acquired before and after ECT for the ECT group and at equivalent intervals for the medication-only group. The gray matter volume and MRI texture, calculated from the gray level size zone matrix (GLSZM), were extracted from limbic structures. After normalizing texture features to HC data, group-time interactions were estimated with repeated-measures mixed models. Repeated-measures correlations between clinical variables and texture were analyzed. Volumetric group-time interactions were observed in seven of fourteen limbic structures. Group-time interactions of the normalized GLSZM large area emphasis of the left hippocampus and the right amygdala reached statistical significance. Changes in these texture features were correlated with changes in psychotic symptoms in the ECT group but not in the medication-only group. These findings provide in vivo evidence that microstructural changes in key limbic structures, hypothetically reflected by MRI texture, are associated with clinical response to ECT for psychosis. These findings support the neuroplasticity hypothesis of ECT and highlight the hippocampus and amygdala as potential targets for neuromodulation in psychosis.

Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline.

Type 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD). The study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-α in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis. T2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, P=0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance. T2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD.

Diagnostic utility of brain MRI volumetry in comparing traumatic brain injury, Alzheimer disease and behavioral variant frontotemporal dementia

BackgroundBrain MRI with volumetric quantification, MRI volumetry, can improve diagnostic delineation of patients with neurocognitive disorders by identifying brain atrophy that may not be evident on visual assessments.ObjectiveTo investigate diagnostic utility of MRI volumetry in traumatic brain injury (TBI), early-onset Alzheimer disease (EOAD), late-onset Alzheimer disease, and behavioral variant frontotemporal dementia (bvFTD).MethodWe utilized 137 participants of TBI (n = 40), EOAD (n = 45), LOAD (n = 32), and bvFTD (n = 20). Participants had 3D T1 brain MRI imaging amendable to MRI volumetry. Scan volumes were analyzed with Neuroreader. One-way ANOVA compared brain volumes across diagnostic groups. Discriminant analysis was done with leave-one-out cross validation on Neuroreader metrics to determine diagnostic delineation across groups.ResultLOAD was the oldest compared to other groups (F = 27.5, p < .001). There were no statistically significant differences in sex (p = .58) with women comprising 54.7% of the entire cohort. EOAD and LOAD had the lowest Mini-Mental State Exam (MMSE) scores compared to TBI (p = .04 for EOAD and p = .01 for LOAD). LOAD had lowest hippocampal volumes (Left Hippocampus F = 13.1, Right Hippocampus F = 7.3, p < .001), low white matter volume in TBI (F = 5.9, p < .001), lower left parietal lobe volume in EOAD (F = 9.4, p < .001), and lower total gray matter volume in bvFTD (F = 32.8, p < .001) and caudate atrophy (F = 1737.5, p < .001). Areas under the curve ranged from 92.3 to 100%, sensitivity between 82.2 and 100%, specificity of 78.1-100%. TBI was the most accurately delineated diagnosis. Predictive features included caudate, frontal, parietal, temporal lobar and total white matter volumes.ConclusionWe identified the diagnostic utility of regional volumetric differences across multiple neurocognitive disorders. Brain MRI volumetry is widely available and can be applied in distinguishing these disorders.

Differences in Grey Matter Concentrations and Functional Connectivity between Young Carriers and Non-Carriers of the APOE ε4 Genotype.

Background: The pathophysiology of Alzheimer's disease (AD) may begin developing years or even decades prior to the manifestation of its first symptoms. The APOE ε4 genotype is a prominent genetic risk for AD that has been found to be associated with brain changes across the lifespan since early adulthood. Thus, studying brain changes that may occur in young adults with an APOE ε4 status is highly relevant. Objective: Examine potential differences in grey matter (GM) and functional connectivity (FC) in brains of cognitively healthy young APOE ε4 carriers and non-carriers, denoted here as ε4(+) and ε4(-), respectively. Methods: Three Tesla magnetic resonance imaging (MRI) brain scans were acquired from cognitively healthy young participants aged approximately 20 years (n = 151). Voxel-based morphometry (VBM) analysis was employed to identify potential structural differences in GM between ε4(+) and ε4(-). In a subsequent seed-based connectivity (SBC) analysis, brain regions that structurally differed in the VBM analysis were considered as seeds and correlated with all the remaining voxels across the brains to then measure the differences in FC between groups. Results: The VBM analysis suggested that ε4(+) (n = 28) had greater GM densities relative to ε4(-) (n = 123) in the left hippocampus and the left posterior insula (puncorr < 0.001). However, the effect did not survive the correction for multiple comparisons, suggesting minimal structural differences in this age range. In contrast, the SBC analysis indicated that ε4(+) exhibited significantly decreased FC between the left hippocampus and areas of the left middle temporal gyrus (n = 27) compared to ε4(-) (n = 102). These results remained significant after multiple comparisons (pFDR < 0.05). Lastly, no statistically significant differences in FC between groups were observed for the left insular seed (pFDR > 0.05). Discussion: These results suggest early structural and functional brain changes associated with the APOE ε4 genotype on young adults. Yet, they must be cautiously interpreted and contrasted with both older adults with genetic risk for AD and patients diagnosed with AD.

A eficácia do canabidiol no tratamento de transtornos mentais: Uma revisão sistemática de ensaios clínicos randomizados duplo-cegos

INTRODUCTION: The therapeutic application of cannabidiol (CBD) is gaining interest due to the growing body of evidence supporting its use in the treatment of mental disorders. OBJECTIVES: To develop a systematic review to evaluate the scientific evidence supporting the use of CBD in the treatment of psychiatric disorders. METHODS: Only double-blind randomized clinical trials were used. The search for scientific evidence was carried out in the PubMed and VHL databases, with the descriptors "cannabidiol" and "mental disorders". Between 2020 and 2022, 219 articles were found in PubMed and 79 in the VHL. Review articles, observational studies, manuscripts, repeated articles, and articles that did not focus on the treatment of mental disorders by the use of cannabidiol were excluded. Thus, 10 relevant studies remained for the present systematic review. RESULTS: Of the 10 articles selected, 90% presented positive results for the use of CBD in the treatment of various mental disorders. Among them, there was a higher prevalence of drug use for the treatment of psychosis, anxiety and behavioral mechanisms; evidencing its usefulness and benefits. It was observed that in cases of psychosis, CBD significantly increased glutamate levels in the left hippocampus of patients, proving its effectiveness. In research involving behavioral mechanisms, it was possible to verify that the use of CBD linearly decreased the levels of cortisol linked to stress in the patient's body, evidencing its therapeutic capacity. CONCLUSION: The use of CBD was useful to relieve the symptoms of some mental disorders, such as psychosis, anxiety, schizophrenia, autism, behavioral problems and stress. In addition, research has still shown uncertain and sometimes even contradictory results, which reinforces the need for more research on the action of this drug in the treatment of mental disorders.

Stereotactically intracerebral transplantation of neural stem cells for ischemic stroke attenuated inflammatory responses and promoted neurogenesis: an experimental study with monkeys.

Ischemic stroke is a common neurovascular disorder with high morbidity and mortality. However, the underlying mechanism of stereotactically intracerebral transplantation of human neural stem cells (hNSCs) is not well elucidated. Four days after ischemic stroke induced by Rose Bengal photothrombosis, seven cynomolgus monkeys were transplanted with hNSCs or vehicles stereotactically and followed up for 84 days. Behavioral assessments, magnetic resonance imaging, blood tests, and pathological analysis were performed before and after treatment. The proteome profiles of the left and right precentral gyrus and hippocampus were evaluated. Extracellular vesicle micro-RNA (miRNA) from the peripheral blood was extracted and analyzed. hNSC transplantation reduced the remaining infarcted lesion volume of cynomolgus monkeys with ischemic stroke without remarkable side effects. Proteomic analyses indicated that hNSC transplantation promoted GABAergic and glutamatergic neurogenesis and restored the mitochondrial electron transport chain function in the ischemic infarcted left precentral gyrus or hippocampus. Immunohistochemical staining and quantitative real-time reverse transcription PCR confirmed the promoting effects on neurogenesis and revealed that hNSCs attenuated post-infarct inflammatory responses by suppressing resident glia activation and mediating peripheral immune cell infiltration. Consistently, miRNA-sequencing revealed the miRNAs that were related to these pathways were downregulated after hNSC transplantation. This study indicates that hNSCs can be effectively and safely used to treat ischemic stroke by promoting neurogenesis, regulating post-infarct inflammatory responses, and restoring mitochondrial function in both the infarct region and hippocampus.