Medial Temporal Research Articles

Multimodal study of multilevel pulvino-temporal connections: a new piece in the puzzle of lexical retrieval networks.

Advanced methods of imaging and mapping the healthy and lesioned brain have allowed for the identification of the cortical nodes and white matter tracts supporting the dual neurofunctional organization of language networks in a dorsal phonological and a ventral semantic stream. Much less understood are the anatomical correlates of the interaction between the two streams; one hypothesis being that of a subcortically mediated interaction, through crossed cortico-striato-thalamo-cortical and cortico-thalamo-cortical loops. In this regard, the pulvinar is the thalamic subdivision that has most regularly appeared as implicated in the processing of lexical retrieval. However, descriptions of its connections with temporal (language) areas remain scarce. Here we assess this pulvino-temporal connectivity using a combination of state-of-the-art techniques: white matter stimulation in awake surgery and postoperative diffusion MRI (n = 4), virtual dissection from the Human Connectome Project 3 and 7 T datasets (n = 172) and operative microscope-assisted post-mortem fibre dissection (n = 12). We demonstrate the presence of four fundamental fibre contingents: (i) the anterior component (Arnold's bundle proper) initially described by Arnold in the 19th century and destined to the anterior temporal lobe; (ii) the optic radiations-like component, which leaves the pulvinar accompanying the optical radiations and reaches the posterior basal temporal cortices; (iii) the lateral component, which crosses the temporal stem orthogonally and reaches the middle temporal gyrus; and (iv) the auditory radiations-like component, which leaves the pulvinar accompanying the auditory radiations to the superomedial aspect of the temporal operculum, just posteriorly to Heschl's gyrus. Each of those components might correspond to a different level of information processing involved in the lexical retrieval process of picture naming.

Differential effects of specific emotions on spatial decision-making: evidence from cross-frequency functionally independent brain networks.

Emotions significantly shape the way humans make decisions. However, the underlying neural mechanisms of this influence remain elusive. In this study, we designed an experiment to investigate how emotions (specifically happiness, fear, and sadness) impact spatial decision-making, utilizing EEG data. To address the inherent limitations of sensor-level investigations previously conducted, we employed standard low-resolution brain electromagnetic tomography and functional independent component analysis to analyze the EEG data at the cortical source level. Our findings showed that across various spectral-spatial networks, positive emotion activated the decision-making network in the left middle temporal gyrus and inferior temporal gyrus, in contrast to negative emotions. We also identified the common spectral-spatial networks and observed significant differences in network strength across emotions. These insights further revealed the important role of the gamma-band prefrontal network. Our research provides a basis for deciphering the roles of brain networks in the impact of emotions on decision-making.

Lifespan adversities affect neural correlates of behavioral inhibition in adults.

Growing evidence suggests that adverse experiences have long-term effects on executive functioning and underlying neural circuits. Previous work has identified functional abnormalities during inhibitory control in frontal brain regions in individuals exposed to adversities. However, these findings were mostly limited to specific adversity types such as maltreatment and prenatal substance abuse. We used data from a longitudinal birth cohort study (n = 121, 70 females) to investigate the association between adversities and brain responses during inhibitory control. At the age of 33 years, all participants completed a stop-signal task during fMRI and an Adult Self-Report scale. We collected seven prenatal and postnatal adversity measures across development and performed a principal component analysis to capture common variations across those adversities, which resulted in a three-factor solution. Multiple regression analysis was performed to identify links between adversities and brain responses during inhibitory control using the identified adversity factors to show the common effect and single adversity measures to show the specific contribution of each adversity. To find neural correlates of current psychopathology during inhibitory control, we performed additional regression analyses using Adult Self-Report subscales. The first adversity factor reflecting prenatal maternal smoking and postnatal psychosocial adversities was related to higher activation during inhibitory control in bilateral inferior frontal gyri, insula, anterior cingulate cortex, and middle temporal gyri. Similar results were found for the specific contribution of the adversities linked to the first adversity factor. In contrast, we did not identify any significant association between brain responses during inhibitory control and the second adversity factor reflecting prenatal maternal stress and obstetric risk or the third adversity factor reflecting lower maternal sensitivity. Higher current depressive symptoms were associated with higher activation in the bilateral insula and anterior cingulate cortex during inhibitory control. Our findings extended previous work and showed that early adverse experiences have a long-term effect on the neural circuitry of inhibitory control in adulthood. Furthermore, the overlap between neural correlates of adversity and depressive symptomatology suggests that adverse experiences might increase vulnerability via neural alterations, which needs to be investigated by future longitudinal research.

Left-sided epileptiform activity influences language lateralization in right mesial temporal sclerosis.

To investigate the association between left epileptiform activity and language laterality indices (LI) in patients with right mesial temporal sclerosis (MTS). Twenty-two patients with right MTS and 22 healthy subjects underwent fMRI scanning while performing a language task. LI was calculated in multiple regions of interest (ROI). Data on the presence of left epileptiform abnormalities were obtained during prolonged video-EEG monitoring. After correction for multiple comparisons, LI was reduced in the middle temporal gyrus in the left interictal epileptiform discharges (IED+) group, compared with the left IED- group (p < 0.05). Using a responsive reading naming fMRI paradigm, right MTS patients who presented left temporal interictal epileptiform abnormalities on video-EEG showed decreased LI in the middle temporal gyrus, indicating decreased left middle temporal gyrus activation, increased right middle temporal gyrus activation or a combination of both, demonstrative of language network reorganization, specially in the MTG, in this patient population. This research studied 22 patients with right mesial temporal sclerosis (a specific type of epilepsy) comparing them to 22 healthy individuals. Participants were asked to perform a language task while undergoing a special brain imaging technique (fMRI). The findings showed that patients with epilepsy displayed a change in the area of the brain typically responsible for language processing. This suggests that their brains may have adapted due to their condition, altering the way language is processed.

Transcranial direct current stimulation over the left posterior temporal lobe modulates semantic control: Evidence from episodic memory distortions

Evidence accumulates to show that semantic cognition requires, in addition to semantic representations, control processes that regulate the accessibility and use of semantic knowledge in a task- and time-appropriate fashion. Semantic control has been recently proposed to rely on a distributed network that includes the posterior temporal cortex. Along these lines, recent meta-analyses of neuroimaging data and studies with patients suffering from semantic aphasia have suggested that the left posterior middle temporal gyrus (pMTG) is critically involved whenever situational context must constrain semantic retrieval. In the present experiment, we used transcranial direct current stimulation over the left posterior temporal lobe in an attempt to interfere with semantic control while participants performed a DRM task, a procedure for inducing conceptually-based false recognition that is contingent on both activation and control processes. Paralleling findings with patients suffering from brain damage restricted to the temporoparietal cortex, anodal stimulation (relative to sham stimulation) resulted in increased false recognition but intact true recognition. These findings fit well with the idea that the left pMTG is a key component of a semantic control network, the alteration of which results in memory performance that is affected by the intrusion of contextually-inappropriate semantic information.

Exploring the central mechanism of mind-regulation electroacupuncture in treatment of chronic fatigue syndrome with anxiety and depression comorbidity based on functional magnetic resonance imaging.

To observe the changes in the regional homogeneity (ReHo) and functional brain network in treatment of chronic fatigue syndrome (CFS) with anxiety and depression comorbidity with the mind-regulation electroacupuncture (EA), using resting-state functional magnetic resonance imaging (rs-fMRI). Thirty CFS patients with anxiety and depression comorbidity were enrolled from medical staffs as the observation group. The other 30 healthy subjects were recruited from medical university students as the control group, matching gender, age and education years with the observation group. No any acupuncture intervention was delivered in the control group, and EA for regulating the mind was operated in the observation group. Main points were the emotional area of Sun's scalp acupuncture, the regions 1 and 8 of Sun's abdominal acupuncture. Supplementary acupoints included Baihui (GV 20), Guanyuan (CV 4) and bilateral. The scores of the five domains in MFI-20 (i.e. general fatigue, physical fatigue, mental fatigue, reduced motivation and reduced activity), the total score of MFI-20, and the scores of SDS, SAS and PSQI in the observation group before treatment were higher than those of the control group (P<0.05). Except the score of reduced motivation in MFI-20, the scores of the other domains and the total score of MFI-20, as well as the scores of SDS, SAS and PSQI after treatment were lower than those before treatment in the observation group (P<0.05). Compared with the values before treatment, ReHo value was increased in the the right precuneus and decreased in the left inferior temporal gyrus and the left angular gyrus of the brain in the observation group after treatment. In the observation group, when compared with the control group, ReHo values were increased in the left inferior cerebral lobe, the interhemispheric region, the right occipital lobe and the thalamus; and it was reduced in the left middle temporal gyrus, the right posterior central gyrus, the right middle temporal gyrus, the right orbital middle frontal gyrus, the paracentral lobule and the right fusiform gyrus before treatment. In the observation group, the functional connectivity was decreased between the right thalamus and the left posterior central gyrus, the right hippocampus and the right fusiform gyrus before treatment, respectively; it was re-constructed after treatment between the right thalamus and the left posterior central gyrus, and the right fusiform gyrus. Compared with the control group, the functional connectivity between the right thalamus and the left posterior central gyrus, the right hippocampus, and the right fusiform gyrus was reduced before treatment; while after treatment, the functional connectivity was reduced between the right thalamus and the hippocampus in the observation group. With Spearman correlation analysis between the differential brain regions and the scores of MFI-20, SAS, SDS and PSQI, it was found that the left middle temporal gyrus, the paracentral lobule, the right precuneus, and the left inferior temporal gyrus had a partial positive correlation with the above clinical scales; and the interhemispheric region, the thalamus, the right fusiform gyrus, and the right middle temporal gyrus showed a partial negative correlation. There is the decrease of ReHo in many brain regions and the numbers of the local brain functional network connectivity in CFS patients with anxiety and depression comorbidity. The mind-regulation electroacupuncture therapy may relieve the clinical symptoms of the patients through adjusting the abnormal brain regions and activating emotion-related brain regions.

Exploration of the effects of Yang's pricking-cupping therapy on eczema-induced pruritus based on rs-fMRI.

To explore the clinical effect of Yang's pricking-cupping therapy and its central mechanism in treatment of eczema-induced pruritus using resting-state functional magnetic resonance imaging (rs-fMRI). Fifty patients with eczema-induced pruritus were enrolled in the observation group, and 50 healthy subjects were enrolled in the control group. No any intervention was delivered in the control group. Yang's pricking-cupping therapy was operated at Dazhui (GV 14) and bilateral Quchi (LI 11), Xuehai (SP 10) and Sanyinjiao (SP 6), once a week, lasting 6 weeks in the observation group. The scores of the 12-item pruritus severity scale (12-PSS), the eczema area and severity index (EASI), the dermatology life quality index (DLQI), the Pittsburgh sleep quality index (PSQI), and the self-rating anxiety scale (SAS) were compared before and after treatment in the observation group. The rs-fMRI scanning was conducted and the regional homogeneity (ReHo) analysis performed in all of the participants before and after treatment in the observation group, as well as at the time of subject enrollment in the control group. The correlation was analyzed between ReHo values in the different areas of the brain and the scores of the above scales. Compared with those before treatment, the scores of 12-PSS, EASI, DLQI, PSQI, and SAS were reduced after treatment in the observation group (P<0.01, P<0.05). ReHo values were increased in the right caudate nucleus, the right middle temporal gyrus, the right orbitofrontal gyrus, the right thalamus and the left angular gyrus before treatment in the observation group when compared with those in the control group (P<0.001); and ReHo values in the above areas of the brain were decreased after treatment when compared with those before treatment in the observation group (P<0.001). In comparison with the control group, ReHo values were reduced in the left middle temporal gyrus, the left superior parietal lobule and the left supplementary motor area in the observation group before treatment (P<0.001); while when compared with those before treatment, ReHo values in the above areas of the brain were elevated after treatment in the observation group (P<0.001). Before treatment, ReHo value in the left supplementary motor area was positively correlated with 12-PSS score (r=0.432, P=0.004), and the value in the right orbitofrontal gyrus was negatively correlated with PSQI score (r=-0.318, P=0.04) in the observation group. After treatment, ReHo value in the left superior parietal lobule was positively correlated with 12-PSS score (r=0.384, P=0.012) in the observation group. The abnormal cerebral functional activities are exhibited in multiple areas of the brain involved in stimulus response, emotional regulation, behavior control and attention in the patients with eczema-induced pruritus. Yang's pricking-cupping therapy can effectively relieve the pruritus symptoms and skin lesions of the patients, which may be related to reversing the abnormal cerebral functional activities induced by pruritus.

Exploring the regulatory effect of acupuncture for Ningshen Tongqiao on the functional connectivity between the anterior cingulate cortex and the whole brain in the patients with subjective tinnitus based on fMRI.

To explore the effect of acupuncture for Ningshen Tongqiao (tranquilizing the spirit and unblocking the orifices) on the functional connectivity (FC) between the anterior cingulate cortex (ACC) and the whole brain in the patients with subjective tinnitus using the resting-state functional magnetic resonance imaging (fMRI). Forty patients with subjective tinnitus and 40 healthy subjects were recruited. The patients with subjective tinnitus were treated with acupuncture for Ningshen Tongqiao at Yamen (GV 15) and Baihui (GV 20), as well as Tinggong (SI 19), Touqiaoyin (GB 11) and Shuaigu (GB 8) on the affected side; and Tinggong (SI 19) and Touqiaoyin (GB 11) were attached to the electric acupuncture apparatus and stimulated with disperse-dense wave and 2 Hz/50 Hz in frequency. Acupuncture was operated once daily, 3 times a week and 10 treatments were required. Before and after treatment, the scores of tinnitus evaluation questionnaire (TEQ), tinnitus handicap inventory (THI) and tinnitus visual analogue scale (VAS) were evaluated; and the clinical therapeutic effect was assessed. Separately, the patients with subjective tinnitus received one time of fMRI within 2 days before and after treatment, and the healthy subjects underwent one time of fMRI after enrollment. The bilateral ACC was taken as the region of interest (ROI). Using matlab R2017b software, FC between ACC and the whole brain was calculated. After treatment, the scores of THI, TEQ and VAS were reduced in the subjective tinnitus patients compared with those before treatment (P<0.01); and the total effective rate was 92.5% (37/40). Before treatment, compared with the healthy subjects, FC between the right ACC and the left middle temporal gyrus, the left superior temporal gyrus and the left superior frontal gyrus decreased in the subjective tinnitus patients. FC between the right ACC and the left middle frontal gyrus and the bilateral angular gyrus was dropped, while that between the left ACC and the left middle frontal gyrus, the left thalamus, the left angular gyrus and the left middle temporal gyrus was decreased in the subjective tinnitus patients when compared with the healthy subjects after treatment. Compared with those before treatment, FC between the right ACC and the left lingual gyrus and the left thalamus were declined, and that between the left ACC and the right middle frontal gyrus and the right superior frontal gyrus was decreased in the subjective tinnitus patients after treatment. Acupuncture can effectively relieve the clinical symptoms of subjective tinnitus patients, and promote the functional re-construction of the auditory regions (temporal lobe, frontal lobe and thalamus) and the emotion-related brain regions.

Ferroptosis, M6A and immune checkpoint-related gene expression in the middle temporal gyrus of the Alzheimer's disease brain

Alzheimer's disease (AD) is a common genetically related cognitive disorder. Studies have shown that ferroptosis, N⁶-Methyladenosine (M6A) and immune checkpoint are related to the development of AD. However, the effects of these three gene pathways on AD progression are still unclear. Here, we used genes expressed in the middle temporal gyrus (MTG) to study the differences in ferroptosis, M6A and immune checkpoint-related gene in 97 Alzheimer's disease and 98 normal controls (NC). We then conducted correlation analysis between ferroptosis, M6A and immune checkpoint-related gene expression levels to investigate the relationship between these genes and AD. Compared to the NC, the gene expression from MTG in AD are as follows: (1) in ferroptosis related genes, the expression of CARS, CDKN1A, HSPB1, MT1G, EMC2, SAT1 and SLC1A5 was increased, while the expression of ACSL4, ATP5MC3, CSID1, CS, DPP4, GLS2 and GPX4 was decreased; (2) in M6A-related genes, the expression of HNRNPA2B1, IGF2BP2, RBM15B and YTHDC1 was increased, while the expression of FTO, YTHDC2 and YTHDF2 was decreased; (3) the expression of immune checkpoint-related genes (including CTLA4, HAVCR2 and LAG3) was increased. Further, we determined related gene pathways among these genes by conducting a literature review. By verifying the dataset, we can well verify our results and prove that our results have good robustness. We concluded of gene expression that a complete set of ferroptosis, M6A and immune checkpoint regulatory mechanisms is activated in the MTG during AD development.

Machine learning research based on diffusion tensor images to distinguish between anorexia nervosa and bulimia nervosa.

Anorexia nervosa (AN) and bulimia nervosa (BN), two subtypes of eating disorders, often present diagnostic challenges due to their overlapping symptoms. Machine learning has proven its capacity to improve group classification without requiring researchers to specify variables. The study aimed to distinguish between AN and BN using machine learning models based on diffusion tensor images (DTI). This is a cross-sectional study, drug-naive females diagnosed with anorexia nervosa (AN) and bulimia nervosa (BN) were included. Demographic data and DTI were collected for all patients. Features for machine learning included Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). Support vector machine was constructed by LIBSVM, MATLAB2013b, and FSL5.0.9 software. A total of 58 female patients (24 AN, 34 BN) were included in this study. Statistical analysis revealed no significant differences in age, years of education, or course of illness between the two groups. AN patients had significantly lower BMI than BN patients. The AD model exhibited an area under the curve was 0.793 (accuracy: 75.86%, sensitivity: 66.67%, specificity: 88.23%), highlighting the left middle temporal gyrus (MTG_L) and the left superior temporal gyrus (STG_L) as differentiating brain regions. AN patients exhibited lower AD features in the STG_L and MTG_L than BN. Machine learning analysis indicated no significant differences in FA, MD, and RD values between AN and BN groups (p > 0.001). Machine learning based on DTI could effectively distinguish between AN and BN, with MTG_L and STG_L potentially serving as neuroimaging biomarkers.

Distinct tau and alpha-synuclein molecular signatures in Alzheimer’s disease with and without Lewy bodies and Parkinson’s disease with dementia

Alpha-synuclein (aSyn) pathology is present in approximately 50% of Alzheimer’s disease (AD) cases at autopsy and might impact the age-of-onset and disease progression in AD. Here, we aimed to determine whether tau and aSyn profiles differ between AD cases with Lewy bodies (AD-LB), pure AD and Parkinson’s disease with dementia (PDD) cases using epitope-, post-translational modification- (PTM) and isoform-specific tau and aSyn antibody panels spanning from the N- to C-terminus. We included the middle temporal gyrus (MTG) and amygdala (AMY) of clinically diagnosed and pathologically confirmed cases and performed dot blotting, western blotting and immunohistochemistry combined with quantitative and morphological analyses. All investigated phospho-tau (pTau) species, except pT181, were upregulated in AD-LB and AD cases compared to PDD and control cases, but no significant differences were observed between AD-LB and AD subjects. In addition, tau antibodies targeting the proline-rich regions and C-terminus showed preferential binding to AD-LB and AD brain homogenates. Antibodies targeting C-terminal aSyn epitopes and pS129 aSyn showed stronger binding to AD-LB and PDD cases compared to AD and control cases. Two pTau species (pS198 and pS396) were specifically detected in the soluble protein fractions of AD-LB and AD subjects, indicative of early involvement of these PTMs in the multimerization process of tau. Other phospho-variants for both tau (pT212/S214, pT231 and pS422) and aSyn (pS129) were only detected in the insoluble protein fraction of AD-LB/AD and AD-LB/PDD cases, respectively. aSyn load was higher in the AMY of AD-LB cases compared to PDD cases, suggesting aggravated aSyn pathology under the presence of AD pathology, while tau load was similar between AD-LB and AD cases. Co-localization of pTau and aSyn could be observed within astrocytes of AD-LB cases within the MTG. These findings highlight a unique pathological signature for AD-LB cases compared to pure AD and PDD cases.

Symptom dimensions of resting-state electroencephalographic functional connectivity in autism.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by social and communication deficits (SCDs), restricted and repetitive behaviors (RRBs) and fixated interests. Despite its prevalence, development of effective therapy for ASD is hindered by its symptomatic and neurophysiological heterogeneities. To comprehensively explore these heterogeneities, we developed a new analytical framework combining contrastive learning and sparse canonical correlation analysis that identifies symptom-linked resting-state electroencephalographic connectivity dimensions within 392 ASD samples. We present two dimensions with multivariate connectivity basis exhibiting significant correlations with SCD and RRB, confirm their robustness through cross-validation and demonstrate their conceptual generalizability using an independent dataset (n = 222). Specifically, the right inferior parietal lobe is the core region for RRB, while connectivity between the left angular gyrus and the right middle temporal gyrus show key contribution to SCD. These findings provide a promising avenue to parse ASD heterogeneity with high clinical translatability, paving the way for ASD treatment development and precision medicine.

Brain connectivity patterns associated with individual differences in the access to experience-near personal semantics: a resting-state fMRI study

It has been proposed that a continuum of specificity exists between episodic and semantic autobiographical memory. Personal semantics have been theorized to situate intermediately on this continuum, with more “experience-near” personal semantics (enPS) closer to the episodic end. We used individual differences in behavior as a model to investigate brain networks associated with the access to episodic autobiographical (EAM) and enPS information, assessing the relation between performance in the EAM and enPS conditions of the Autobiographical Fluency Task (AFT) and intrinsic brain connectivity. Results of an intrinsic connectivity contrast analysis showed that the global connectivity of two clusters in the left and right posterior cingulate cortex (PCC) was predicted by performance in the enPS conditions. Moreover, enPS scores predicted the connectivity strength of the right PCC with the bilateral anterior hippocampus (aHC), anterior middle temporal gyrus (aMTG) and medial orbitofrontal cortex, and the left aMTG and PCC. enPS scores also predicted the connectivity strength of the left PCC with the bilateral HC and MTG. The network highlighted involves parts of the core and of the dorsal medial subsystems of the Default Mode Network, in line with the proposal that enPS represents an intermediate entity between episodic and semantic memory.

The neural correlates of perceived social support and its relationship to psychological well-being.

Perceived social support is considered to play a significant role in promoting individuals' health and well-being, and yet the neural correlates of perceived social support were not fully understood. An exploration of the neural correlates of individual differences in the SPS can help us to gain more comprehensive understanding about the neural correlates of perceived social support. What's more, our study will explore the relationship among perceived social support, brain regions, and psychological well-being, which may provide new insights into the neural correlates underlying the relationship between perceived social support and psychological well-being from the perspective of cognitive neuroscience. Herein, we used the Social Provisions Scale to assess individuals' perceived social support, and magnetic resonance imaging was used to measure the gray matter (GM) volume of the whole brain. What's more, we also measured psychological well-being using the Psychological Well-Being Scale, and mediation analysis was used to explore the relationship among perceived social support, brain regions, and psychological well-being. The voxel-based morphometry analysis of the whole brain revealed that perceived social support was positively correlated with GM volume of the left middle temporal gyrus (MTG). The finding indicated that a person with greater GM volume in the left MTG perceived more social support. More importantly, the left MTG GM volume observed above was also associated with psychological well-being, and the link between the two was mediated by perceived social support. These results revealed the importance of MTG for perceived social support and psychological well-being, and also suggested that perceived social support might explain the relationship between MTG and psychological well-being.

Unveiling DNA methylation in Alzheimer's disease: a review of array-based human brain studies.

The intricacies of Alzheimer's disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms, particularly DNA methylation. This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer's disease neuropathology. The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer's disease progression. The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus. Notably, ANK1 hypermethylation, a protein implicated in neurofibrillary tangle formation, was recurrently identified in the entorhinal cortex. Further, the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3, RHBDF2, and MCF2L, potentially influencing neuroinflammatory processes. The complex role of BIN1 in late-onset Alzheimer's disease is underscored by its association with altered methylation patterns. Despite the disparities across studies, these findings highlight the intricate interplay between epigenetic modifications and Alzheimer's disease pathology. Future research efforts should address methodological variations, incorporate diverse cohorts, and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer's disease progression.

Relationship between lifestyle proxies of cognitive reserve and cortical regions in older adults.

With the rapid increase in the population over 65 years old, research on healthy aging has become one of the priorities in the research community, looking for a cost-effective method to prevent or delay symptoms of mild cognitive disorder or dementia. Studies indicate that cognitive reserve theory could be beneficial in this regard. The aim of this study was to investigate the potential relationship between lifestyle socio-behavioral proxies of cognitive reserve and cortical regions in adults with no subjective cognitive decline. Overall, 58 participants, aged 65-85 years, were included in the data analysis (M = 71.83, SD = 5.02, 20.7% male). Cognitive reserve proxies were measured using the Cognitive Reserve Index questionnaire, while cortical volumes were obtained with the Siemens 1.5 T Avanto MRI scanner and further mapped using the Desikan-Killiany-Tourville (DKT) Atlas. Estimated intracranial volume and age were used as covariates. The results indicated that higher occupational complexity was associated with larger cortical volume in the left middle temporal gyrus, the left and right inferior temporal gyrus, and the left inferior parietal lobule, while a combined proxy (the total CRI score) showed a positive relationship with the volume of left middle temporal gyrus and inferior parietal lobule, and pars orbitalis in the right hemisphere. These results might indicate that more complex occupational activities and overall more intellectually and socially active life-style could contribute to better brain health, especially in regions known to be more vulnerable to Alzheimer's disease.

Comparative Study of Cerebral Volumetric Variations in Patients with Schizophrenia with their Unaffected First-degree Relatives, using Magnetic Resonance Imaging Technique, a Case-control Study

Background and purpose: Schizophrenia (SZH) is a chronic mental disorder affecting the individuals` thoughts, perceptions, emotions, and behaviors. People with SZH may experience a wide range of positive, negative, and cognitive symptoms. Since there are no laboratory assays for definite SZH diagnosis, the authors aimed to identify the cerebral volumetric variations in SZH patients with the most prevalent positive symptoms as a diagnostic tool. This study selected 15 SZH patients displaying the most prevalent positive symptoms based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Assessment tools included the Mini-Mental State Examination (MMSE) for cognitive impairment, the Positive and Negative Syndrome Scale (PANSS) for symptom evaluation, and the Wechsler Intelligence Scale (WIS) for intelligence assessment. Additionally, 15 Healthy Controls (HC) without cerebral pathologies were recruited. T1w MRI images underwent analysis using Freesurfer software. Data analysis employed Mann-Whitney U and χ² tests, considering p &lt; 0.05 as significant. Results: SZH and HC groups showed no significant differences in age and gender. However, significant (p &lt; 0.05) alterations in Gray Matter (GM) volume were observed in SZH patients compared to HC. In the right hemisphere, several regions exhibited volume reduction, including the Fusiform sulcus, Rostral middle frontal gyrus, isthmus cingulate, Frontal pole, Middle temporal gyrus, Lateral occipital gyrus, and Inferior Parietal gyrus. Notably, the Precentral sulcus and Postcentral gyrus demonstrated volume acceleration. Similarly, in the left hemisphere, various regions showed volume reduction while the Paracentral gyrus indicated volume acceleration, all significant (p &lt; 0.05). Conclusion: SZH patients display significant volumetric brain changes, indicating potential for future diagnostic procedures in SZH.

Regional differences in synaptic degeneration are linked to alpha-synuclein burden and axonal damage in Parkinson’s disease and dementia with Lewy bodies

Regional differences in synaptic degeneration may underlie differences in clinical presentation and neuropathological disease progression in Parkinson’s Disease (PD) and Dementia with Lewy bodies (DLB). Here, we mapped and quantified synaptic degeneration in cortical brain regions in PD, PD with dementia (PDD) and DLB, and assessed whether regional differences in synaptic loss are linked to axonal degeneration and neuropathological burden. We included a total of 47 brain donors, 9 PD, 12 PDD, 6 DLB and 20 non-neurological controls. Synaptophysin+ and SV2A+ puncta were quantified in eight cortical regions using a high throughput microscopy approach. Neurofilament light chain (NfL) immunoreactivity, Lewy body (LB) density, phosphorylated-tau and amyloid-β load were also quantified. Group differences in synaptic density, and associations with neuropathological markers and Clinical Dementia Rating (CDR) scores, were investigated using linear mixed models. We found significantly decreased synaptophysin and SV2A densities in the cortex of PD, PDD and DLB cases compared to controls. Specifically, synaptic density was decreased in cortical regions affected at Braak α-synuclein stage 5 in PD (middle temporal gyrus, anterior cingulate and insula), and was additionally decreased in cortical regions affected at Braak α-synuclein stage 4 in PDD and DLB compared to controls (entorhinal cortex, parahippocampal gyrus and fusiform gyrus). Synaptic loss associated with higher NfL immunoreactivity and LB density. Global synaptophysin loss associated with longer disease duration and higher CDR scores. Synaptic neurodegeneration occurred in temporal, cingulate and insular cortices in PD, as well as in parahippocampal regions in PDD and DLB. In addition, synaptic loss was linked to axonal damage and severe α-synuclein burden. These results, together with the association between synaptic loss and disease progression and cognitive impairment, indicate that regional synaptic loss may underlie clinical differences between PD and PDD/DLB. Our results might provide useful information for the interpretation of synaptic biomarkers in vivo.

Using ALE coordinate-based meta-analysis to observe resting-state brain abnormalities in subjective tinnitus.

A systematic search on MEDLINE/PubMed, Google Scholar, and Scopus databases was performed to identify rsfMRI studies on tinnitus published up to October 2022. Coordinates related to the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) brain maps that showed significant differences between tinnitus patients and controls were extracted. Meta-analysis was performed using the activation likelihood estimation method. Data were included from 17 rsfMRI studies that reported a total of 63 distinct foci in ALFF and 46 foci in ReHo. Our meta-analysis revealed several regions where tinnitus patients demonstrated increased ALFF and ReHO values, both individually and collectively, when compared to control subjects. These regions encompassed the insula, middle temporal gyrus, and inferior frontal gyrus on both sides. Additionally, increased activity was also noted in the cerebellum posterior lobe bilaterally and the right superior frontal gyrus. This meta-analysis demonstrates a unique pattern of resting-state brain abnormalities involving both the auditory and non-auditory brain regions as neuroimaging markers, which helps understand the neuro-pathophysiological mechanisms of tinnitus.

Aggregate-prone brain regions in Parkinson’s disease are rich in unique N-terminus α-synuclein conformers with high proteolysis susceptibility

In Parkinson’s disease (PD), and other α-synucleinopathies, α-synuclein (α-Syn) aggregates form a myriad of conformational and truncational variants. Most antibodies used to detect and quantify α-Syn in the human brain target epitopes within the C-terminus (residues 96–140) of the 140 amino acid protein and may fail to capture the diversity of α-Syn variants present in PD. We sought to investigate the heterogeneity of α-Syn conformations and aggregation states in the PD human brain by labelling with multiple antibodies that detect epitopes along the entire length of α-Syn. We used multiplex immunohistochemistry to simultaneously immunolabel tissue sections with antibodies mapping the three structural domains of α-Syn. Discrete epitope-specific immunoreactivities were visualised and quantified in the olfactory bulb, medulla, substantia nigra, hippocampus, entorhinal cortex, middle temporal gyrus, and middle frontal gyrus of ten PD cases, and the middle temporal gyrus of 23 PD, and 24 neurologically normal cases. Distinct Lewy neurite and Lewy body aggregate morphologies were detected across all interrogated regions/cases. Lewy neurites were the most prominent in the olfactory bulb and hippocampus, while the substantia nigra, medulla and cortical regions showed a mixture of Lewy neurites and Lewy bodies. Importantly, unique N-terminus immunoreactivity revealed previously uncharacterised populations of (1) perinuclear, (2) glial (microglial and astrocytic), and (3) neuronal lysosomal α-Syn aggregates. These epitope-specific N-terminus immunoreactive aggregate populations were susceptible to proteolysis via time-dependent proteinase K digestion, suggesting a less stable oligomeric aggregation state. Our identification of unique N-terminus immunoreactive α-Syn aggregates adds to the emerging paradigm that α-Syn pathology is more abundant and complex in human brains with PD than previously realised. Our findings highlight that labelling multiple regions of the α-Syn protein is necessary to investigate the full spectrum of α-Syn pathology and prompt further investigation into the functional role of these N-terminus polymorphs.