-
The Journal of Neuroscience : the... Apr 2024The subiculum (SUB), a hippocampal formation structure, is among the earliest brain regions impacted in Alzheimer's disease (AD). Toward a better understanding of AD...
The subiculum (SUB), a hippocampal formation structure, is among the earliest brain regions impacted in Alzheimer's disease (AD). Toward a better understanding of AD circuit-based mechanisms, we mapped synaptic circuit inputs to dorsal SUB using monosynaptic rabies tracing in the 5xFAD mouse model by quantitatively comparing the circuit connectivity of SUB excitatory neurons in age-matched controls and 5xFAD mice at different ages for both sexes. Input-mapped brain regions include the hippocampal subregions (CA1, CA2, CA3), medial septum and diagonal band, retrosplenial cortex, SUB, postsubiculum (postSUB), visual cortex, auditory cortex, somatosensory cortex, entorhinal cortex, thalamus, perirhinal cortex (Prh), ectorhinal cortex, and temporal association cortex. We find sex- and age-dependent changes in connectivity strengths and patterns of SUB presynaptic inputs from hippocampal subregions and other brain regions in 5xFAD mice compared with control mice. Significant sex differences for SUB inputs are found in 5xFAD mice for CA1, CA2, CA3, postSUB, Prh, lateral entorhinal cortex, and medial entorhinal cortex: all of these areas are critical for learning and memory. Notably, we find significant changes at different ages for visual cortical inputs to SUB. While the visual function is not ordinarily considered defective in AD, these specific connectivity changes reflect that altered visual circuitry contributes to learning and memory deficits. Our work provides new insights into SUB-directed neural circuit mechanisms during AD progression and supports the idea that neural circuit disruptions are a prominent feature of AD.
Topics: Mice; Female; Male; Animals; Rabies; Alzheimer Disease; Hippocampus; Entorhinal Cortex; Neurons
PubMed: 38503494
DOI: 10.1523/JNEUROSCI.1796-23.2024 -
Radiology Mar 2024Background Blood-brain barrier (BBB) permeability change is a possible pathologic mechanism of autoimmune encephalitis. Purpose To evaluate the change in BBB...
Background Blood-brain barrier (BBB) permeability change is a possible pathologic mechanism of autoimmune encephalitis. Purpose To evaluate the change in BBB permeability in patients with autoimmune encephalitis as compared with healthy controls by using dynamic contrast-enhanced (DCE) MRI and to explore its predictive value for treatment response in patients. Materials and Methods This single-center retrospective study included consecutive patients with probable or possible autoimmune encephalitis and healthy controls who underwent DCE MRI between April 2020 and May 2021. Automatic volumetric segmentation was performed on three-dimensional T1-weighted images, and volume transfer constant () values were calculated at encephalitis-associated brain regions. values were compared between the patients and controls, with adjustment for age and sex with use of a nonparametric approach. The Wilcoxon rank sum test was performed to compare values of the good (improvement in modified Rankin Scale [mRS] score of at least two points or achievement of an mRS score of ≤2) and poor (improvement in mRS score of less than two points and achievement of an mRS score >2) treatment response groups among the patients. Results Thirty-eight patients with autoimmune encephalitis (median age, 38 years [IQR, 29-59 years]; 20 [53%] female) and 17 controls (median age, 71 years [IQR, 63-77 years]; 12 [71%] female) were included. All brain regions showed higher values in patients as compared with controls ( < .001). The median difference in between the patients and controls was largest in the right parahippocampal gyrus (25.1 × 10 min [95% CI: 17.6, 43.4]). Among patients, the poor treatment response group had higher baseline values in both cerebellar cortices ( = .03), the left cerebellar cortex ( = .02), right cerebellar cortex ( = .045), left cerebral cortex ( = .045), and left postcentral gyrus ( = .03) than the good treatment response group. Conclusion DCE MRI demonstrated that BBB permeability was increased in all brain regions in patients with autoimmune encephalitis as compared with controls, and baseline values were higher in patients with poor treatment response in the cerebellar cortex, left cerebral cortex, and left postcentral gyrus as compared with the good response group. © RSNA, 2024 See also the editorial by Filippi and Rocca in this issue.
Topics: Humans; Female; Adult; Aged; Male; Capillary Permeability; Retrospective Studies; Encephalitis; Magnetic Resonance Imaging; Autoimmune Diseases of the Nervous System; Hashimoto Disease
PubMed: 38501951
DOI: 10.1148/radiol.230701 -
Frontiers in Neuroscience 2024The previous studies have demonstrated that patients with Crohn's disease in remission (CD-R) have abnormal alterations in brain function. However, whether brain...
BACKGROUND
The previous studies have demonstrated that patients with Crohn's disease in remission (CD-R) have abnormal alterations in brain function. However, whether brain function changes in patients with Crohn's disease in activity (CD-A) and the relationship with CD-R are still unclear. In this study, we aimed to investigate whether the different levels of disease activity may differentially affect the brain function and to find the brain functional biomarker distinguishing patients with different disease stages by measuring the amplitude of low frequency fluctuations (ALFF).
METHODS
121 patients with CD and 91 healthy controls (HCs) were recruited. The clinical and psychological assessment of participants were collected. The criteria for the disease activity were the Crohn's disease activity index (CDAI) scores. CD-R refers to CD patients in remission which the CDAI score is less than 150. Conversely, CD-A refers to CD patients in activity which the CDAI score is ≥150. The ALFF was compared among three groups by performing one-way analysis of variance, followed by a two-sample t-test. Differences among the groups were selected as seeds for functional connectivity analyses. We also investigated the correlation among clinical, psychological scores and ALFF. Binary logistic regression analysis was used to examine the unique contribution of the ALFF characteristics of the disease stages.
RESULTS
There were widespread differences of ALFF values among the 3 groups, which included left frontal pole (FP_L), right supramarginal gyrus (SG_R), left angular gyrus (AG_L), right cingulate gyrus (CG_R), right intracalcarine cortex (IC_R), right parahippocampal gyrus (PG_R), right lingual gyrus (LG_R), right precuneous cortex (PC_R), left occipital fusiform gyrus (OFG_L). Significant brain regions showing the functional connections (FC) increased in FP_L, SG_R, PC_R and OFG_L between CD-A and HCs. The erythrocyte sedimentation rate had a negative correlation with the ALFF values in PC_R in the patients with CD. The phobic anxiety values had a negative correlation with the ALFF values in OFG_L. The psychoticism values had a negative correlation with ALFF values in the IC_R. And the hostility values had a positive correlation with the ALFF values in CG_R. Significant brain regions showing the FC increased in FP_L, SG_R, CG_R, PG_R, LG_R and OFG_L between CD-R and HCs. In binary logistic regression models, the LG_R (beta = 5.138, = 0.031), PC_R (beta = 1.876, = 0.002) and OFG_L (beta = 3.937, = 0.044) was disease stages predictors.
CONCLUSION
The results indicated the significance of the altered brain activity in the different disease stages of CD. Therefore, these findings present a potential identify neuroimaging-based brain functional biomarker in CD. Additionally, the study provides a better understanding of the pathophysiology of CD.
PubMed: 38500485
DOI: 10.3389/fnins.2024.1361320 -
NeuroImage Apr 2024Face perception is a complex process that involves highly specialized procedures and mechanisms. Investigating into face perception can help us better understand how the...
Face perception is a complex process that involves highly specialized procedures and mechanisms. Investigating into face perception can help us better understand how the brain processes fine-grained, multidimensional information. This research aimed to delve deeply into how different dimensions of facial information are represented in specific brain regions or through inter-regional connections via an implicit face recognition task. To capture the representation of various facial information in the brain, we employed support vector machine decoding, functional connectivity, and model-based representational similarity analysis on fMRI data, resulting in the identification of three crucial findings. Firstly, despite the implicit nature of the task, emotions were still represented in the brain, contrasting with all other facial information. Secondly, the connection between the medial amygdala and the parahippocampal gyrus was found to be essential for the representation of facial emotion in implicit tasks. Thirdly, in implicit tasks, arousal representation occurred in the parahippocampal gyrus, while valence depended on the connection between the primary visual cortex and the parahippocampal gyrus. In conclusion, these findings dissociate the neural mechanisms of emotional valence and arousal, revealing the precise spatial patterns of multidimensional information processing in faces.
Topics: Humans; Magnetic Resonance Imaging; Emotions; Brain; Brain Mapping; Parahippocampal Gyrus; Facial Expression
PubMed: 38499051
DOI: 10.1016/j.neuroimage.2024.120578 -
Frontiers in Neurology 2024To explore the effect of cognitive reserve (CR) on brain volume and cerebrospinal fluid (CSF) in patients with mild cognitive impairment (MCI) and healthy elders (HE).
OBJECTIVE
To explore the effect of cognitive reserve (CR) on brain volume and cerebrospinal fluid (CSF) in patients with mild cognitive impairment (MCI) and healthy elders (HE).
METHODS
31 HE and 50 MCI patients were collected in this study to obtain structural MRI, cognitive function, and composite CR scores. Educational attainment, leisure time, and working activity ratings from two groups were used to generate cognitive reserve index questionnaire (CRIq) scores. The different volumes of brain regions and CSF were obtained using uAI research portal in both groups, which were taken as the regions of interest (ROI), the correlation analysis between ROIs and CRIq scores were conducted.
RESULTS
The scores of CRIq, CRIq-leisure time, and CRIq-education in HE group were significantly higher than patients in MCI group, and the montreal cognitive assessment (MoCA) and minimum mental state examination (MMSE) scores were positively correlated with the CRIq, CRIq-education in both groups, and were positively correlated with CRIq-leisure time in MCI group. The scores of auditory verbal learning test (AVLT) and verbal fluency test (VFT) were also positively correlated with CRIq, CRIq-leisure time, and CRIq-education in MCI group, but the score of AVLT was only positively correlated with CRIq in HE group. Moreover, in MCI group, the volume of the right middle cingulate cortex and the right parahippocampal gyrus were negatively correlated with the CRIq, and the volume of CSF, peripheral CSF, and third ventricle were positively correlated with the CRIq-leisure time score. The result of mediation analysis suggested that right parahippocampal gryus mediated the main effect of the relationship between CRIq and MoCA score in MCI group.
CONCLUSION
People with higher CR show better levels of cognitive function, and MCI patients with higher CR showed more severe volume atrophy of the right middle cingulate cortex and the right parahippocampal gyrus, but more CSF at a given level of global cognition.
PubMed: 38497043
DOI: 10.3389/fneur.2024.1355546 -
Changes in spatial self-consciousness elicit grid cell-like representation in the entorhinal cortex.Proceedings of the National Academy of... Mar 2024Grid cells in the entorhinal cortex (EC) encode an individual's location in space, integrating both environmental and multisensory bodily cues. Notably, body-derived...
Grid cells in the entorhinal cortex (EC) encode an individual's location in space, integrating both environmental and multisensory bodily cues. Notably, body-derived signals are also primary signals for the sense of self. While studies have demonstrated that continuous application of visuo-tactile bodily stimuli can induce perceptual shifts in self-location, it remains unexplored whether these illusory changes suffice to trigger grid cell-like representation (GCLR) within the EC, and how this compares to GCLR during conventional virtual navigation. To address this, we systematically induced illusory drifts in self-location toward controlled directions using visuo-tactile bodily stimulation, while maintaining the subjects' visual viewpoint fixed (absent conventional virtual navigation). Subsequently, we evaluated the corresponding GCLR in the EC through functional MRI analysis. Our results reveal that illusory changes in perceived self-location (independent of changes in environmental navigation cues) can indeed evoke entorhinal GCLR, correlating in strength with the magnitude of perceived self-location, and characterized by similar grid orientation as during conventional virtual navigation in the same virtual room. These data demonstrate that the same grid-like representation is recruited when navigating based on environmental, mainly visual cues, or when experiencing illusory forward drifts in self-location, driven by perceptual multisensory bodily cues.
Topics: Humans; Entorhinal Cortex; Grid Cells; Consciousness; Illusions; Touch; Spatial Navigation
PubMed: 38489383
DOI: 10.1073/pnas.2315758121 -
Journal of Alzheimer's Disease : JAD 2024The impairment of neural circuits controlling cognitive processes has been implicated in the pathophysiology of Alzheimer's disease and related disorders (ADRD)....
BACKGROUND
The impairment of neural circuits controlling cognitive processes has been implicated in the pathophysiology of Alzheimer's disease and related disorders (ADRD). However, it is largely unclear what circuits are specifically changed in ADRD, particularly at the early stage.
OBJECTIVE
Our goal of this study is to reveal the functional changes in the circuit of entorhinal cortex (EC), an interface between neocortex and hippocampus, in AD.
METHODS
Electrophysiological, optogenetic and chemogenetic approaches were used to examine and manipulate entorhinal cortical circuits in amyloid-β familial AD model (5×FAD) and tauopathy model (P301S Tau).
RESULTS
We found that, compared to wild-type mice, electrical stimulation of EC induced markedly smaller responses in subiculum (hippocampal output) of 5×FAD mice (6-month-old), suggesting that synaptic communication in the EC to subiculum circuit is specifically blocked in this AD model. In addition, optogenetic stimulation of glutamatergic terminals from prefrontal cortex (PFC) induced smaller responses in EC of 5×FAD and P301S Tau mice (6-month-old), suggesting that synaptic communication in the PFC to EC pathway is compromised in both ADRD models. Chemogenetic activation of PFC to EC pathway did not affect the bursting activity of EC neurons in 5×FAD mice, but partially restored the diminished EC neuronal activity in P301S Tau mice.
CONCLUSIONS
These data suggest that 5×FAD mice has a specific impairment of short-range hippocampal gateway (EC to subiculum), which may be caused by amyloid-β deposits; while two ADRD models have a common impairment of long-range cortical to hippocampal circuit (PFC to EC), which may be caused by microtubule/tau-based transport deficits. These circuit deficits provide a pathophysiological basis for unique and common impairments of various cognitive processes in ADRD conditions.
Topics: Mice; Animals; Alzheimer Disease; Entorhinal Cortex; Mice, Transgenic; Hippocampus; Tauopathies; Amyloid beta-Peptides; Disease Models, Animal
PubMed: 38489190
DOI: 10.3233/JAD-231413 -
Experimental Brain Research May 2024Mental Time Travel (MTT) allows us to remember past events and imagine future ones. According to previous literature, the Temporal Distance of events affects MTT: our...
Mental Time Travel (MTT) allows us to remember past events and imagine future ones. According to previous literature, the Temporal Distance of events affects MTT: our ability to order events worsens for close, compared to far, events. However, those studies established distances a-priori, albeit the way we perceive events' temporal distance may subjectively differ from their objective distance. Thus, in the current study, we aimed to investigate the effects of Perceived Temporal Distance (PTD) on the MTT ability and the brain areas mediating this process. Thirty-three healthy volunteers took part in an fMRI MTT task. Participants were asked to project themselves into the past, present, or future, and to judge a series of events as relative-past or relative-future, in relation to the adopted time location. Outside the scanner, participants provided PTD estimates for each stimulus of the MTT task. Participants' performance and functional activity were analyzed as a function of these estimations. At the behavioural level, PTD predicts the modulation of the performance for relative-past and relative-future. Bilateral angular gyrus, retrosplenial cortex, temporo-parietal region and medial, middle and superior frontal gyri mediate the PTD effect. In addition to these areas, the closer the relative-future events are perceived, the higher the involvement of left parahippocampal and lingual gyri and right cerebellum. Thus, perceived proximity of events activates frontal and posterior parietal areas, which therefore might mediate the processing of PTD in the cognitive spatial representation of time. Future proximity also activates cerebellum and medial temporal areas, known to be involved in imaginative and constructive cognitive functions.
Topics: Humans; Male; Female; Adult; Time Perception; Magnetic Resonance Imaging; Young Adult; Brain; Imagination; Brain Mapping
PubMed: 38489024
DOI: 10.1007/s00221-024-06806-x -
Journal of Affective Disorders Jun 2024The dynamic and hierarchical nature of the functional brain network. The neural dynamical systems tend to converge to multiple attractors (stable fixed points or...
BACKGROUND
The dynamic and hierarchical nature of the functional brain network. The neural dynamical systems tend to converge to multiple attractors (stable fixed points or dynamical states) in long run. Little is known about how the changes in this brain dynamic "long-term" behavior of the connectivity flow of brain network in generalized anxiety disorder (GAD).
METHODS
This study recruited 92 patients with GAD and 77 healthy controls (HC). We applied a reachable probability approach combining a Non-homogeneous Markov model with transition probability to quantify all possible connectivity flows and the hierarchical structure of brain functional systems at the dynamic level and the stationary probability vector (10-step transition probabilities) to describe the steady state of the system in the long run. A random forest algorithm was conducted to predict the severity of anxiety.
RESULTS
The dynamic functional patterns in distributed brain networks had larger possibility to converge in bilateral thalamus, posterior cingulate cortex (PCC), right superior occipital gyrus (SOG) and smaller possibility to converge in bilateral superior temporal gyrus (STG) and right parahippocampal gyrus (PHG) in patients with GAD compared to HC. The abnormal transition probability pattern could predict anxiety severity in patients with GAD.
LIMITATIONS
Small samples and subjects taking medications may have influenced our results. Future studies are expected to rule out the potential confounding effects.
CONCLUSION
Our results have revealed abnormal dynamic neural communication and integration in emotion regulation in patients with GAD, which give new insights to understand the dynamics of brain function of patients with GAD.
Topics: Humans; Magnetic Resonance Imaging; Brain; Anxiety Disorders; Brain Mapping; Temporal Lobe
PubMed: 38484883
DOI: 10.1016/j.jad.2024.03.038 -
AJNR. American Journal of Neuroradiology Jun 2024The efficacy of long-term chronic subthalamic nucleus deep brain stimulation (STN-DBS) in treating Parkinson disease (PD) exhibits substantial variability among...
BACKGROUND AND PURPOSE
The efficacy of long-term chronic subthalamic nucleus deep brain stimulation (STN-DBS) in treating Parkinson disease (PD) exhibits substantial variability among individuals. The preoperative identification of suitable deep brain stimulation (DBS) candidates through predictive means becomes crucial. Our study aims to investigate the predictive value of characterizing individualized structural covariance networks for long-term efficacy of DBS, offering patients a precise and cost-effective preoperative screening tool.
MATERIALS AND METHODS
We included 138 patients with PD and 40 healthy controls. We developed individualized structural covariance networks from T1-weighted images utilizing network template perturbation, and computed the networks' topological characteristics. Patients were categorized according to their long-term motor improvement following STN-DBS. Intergroup analyses were conducted on individual network edges and topological indices, alongside correlation analyses with long-term outcomes for the entire patient cohort. Finally, machine learning algorithms were employed for regression and classification to predict post-DBS motor improvement.
RESULTS
Among the patients with PD, 6 edges (left middle frontal and left caudate nucleus, right olfactory and right insula, left superior medial frontal gyrus and right insula, right middle frontal and left paracentral lobule, right middle frontal and cerebellum, left lobule VIIb of the cerebellum and the vermis of the cerebellum) exhibited significant results in intergroup comparisons and correlation analyses. Increased degree centrality and local efficiency of the cerebellum, parahippocampal gyrus, and postcentral gyrus were associated with DBS improvement. A regression model constructed from these 6 edges revealed a significant correlation between predicted and observed changes in the unified PD rating scale ( = 0.671, < .001) and receiver operating characteristic analysis demonstrated an area under the curve of 0.802, effectively distinguishing between patients with good and moderate improvement post-DBS.
CONCLUSIONS
Our findings reveal the link between individual structural covariance network fingerprints in patients with PD and long-term motor outcome following STN-DBS. Additionally, binary and continuous cerebellum-basal ganglia-frontal structural covariance network edges have emerged as potential predictive biomarkers for DBS motor outcome.
PubMed: 38471785
DOI: 10.3174/ajnr.A8245