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Current Opinion in Neurobiology Apr 2024The entorhinal cortex and hippocampus form a recurrent network that informs many cognitive processes, including memory, planning, navigation, and imagination. Neural... (Review)
Review
The entorhinal cortex and hippocampus form a recurrent network that informs many cognitive processes, including memory, planning, navigation, and imagination. Neural recordings from these regions reveal spatially organized population codes corresponding to external environments and abstract spaces. Aligning the former cognitive functionalities with the latter neural phenomena is a central challenge in understanding the entorhinal-hippocampal circuit (EHC). Disparate experiments demonstrate a surprising level of complexity and apparent disorder in the intricate spatiotemporal dynamics of sequential non-local hippocampal reactivations, which occur particularly, though not exclusively, during immobile pauses and rest. We review these phenomena with a particular focus on their apparent lack of physical simulative realism. These observations are then integrated within a theoretical framework and proposed neural circuit mechanisms that normatively characterize this neural complexity by conceiving different regimes of hippocampal microdynamics as neuromarkers of diverse cognitive computations.
Topics: Space Perception; Entorhinal Cortex; Hippocampus; Cognition; Models, Neurological
PubMed: 38428170
DOI: 10.1016/j.conb.2024.102855 -
STAR Protocols Mar 2024Multiple patch-clamp recordings and morphological reconstruction are powerful approaches for neuronal microcircuitry dissection and cell type classification but are...
Multiple patch-clamp recordings and morphological reconstruction are powerful approaches for neuronal microcircuitry dissection and cell type classification but are challenging due to the sophisticated expertise needed. Here, we present a protocol for applying these techniques to neurons in the medial entorhinal cortex (MEC) of mice. We detail steps to prepare brain slices containing MEC and perform simultaneous multiple whole-cell recordings, followed by procedures of histological staining and neuronal reconstruction. We then describe how we analyze morphological and electrophysiological features. For complete details on the use and execution of this protocol, please refer to Shi et al..
Topics: Mice; Animals; Entorhinal Cortex; Neurons; Cytoplasm; Patch-Clamp Techniques; Brain
PubMed: 38421863
DOI: 10.1016/j.xpro.2024.102917 -
Alzheimer's & Dementia : the Journal of... Apr 2024Entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of...
INTRODUCTION
Entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration (PI)-based spatial behaviors, we predicted that PI impairment would represent the first behavioral change in adults at risk of AD.
METHODS
We compared immersive virtual reality (VR) PI ability to other cognitive domains in 100 asymptomatic midlife adults stratified by hereditary and physiological AD risk factors. In some participants, behavioral data were compared to 7T magnetic resonance imaging (MRI) measures of brain structure and function.
RESULTS
Midlife PI impairments predicted both hereditary and physiological AD risk, with no corresponding multi-risk impairment in episodic memory or other spatial behaviors. Impairments associated with altered functional MRI signal in the posterior-medial EC.
DISCUSSION
Altered PI may represent the transition point from at-risk state to disease manifestation in AD, prior to impairment in other cognitive domains.
Topics: Adult; Humans; Alzheimer Disease; Entorhinal Cortex; Brain; Magnetic Resonance Imaging
PubMed: 38421123
DOI: 10.1002/alz.13733 -
CNS Neuroscience & Therapeutics Feb 2024The aim of this study is to investigate differences in gray matter volume and cortical complexity between Parkinson's disease with depression (PDD) patients and...
AIMS
The aim of this study is to investigate differences in gray matter volume and cortical complexity between Parkinson's disease with depression (PDD) patients and Parkinson's disease without depression (PDND) patients.
METHODS
A total of 41 PDND patients, 36 PDD patients, and 38 healthy controls (HC) were recruited and analyzed by Voxel-based morphometry (VBM) and surface-based morphometry (SBM). Differences in gray matter volume and cortical complexity were compared using the one-way analysis of variance (ANOVA) and correlated with the Hamilton Depression Scale-17 (HAMD-17) scores.
RESULTS
PDD patients exhibited significant cortical atrophy in various regions, including bilateral medial parietal-occipital-temporal lobes, right dorsolateral temporal lobes, bilateral parahippocampal gyrus, and bilateral hippocampus, compared to HC and PDND groups. A negative correlation between the GMV of left precuneus and HAMD-17 scores in the PDD group tended to be significant (r = -0.318, p = 0.059). Decreased gyrification index was observed in the bilateral insular and dorsolateral temporal cortex. However, there were no significant differences found in fractal dimension and sulcal depth.
CONCLUSION
Our research shows extensive cortical structural changes in the insular cortex, parietal-occipital-temporal lobes, and hippocampal regions in PDD. This provides a morphological perspective for understanding the pathophysiological mechanism underlying depression in Parkinson's disease.
Topics: Humans; Brain; Parkinson Disease; Depression; Magnetic Resonance Imaging; Gray Matter
PubMed: 38421103
DOI: 10.1111/cns.14582 -
Nature Communications Feb 2024The hippocampus and entorhinal cortex exhibit rich oscillatory patterns critical for cognitive functions. In the hippocampal region CA1, specific gamma-frequency...
The hippocampus and entorhinal cortex exhibit rich oscillatory patterns critical for cognitive functions. In the hippocampal region CA1, specific gamma-frequency oscillations, timed at different phases of the ongoing theta rhythm, are hypothesized to facilitate the integration of information from varied sources and contribute to distinct cognitive processes. Here, we show that gamma elements -a multidimensional characterization of transient gamma oscillatory episodes- occur at any frequency or phase relative to the ongoing theta rhythm across all CA1 layers in male mice. Despite their low power and stochastic-like nature, individual gamma elements still carry behavior-related information and computational modeling suggests that they reflect neuronal firing. Our findings challenge the idea of rigid gamma sub-bands, showing that behavior shapes ensembles of irregular gamma elements that evolve with learning and depend on hippocampal layers. Widespread gamma diversity, beyond randomness, may thus reflect complexity, likely functional but invisible to classic average-based analyses.
Topics: Male; Mice; Animals; Hippocampus; Neurons; Entorhinal Cortex; Theta Rhythm; Computer Simulation; Gamma Rhythm; CA1 Region, Hippocampal
PubMed: 38418832
DOI: 10.1038/s41467-024-46012-5 -
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Feb 2024Physiological studies have revealed that rats perform spatial localization relying on grid cells and place cells in the entorhinal-hippocampal CA3 structure. The dynamic...
Physiological studies have revealed that rats perform spatial localization relying on grid cells and place cells in the entorhinal-hippocampal CA3 structure. The dynamic connection between the entorhinal-hippocampal structure and the prefrontal cortex is crucial for navigation. Based on these findings, this paper proposes a spatial navigation method based on the entorhinal-hippocampal-prefrontal information transmission circuit of the rat's brain, with the aim of endowing the mobile robot with strong spatial navigation capability. Using the hippocampal CA3-prefrontal spatial navigation model as a foundation, this paper constructed a dynamic self-organizing model with the hippocampal CA1 place cells as the basic unit to optimize the navigation path. The path information was then fed back to the impulse neural network via hippocampal CA3 place cells and prefrontal cortex action neurons, improving the convergence speed of the model and helping to establish long-term memory of navigation habits. To verify the validity of the method, two-dimensional simulation experiments and three-dimensional simulation robot experiments were designed in this paper. The experimental results showed that the method presented in this paper not only surpassed other algorithms in terms of navigation efficiency and convergence speed, but also exhibited good adaptability to dynamic navigation tasks. Furthermore, our method can be effectively applied to mobile robots.
Topics: Rats; Animals; Entorhinal Cortex; Spatial Navigation; Hippocampus; Neurons; Prefrontal Cortex; Models, Neurological
PubMed: 38403607
DOI: 10.7507/1001-5515.202303047 -
Diagnostics (Basel, Switzerland) Feb 2024Major depressive disorder (MDD) and bipolar disorder (BD) share clinical features, which complicates their differentiation in clinical settings. This study proposes an...
Major depressive disorder (MDD) and bipolar disorder (BD) share clinical features, which complicates their differentiation in clinical settings. This study proposes an innovative approach that integrates structural connectome analysis with machine learning models to discern individuals with MDD from individuals with BD. High-resolution MRI images were obtained from individuals diagnosed with MDD or BD and from HCs. Structural connectomes were constructed to represent the complex interplay of brain regions using advanced graph theory techniques. Machine learning models were employed to discern unique connectivity patterns associated with MDD and BD. At the global level, both BD and MDD patients exhibited increased small-worldness compared to the HC group. At the nodal level, patients with BD and MDD showed common differences in nodal parameters primarily in the right amygdala and the right parahippocampal gyrus when compared with HCs. Distinctive differences were found mainly in prefrontal regions for BD, whereas MDD was characterized by abnormalities in the left thalamus and default mode network. Additionally, the BD group demonstrated altered nodal parameters predominantly in the fronto-limbic network when compared with the MDD group. Moreover, the application of machine learning models utilizing structural brain parameters demonstrated an impressive 90.3% accuracy in distinguishing individuals with BD from individuals with MDD. These findings demonstrate that combined structural connectome and machine learning enhance diagnostic accuracy and may contribute valuable insights to the understanding of the distinctive neurobiological signatures of these psychiatric disorders.
PubMed: 38396428
DOI: 10.3390/diagnostics14040389 -
GeroScience Jun 2024The long COVID (coronavirus disease), a multisystemic condition following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the... (Review)
Review
The long COVID (coronavirus disease), a multisystemic condition following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the widespread problems. Some of its symptoms affect the nervous system and resemble symptoms of Alzheimer's disease (AD)-a neurodegenerative condition caused by the accumulation of amyloid beta and hyperphosphorylation of tau proteins. Multiple studies have found dependence between these two conditions. Patients with Alzheimer's disease have a greater risk of SARS-CoV-2 infection due to increased levels of angiotensin-converting enzyme 2 (ACE2), and the infection itself promotes amyloid beta generation which enhances the risk of AD. Also, the molecular pathways are alike-misregulations in folate-mediated one-carbon metabolism, a deficit of Cq10, and disease-associated microglia. Medical imaging in both of these diseases shows a decrease in the volume of gray matter, global brain size reduction, and hypometabolism in the parahippocampal gyrus, thalamus, and cingulate cortex. In some studies, a similar approach to applied medication can be seen, including the use of amino adamantanes and phenolic compounds of rosemary. The significance of these connections and their possible application in medical practice still needs further study but there is a possibility that they will help to better understand long COVID.
Topics: Humans; Alzheimer Disease; COVID-19; SARS-CoV-2; Post-Acute COVID-19 Syndrome; Amyloid beta-Peptides; Chronic Disease
PubMed: 38393535
DOI: 10.1007/s11357-024-01096-1 -
Brain Sciences Jan 2024Structural plasticity changes and functional differences in executive control tasks have been reported in bilinguals compared to monolinguals, supporting a proposed...
Structural plasticity changes and functional differences in executive control tasks have been reported in bilinguals compared to monolinguals, supporting a proposed bilingual 'advantage' in executive control functions (e.g., task switching) due to continual usage of control mechanisms that inhibit one of the coexisting languages. However, it remains unknown whether these differences are also apparent in the spatial domain. The present fMRI study explores the use of spatial cues in 15 bilinguals and 14 monolinguals while navigating in an open-field virtual environment. In each trial, participants had to navigate towards a target object that was visible during encoding but hidden in retrieval. An extensive network was activated in bilinguals compared to monolinguals in the encoding and retrieval phase. During encoding, bilinguals activated the right temporal and left parietal regions (object trials) and left inferior frontal, precentral, and lingual regions more than monolinguals. During retrieval, the same contrasts activated the left caudate nucleus and the right dorsolateral prefrontal cortex (DLPFC), the left parahippocampal gyrus, as well as caudate regions. These results suggest that bilinguals may recruit neural networks known to subserve not only executive control processes but also spatial strategies.
PubMed: 38391709
DOI: 10.3390/brainsci14020134 -
International Journal of Bipolar... Feb 2024Systemic inflammation-immune dysregulation and brain abnormalities are believed to contribute to the pathogenesis of bipolar disorder (BD). However, the connections... (Review)
Review
BACKGROUND
Systemic inflammation-immune dysregulation and brain abnormalities are believed to contribute to the pathogenesis of bipolar disorder (BD). However, the connections between peripheral inflammation and the brain, especially the interactions between different BD subtypes and episodes, remain to be elucidated. Therefore, we conducted the present study to provide a comprehensive understanding of the complex association between peripheral inflammation and neuroimaging findings in patients with bipolar spectrum disorders.
METHODS
This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42023447044) and conducted according to the Population, Intervention, Comparison, Outcomes, and Study Design (PICOS) framework. Online literature databases (PubMed, Web of Science, Scopus, EMBASE, MEDLINE, PsycINFO, and the Cochrane Library) were searched for studies that simultaneously investigated both peripheral inflammation-related factors and magnetic resonance neurography of BD patients up to July 01, 2023. Then, we analysed the correlations between peripheral inflammation and neuroimaging, as well as the variation trends and the shared and specific patterns of these correlations according to different clinical dimensions.
RESULTS
In total, 34 publications ultimately met the inclusion criteria for this systematic review, with 2993 subjects included. Among all patterns of interaction between peripheral inflammation and neuroimaging, the most common pattern was a positive relationship between elevated inflammation levels and decreased neuroimaging measurements. The brain regions most susceptible to inflammatory activation were the anterior cingulate cortex, amygdala, prefrontal cortex, striatum, hippocampus, orbitofrontal cortex, parahippocampal gyrus, postcentral gyrus, and posterior cingulate cortex.
LIMITATIONS
The small sample size, insufficiently explicit categorization of BD subtypes and episodes, and heterogeneity of the research methods limited further implementation of quantitative data synthesis.
CONCLUSIONS
Disturbed interactions between peripheral inflammation and the brain play a critical role in BD, and these interactions exhibit certain commonalities and differences across various clinical dimensions of BD. Our study further confirmed that the fronto-limbic-striatal system may be the central neural substrate in BD patients.
PubMed: 38388844
DOI: 10.1186/s40345-024-00327-w