Entorhinal Cortex/physiology* ; Hippocampus/physiology* ; Neural Pathways/physiology*

Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus (LEC-DG) are considered responsible for the chronification of pain. However, the underlying alterations in fan cells, which are the predominant neurons in the LEC that project to the DG, remain elusive. Here, we investigated possible mechanisms using a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain. We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents (I_h), which led to the hyperexcitability of LEC fan cells of CFA slices. This phenomenon was attenuated in CFA slices by activating dopamine D2, but not D1, receptors. Chemogenetic activation of the ventral tegmental area -LEC projection had a D2 receptor-dependent analgesic effect. Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity, and this effect was attenuated by pre-activation of the I_h. Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.
Animals ; Chronic Pain ; Entorhinal Cortex/metabolism* ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Neurons/metabolism* ; Rats ; Receptors, Dopamine D1/metabolism* ; Receptors, Dopamine D2

Mice ; Animals ; Alzheimer Disease/complications* ; Entorhinal Cortex/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Memory Disorders/etiology* ; Thalamus/metabolism* ; Disease Models, Animal

The method of directly using speed information and angle information to drive attractors model of grid cells to encode environment has poor anti-interference ability and is not bionic. In response to the problem, this paper proposes a grid field calculation model based on perceived speed and perceived angle. The model has the following characteristics. Firstly, visual stream is decoded to obtain visual speed, and speed cell is modeled and decoded to obtain body speed. Visual speed and body speed are integrated to obtain perceived speed information. Secondly, a one-dimensional circularly connected cell model with excitatory connection is used to simulate the firing mechanism of head direction cells, so that the robot obtains current perception angle information in a biomimetic manner. Finally, the two kinds of perceptual information of speed and angle are combined to realize the driving of grid cell attractors model. The proposed model was experimentally verified. The results showed that this model could realize periodic hexagonal firing field mode of grid cells and precise path integration function. The proposed algorithm may provide a foundation for the research on construction method of robot cognitive map based on hippocampal cognition mechanism.
Action Potentials ; Computer Simulation ; Computer Systems ; Entorhinal Cortex ; Grid Cells ; Hippocampus ; Models, Neurological

BACKGROUND/AIMS: Functional dyspepsia (FD) remains a great clinical challenge since the FD subtypes, defined by Rome III classification, still have heterogeneous pathogenesis. Previous studies have shown notable differences in visceral sensation processing in the CNS in FD compared to healthy subjects (HS). However, the role of CNS in the pathogenesis of each FD subtype has not been recognized. METHODS: Twenty-eight FD patients, including 10 epigastric pain syndrome (EPS), 9 postprandial distress syndrome (PDS), and 9 mixed-type, and 10 HS, were enrolled. All subjects underwent a proximal gastric perfusion water load test and the regional brain activities during resting state and water load test were investigated by functional magnetic resonance imaging. RESULTS: For regional brain activities during the resting state and water load test, each FD subtype was significantly different from HS (P < 0.05). Focusing on EPS and PDS, the regional brain activities of EPS were stronger than PDS in the left paracentral lobule, right inferior frontal gyrus pars opercularis, postcentral gyrus, precuneus, insula, parahippocampal gyrus, caudate nucleus, and bilateral cingulate cortices at the resting state (P < 0.05), and stronger than PDS in the left inferior temporal and fusiform gyri during the water load test (P < 0.05). CONCLUSIONS: Compared to HS, FD subtypes had different regional brain activities at rest and during water load test, whereby the differences displayed distinct manifestations for each subtype. Compared to PDS, EPS presented more significant differences from HS at rest, suggesting that the abnormality of central visceral pain processing could be one of the main pathogenesis mechanisms for EPS.
Brain ; Broca Area ; Caudate Nucleus ; Classification ; Dyspepsia ; Functional Neuroimaging ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Parahippocampal Gyrus ; Parietal Lobe ; Perfusion ; Prefrontal Cortex ; Sensation ; Somatosensory Cortex ; Visceral Pain ; Water

OBJECTIVE: Anxiety is prevalent in patients with mild cognitive impairment (MCI) and are considered to be a risk factor for conversion to dementia. The purpose of this study was to evaluate whether Anxiety symptoms in MCI promote disease progression in a manner related to amyloid status, and to determine the relationship between anxiety symptoms and longitudinal cerebral structural changes. METHODS: Baseline data for 230 patients with amyloid-positive MCI (52 with anxiety and 178 without) from the Alzheimer's Disease Neuroimaging Initiative study were analyzed. All participants underwent comprehensive cognitive testing, volumetric MRI, and [18F]AV45 positron emission tomography amyloid imaging. Anxiety symptoms were measured using the Neuropsychiatric Inventory Questionnaire. A voxel-based morphometric analysis using volumetric brain MRI data was used to compare longitudinal structural changes related to anxiety symptoms. RESULTS: The conversion rate to dementia was different between patients with and without anxiety in amyloid-positive MCI (37.7% vs. 16.1%, respectively ; p=0.001). Anxiety in amyloid-positive MCI was associated with longitudinal cortical atrophy in the left superior temporal gyrus, left Heschl's gyrus, left parahippocampal gyrus, left anterior cingulum, bilateral anterior cingulum and right superior orbital gyrus. CONCLUSION: Our study indicates that the presence of anxiety in patients with amyloid-positive MCI is associated with higher conversion to dementia and longitudinal cortical atrophy.
Alzheimer Disease ; Amyloid ; Anxiety* ; Atrophy ; Brain ; Dementia* ; Disease Progression ; Humans ; Magnetic Resonance Imaging ; Mild Cognitive Impairment* ; Neuroimaging ; Parahippocampal Gyrus ; Positron-Emission Tomography ; Prefrontal Cortex ; Risk Factors ; Temporal Lobe

OBJECTIVE: The aim of this study was to explore the prognostic values of biomarkers of neurodegeneration as measured by magnetic resonance imaging (MRI) and amyloid burden as measured by amyloid positron emission tomography (PET) in predicting conversion to Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI). METHODS: PubMed and EMBASE databases were searched for structural MRI or amyloid PET imaging studies published between January 2000 and July 2014 that reported conversion to AD in patients with MCI. Means and standard deviations or individual numbers of biomarkers with positive or negative status at baseline and corresponding numbers of patients who had progressed to AD at follow-up were retrieved from each study. The effect size of each biomarker was expressed as Hedges's g. RESULTS: Twenty-four MRI studies and 8 amyloid PET imaging studies were retrieved. 674 of the 1741 participants (39%) developed AD. The effect size for predicting conversion to AD was 0.770 [95% confidence interval (CI) 0.607–0.934] for across MRI and 1.316 (95% CI 0.920–1.412) for amyloid PET imaging (p<0.001). The effect size was 1.256 (95% CI 0.902–1.609) for entorhinal cortex volume from MRI. CONCLUSION: Our study suggests that volumetric MRI measurement may be useful for the early detection of AD.
Alzheimer Disease* ; Amyloid* ; Biomarkers ; Entorhinal Cortex ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging* ; Mild Cognitive Impairment* ; Positron-Emission Tomography

Epileptic spike is an indicator of hyper-excitability and hyper-synchrony in the neural networks. The inhibitory effects of spikes on theta rhythms (4-8 Hz) might be helpful to understand the mechanism of epileptic damage on the cognitive functions. To quantitatively evaluate the inhibitory effects of spikes on theta rhythms, intracerebral electroencephalogram (EEG) recordings with both sporadic spikes (SSs) and spike-free transient period between adjacent spikes were selected in 4 patients in the status of rapid eyes movement (REM) sleep with temporal lobe epilepsy (TLE) under the pre-surgical monitoring. The electrodes of hippocampal CA3 and entorhinal cortex (EC) were employed, since CA3 and EC built up one of key loops to investigate cognition and epilepsy. These SSs occurred only in CA3, only in EC, or in both CA3 and EC synchronously. Theta power was respectively estimated around SSs and during the spike-free transient period by Gabor wavelet transform and Hilbert transform. The intermittent extent was then estimated to represent for the loss of theta rhythms during the spike-free transient period. The following findings were obtained: (1) The prominent rhythms were in theta frequency band; (2) The spikes could transiently reduce theta power, and the inhibitory effect was severer around SSs in both CA3 and EC synchronously than that around either SSs only in EC or SSs only in CA3; (3) During the spike-free transient period, theta rhythms were interrupted with the intermittent theta rhythms left and theta power level continued dropping, implying the inhibitory effect was sustained. Additionally, the intermittent extent of theta rhythms was converged to the inhibitory extent around SSs; (4) The average theta power level during the spike-free transient period might not be in line with the inhibitory extent of theta rhythms around SSs. It was concluded that the SSs had negative effects on theta rhythms transiently and directly, the inhibitory effects aroused by SSs sustained during the spike-free transient period and were directly related to the intermittent extent. It was indicated that the loss of theta rhythms might qualify exactly the sustained inhibitory effects on theta rhythms aroused by spikes in EEG. The work provided an argumentation about the relationship between the transient negative impact of interictal spike and the loss of theta rhythms during spike-free activity for the first time, offered an intuitive methodology to estimate the inhibitory effect of spikes by EEG, and might be helpful to the analysis of EEG rhythms based on local field potentials (LFPs) in deep brain.
CA3 Region, Hippocampal ; physiopathology ; Electroencephalography ; Entorhinal Cortex ; physiopathology ; Epilepsy, Temporal Lobe ; physiopathology ; Humans ; Male ; Theta Rhythm

Feature outcome of hippocampus and extra-hippocampal cortices was evaluated in melatonin treated lithium-pilocarpine epileptic rats during early and chronic phases of temporal lobe epilepsy (TLE). After status epilepticus (SE) induction, 5 and 20 mg/kg melatonin were administered for 14 days or 60 days. All animals were killed 60 days post SE induction and the histological features of the rosrto-caudal axis of the dorsal hippocampus, piriform and entorhinal cortices were evaluated utilizing Nissl, Timm, and synapsin I immunoflorescent staining. Melatonin (20 mg/kg) effect on CA1 and CA3 neurons showed a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. The number of counted granular cells by melatonin (20 mg/kg) treatment increased along the rostro-caudal axis of the dorsal hippocampus in comparison to the untreated epileptic group. The density of Timm granules in the inner molecular layer of the dentate gyrus decreased significantly in all melatonin treated groups in comparison to the untreated epileptic animals. The increased density of synapsin I immunoreactivity in the outer molecular layer of the dentate gyrus of untreated epileptic rats showed a profound decrease following melatonin treatment. There was no neuronal protection in the piriform and entorhinal cortices whatever the melatonin treatment. Long-term melatonin administration as a co-adjuvant probably could reduce the post-lesion histological consequences of TLE in a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus.
Animals ; Axis, Cervical Vertebra* ; Axons* ; Dentate Gyrus ; Entorhinal Cortex ; Epilepsy, Temporal Lobe* ; Hippocampus* ; Melatonin* ; Neurons* ; Rats ; Status Epilepticus ; Synapsins ; Temporal Lobe*

OBJECTIVE: We hypothesize that the amplitude of low-frequency fluctuations (ALFF) is involved in the altered regional baseline brain function in social anxiety disorder (SAD). The aim of the study was to analyze the altered baseline brain activity in drug-naive adult patients with SAD. METHODS: We investigated spontaneous and baseline brain activities by obtaining the resting-state functional magnetic resonance imaging data of 20 drug-naive adult SAD patients and 19 healthy controls. Voxels were used to analyze the ALFF values using one- and two-sample t-tests. A post-hoc correlation of clinical symptoms was also performed. RESULTS: Our findings show decreased ALFF in the bilateral insula, left medial superior frontal gyrus, left precuneus, left middle temporal gyrus, right middle temporal pole, and left fusiform gyrus of the SAD group. The SAD patients exhibited significantly increased ALFF in the right inferior temporal gyrus, right middle temporal gyrus, bilateral middle occipital gyrus, orbital superior frontal gyrus, right fusiform gyrus, right medial superior frontal gyrus, and left parahippocampal gyrus. Moreover, the Liebowitz Social Anxiety Scale results for the SAD patients were positively correlated with the mean Z values of the right middle occipital and right inferior occipital but showed a negative correlation with the mean Z values of the right superior temporal gyrus and right medial superior frontal gyrus. CONCLUSION: These results of the altered regional baseline brain function in SAD suggest that the regions with abnormal spontaneous activities are involved in the underlying pathophysiology of SAD patients.
Adult* ; Anxiety ; Anxiety Disorders* ; Brain* ; Humans ; Magnetic Resonance Imaging* ; Orbit ; Parahippocampal Gyrus