Heightened cortical excitability in aged rodents with memory impairment.
Ontology highlight
ABSTRACT:
SUBMITTER: Haberman RP
PROVIDER: S-EPMC5401793 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
Publications
Heightened cortical excitability in aged rodents with memory impairment.
Haberman Rebecca P RP Koh Ming Teng MT Gallagher Michela M
Neurobiology of aging 20170103
Elevated excitability in the hippocampus has emerged as a key contributor to reduced memory function in aging and in cognitive impairment prodromal to Alzheimer's disease. Here, we investigated the relationship between neural activity and memory in the hippocampus and a connectional cortical network using an aged rat model of individual differences for memory impairment. The expression of cFos was used as a measure of pharmacologically induced neural activity. Aged memory-impaired rats exhibited ...[more]
Similar Datasets
Project description:Prolonged wakefulness alters cortical excitability, which is essential for proper brain function and cognition. However, besides prior wakefulness, brain function and cognition are also affected by circadian rhythmicity. Whether the regulation of cognition involves a circadian impact on cortical excitability is unknown. Here, we assessed cortical excitability from scalp electroencephalography (EEG) responses to transcranial magnetic stimulation in 22 participants during 29?h of wakefulness under constant conditions. Data reveal robust circadian dynamics of cortical excitability that are strongest in those individuals with highest endocrine markers of circadian amplitude. In addition, the time course of cortical excitability correlates with changes in EEG synchronization and cognitive performance. These results demonstrate that the crucial factor for cortical excitability, and basic brain function in general, is the balance between circadian rhythmicity and sleep need, rather than sleep homoeostasis alone. These findings have implications for clinical applications such as non-invasive brain stimulation in neurorehabilitation.
| S-EPMC4931032 | biostudies-literature
Project description:BackgroundLittle is known about the modulation of cortical excitability in the prefrontal cortex during fear processing in humans. Here, we aimed to transiently modulate and test the cortical excitability during fear processing using transcranial magnetic stimulation (TMS) and brain oscillations in theta and alpha frequency bands with electroencephalography (EEG).MethodsWe conducted two separate experiments (no-TMS and TMS). In the no-TMS experiment, EEG recordings were performed during the instructed fear paradigm in which a visual cue (CS+) was paired with an aversive unconditioned stimulus (electric shock), while the other visual cue was unpaired (CS-). In the TMS experiment, in addition the TMS was applied on the right dorsomedial prefrontal cortex (dmPFC). The participants also underwent structural MRI (magnetic resonance imaging) scanning and were assigned pseudo-randomly to both experiments, such that age and gender were matched. The cortical excitability was evaluated by time-frequency analysis and functional connectivity with weighted phase lag index (WPLI). We further linked the excitability patterns with markers of stress coping capability.ResultsAfter visual cue onset, we found increased theta power in the frontal lobe and decreased alpha power in the occipital lobe during CS+ relative to CS- trials. TMS of dmPFC increased theta power in the frontal lobe and reduced alpha power in the occipital lobe during CS+. The TMS pulse increased the information flow from the sensorimotor region to the prefrontal and occipital regions in the theta and alpha bands, respectively during CS+ compared to CS-. Pre-stimulation frontal theta power (0.75-1 s) predicted the magnitude of frontal theta power changes after stimulation (1-1.25 s). Finally, the increased frontal theta power during CS+ compared to CS- was positively correlated with stress coping behavior.ConclusionOur results show that TMS over dmPFC transiently modulated the regional cortical excitability and the fronto-occipital information flows during fear processing, while the pre-stimulation frontal theta power determined the strength of achieved effects. The frontal theta power may serve as a biomarker for fear processing and stress-coping responses in individuals and could be clinically tested in mental disorders.
| S-EPMC6593288 | biostudies-literature
Project description:Theoretical approaches based on dynamical systems theory can provide useful frameworks to guide experiments and analysis techniques when investigating cortical network activity. The notion of phase transitions between qualitatively different kinds of network dynamics has been such a framework inspiring novel approaches to neurophysiological data analysis over the recent years. One particular intriguing hypothesis has been that cortical networks reside in the vicinity of a phase transition. Although the final verdict on this hypothesis is still out, trying to understand cortex dynamics from this viewpoint has recently led to interesting insights on cortical network function with relevance for clinical practice.
| S-EPMC4802746 | biostudies-other
Project description:ImportancePerioperative neurocognitive disorder, particularly postoperative cognitive impairment, is common and associated with multiple medical and social adversities, although data from China are lacking.ObjectiveTo examine the incidence, trajectory, and risk factors for subjective cognitive and short-term memory impairment after surgery in the Chinese population.Design, setting, and participantsThis cohort study used data from the China Surgery and Anesthesia Cohort to assess surgical patients aged 40 to 65 years from 2 medical centers between July 15, 2020, and March 31, 2023, with active follow-up within 1 year after the surgery. Of 11 158 patients who were successfully recruited (response rate, 94.4%), 10 149 participants were eligible and available for analysis. From this population, separate cohorts were constructed for analyzing subjective cognitive impairment (8105 noncardiac and 678 cardiac surgery patients) and short-term memory impairment (5246 noncardiac and 454 cardiac surgery patients).ExposuresTwenty-four potential risk factors regarding comorbidities, preoperative psychological conditions, anesthesia- or surgery-related factors, and postsurgical events were included.Main outcomes and measuresOutcomes included subjective cognitive function measured by the 8-Item Informant Interview to Differentiate Aging and Dementia (AD8; scores range from 0 to 8, with higher scores indicating more severe cognitive impairment) and short-term memory measured by the 3-Word Recall Test (TRT; scores range from 0 to 3, with lower scores indicating more severe short-term memory impairment) at 1, 3, 6, and 12 months after noncardiac and cardiac surgery. Generalized linear mixed models were used to identify risk factors associated with the presence of AD8 (score ≥2) or TRT (score <3) abnormality as well as the aggressively deteriorative trajectories of those cognitive measurements.ResultsFor noncardiac surgery patients, the AD8 analysis included 8105 patients (mean [SD] age, 52.3 [7.1] years; 3378 [41.7%] male), and the TRT analysis included 5246 patients (mean [SD] age, 51.4 [7.0] years; 1969 [37.5%] male). The AD8 abnormality incidence rates after noncardiac surgery increased from 2.2% (175 of 8105) at 7 days to 17.1% (1059 of 6191) at 6 months after surgery, before appearing to decrease. In contrast, the TRT abnormality incidence rates followed a U-shaped pattern, with the most pronounced incidence rates seen at 7 days (38.9% [2040 of 5246]) and 12 months (49.0% [1394 of 2845]). Similar patterns were seen among cardiac surgery patients for the AD8 analysis (678 patients; mean [SD] age, 53.2 [6.3] years; 393 [58.0%] male) and TRT analysis (454 patients; mean [SD] age, 52.4 [6.4] years; 248 [54.6%] male). Among noncardiac surgery patients, the top risk factors for aggressively deteriorative AD8 trajectory and for AD8 abnormality, respectively, after surgery were preoperative sleep disturbances (Pittsburgh Sleep Quality Index ≥16 vs 0-5: odds ratios [ORs], 4.04 [95% CI, 2.20-7.40] and 4.54 [95% CI, 2.40-8.59]), intensive care unit stay of 2 days or longer (ORs, 2.43 [95% CI, 1.26-4.67] and 3.07 [95% CI, 1.67-5.65]), and preoperative depressive symptoms (ORs, 1.76 [95% CI, 1.38-2.24] and 2.23 [95% CI, 1.79-2.77]). Analyses for TRT abnormality and trajectory, as well as the analyses conducted among cardiac surgery patients, found fewer associated factors.Conclusions and relevanceThis cohort study of middle-aged Chinese surgery patients found subjective cognitive and short-term memory impairment within 12 months after both cardiac and noncardiac surgery, with multiple identified risk factors, underscoring the potential of preoperative psychological interventions and optimized perioperative management for postoperative cognitive impairment prevention.
| S-EPMC10565601 | biostudies-literature
Project description:Studies in rodents show that transient receptor potential vanilloid 1 (TRPV1) channels regulate glutamate release at central and peripheral synapses. In humans, a number of nonsynonymous single-nucleotide polymorphisms (SNPs) have been described in the TRPV1 gene, and some of them significantly alter the functionality of the channel. To address the possible role of TRPV1 channels in the regulation of synaptic transmission in humans, we studied how TRPV1 genetic polymorphisms affect cortical excitability measured with transcranial magnetic stimulation (TMS). Two SNPs of the TRPV1 gene were selected and genotyped (rs222747 and rs222749) in a sample of 77 healthy subjects. In previous cell expression studies, the "G" allele of rs222747 was found to enhance the activity of the channel, whereas rs222749 had no functional effect. Allelic variants in the rs222749 region were not associated with altered cortical response to single, paired, and repetitive TMS. In contrast, subjects homozygous for the G allele in rs222747 exhibited larger short-interval intracortical facilitation (a measure of glutamate transmission) explored through paired-pulse TMS of the primary motor cortex. Recruitment curves, short-interval intracortical inhibition, intracortical facilitation, and long-interval intracortical inhibition were unchanged. LTP- and LTD-like plasticity explored through intermittent or continuous theta-burst stimulation was also similar in the "G" and "non-G" subjects. To our knowledge, our results provide the first evidence that TRPV1 channels regulate cortical excitability to paired-pulse stimulation in humans.
| S-EPMC6621142 | biostudies-literature
Project description:ObjectiveTo investigate whether gait dysfunction is a predictor of severe spatial learning and memory impairment in aged mice.MethodsA total of 100 12-month-old male mice that had no obvious abnormal motor ability and whose Morris water maze performances were not significantly different from those of two-month-old male mice were selected for the study. The selected aged mice were then divided into abnormal or normal gait groups according to the results from the quantitative gait assessment. Gaits of aged mice were defined as abnormal when the values of quantitative gait parameters were two standard deviations (SD) lower or higher than those of 2-month-old male mice. Gait parameters included stride length, variability of stride length, base of support, cadence, and average speed. After nine months, mice exhibiting severe spatial learning and memory impairment were separated from mice with mild or no cognitive dysfunction. The rate of severe spatial learning and memory impairment in the abnormal and normal gait groups was tested by a chi-square test and the correlation between gait dysfunction and decline in cognitive function was tested using a diagnostic test.ResultsThe 12-month-old aged mice were divided into a normal gait group (n = 75) and an abnormal gait group (n = 25). Nine months later, three mice in the normal gait group and two mice in the abnormal gait group had died. The remaining mice were subjected to the Morris water maze again, and 17 out of 23 mice in the abnormal gait group had developed severe spatial learning and memory impairment, including six with stride length deficits, 15 with coefficient of variation (CV) in stride length, two with base of support (BOS) deficits, five with cadence dysfunction, and six with average speed deficits. In contrast, only 15 out of 72 mice in the normal gait group developed severe spatial learning and memory impairment. The rate of severe spatial learning and memory impairment was significantly higher in the abnormal gait group as compared to that in the normal gait group (x = 21.986, P < 0.001). All five parameters used to assess gait predicted severe spatial learning and memory impairment in aged mice (P < 0.01). However, the difference of the area under the ROC (receiver operating characteristic) curve for each quantitative gait parameter was not statistically significant.ConclusionGait disorders are a predictor of severe spatial learning and memory impairment in aged mice, and stride length, variability of stride length, base of support, cadence, and average speed are all sensitive parameters for assessing gait.
| S-EPMC5289446 | biostudies-literature
Project description:BackgroundAdaptive computerized working memory (WM) training has shown favorable effects on cerebral cortical thickness as compared to non-adaptive training in healthy individuals. However, knowledge of WM training-related morphological changes in mild cognitive impairment (MCI) is limited.ObjectiveThe primary objective of this double-blind randomized study was to investigate differences in longitudinal cortical thickness trajectories after adaptive and non-adaptive WM training in patients with MCI. We also investigated the genotype effects on cortical thickness trajectories after WM training combining these two training groups using longitudinal structural magnetic resonance imaging (MRI) analysis in Freesurfer.MethodMagnetic resonance imaging acquisition at 1.5 T were performed at baseline, and after four- and 16-weeks post training. A total of 81 individuals with MCI accepted invitations to undergo 25 training sessions over 5 weeks. Longitudinal Linear Mixed effect models investigated the effect of adaptive vs. non-adaptive WM training. The LME model was fitted for each location (vertex). On all statistical analyzes, a threshold was applied to yield an expected false discovery rate (FDR) of 5%. A secondary LME model investigated the effects of LMX1A and APOE-ε4 on cortical thickness trajectories after WM training.ResultsA total of 62 participants/patients completed the 25 training sessions. Structural MRI showed no group difference between the two training regimes in our MCI patients, contrary to previous reports in cognitively healthy adults. No significant structural cortical changes were found after training, regardless of training type, across all participants. However, LMX1A-AA carriers displayed increased cortical thickness trajectories or lack of decrease in two regions post-training compared to those with LMX1A-GG/GA. No training or training type effects were found in relation to the APOE-ε4 gene variants.ConclusionThe MCI patients in our study, did not have improved cortical thickness after WM training with either adaptive or non-adaptive training. These results were derived from a heterogeneous population of MCI participants. The lack of changes in the cortical thickness trajectory after WM training may also suggest the lack of atrophy during this follow-up period. Our promising results of increased cortical thickness trajectory, suggesting greater neuroplasticity, in those with LMX1A-AA genotype need to be validated in future trials.
| S-EPMC9014119 | biostudies-literature
Project description:Sleep deprivation (SD) is the hallmark of modern society and may increase risk of Alzheimer's disease (AD). However, it is unclear how SD facilitates early cognitive impairments observed in AD models, as the underlying molecular mechanism is largely unknown. Here, we aim to investigate SD-induced cellular and molecular alterations in hippocampus of young APP/PS1 mice and whether jujuboside A (JuA) treatment could negate these alterations. Our results reveal that although SD causes spatial memory impairments in both genotypes, SD decreases frequency and amplitude of mEPSCs and pCREB levels in WT, but increases frequency and amplitude of mEPSCs, NMDAR, GluR1, pCaMKII (β, α) and decreases CREB levels in APP/PS1 mice, implicating that SD may facilitate abnormalities in young APP/PS1 mice via enhancing neuronal excitability. Moreover, JuA suppresses SD-induced enhancement of mEPSCs and prevents memory impairment in APP/PS1 mice. Further, whole-cell puff experiment suggests that JuA may function to activate GABAergic inhibition to reduce SD-induced enhancement of excitatory synaptic transmission in APP/PS1 mice. The present study reveals that sleep loss induces spatial memory impairment in an AD mouse model by disrupting the excitatory signaling pathway, and JuA prevents this via GABAergic mechanism.
| S-EPMC6418242 | biostudies-literature
Project description:Mental imagery provides an essential simulation tool for remembering the past and planning the future, with its strength affecting both cognition and mental health. Research suggests that neural activity spanning prefrontal, parietal, temporal, and visual areas supports the generation of mental images. Exactly how this network controls the strength of visual imagery remains unknown. Here, brain imaging and transcranial magnetic phosphene data show that lower resting activity and excitability levels in early visual cortex (V1-V3) predict stronger sensory imagery. Further, electrically decreasing visual cortex excitability using tDCS increases imagery strength, demonstrating a causative role of visual cortex excitability in controlling visual imagery. Together, these data suggest a neurophysiological mechanism of cortical excitability involved in controlling the strength of mental images.
| S-EPMC7200162 | biostudies-literature
Project description:Amyotrophic lateral sclerosis (ALS) is characterized by its marked clinical heterogeneity. Although the coexistence of upper and lower motor neuron signs is a common clinical feature for most patients, there is a wide range of atypical motor presentations and clinical trajectories, implying a heterogeneity of underlying pathogenic mechanisms. Corticomotoneuronal dysfunction is increasingly postulated as the harbinger of clinical disease, and neurophysiological exploration of the motor cortex in vivo using transcranial magnetic stimulation (TMS) has suggested that motor cortical hyperexcitability may be a critical pathogenic factor linked to clinical features and survival. Region-specific selective vulnerability at the level of the motor cortex may drive the observed differences of clinical presentation across the ALS motor phenotypes, and thus, further understanding of phenotypic variability in relation to cortical dysfunction may serve as an important guide to underlying disease mechanisms. This review article analyses the cortical excitability profiles across the clinical motor phenotypes, as assessed using TMS, and explores this relationship to clinical patterns and survival. This understanding will remain essential to unravelling central disease pathophysiology and for the development of specific treatment targets across the ALS clinical motor phenotypes.
| S-EPMC8230203 | biostudies-literature