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PloS One 2024Sleep spindles are one of the prominent EEG oscillatory rhythms of non-rapid eye movement sleep. In the memory consolidation, these oscillations have an important role...
Sleep spindles are one of the prominent EEG oscillatory rhythms of non-rapid eye movement sleep. In the memory consolidation, these oscillations have an important role in the processes of long-term potentiation and synaptic plasticity. Moreover, the activity (spindle density and/or sigma power) of spindles has a linear association with learning performance in different paradigms. According to the experimental observations, the sleep spindle activity can be improved by closed loop acoustic stimulations (CLAS) which eventually improve memory performance. To examine the effects of CLAS on spindles, we propose a biophysical thalamocortical model for slow oscillations (SOs) and sleep spindles. In addition, closed loop stimulation protocols are applied on a thalamic network. Our model results show that the power of spindles is increased when stimulation cues are applied at the commencing of an SO Down-to-Up-state transition, but that activity gradually decreases when cues are applied with an increased time delay from this SO phase. Conversely, stimulation is not effective when cues are applied during the transition of an Up-to-Down-state. Furthermore, our model suggests that a strong inhibitory input from the reticular (RE) layer to the thalamocortical (TC) layer in the thalamic network shifts leads to an emergence of spindle activity at the Up-to-Down-state transition (rather than at Down-to-Up-state transition), and the spindle frequency is also reduced (8-11 Hz) by thalamic inhibition.
Topics: Humans; Sleep, Slow-Wave; Electroencephalography; Thalamus; Acoustic Stimulation; Computer Simulation; Models, Neurological; Sleep
PubMed: 38924001
DOI: 10.1371/journal.pone.0306218 -
Proceedings of the National Academy of... Jul 2024Biologically detailed models of brain circuitry are challenging to build and simulate due to the large number of neurons, their complex interactions, and the many...
Biologically detailed models of brain circuitry are challenging to build and simulate due to the large number of neurons, their complex interactions, and the many unknown physiological parameters. Simplified mathematical models are more tractable, but harder to evaluate when too far removed from neuroanatomy/physiology. We propose that a multiscale model, coarse-grained (CG) while preserving local biological details, offers the best balance between biological realism and computability. This paper presents such a model. Generally, CG models focus on the interaction between groups of neurons-here termed "pixels"-rather than individual cells. In our case, dynamics are alternately updated at intra- and interpixel scales, with one informing the other, until convergence to equilibrium is achieved on both scales. An innovation is how we exploit the underlying biology: Taking advantage of the similarity in local anatomical structures across large regions of the cortex, we model intrapixel dynamics as a single dynamical system driven by "external" inputs. These inputs vary with events external to the pixel, but their ranges can be estimated . Precomputing and tabulating all potential local responses speed up the updating procedure significantly compared to direct multiscale simulation. We illustrate our methodology using a model of the primate visual cortex. Except for local neuron-to-neuron variability (necessarily lost in any CG approximation) our model reproduces various features of large-scale network models at a tiny fraction of the computational cost. These include neuronal responses as a consequence of their orientation selectivity, a primary function of visual neurons.
Topics: Models, Neurological; Animals; Neurons; Visual Cortex; Humans; Nerve Net; Cerebral Cortex; Computer Simulation
PubMed: 38923983
DOI: 10.1073/pnas.2320454121 -
Journal of Biochemical and Molecular... Jul 2024Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder. Oxidative stress and inflammatory responses have a vital role in the pathophysiology of IBD as...
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder. Oxidative stress and inflammatory responses have a vital role in the pathophysiology of IBD as well as seizure. IBD is associated with extraintestinal manifestations. This study aimed to explore the relationship between colitis and susceptibility to seizures, with a focus on the roles of neuroinflammation and oxidative stress in acetic acid-induced colitis in mice. Forty male Naval Medical Research Institute mice were divided into four groups: control, colitis, pentylenetetrazole (PTZ), and colitis + PTZ. Colitis was induced by intrarectal administration of acetic acid, and seizures were induced by intravenous injection of PTZ 7 days postcolitis induction. Following the measurement of latency to seizure, the mice were killed, and their colons and prefrontal cortex (PFC) were dissected. Gene expression of inflammatory markers including interleukin-1β, tumor necrosis factor-alpha, NOD-like receptor protein 3, and toll-like receptor 4, as well as total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels were measured in the colon and PFC. Histopathological evaluations were performed on the colon samples. Data were analyzed by t-test or one-way variance analysis. Colitis decreased latency to seizure, increased gene expression of inflammatory markers, and altered levels of MDA, nitrite, and TAC in both the colon and PFC. Simultaneous induction of colitis and seizure exacerbated the neuroimmune response and oxidative stress in the PFC and colon. Results concluded that neuroinflammation and oxidative stress in the PFC at least partially mediate the comorbid decrease in seizure latency in mice with colitis.
Topics: Animals; Male; Oxidative Stress; Mice; Prefrontal Cortex; Seizures; Colitis; Neuroimmunomodulation; Disease Models, Animal
PubMed: 38923727
DOI: 10.1002/jbt.23755 -
Human Brain Mapping Jun 2024Closed-loop neurofeedback training utilizes neural signals such as scalp electroencephalograms (EEG) to manipulate specific neural activities and the associated...
Closed-loop neurofeedback training utilizes neural signals such as scalp electroencephalograms (EEG) to manipulate specific neural activities and the associated behavioral performance. A spatiotemporal filter for high-density whole-head scalp EEG using a convolutional neural network can overcome the ambiguity of the signaling source because each EEG signal includes information on the remote regions. We simultaneously acquired EEG and functional magnetic resonance images in humans during the brain-computer interface (BCI) based neurofeedback training and compared the reconstructed and modeled hemodynamic responses of the sensorimotor network. Filters constructed with a convolutional neural network captured activities in the targeted network with spatial precision and specificity superior to those of the EEG signals preprocessed with standard pipelines used in BCI-based neurofeedback paradigms. The middle layers of the trained model were examined to characterize the neuronal oscillatory features that contributed to the reconstruction. Analysis of the layers for spatial convolution revealed the contribution of distributed cortical circuitries to reconstruction, including the frontoparietal and sensorimotor areas, and those of temporal convolution layers that successfully reconstructed the hemodynamic response function. Employing a spatiotemporal filter and leveraging the electrophysiological signatures of the sensorimotor excitability identified in our middle layer analysis would contribute to the development of a further effective neurofeedback intervention.
Topics: Humans; Electroencephalography; Magnetic Resonance Imaging; Adult; Brain-Computer Interfaces; Male; Neurofeedback; Young Adult; Sensorimotor Cortex; Female; Neural Networks, Computer
PubMed: 38923184
DOI: 10.1002/hbm.26767 -
Developmental Psychobiology Sep 2024Repeated exposure to abused drugs leads to reorganizing synaptic connections in the brain, playing a pivotal role in the relapse process. Additionally, recent research...
Repeated exposure to abused drugs leads to reorganizing synaptic connections in the brain, playing a pivotal role in the relapse process. Additionally, recent research has highlighted the impact of parental drug exposure before gestation on subsequent generations. This study aimed to explore the influence of parental morphine exposure 10 days prior to pregnancy on drug-induced locomotor sensitization. Adult male and female Wistar rats were categorized into morphine-exposed and control groups. Ten days after their last treatment, they were mated, and their male offspring underwent morphine, methamphetamine, cocaine, and nicotine-induced locomotor sensitization tests. The results indicated increased locomotor activity in both groups after drug exposure, although the changes were attenuated in morphine and cocaine sensitization among the offspring of morphine-exposed parents (MEPs). Western blotting analysis revealed altered levels of D2 dopamine receptors (D2DRs) in the prefrontal cortex and nucleus accumbens of the offspring from MEPs. Remarkably, despite not having direct in utero drug exposure, these offspring exhibited molecular alterations affecting morphine and cocaine-induced sensitization. The diminished sensitization to morphine and cocaine suggested the development of a tolerance phenotype in these offspring. The changes in D2DR levels in the brain might play a role in these adaptations.
Topics: Animals; Female; Morphine; Male; Cocaine; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Wistar; Rats; Receptors, Dopamine D2; Nucleus Accumbens; Prefrontal Cortex; Locomotion; Behavior, Animal; Narcotics; Paternal Exposure; Dopamine Uptake Inhibitors; Motor Activity
PubMed: 38922890
DOI: 10.1002/dev.22514 -
Journal of Clinical Neurophysiology :... Jul 2024The corpus callosum is crucial for interhemispheric interactions in the motor control of limb functions. Human and animal studies suggested spinal cord pathologies may...
PURPOSE
The corpus callosum is crucial for interhemispheric interactions in the motor control of limb functions. Human and animal studies suggested spinal cord pathologies may induce cortical reorganization in sensorimotor areas. We investigate participation of the corpus callosum in executions of a simple motor task in patients with cervical spondylotic myelopathy (CSM) using transcranial magnetic stimulation.
METHODS
Twenty patients with CSM with various MRI grades of severity of cord compression were compared with 19 normal controls. Ipsilateral silent period, contralateral silent period, central motor conduction time, and transcallosal conduction time (TCT) were determined.
RESULTS
In both upper and lower limbs, TCTs were significantly increased for patients with CSM than normal controls ( p < 0.001 for all), without side-to-side differences. Ipsilateral silent period and contralateral silent period durations were significantly increased bilaterally for upper limbs in comparison to controls ( p < 0.01 for all), without side-to-side differences. There were no significant correlations of TCT with central motor conduction time nor severity of CSM for both upper and lower limbs ( p > 0.05 for all) bilaterally.
CONCLUSIONS
Previous transcranial magnetic stimulation studies show increased motor cortex excitability in CSM; hence, increased TCTs observed bilaterally may be a compensatory mechanism for effective unidirectional and uniplanar execution of muscle activation in the distal limb muscles. Lack of correlation of TCTs with severity of CSM or central motor conduction time may be in keeping with a preexistent role of the corpus callosum as a predominantly inhibitory pathway for counteracting redundant movements resulting from increased motor cortex excitability occurring after spinal cord lesions.
Topics: Humans; Corpus Callosum; Male; Transcranial Magnetic Stimulation; Female; Middle Aged; Spondylosis; Evoked Potentials, Motor; Adult; Aged; Cervical Vertebrae; Neural Conduction; Spinal Cord Diseases; Spinal Cord Compression
PubMed: 38922289
DOI: 10.1097/WNP.0000000000000979 -
Einstein (Sao Paulo, Brazil) 2024This study aimed at assessing the alterations in upper limb motor impairment and connectivity between motor areas following the post-stroke delivery of cathodal... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study aimed at assessing the alterations in upper limb motor impairment and connectivity between motor areas following the post-stroke delivery of cathodal transcranial direct current stimulation sessions.
METHODS
Modifications in the Fugl-Meyer Assessment scores, connectivity between the primary motor cortex of the unaffected and affected hemispheres, and between the primary motor and premotor cortices of the unaffected hemisphere were compared prior to and following six sessions of cathodal transcranial direct current stimulation application in 13 patients (active = 6; sham = 7); this modality targets the primary motor cortex of the unaffected hemisphere early after a stroke.
RESULTS
Clinically relevant distinctions in Fugl-Meyer Assessment scores (≥9 points) were observed more frequently in the Sham Group than in the Active Group. Between-group differences in the alterations in Fugl-Meyer Assessment scores were not statistically significant (Mann-Whitney test, p=0.133). ROI-to-ROI correlations between the primary motor cortices of the affected and unaffected hemispheres post-therapeutically increased in 5/6 and 2/7 participants in the Active and Sham Groups, respectively. Between-group differences in modifications in connectivity between the aforementioned areas were not statistically significant. Motor performance enhancements were more frequent in the Sham Group compared to the Active Group.
CONCLUSION
The results of this hypothesis-generating investigation suggest that heightened connectivity may not translate into early clinical benefits following a stroke and will be crucial in designing larger cohort studies to explore mechanisms underlying the impacts of this intervention. ClinicalTrials.gov Identifier: NCT02455427.
Topics: Humans; Transcranial Direct Current Stimulation; Pilot Projects; Male; Female; Motor Cortex; Middle Aged; Stroke Rehabilitation; Aged; Stroke; Treatment Outcome; Recovery of Function; Upper Extremity; Time Factors
PubMed: 38922218
DOI: 10.31744/einstein_journal/2024AO0450 -
Cells Jun 2024Glial cell line-derived neurotrophic factor (GDNF) is among the strongest dopamine neuron function- and survival-promoting factors known. Due to this reason, it has...
Glial cell line-derived neurotrophic factor (GDNF) is among the strongest dopamine neuron function- and survival-promoting factors known. Due to this reason, it has clinical relevance in dopamine disorders such as Parkinson's disease and schizophrenia. In the striatum, GDNF is exclusively expressed in interneurons, which make up only about 0.6% of striatal cells. Despite clinical significance, histological analysis of striatal GDNF system arborization and relevance to incoming dopamine axons, which bear its receptor RET, has remained enigmatic. This is mainly due to the lack of antibodies able to visualize GDNF- and RET-positive cellular processes; here, we overcome this problem by using knock-in marker alleles. We find that GDNF neurons chemoattract RET+ axons at least seven times farther in distance than medium spiny neurons (MSNs), which make up 95% of striatal neurons. Furthermore, we provide evidence that tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, is enriched towards GDNF neurons in the dopamine axons. Finally, we find that GDNF neuron arborizations occupy approximately only twelve times less striatal volume than 135 times more abundant MSNs. Collectively, our results improve our understanding of how endogenous GDNF affects striatal dopamine system function.
Topics: Animals; Glial Cell Line-Derived Neurotrophic Factor; Axons; Corpus Striatum; Mice; Proto-Oncogene Proteins c-ret; Dopaminergic Neurons; Dopamine; Tyrosine 3-Monooxygenase; Mice, Inbred C57BL; Neurons; Medium Spiny Neurons
PubMed: 38920687
DOI: 10.3390/cells13121059 -
Cells Jun 2024Neuroplasticity in the amygdala and its central nucleus (CeA) is linked to pain modulation and pain behaviors, but cellular mechanisms are not well understood. Here, we...
Dysfunction of Small-Conductance Ca-Activated Potassium (SK) Channels Drives Amygdala Hyperexcitability and Neuropathic Pain Behaviors: Involvement of Epigenetic Mechanisms.
Neuroplasticity in the amygdala and its central nucleus (CeA) is linked to pain modulation and pain behaviors, but cellular mechanisms are not well understood. Here, we addressed the role of small-conductance Ca-activated potassium (SK) channels in pain-related amygdala plasticity. The facilitatory effects of the intra-CeA application of an SK channel blocker (apamin) on the pain behaviors of control rats were lost in a neuropathic pain model, whereas an SK channel activator (NS309) inhibited pain behaviors in neuropathic rats but not in sham controls, suggesting the loss of the inhibitory behavioral effects of amygdala SK channels. Brain slice electrophysiology found hyperexcitability of CeA neurons in the neuropathic pain condition due to the loss of SK channel-mediated medium afterhyperpolarization (mAHP), which was accompanied by decreased SK2 channel protein and mRNA expression, consistent with a pretranscriptional mechanisms. The underlying mechanisms involved the epigenetic silencing of the SK2 gene due to the increased DNA methylation of the CpG island of the SK2 promoter region and the change in methylated CpG sites in the CeA in neuropathic pain. This study identified the epigenetic dysregulation of SK channels in the amygdala (CeA) as a novel mechanism of neuropathic pain-related plasticity and behavior that could be targeted to control abnormally enhanced amygdala activity and chronic neuropathic pain.
Topics: Animals; Male; Rats; Amygdala; Behavior, Animal; DNA Methylation; Epigenesis, Genetic; Neuralgia; Neurons; Rats, Sprague-Dawley; Small-Conductance Calcium-Activated Potassium Channels
PubMed: 38920682
DOI: 10.3390/cells13121055 -
Cells Jun 2024(1) Background: The effects of short-term social isolation during adulthood have not yet been fully established in rats behaviourally, and not at all transcriptomically...
(1) Background: The effects of short-term social isolation during adulthood have not yet been fully established in rats behaviourally, and not at all transcriptomically in the medial prefrontal cortex (mPFC). (2) Methods: We measured the behavioural effects of housing adult male rats in pairs or alone for 10 days. We also used RNA sequencing to measure the accompanying gene expression alterations in the mPFC of male rats. (3) Results: The isolated animals exhibited reduced sociability and social novelty preference, but increased social interaction. There was no change in their aggression, anxiety, or depression-like activity. Transcriptomic analysis revealed a differential expression of 46 genes between the groups. The KEGG pathway analysis showed that differentially expressed genes are involved in neuroactive ligand-receptor interactions, particularly in the dopaminergic and peptidergic systems, and addiction. Subsequent validation confirmed the decreased level of three altered genes: regulator of G protein signalling 9 (Rgs9), serotonin receptor 2c (Htr2c), and Prodynorphin (Pdyn), which are involved in dopaminergic, serotonergic, and peptidergic function, respectively. Antagonizing Htr2c confirmed its role in social novelty discrimination. (4) Conclusions: Social homeostatic regulations include monoaminergic and peptidergic systems of the mPFC.
Topics: Animals; Prefrontal Cortex; Male; Social Isolation; Rats; Signal Transduction; Biogenic Monoamines; Rats, Sprague-Dawley; Behavior, Animal; Receptor, Serotonin, 5-HT2C; Enkephalins; Protein Precursors; Transcriptome; Gene Expression Regulation
PubMed: 38920671
DOI: 10.3390/cells13121043