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Gamma oscillations nested in a theta rhythm are observed in the hippocampus, where are assumed to play a role in sequential episodic memory, i.e., memorization and retrieval of events that unfold in time. In this work, we present an original neurocomputational model based on neural masses, which simulates the encoding of sequences of events in the hippocampus and subsequent retrieval by exploiting the theta-gamma code. The model is based on a three-layer structure in which individual Units oscillate with a gamma rhythm and code for individual features of an episode. The first layer (working memory in the prefrontal cortex) maintains a cue in memory until a new signal is presented. The second layer (CA3 cells) implements an auto-associative memory, exploiting excitatory and inhibitory plastic synapses to recover an entire episode from a single feature. Units in this layer are disinhibited by a theta rhythm from an external source (septum or Papez circuit). The third layer (CA1 cells) implements a hetero-associative net with the previous layer, able to recover a sequence of episodes from the first one. During an encoding phase, simulating high-acetylcholine levels, the network is trained with Hebbian (synchronizing) and anti-Hebbian (desynchronizing) rules. During retrieval (low-acetylcholine), the network can correctly recover sequences from an initial cue using gamma oscillations nested inside the theta rhythm. Moreover, in high noise, the network isolated from the environment simulates a mind-wandering condition, randomly replicating previous sequences. Interestingly, in a state simulating sleep, with increased noise and reduced synapses, the network can "dream" by creatively combining sequences, exploiting features shared by different episodes. Finally, an irrational behavior (erroneous superimposition of features in various episodes, like "delusion") occurs after pathological-like reduction in fast inhibitory synapses. The model can represent a straightforward and innovative tool to help mechanistically understand the theta-gamma code in different mental states.
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Ritmo Gamma , Imaginación , Modelos Neurológicos , Ritmo Teta , Ritmo Gamma/fisiología , Ritmo Teta/fisiología , Humanos , Imaginación/fisiología , Memoria/fisiología , Hipocampo/fisiología , Redes Neurales de la Computación , AnimalesRESUMEN
Theta-gamma coupling (TGC) is a neurophysiological process that supports working memory. Working memory is associated with other clinical and biological features. The extent to which TGC is associated with these other features and whether it contributes to working memory beyond these features is unknown. Two-hundred-and-three older participants at risk for Alzheimer's dementia-98 with mild cognitive impairment (MCI), 39 with major depressive disorder (MDD) in remission, and 66 with MCI and MDD (MCI + MDD)-completed a clinical assessment, N-back-EEG, and brain MRI. Among them, 190 completed genetic testing, and 121 completed [11C] Pittsburgh Compound B ([11C] PIB) PET imaging. Hierarchical linear regressions were used to assess whether TGC is associated with demographic and clinical variables; Alzheimer's disease-related features (APOE ε4 carrier status and ß-amyloid load); and structural features related to working memory. Then, linear regressions were used to assess whether TGC is associated with 2-back performance after accounting for these features. Other than age, TGC was not associated with any non-neurophysiological features. In contrast, TGC (ß = 0.27; p = 0.006), age (ß = - 0.29; p = 0.012), and parietal cortical thickness (ß = 0.24; p = 0.020) were associated with 2-back performance. We also examined two other EEG features that are linked to working memory-theta event-related synchronization and alpha event-related desynchronization-and found them not to be associated with any feature or performance after accounting for TGC. Our findings suggest that TGC is a process that is independent of other clinical, genetic, neurochemical, and structural variables, and supports working memory in older adults at risk for dementia. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09938-y.
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OBJECTIVE: Sex determines cognitive outcome in animal models of early life seizure, where males exhibit impaired hippocampal-dependent learning and memory compared with females. The physiological underpinnings of this sex effect are unclear. Cholinergic signaling is essential for the generation of hippocampal oscillations, and supplementation of cholinergic precursors prior to status epilepticus in immature male rats prevents subsequent memory deficits. We hypothesized that there are sex differences in acetylcholine circuits and their response to experimental febrile status epilepticus (eFSE). METHODS: eFSE was induced in male and female rat pups. We transversed the hippocampus of postnatal day >60 control (CTL) and eFSE rats with a 64-channel laminar silicon probe to assay cholinergic-dependent theta oscillations under urethane anesthesia. Local field potential properties were compared during (1) baseline sensory stimulation, (2) pharmacological stimulation via acetylcholine reuptake blockade, and (3) sensory stimulation after muscarinic acetylcholine receptor block (atropine). RESULTS: In all groups, a baseline tail pinch could elicit theta oscillations via corticohippocampal synaptic input. Following atropine, a tail pinch response could no longer be elicited in CTL male, CTL female, or eFSE female rats. In contrast, induced slow theta power in eFSE males after atropine was not decreased to spontaneous levels. Analysis of oscillation bandwidths revealed sex differences in acetylcholine modulation of theta frequency and slow gamma frequency and power. This study also identified significant effects of both sex and eFSE on baseline theta-gamma comodulation, indicating a loss of coupling in eFSE males and a potential gain of function in eFSE females. SIGNIFICANCE: There are differences in cholinergic modulation of theta and gamma signal coordination between male and female rats. These differences may underlie worse cognitive outcomes in males following eFSE. Promoting the efficacy of muscarinic acetylcholine signaling prior to or following early life seizures could elucidate a mechanism for the temporal discoordination of neural signals within and between hippocampus and neocortex and provide a novel therapeutic approach for improving cognitive outcomes.
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Ritmo Gamma , Hipocampo , Caracteres Sexuales , Estado Epiléptico , Ritmo Teta , Animales , Femenino , Masculino , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Ratas , Ritmo Teta/efectos de los fármacos , Ritmo Teta/fisiología , Ritmo Gamma/efectos de los fármacos , Ritmo Gamma/fisiología , Estado Epiléptico/fisiopatología , Estado Epiléptico/tratamiento farmacológico , Ratas Sprague-Dawley , Convulsiones Febriles/fisiopatología , Acetilcolina/metabolismo , Atropina/farmacologíaRESUMEN
High-frequency rTMS has been widely used to improve working memory (WM) impairment; however, the underlying neurophysiological mechanisms are unclear. We evaluated the effect of high-frequency rTMS on behaviors relevant to WM as well as coupling between theta and gamma oscillations in the prefrontal cortex (PFC) of rats. Accordingly, Wistar rats received high-frequency rTMS daily for 14 days (5 Hz, 10 Hz, and 15 Hz stimulation; 600 pulses; n = 6 per group), whereas the control group received sham stimulation. Electrophysiological signals were recorded simultaneously to obtain the local field potential (LFP) from the PFC, while the rats performed T-maze tasks for the evaluation of WM. Phase-amplitude coupling (PAC) was utilized to determine the effect of high-frequency rTMS on the theta-gamma coupling of LFPs. We observed that rats in the rTMS groups needed a smaller number of training days to complete the WM task as compared to the control group. High-frequency rTMS reinforced the coupling connection strength in the PFC of rats. Notably, the effect of rTMS at 15 Hz was the most effective among the three frequencies, i.e., 5 Hz, 10 Hz, and 15 Hz. The results suggested that rTMS can improve WM impairment in rats by modulating the coupling of theta and gamma rhythms. Hence, the current study provides a scientific basis for the optimization of TMS models, which would be relevant for clinical application.
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Ritmo Gamma , Estimulación Magnética Transcraneal , Ratas , Animales , Estimulación Magnética Transcraneal/métodos , Ritmo Gamma/fisiología , Memoria a Corto Plazo/fisiología , Ratas Wistar , Corteza Prefrontal/fisiologíaRESUMEN
OBJECTIVE: Neural oscillations during sensory and cognitive events interact at different frequencies. However, such evidence in major depressive disorder (MDD) remains scarce. We explored the possible abnormal neural oscillations in MDD by analyzing theta-phase/gamma-amplitude coupling (TGC). METHODS: Resting-state and auditory steady-state response (ASSR) electroencephalography recordings were obtained from 35 first-episode MDD and 35 healthy controls (HCs). TGC during rest, ASSR stimulation, and ASSR baseline between and within groups were analyzed to evaluate MDD alterations. Receiver operating characteristic (ROC), TGC comparison between MDD severity subgroups (mild, moderate, major), and correlations were investigated to determine the potential use of altered TGC for identifying MDD. RESULTS: In MDD, left fronto-central TGC decreased during stimulation, while right fronto-central TGC increased during baseline. The area under ROC curve for altered TGC was 0.863. Furthermore, during stimulation, moderate and major MDD groups exhibited significantly lower TGC than mild group, and fronto-central TGC was negatively correlated with depression scale scores. CONCLUSIONS: Our results provided the first evidence for an abnormal TGC response of fronto-central regions in MDD during an ASSR task. Importantly, altered TGC may be promising biomarkers of MDD. SIGNIFICANCE: Our findings enhance the understanding of physiological mechanisms underlying MDD and aid in its clinical diagnosis.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico , Electroencefalografía , Ritmo Gamma/fisiología , Curva ROCRESUMEN
DESIGN: Pilot randomized double-blind-controlled trial of repetitive paired associative stimulation (rPAS), a paradigm that combines transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) with peripheral median nerve stimulation. OBJECTIVES: To study the impact of rPAS on DLPFC plasticity and working memory performance in Alzheimer's disease (AD). METHODS: Thirty-two patients with AD (females = 16), mean (SD) age = 76.4 (6.3) years were randomized 1:1 to receive a 2-week (5 days/week) course of active or control rPAS. DLPFC plasticity was assessed using single session PAS combined with electroencephalography (EEG) at baseline and on days 1, 7, and 14 post-rPAS. Working memory and theta-gamma coupling were assessed at the same time points using the N-back task and EEG. RESULTS: There were no significant differences between the active and control rPAS groups on DLPFC plasticity or working memory performance after the rPAS intervention. There were significant main effects of time on DLPFC plasticity, working memory, and theta-gamma coupling, only for the active rPAS group. Further, on post hoc within-group analyses done to generate hypotheses for future research, as compared to baseline, only the rPAS group improved on post-rPAS day 1 on all three indices. Finally, there was a positive correlation between working memory performance and theta-gamma coupling. CONCLUSIONS: This study did not show a beneficial effect of rPAS for DLPFC plasticity or working memory in AD. However, post hoc analyses showed promising results favoring rPAS and supporting further research on this topic. (Clinicaltrials.gov-NCT01847586).
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Enfermedad de Alzheimer , Memoria a Corto Plazo , Femenino , Humanos , Anciano , Memoria a Corto Plazo/fisiología , Enfermedad de Alzheimer/terapia , Proyectos Piloto , Corteza Prefrontal/fisiología , Plasticidad Neuronal/fisiologíaRESUMEN
A tic disorder (TD) is a neurodevelopmental disorder characterized by tics, which are repetitive movements and/or vocalizations that occur due to aberrant sensory gating. Its pathophysiology involves dysfunction in multiple parts of the cortico-striato-thalamo-cortical circuits. Spontaneous brain activity during the resting state can be used to evaluate the baseline brain state, and it is associated with various aspects of behavior and cognitive processes. Theta-gamma coupling (TGC) is an emerging technique for examining how neural networks process information through interactions. However, the resting-state TGC of patients with TD and its correlation with cognitive function have not yet been studied. We investigated the resting-state TGC of 13 patients with TD and compared it with that of 13 age-matched healthy children. The participants underwent resting-state electroencephalography with their eyes closed. At the global level, patients with TD showed a significantly lower resting-state TGC than healthy children. Resting-state TGC with the eyes closed was significantly negatively correlated with the attention quotient calculated for omission errors in a selective visual attention test. These findings indicate that the resting-state brain network, which is important for the attentional processing of visual information, is dysfunctional in patients with TD. Additionally, these findings support the view that TGC reflects information processing and signal interactions at the global level. Patients with TD may have difficulty gating irrelevant sensory information in the resting state while their eyes are closed.
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It remains a dogma in cognitive neuroscience to separate human attention and memory into distinct modules and processes. Here we propose that brain rhythms reflect the embedded nature of these processes in the human brain, as evident from their shared neural signatures: gamma oscillations (30-90 Hz) reflect sensory information processing and activated neural representations (memory items). The theta rhythm (3-8 Hz) is a pacemaker of explicit control processes (central executive), structuring neural information processing, bit by bit, as reflected in the theta-gamma code. By representing memory items in a sequential and time-compressed manner the theta-gamma code is hypothesized to solve key problems of neural computation: (1) attentional sampling (integrating and segregating information processing), (2) mnemonic updating (implementing Hebbian learning), and (3) predictive coding (advancing information processing ahead of the real time to guide behavior). In this framework, reduced alpha oscillations (8-14 Hz) reflect activated semantic networks, involved in both explicit and implicit mnemonic processes. Linking recent theoretical accounts and empirical insights on neural rhythms to the embedded-process model advances our understanding of the integrated nature of attention and memory - as the bedrock of human cognition.
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We hypothesize that hippocampal local field potentials in acetylcholine (ACh)-deficient mutant mice, compared to wild-type (WT) mice, will show lower sensitivity to muscarinic cholinergic antagonist scopolamine (5 mg/kg i.p.) but higher sensitivity to NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP, 10 mg/kg i.p.). Recordings were made during walk and awake-immobility (IMM) in WT mice, and in mice with forebrain knockout (KO) of the vesicular acetylcholine transporter (VAChT) gene, or heterozygous knockdown of VAChT gene (KD). Scopolamine or CPP did not significantly alter walk theta frequency, which was higher in KD than WT/KO mice. Scopolamine decreased theta power peak rise during walk in WT/KD mice but not in KO mice, while CPP suppressed theta peak rise more in WT/KO mice than KD mice. During IMM, scopolamine decreased gamma1 (γ1, 30-58 Hz) power more in KD/WT mice than KO mice, while delta (1-4 Hz) power and delta-gamma cross-frequency coherence (CFC) were increased in all mouse groups during IMM or walk. During walk, scopolamine increased delta and beta (13-30 Hz) power and decreased gamma2 (γ2, 62-100 Hz) power and theta-γ2 CFC more in WT/KD than KO mice. Theta-γ2, but not theta-γ1, CFC increased with theta-peak-frequency in WT/KD mice, and was suppressed by scopolamine at high theta (8-10 Hz) frequency; theta-γ2 CFC in KO mice was not significantly altered by scopolamine. CPP decreased beta and gamma power more in KD/KO mice compared to WT mice, while delta power and delta-gamma CFC were increased in all mouse groups. ACh deficiency exacerbates the attenuation of beta and gamma power by CPP. We conclude that both muscarinic and NMDA transmission contribute toward hippocampal theta, beta, and gamma power, and a decrease in gamma power or theta-gamma CFC may be associated with loss of arousal and cognitive functions.
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Acetilcolina , Receptores de N-Metil-D-Aspartato , Animales , Hipocampo/fisiología , Ratones , Ratones Noqueados , Antagonistas Muscarínicos/farmacología , N-Metilaspartato , Escopolamina/farmacología , Proteínas de Transporte Vesicular de AcetilcolinaRESUMEN
Neurophysiological research on the bilingual activity of interpretation or interpreting has been very fruitful in understanding the bilingual brain and has gained increasing popularity recently. Issues like word interpreting and the directionality of interpreting have been attended to by many researchers, mainly with localizing techniques. Brain structures such as the dorsolateral prefrontal cortex have been repeatedly identified during interpreting. However, little is known about the oscillation and synchronization features of interpreting, especially sentence-level overt interpreting. In this study we implemented a Chinese-English sentence-level overt interpreting experiment with electroencephalography on 43 Chinese-English bilinguals and compared the oscillation and synchronization features of interpreting with those of listening, speaking and shadowing. We found significant time-frequency power differences in the delta-theta (1-7 Hz) and gamma band (above 30 Hz) between motor and silent tasks. Further theta-gamma coupling analysis revealed different synchronization networks in between speaking, shadowing and interpreting, indicating an idea-formulation dependent mechanism. Moreover, interpreting incurred robust right frontotemporal gamma coactivation network compared with speaking and shadowing, which we think may reflect the language conversion process inherent in interpreting.
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Chronic stroke patients with upper-limb motor disabilities are now beginning to see treatment options that were not previously available. To date, the two options recently approved by the United States Food and Drug Administration include vagus nerve stimulation and brain-computer interface therapy. While the mechanisms for vagus nerve stimulation have been well defined, the mechanisms underlying brain-computer interface-driven motor rehabilitation are largely unknown. Given that cross-frequency coupling has been associated with a wide variety of higher-order functions involved in learning and memory, we hypothesized this rhythm-specific mechanism would correlate with the functional improvements effected by a brain-computer interface. This study investigated whether the motor improvements in chronic stroke patients induced with a brain-computer interface therapy are associated with alterations in phase-amplitude coupling, a type of cross-frequency coupling. Seventeen chronic hemiparetic stroke patients used a robotic hand orthosis controlled with contralesional motor cortical signals measured with EEG. Patients regularly performed a therapeutic brain-computer interface task for 12 weeks. Resting-state EEG recordings and motor function data were acquired before initiating brain-computer interface therapy and once every 4 weeks after the therapy. Changes in phase-amplitude coupling values were assessed and correlated with motor function improvements. To establish whether coupling between two different frequency bands was more functionally important than either of those rhythms alone, we calculated power spectra as well. We found that theta-gamma coupling was enhanced bilaterally at the motor areas and showed significant correlations across brain-computer interface therapy sessions. Importantly, an increase in theta-gamma coupling positively correlated with motor recovery over the course of rehabilitation. The sources of theta-gamma coupling increase following brain-computer interface therapy were mostly located in the hand regions of the primary motor cortex on the left and right cerebral hemispheres. Beta-gamma coupling decreased bilaterally at the frontal areas following the therapy, but these effects did not correlate with motor recovery. Alpha-gamma coupling was not altered by brain-computer interface therapy. Power spectra did not change significantly over the course of the brain-computer interface therapy. The significant functional improvement in chronic stroke patients induced by brain-computer interface therapy was strongly correlated with increased theta-gamma coupling in bihemispheric motor regions. These findings support the notion that specific cross-frequency coupling dynamics in the brain likely play a mechanistic role in mediating motor recovery in the chronic phase of stroke recovery.
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Cortical oscillations in different frequency bands have been shown to be intimately involved in exploration of environment and cognition. Here, the local field potentials in the hippocampus, the medial prefrontal cortex (mPFC), and the medial entorhinal cortex (mEC) were recorded simultaneously in rats during the execution of the episodic-like memory task. The power of theta (~4-10 Hz), slow gamma (~25-50 Hz), and fast gamma oscillations (~55-100 Hz) was analyzed in all structures examined. Particular attention was paid to the theta coherence between three mentioned structures. The modulation of the power of gamma rhythms by the phase of theta cycle during the execution of the episodic-like memory test by rats was also closely studied. Healthy rats and rats one month after kainate-induced status epilepticus (SE) were examined. Paroxysmal activity in the hippocampus (high amplitude interictal spikes), excessive excitability of animals, and the death of hippocampal and dentate granular cells in rats with kainate-evoked SE were observed, which indicated the development of seizure focus in the hippocampus (epileptogenesis). One month after SE, the rats exhibited a specific impairment of episodic memory for the what-where-when triad: unlike healthy rats, epileptogenic SE animals did not identify the objects during the test. This impairment was associated with the changes in the characteristics of theta and gamma rhythms and specific violation of theta coherence and theta/gamma coupling in these structures in comparison with the healthy animals. We believe that these disturbances in the cortical areas play a role in episodic memory dysfunction in kainate-treated animals. These findings can shed light on the mechanisms of cognitive deficit during epileptogenesis.
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Neocórtex , Estado Epiléptico , Animales , Ritmo Gamma , Hipocampo/fisiología , Ácido Kaínico/toxicidad , Ratas , Ritmo Teta/fisiologíaRESUMEN
Investigating effects of aging on neurophysiological mechanisms underlying working memory provides a better understanding of potential targets for brain intervention to prevent cognitive decline. Theta-gamma coupling (TGC) indexes the ability to order information processed during working memory tasks. Frontal theta event-related synchronization (ERS) and parietal alpha event-related desynchronization (ERD) index cognitive control and interference inhibition, respectively. Relative contributions of TGC, theta ERS, and alpha ERD in relation to stimulus presentation are not characterized. Further, differential effect of normal aging on pre- or post-stimulus processes is unknown. Electroencephalography was recorded in 66 younger and 41 older healthy participants while performing 3-back working memory task. We assessed relationships between 3-back task performance and each of post-stimulus TGC, pre-stimulus parietal alpha ERD, and pre-stimulus frontal theta ERS in each age group. While older adults performed worse on 3-back task than younger adults, TGC, alpha ERD, or theta ERS did not differ between the two groups. TGC was positively associated with 3-back performance in both age groups; pre-stimulus alpha ERD was associated with performance among younger adults; and pre-stimulus theta ERS was not associated with performance in either group. Our findings suggest that both pre-stimulus interference inhibition and post-stimulus ordering of information are important for working memory in younger adults. In contrast, performance in older adults appears to depend only on post-stimulus ordering of information. These specific contributions of neurophysiological resources may explain the poorer performance of older adults and suggest different targets to enhance working memory in age groups.
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Disfunción Cognitiva , Memoria a Corto Plazo , Humanos , Anciano , Memoria a Corto Plazo/fisiología , Electroencefalografía , Envejecimiento/fisiología , Cognición/fisiologíaRESUMEN
Cross-frequency coupling (CFC), an electrophysiologically derived measure of oscillatory coupling in the brain, is believed to play a critical role in neuronal computation, learning and communication. It has received much recent attention in the study of both health and disease. We searched for literature that studied CFC during resting state and task-related activities during electroencephalography and magnetoencephalography in psychiatric disorders. Thirty-eight studies were identified, which included attention-deficit hyperactivity disorder, Alzheimer's dementia, autism spectrum disorder, bipolar disorder, depression, obsessive compulsive disorder, social anxiety disorder and schizophrenia. The systematic review was registered with PROSPERO (ID#CRD42021224188). The current review indicates measurable differences exist between CFC in disease states vs. healthy controls. There was variance in CFC at different regions of the brain within the same psychiatric disorders, perhaps this could be explained by the mechanisms and functionality of CFC. There was heterogeneity in methodologies used, which may lead to spurious CFC analyses. Going forward, standardized methodologies need to be established and utilized in further research to understand the neuropathophysiology associated with psychiatric disorders.
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Trastorno del Espectro Autista , Trastorno Obsesivo Compulsivo , Encéfalo/fisiología , Electroencefalografía/métodos , Humanos , Neuronas/fisiologíaRESUMEN
Theta phase-gamma amplitude coupling (TGC) plays an important role in several different cognitive processes. Although spontaneous brain activity at the resting state is crucial in preparing for cognitive performance, the functional role of resting-state TGC remains unclear. To investigate the role of resting-state TGC, electroencephalogram recordings were obtained for 56 healthy volunteers while they were in the resting state, with their eyes closed, and then when they were engaged in a retention interval period in the visual memory task. The TGCs of the two different conditions were calculated and compared. The results indicated that the modulation index of TGC during the retention interval of the visual working memory (VWM) task was not higher than that during the resting state; however, the topographical distribution of TGC during the resting state was negatively correlated with TGC during VWM task at the local level. The topographical distribution of TGC during the resting state was negatively correlated with TGC coordinates' engagement of brain areas in local and large-scale networks and during task performance at the local level. These findings support the view that TGC reflects information-processing and signal interaction across distant brain areas. These results demonstrate that TGC could explain the efficiency of competing brain networks.
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To investigate neuromodulation of functional and directional connectivity features in both visual and non-visual brain cortices after short-term and long-term retinal electrical stimulation in retinal degeneration mice. We performed spontaneous electrocorticography (ECoG) in retinal degeneration (rd) mice following prolonged transcorneal electrical stimulation (pTES) at varying currents (400, 500 and 600 µA) and different time points (transient or day 1 post-stimulation, 1-week post-stimulation and 2-weeks post-stimulation). We also set up a sham control group of rd mice which did not receive any electrical stimulation. Subsequently we analyzed alterations in cross-frequency coupling (CFC), coherence and directional connectivity of the primary visual cortex and the prefrontal cortex. It was observed that the sham control group did not display any significant changes in brain connectivity across all stages of electrical stimulation. For the stimulated groups, we observed that transient electrical stimulation of the retina did not significantly alter brain coherence and connectivity. However, for 1-week post-stimulation, we identified enhanced increase in theta-gamma CFC. Meanwhile, enhanced coherence and directional connectivity appeared predominantly in theta, alpha and beta oscillations. These alterations occurred in both visual and non-visual brain regions and were dependent on the current amplitude of stimulation. Interestingly, 2-weeks post-stimulation demonstrated long-lasting enhancement in network coherence and connectivity patterns at the level of cross-oscillatory interaction, functional connectivity and directional inter-regional communication between the primary visual cortex and prefrontal cortex. Application of electrical stimulation to the retina evidently neuromodulates brain coherence and connectivity of visual and non-visual cortices in retinal degeneration mice and the observed alterations are largely maintained. pTES holds strong possibility of modulating higher cortical functions including pathways of cognition, awareness, emotion and memory.
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Skill learning is a fundamental adaptive process, but the mechanisms remain poorly understood. Some learning paradigms, particularly in the memory domain, are closely associated with gamma activity that is amplitude modulated by the phase of underlying theta activity, but whether such nested activity patterns also underpin skill learning is unknown. Here, we addressed this question by using transcranial alternating current stimulation (tACS) over sensorimotor cortex to modulate theta-gamma activity during motor skill acquisition, as an exemplar of a non-hippocampal-dependent task. We demonstrated, and then replicated, a significant improvement in skill acquisition with theta-gamma tACS, which outlasted the stimulation by an hour. Our results suggest that theta-gamma activity may be a common mechanism for learning across the brain and provides a putative novel intervention for optimizing functional improvements in response to training or therapy.
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Aprendizaje/fisiología , Destreza Motora/fisiología , Adulto , Femenino , Humanos , Masculino , Desempeño Psicomotor , Estimulación Transcraneal de Corriente Directa , Adulto JovenRESUMEN
Working memory (WM) is the active retention and processing of information over a few seconds and is considered an essential component of cognitive function. The reduced WM capacity is a common feature in many diseases, such as schizophrenia, attention deficit hyperactivity disorder (ADHD), mild cognitive impairment (MCI), and Alzheimer's disease (AD). The theta-gamma neural code is an essential component of memory representations in the multi-item WM. A large body of studies have examined the association between cross-frequency coupling (CFC) across the cerebral cortices and WM performance; electrophysiological data together with the behavioral results showed the associations between CFC and WM performance. The oscillatory entrainment (sensory, non-invasive electrical/magnetic, and invasive electrical) remains the key method to investigate the causal relationship between CFC and WM. The frequency-tuned non-invasive brain stimulation is a promising way to improve WM performance in healthy and non-healthy patients with cognitive impairment. The WM performance is sensitive to the phase and rhythm of externally applied stimulations. CFC-transcranial-alternating current stimulation (CFC-tACS) is a recent approach in neuroscience that could alter cognitive outcomes. The studies that investigated (1) the association between CFC and WM and (2) the brain stimulation protocols that enhanced WM through modulating CFC by the means of the non-invasive brain stimulation techniques have been included in this review. In principle, this review can guide the researchers to identify the most prominent form of CFC associated with WM processing (e.g., theta/gamma phase-amplitude coupling), and to define the previously published studies that manipulate endogenous CFC externally to improve WM. This in turn will pave the path for future studies aimed at investigating the CFC-tACS effect on WM. The CFC-tACS protocols need to be thoroughly studied before they can be considered as therapeutic tools in patients with WM deficits.
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We propose a model of the main rhythms in the hippocampal CA1 field: theta rhythm; slow, middle, and fast gamma rhythms; and ripple oscillations. We have based this on data obtained from animals behaving freely. We have considered the modes of neuronal discharges and the occurrence of local field potential oscillations in the theta and non-theta states at different inputs from the CA3 field, the medial entorhinal cortex, and the medial septum. In our work, we tried to reproduce the main experimental phenomena about rhythms in the CA1 field: the coupling of neurons to the phase of rhythms, cross-rhythm phase-phase coupling, and phase-amplitude coupling. Using computational experiments, we have proved the hypothesis that the descending phase of the theta rhythm in the CA1 field is formed by the input from the CA3 field via the Shaffer collaterals, and the ascending phase of the theta rhythm is formed by the IPSPs from CCK basket cells. The slow gamma rhythm is coupled to the descending phase of the theta rhythm, since it also depends on the arrival of the signal via the Shaffer collaterals. The middle gamma rhythm is formed by the EPSPs of the principal neurons of the third layer of the entorhinal cortex, corresponds to experimental data. We were able to unite in a single mathematical model several theoretical ideas about the mechanisms of rhythmic processes in the CA1 field of the hippocampus.
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Región CA1 Hipocampal , Ritmo Gamma , Animales , Corteza Entorrinal , Hipocampo , Ritmo TetaRESUMEN
The effects of acetylcholine on cortical activation were studied in wild-type (WT) mice, compared to knockout (KO) mice depleted of the vesicular acetylcholine transporter (VAChT) gene in the basal forebrain, and knockdown (KD) mice with heterogeneous depletion of VAChT gene in the brain. Cortical activation was assessed by comparing power spectra of local field potentials (LFPs) during activated states of rapid-eye-movement sleep (REM) or walk (WLK), with those during non-activated states of slow-wave sleep (SWS) or awake-immobility (IMM). Activation-induced suppression of delta (1-4 Hz) and beta (13-30 Hz) power in the hippocampus, and delta power in frontal cortex, were reduced in KO and KD mice compared to WT mice. Mean theta frequency was higher in KD than KO mice during WLK and REM, but not different between WT and KO mice. Peak theta (4-12 Hz) and integrated gamma (30-150 Hz) power were not significantly different among mouse groups. However, theta-peak-frequency selected gamma2 (62-100 Hz) power was lower in KO than WT or KD mice during WLK, and theta-peak-frequency selected theta power during REM decreased faster with high theta frequency in KO than WT/ KD mice. Theta power increase during REM compared to WLK was lower in KO and KD mice compared to WT mice. Theta-gamma cross-frequency coherence, a measure of synchronization of gamma with theta phase, was not different among mouse groups. However, during REM, SWS, and IMM, delta-gamma coherence was significantly higher and proximal-distal delta coherence in CA1 was lower in KO than WT/KD mice. We conclude that a deficiency in basal forebrain acetylcholine release not only enhances slow waves and suppresses theta-associated gamma waves during activation, but also increases delta-gamma cross-frequency coherence during nonactivated states, with a possible effect of disrupting cognitive processing during any brain state.