Thalamocortical System Research Articles

Bioelectric brain activity in workers with hand-arm vibration in dynamics

Introduction. A few neurophysiologic studies have shown that changes of the bioelectrical brain activity are observed in hand-arm vibration syndrome (HAVS) patients. There is practically no information about the state of bioelectrical brain activity in the hand-arm vibration. The purpose is to study the dynamics of the formation of neurophysiologic changes in workers exposed to hand-arm vibration. Materials and methods. Electroencephalography (EEG) and registration of evoked potentials (EP) was carried out in workers exposed to hand-arm vibration (practically healthy workers, HAVS individuals who continue to work in their occupation), twice in a connected sample. The results are presented as median, upper and lower quartiles, and extensive indicators. The significance of differences was assessed using Pearson’s χ2 test, Fisher’s angular transformation, and Wilcoxon T-test. Results. In dynamics, there is a change in the EEG pattern from disorganized with a predominance of alpha activity to disorganized with a predominance of delta, and theta activity; a decrease in the spectral power of the main EEG rhythms in all main functional leads in both examined groups. Diffuse changes in the EEG indicate a multisystem nature of bioelectrical brain activity disorders with involvement of the cerebral cortex, stem, and diencephalic structures of the brain. Changes in the amplitude-temporal parameters of EP manifested by an excess of the latency of the main peaks and a decrease in amplitude, indicate an imbalance in the central nervous system, general modulating influences on the cerebral cortex of the thalamocortical systems of the brain. Limitations. One occupational group with different levels of health status – practically healthy workers, HAVS individuals who continue to work in their occupation – was enrolled in the study. Conclusion. The one-direction and progressive development of changes in the bioelectrical brain activity has been established, manifested by a restructuring of the electrical activity of the brain, desynchronization of neuronal activity, an increase in the level of functional activity of the brain, and an imbalance of general modulating influences on the cerebral cortex. The identified changes are a manifestation of the nonspecific part of the pathogenesis of HAVS.

Aberrant dynamic functional connectivity of thalamocortical circuitry in major depressive disorder.

Thalamocortical circuitry has a substantial impact on emotion and cognition. Previous studies have demonstrated alterations in thalamocortical functional connectivity (FC), characterized by region-dependent hypo- or hyper-connectivity, among individuals with major depressive disorder (MDD). However, the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear. Hence, we analyzed dynamic FC (dFC) between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls (HCs) to investigate time-varying changes in thalamocortical FC in patients with MDD. Moreover, dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time. Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated. We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks, compared with the HCs. In addition, MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration. The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort. Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms. Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients. The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.

Semi-Automatic Analysis of Specific Electroencephalographic Patterns during NREM2 Sleep in a Pediatric Population after SARS-CoV-2 Infection.

The post-COVID-19 condition is defined by the World Health Organization as the persistence of symptoms or development of new symptoms three months after the initial SARS-CoV-2 infection, lasting for at least two months without a clear explanation. Neuropsychiatric disorders associated with this condition include asthenia, memory and concentration problems, and sleep disturbances. Our study aims to investigate sleep patterns following SARS-CoV-2 infection using EEG findings and a sleep quality questionnaire completed by parents (Sleep Disturbance Scale for Children-SDSC). Notably, our investigation is based on a convenience sample. The patients in our sample, aged 1 to 14 years, are not currently taking any medications; rather, they are undergoing follow-up assessments at the Child Neuropsychiatry department of the University Hospital of Messina for neurodevelopmental evaluations. Specifically, we are analyzing amplitude and power spectrum data in the first five minutes of NREM2 sleep, calculated from EEG recordings obtained via bipolar leads within three months after the onset of the disease. These results will be compared with controls performed on the same subjects in the six months preceding the infection. The focus of the study was sleep spindles, which are generated by the thalamocortical systems and play a role in sleep modulation, memory, and learning. Preliminary analysis suggests a predominant increase in the slow component of the spindles in the right-frontal lead.

Layer 6b controls brain state via apical dendrites and the higher-order thalamocortical system

The deepest layer of the cortex (layer 6b [L6b]) contains relatively few neurons, but it is the only cortical layer responsive to the potent wake-promoting neuropeptide orexin/hypocretin. Can these few neurons significantly influence brain state? Here, we show that L6b-photoactivation causes a surprisingly robust enhancement of attention-associated high-gamma oscillations and population spiking while abolishing slow waves in sleep-deprived mice. To explain this powerful impact on brain state, we investigated L6b's synaptic output using optogenetics, electrophysiology, and monoCaTChR exvivo. We found powerful output in the higher-order thalamus and apical dendrites of L5 pyramidal neurons, via L1a and L5a, as well as in superior colliculus and L6 interneurons. L6b subpopulations with distinct morphologies and short- and long-term plasticities project to these diverse targets. The L1a-targeting subpopulation triggered powerful NMDA-receptor-dependent spikes that elicited burst firing in L5. We conclude that orexin/hypocretin-activated cortical neurons form a multifaceted, fine-tuned circuit for the sustained control of the higher-order thalamocortical system.

Propagating population activity patterns during spontaneous slow waves in the thalamus of rodents

Slow waves (SWs) represent the most prominent electrophysiological events in the thalamocortical system under anesthesia and during deep sleep. Recent studies have revealed that SWs have complex spatiotemporal dynamics and propagate across neocortical regions. However, it is still unclear whether neuronal activity in the thalamus exhibits similar propagation properties during SWs. Here, we report propagating population activity in the thalamus of ketamine/xylazine-anesthetized rats and mice visualized by high-density silicon probe recordings. In both rodent species, propagation of spontaneous thalamic activity during up-states was most frequently observed in dorsal thalamic nuclei such as the higher order posterior (Po), lateral posterior (LP) or laterodorsal (LD) nuclei. The preferred direction of thalamic activity spreading was along the dorsoventral axis, with over half of the up-states exhibiting a gradual propagation in the ventral-to-dorsal direction. Furthermore, simultaneous neocortical and thalamic recordings collected under anesthesia demonstrated that there is a weak but noticeable interrelation between propagation patterns observed during cortical up-states and those displayed by thalamic population activity. In addition, using chronically implanted silicon probes, we detected propagating activity patterns in the thalamus of naturally sleeping rats during slow-wave sleep. However, in comparison to propagating up-states observed under anesthesia, these propagating patterns were characterized by a reduced rate of occurrence and a faster propagation speed. Our findings suggest that the propagation of spontaneous population activity is an intrinsic property of the thalamocortical network during synchronized brain states such as deep sleep or anesthesia. Additionally, our data implies that the neocortex may have partial control over the formation of propagation patterns within the dorsal thalamus under anesthesia.

Thalamocortical dysrhythmia in patients with delirium: an EEG possible marker of prodromal dementia with Lewy bodies

AbstractBackgroundEEG in DLB is characterized by pre‐alpha dominant frequency (DF) [6–7.5] Hz. The appearance of prealpha rhythm in the cortex is linked to a dysfunctional thalamocortical connection, the thalamocortical dysrhythmia (TCD). The hypothesis that TCD is implicated in DLB has been demonstrated by several structural, functional, and molecular imaging studies. TCD has been implicated in the appearance of altered conscious states, including fluctuating cognition and delirium, two clinical core features of DLB. Delirium can represent the onset of DLB and is listed among the symptoms of prodromal DLB. We aimed to assess specific QEEG abnormalities akin to those found in DLB, also in delirium, to detect a prodromal stage of DLB.MethodCross‐sectional multicentre cohort study and longitudinal prospective study, nested in the multicentre. rsEEG activity was compared in hospitalized patients with delirium vs. patients without delirium. In a subset of 23 patients, rsEEG was also recorded in patients with delirium at resolution of symptom and and at 1‐month follow‐up. DF and DF variability (DFV) were analysed. ResultCross‐sectional multicentre study: 65 subjects with acute delirium were matched for age/sex with 41 controls. Abnormal EEGs were found in 100% delirium patients vs. 34% no‐delirium patients. DF was lower in delirium group (p<0.001), which showed pre‐alpha DF; no‐delirium group had alpha DF. DFV was higher in delirium group (p<0.001). Single‐centre longitudinal study: After delirium resolution, 21 patients had EEG normalization and were cognitively unimpaired. 2 patients had abnormal EEG and were respectively diagnosed as DLB and MCI.ConclusionAcute delirium was characterized by pre‐alpha rhythm, expression of TCD. In most patients EEG normalized after resolution, making EEG a state marker of acute delirium, when the thalamocortical system becomes unstable, but it is still able to recover. TCD may become unrecoverable when the neurodegenerative process of DLB progresses.

Adrenergic mechanisms of absence status epilepticus.

Absence status epilepticus is a prolonged, generalized absence seizure that lasts more than half an hour. The mechanisms underlying the absence of status epilepticus are still not entirely understood. In this study, the study concentrates on alpha2-adrenergic mechanisms of absence status using the WAG/Rij rat model. In this model, a prolonged spike-wave activity was associated with a specific behavioral state in transition between sedation («alpha2-wakefulness»)-resembled absence status in human patients. Pharmacological activation of alpha2-adrenoreceptors may target the locus coeruleus (presynaptic alpha2-adrenoreceptors) and the thalamic part of the seizure-generating thalamocortical system (postsynaptic alpha2B-adrenoreceptors). The duration of EEG-behavioral correlates of absence status was not dose-dependent and was predetermined by the intensity of absence seizures at baseline. This model could help scientists better understand the underlying causes of absence status and develop more effective and personalized treatments for each individual.

Synaptic Origin of Early Sensory-evoked Oscillations in the Immature Thalamus.

During the critical period of postnatal development, brain maturation is extremely sensitive to external stimuli. Newborn rodents already have functional somatosensory pathways and the thalamus, but the cortex is still forming. Immature thalamic synapses may produce large postsynaptic potentials in immature neurons, while non-synaptic membrane currents remain relatively weak and slow. The thalamocortical system generates spontaneous and evoked early gamma and spindle-burst oscillations in newborn rodents. How relatively strong synapses and weak intrinsic currents interact with each other and how they contribute to early thalamic activities remains largely unknown. Here, we performed local field potential (LFP), juxtacellular, and patch-clamp recordings in the somatosensory thalamus of urethane-anesthetized rat pups at postnatal days 6-7 with one whisker stimulation. We removed the overlying cortex and hippocampus to reach the thalamus with electrodes. Deflection of only one (the principal) whisker induced spikes in a particular thalamic cell. Whisker deflection evoked a group of large-amplitude excitatory events, likely originating from lemniscal synapses and multiple inhibitory postsynaptic events in thalamocortical cells. Large-amplitude excitatory events produced a group of spike bursts and could evoke a depolarization block. Juxtacellular recordings confirmed the partial inactivation of spikes. Inhibitory events prevented inactivation of action potentials and gamma-modulated neuronal firing. We conclude that the interplay of strong excitatory and inhibitory synapses and relatively weak intrinsic currents produces sensory-evoked early gamma oscillations in thalamocortical cells. We also propose that sensory-evoked large-amplitude excitatory events contribute to evoked spindle-bursts.

Assessing neuroprotective effects of diroximel fumarate and siponimod via modulation of pacemaker channels in an experimental model of remyelination

Cuprizone (CPZ)-induced alterations in axonal myelination are associated with a period of neuronal hyperexcitability and increased activity of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels in the thalamocortical (TC) system. Substances used for the treatment of multiple sclerosis (MS) have been shown to normalize neuronal excitability in CPZ-treated mice. Therefore, we aimed to examine the effects of diroximel fumarate (DRF) and the sphingosine 1-phospate receptor (S1PR) modulator siponimod on action potential firing and the inward current (Ih) carried by HCN ion channels in naive conditions and during different stages of de- and remyelination. Here, DRF application reduced Ih current density in ex vivo patch clamp recordings from TC neurons of the ventrobasal thalamic complex (VB), thereby counteracting the increase of Ih during early remyelination. Siponimod reduced Ih in VB neurons under control conditions but had no effect in neurons of the auditory cortex (AU). Furthermore, siponimod increased and decreased AP firing properties of neurons in VB and AU, respectively. Computational modeling revealed that both DRF and siponimod influenced thalamic bursting during early remyelination by delaying the onset and decreasing the interburst frequency. Thus, substances used in MS treatment normalize excitability in the TC system by influencing AP firing and Ih.

Retinal input integration in excitatory and inhibitory neurons in the mouse superior colliculus in vivo.

The superior colliculus (SC) is a midbrain structure that receives inputs from retinal ganglion cells (RGCs). The SC contains one of the highest densities of inhibitory neurons in the brain but whether excitatory and inhibitory SC neurons differentially integrate retinal activity in vivo is still largely unknown. We recently established a recording approach to measure the activity of RGCs simultaneously with their postsynaptic SC targets in vivo, to study how SC neurons integrate RGC activity. Here, we employ this method to investigate the functional properties that govern retinocollicular signaling in a cell type-specific manner by identifying GABAergic SC neurons using optotagging in VGAT-ChR2 mice. Our results demonstrate that both excitatory and inhibitory SC neurons receive comparably strong RGC inputs and similar wiring rules apply for RGCs innervation of both SC cell types, unlike the cell type-specific connectivity in the thalamocortical system. Moreover, retinal activity contributed more to the spiking activity of postsynaptic excitatory compared to inhibitory SC neurons. This study deepens our understanding of cell type-specific retinocollicular functional connectivity and emphasizes that the two major brain areas for visual processing, the visual cortex and the SC, differently integrate sensory afferent inputs.

Retinal input integration in excitatory and inhibitory neurons in the mouse superior colliculus in vivo

The superior colliculus (SC) is a midbrain structure that receives inputs from retinal ganglion cells (RGCs). The SC contains one of the highest densities of inhibitory neurons in the brain but whether excitatory and inhibitory SC neurons differentially integrate retinal activity in vivo is still largely unknown. We recently established a recording approach to measure the activity of RGCs simultaneously with their postsynaptic SC targets in vivo, to study how SC neurons integrate RGC activity. Here, we employ this method to investigate the functional properties that govern retinocollicular signaling in a cell type-specific manner by identifying GABAergic SC neurons using optotagging in VGAT-ChR2 mice. Our results demonstrate that both excitatory and inhibitory SC neurons receive comparably strong RGC inputs and similar wiring rules apply for RGCs innervation of both SC cell types, unlike the cell type-specific connectivity in the thalamocortical system. Moreover, retinal activity contributed more to the spiking activity of postsynaptic excitatory compared to inhibitory SC neurons. This study deepens our understanding of cell type-specific retinocollicular functional connectivity and emphasizes that the two major brain areas for visual processing, the visual cortex and the SC, differently integrate sensory afferent inputs.

Gene therapy ameliorates spontaneous seizures associated with cortical neuron loss in a Cln2R207X mouse model.

Although a disease-modifying therapy for classic late infantile neuronal ceroid lipofuscinosis (CLN2 disease) exists, poor understanding of cellular pathophysiology has hampered the development of more effective and persistent therapies. Here, we investigated the nature and progression of neurological and underlying neuropathological changes in Cln2R207X mice, which carry one of the most common pathogenic mutations in human patients but are yet to be fully characterized. Long-term electroencephalography recordings revealed progressive epileptiform abnormalities, including spontaneous seizures, providing a robust, quantifiable, and clinically relevant phenotype. These seizures were accompanied by the loss of multiple cortical neuron populations, including those stained for interneuron markers. Further histological analysis revealed early localized microglial activation months before neuron loss started in the thalamocortical system and spinal cord, which was accompanied by astrogliosis. This pathology was more pronounced and occurred in the cortex before the thalamus or spinal cord and differed markedly from the staging seen in mouse models of other forms of neuronal ceroid lipofuscinosis. Neonatal administration of adeno-associated virus serotype 9-mediated gene therapy ameliorated the seizure and gait phenotypes and prolonged the life span of Cln2R207X mice, attenuating most pathological changes. Our findings highlight the importance of clinically relevant outcome measures for judging preclinical efficacy of therapeutic interventions for CLN2 disease.

Brain Circuitry of Consciousness: A Review of Current Models and a Novel Synergistic Model With Clinical Application.

How consciousness arises in the brain has important implications for clinical decision-making. We summarize recent findings in consciousness studies to provide a toolkit for clinicians to assess deficits in consciousness and predict outcomes after brain injury. Commonly encountered disorders of consciousness are highlighted, followed by the clinical scales currently used to diagnose them. We review recent evidence describing the roles of the thalamocortical system and brainstem arousal nuclei in supporting awareness and arousal and discuss the utility of various neuroimaging studies in evaluating disorders of consciousness. We explore recent theoretical progress in mechanistic models of consciousness, focusing on 2 major models, the global neuronal workspace and integrated information theory, and review areas of controversy. Finally, we consider the potential implications of recent research for the day-to-day decision-making of clinical neurosurgeons and propose a simple "three-strikes" model to infer the integrity of the thalamocortical system, which can guide prognosticating return to consciousness.

Bedtime to the brain: how infants' sleep behaviours intertwine with non-rapid eye movement sleep electroencephalography features.

Adequate sleep is critical for development and facilitates the maturation of the neurophysiological circuitries at the basis of cognitive and behavioural function. Observational research has associated early life sleep problems with worse later cognitive, psychosocial, and somatic health outcomes. Yet, the extent to which day-to-day sleep behaviours (e.g., duration, regularity) in early life relate to non-rapid eye movement (NREM) neurophysiology-acutely and the long-term-remains to be studied. We measured sleep behaviours in 32 healthy 6-month-olds assessed with actimetry and neurophysiology with high-density electroencephalography (EEG) to investigate the association between NREM sleep and habitual sleep behaviours. Our study revealed four findings: first, daytime sleep behaviours are related to EEG slow-wave activity (SWA). Second, night-time movement and awakenings from sleep are connected with spindle density. Third, habitual sleep timing is linked to neurophysiological connectivity quantified as delta coherence. And lastly, delta coherence at 6 months predicts night-time sleep duration at 12 months. These novel findings widen our understanding that infants' sleep behaviours are closely intertwined with three particular levels of neurophysiology: sleep pressure (determined by SWA), the maturation of the thalamocortical system (spindles), and the maturation of cortical connectivity (coherence). The crucial next step is to extend this concept to clinical groups to objectively characterise infants' sleep behaviours 'at risk' that foster later neurodevelopmental problems.

Macroscale Thalamic Functional Organization Disturbances and Underlying Core Cytoarchitecture in Early-Onset Schizophrenia.

Schizophrenia is a polygenetic mental disorder with heterogeneous positive and negative symptom constellations, and is associated with abnormal cortical connectivity. The thalamus has a coordinative role in cortical function and is key to the development of the cerebral cortex. Conversely, altered functional organization of the thalamus might relate to overarching cortical disruptions in schizophrenia, anchored in development. Here, we contrasted resting-state fMRI in 86 antipsychotic-naive first-episode early-onset schizophrenia (EOS) patients and 91 typically developing controls to study whether macroscale thalamic organization is altered in EOS. Employing dimensional reduction techniques on thalamocortical functional connectome (FC), we derived lateral-medial and anterior-posterior thalamic functional axes. We observed increased segregation of macroscale thalamic functional organization in EOS patients, which was related to altered thalamocortical interactions both in unimodal and transmodal networks. Using an ex vivo approximation of core-matrix cell distribution, we found that core cells particularly underlie the macroscale abnormalities in EOS patients. Moreover, the disruptions were associated with schizophrenia-related gene expression maps. Behavioral and disorder decoding analyses indicated that the macroscale hierarchy disturbances might perturb both perceptual and abstract cognitive functions and contribute to negative syndromes in patients. These findings provide mechanistic evidence for disrupted thalamocortical system in schizophrenia, suggesting a unitary pathophysiological framework.

Narrowband gamma oscillations propagate and synchronize throughout the mouse thalamocortical visual system

Oscillations of neural activity permeate sensory systems. In the visual system, broadband gamma oscillations (30-80Hz) are thought to act as a communication mechanism underlying perception. However, these oscillations show widely varying frequency and phase, providing constraints for coordinating spike timing across areas. Here, we examined Allen Brain Observatory data and performed causal experiments to show that narrowband gamma (NBG) oscillations (50-70Hz) propagate and synchronize throughout the awake mouse visual system. Lateral geniculate nucleus (LGN) neurons fired precisely relative to NBG phase in primary visual cortex (V1) and multiple higher visual areas (HVAs). NBG neurons across areas showed a higher likelihood of functional connectivity and stronger visual responses; remarkably, NBG neurons in LGN, preferring bright (ON) versus dark (OFF), fired at distinct NBG phases aligned across the cortical hierarchy. NBG oscillations may thus serve to coordinate spike timing across brain areas and facilitate communication of distinct visual features during perception.

Accelerating Maturation of Spatial Memory Systems by Experience: Evidence from Sleep Oscillation Signatures of Memory Processing.

During early development, memory systems gradually mature over time, in parallel with the gradual accumulation of knowledge. Yet, it is unknown whether and to what extent maturation is driven by discrete experience. Sleep is thought to contribute to the formation of long-term memory and knowledge through a systems consolidation process that is driven by specific sleep oscillations (i.e., ripples, spindles, and slow oscillations) in cortical and hippocampal networks. Based on these oscillatory signatures, we show here in rats that discrete spatial experience speeds the functional maturation of spatial memory systems during development. Juvenile male rats were exposed for 5 min periods to changes in the spatial configuration of two identical objects on postnatal day (PD)25, PD27, and PD29 (Spatial experience group), while a Control group was exposed on these occasions to the same two objects without changing their positions. On PD31, both groups were tested on a classical Object Place Recognition (OPR) task with a 3 h retention interval during which the sleep-associated EEG and hippocampal local field potentials were recorded. On PD31, consistent with forgoing studies, Control rats still did not express OPR memory. By contrast, rats with Spatial experience formed significant OPR memory and, in parallel, displayed an increased percentage of hippocampal ripples coupled to parietal slow oscillation-spindle complexes, and a stronger ripple-spindle phase-locking during the retention sleep. Our findings support the idea that experience promotes the maturation of memory systems during development by enhancing cortico-hippocampal information exchange and the formation of integrated knowledge representations during sleep.SIGNIFICANCE STATEMENT Cognitive and memory capabilities mature early in life. We show here that and how discrete spatial experience contributes to this process. Using a simple recognition paradigm in developing rats, we found that exposure of the rat pups to three short-lasting experiences enhances spatial memory capabilities to adult-like levels. The adult-like capability of building spatial memory was connected to a more precise coupling of ripples in the hippocampus with slow oscillation-spindle complexes in the thalamo-cortical system when the memory was formed during sleep. Our findings support the view that discrete experience accelerates maturation of cognitive and memory capabilities by enhancing the dialogue between hippocampus and cortex when these experiences are reprocessed during sleep.

Remembrance of things perceived: Adding thalamocortical function to artificial neural networks.

Recent research has illuminated the complexity and importance of the thalamocortical system but it has been difficult to identify what computational functions it performs. Meanwhile, deep-learning artificial neural networks (ANNs) based on bio-inspired models of purely cortical circuits have achieved surprising success solving sophisticated cognitive problems associated historically with human intelligence. Nevertheless, the limitations and shortcomings of artificial intelligence (AI) based on such ANNs are becoming increasingly clear. This review considers how the addition of thalamocortical connectivity and its putative functions related to cortical attention might address some of those shortcomings. Such bio-inspired models are now providing both testable theories of biological cognition and improved AI technology, much of which is happening outside the usual academic venues.

Fibromyalgia in Pregnancy: Neuro-Endocrine Fluctuations Provide Insight into Pathophysiology and Neuromodulation Treatment

Fibromyalgia (FM) is a chronic pain disorder with unclear pathophysiological mechanisms, which leads to challenges in patient management. In addition to pain, the disorder presents with a broad range of symptoms, such as sleep disruption, chronic fatigue, brain fog, depression, muscle stiffness, and migraine. FM has a considerable female prevalence, and it has been shown that symptoms are influenced by the menstrual cycle and periods of significant hormonal and immunological changes. There is increasing evidence that females with FM experience an aggravation of symptoms in pregnancy, particularly during the third trimester and after childbirth. In this perspective paper, we focus on the neuro-endocrine interactions that occur between progesterone, allopregnanolone, and cortisol during pregnancy, and propose that they align with our previously proposed model of FM pathogenesis based on GABAergic "weakening" in a thalamocortical neural loop system. Based on our hypothesis, we introduce the possibility of utilizing transcranial direct current stimulation (tDCS) as a non-invasive treatment potentially capable of exerting sex-specific effects on FM patients.

Paroxysmal slow-wave discharges in a model of absence seizure are coupled to gamma oscillations in the thalamocortical and limbic systems

ObjectiveUsing the gamma-butyrolactone (GBL) model of absence seizures in Long-Evans rats, this study investigated if gamma (30–160 Hz) activity were cross-frequency modulated by the 2–6 Hz slow-wave discharges induced by GBL in the limbic system. We hypothesized that inactivation of the nucleus reuniens (RE), which projects to frontal cortex (FC) and hippocampus, would affect the cross-frequency coupling of gamma (γ) in different brain regions. MethodsLocal field potentials were recorded by electrodes implanted in the FC, ventrolateral thalamus (TH), basolateral amygdala (BLA), nucleus accumbens (NAC), and dorsal hippocampus (CA1) of behaving rats. At each electrode, the coupling between the γ amplitude envelope to the phase of the 2–6 Hz slow-waves (SW) was measured by modulation index (MI) or cross-frequency coherence (CFC) of γ amplitude with SW. In separate experiments, the RE was infused with saline or GABAA receptor agonist, muscimol, before the injection of GBL. ResultsFollowing GBL injection, an increase in MI and CFC of SW to γ1 (30–58 Hz), γ2 (62–100 Hz) and γ3 (100–160 Hz) bands was observed at the FC, hippocampus and BLA, with significant increase in SW-γ1 and SW-γ3 coupling at TH, and increase in peak SW-γ1 CFC at NAC. Strong SW-γ modulation was also found during baseline immobility high-voltage spindles. Muscimol inactivation of RE, as compared to saline infusion, significantly decreased SW-γ1 CFC in the FC, and peak frequency of the SW-γ1 CFC in the thalamus, but did not significantly alter SW-γ CFCs in the hippocampus, BLA or NAC. SignificanceThe paroxysmal 2–6 Hz SW discharges, a hallmark of absence seizure, significantly modulate γ activity in the hippocampus, BLA and NAC, suggesting a modulation of limbic functions. RE inactivation disrupted the SW modulation of FC and TH, partly supporting our hypothesis that RE participates in the modulation of SW discharges.