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Abstract Background Visual snow syndrome is a disorder characterized by the combination of typical perceptual disturbances. The clinical picture suggests an impairment of visual filtering mechanisms and might involve primary and secondary visual brain areas, as well as higher-order attentional networks. On the level of cortical oscillations, the alpha rhythm is a prominent EEG pattern that is involved in the prioritisation of visual information. It can be regarded as a correlate of inhibitory modulation within the visual network. Methods Twenty-one patients with visual snow syndrome were compared to 21 controls matched for age, sex, and migraine. We analysed the resting-state alpha rhythm by identifying the individual alpha peak frequency using a Fast Fourier Transform and then calculating the power spectral density around the individual alpha peak (+/- 1 Hz). We anticipated a reduced power spectral density in the alpha band over the primary visual cortex in participants with visual snow syndrome. Results There were no significant differences in the power spectral density in the alpha band over the occipital electrodes (O1 and O2), leading to the rejection of our primary hypothesis. However, the power spectral density in the alpha band was significantly reduced over temporal and parietal electrodes. There was also a trend towards increased individual alpha peak frequency in the subgroup of participants without comorbid migraine. Conclusions Our main finding was a decreased power spectral density in the alpha band over parietal and temporal brain regions corresponding to areas of the secondary visual cortex. These findings complement previous functional and structural imaging data at a electrophysiological level. They underscore the involvement of higher-order visual brain areas, and potentially reflect a disturbance in inhibitory top-down modulation. The alpha rhythm alterations might represent a novel target for specific neuromodulation. Trial registration we preregistered the study before preprocessing and data analysis on the platform osf.org (DOI: https://doi.org/10.17605/OSF.IO/XPQHF , date of registration: November 19th 2022). Graphical Abstract

Background: Visual snow syndrome is a disorder characterized by the combination of typical perceptual disturbances. The clinical picture suggests an impairment of visual filtering mechanisms and might involve primary and secondary visual brain areas, as well as higher-order attentional networks. On the level of cortical oscillations, the alpha rhythm is a prominent EEG pattern that is involved in the prioritisation of visual information. It can be regarded as a correlate of inhibitory modulation within the visual network. Methods: Twenty-one patients with visual snow syndrome were compared to 21 controls matched for age, sex, and migraine. We analysed the resting-state alpha rhythm by identifying the individual alpha peak frequency using a Fast Fourier Transform and then calculating the power spectral density around the individual alpha peak (+/- 1 Hz). We anticipated a reduced power spectral density in the alpha band over the primary visual cortex in participants with visual snow syndrome. Results: There were no significant differences in the power spectral density in the alpha band over the occipital electrodes (O1 and O2), leading to the rejection of our primary hypothesis. However, the power spectral density in the alpha band was significantly reduced over temporal and parietal electrodes. There was also a trend towards increased individual alpha peak frequency in the subgroup of participants without comorbid migraine. Conclusions: Our main finding was a decreased power spectral density in the alpha band over parietal and temporal brain regions corresponding to areas of the secondary visual cortex. These findings complement previous functional and structural imaging data at a electrophysiological level. They underscore the involvement of higher-order visual brain areas, and potentially reflect a disturbance in inhibitory top-down modulation. The alpha rhythm alterations might represent a novel target for specific neuromodulation. Trial registration: we preregistered the study before preprocessing and data analysis on the platform osf.org (DOI: https://doi.org/10.17605/OSF.IO/XPQHF, date of registration: November 19th 2022). [ABSTRACT FROM AUTHOR]

Visual snow syndrome (VSS) is a visual perception disorder characterized by persistent positive visual symptoms described by patients as “tiny dots, pixel vision, interference as on TV”. To date, the prevalence of VSS may be as high as 2.2–3.7% of the population, which significantly increases the interest not only of physicians but also of medical researchers. In addition, patients may have other visual symptoms as well as tinnitus, migraine, dizziness, tremor, fibromyalgia, paresthesias, depersonalization, derealization, anxiety, and depression. VSS may affect quality of life, educational, professional and social activities. The article discusses the criteria for diagnosis, pathogenesis, differential diagnosis, clinical cases, and approaches to the treatment of VSS.

It has been suggested that there may be an imbalance of excitation and inhibitory processes in the visual areas of the brain in people with migraine aura (MA). One idea is thalamocortical dysrhythmia, characterized by disordered oscillations, and thus disordered communication between the lateral geniculate nucleus and the cortex. Cross-orientation suppression is a visual task thought to rely on inhibitory processing, possibly originating in the lateral geniculate nucleus. We measured both resting-state oscillations and cross-orientation suppression using EEG over occipital areas in people with MA and healthy volunteers. We found evidence of cross-orientation suppression in the SSVEP responses, but no evidence of any group difference. Therefore, inhibitory processes related to cross-orientation suppression do not appear to be impaired in MA.

A common anatomical core has been described for psychiatric disorders, consisting of the dorsal anterior cingulate cortex (dACC) and anterior insula, processing uncertainty. A common neurophysiological core has been described for other brain related disorders, called thalamocortical dysrhythmia (TCD), consisting of persistent cross-frequency coupling between low and high frequencies. And a common genetic core has been described for yet another set of hypodopaminergic pathologies called reward deficiency syndromes (RDS). Considering that some RDS have the neurophysiological features of TCD, it can be hypothesized that TCD and RDS have a common anatomical core, yet a differentiating associated neurophysiological mechanism. The EEGs of 683 subjects are analysed in source space for both differences and conjunction between TCD and healthy controls, RDS and healthy controls, and between TCD and RDS. A balance between current densities of the pregenual anterior cingulate cortex (pgACC) extending into the ventromedial prefrontal cortex (vmPFC) and dACC is calculated as well. TCD and RDS share a common anatomical and neurophysiological core, consisting of beta activity in the dACC and theta activity in dACC extending into precuneus and dorsolateral prefrontal cortex. TCD and RDS differ in pgACC/vmPFC activity and demonstrate an opposite balance between pgACC/vmPFC and dACC. Based on the Bayesian brain model TCD and RDS can be defined as uncertainty disorders in which the pgACC/vmPFC and dACC have an opposite balance, possibly explained by an inverted-U curve profile of both pgACC/vmPFC and dACC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Until the last 5 years, there was very little in the literature about the phenomenon now known as visual snow syndrome. This review will examine the current thinking on the pathology of visual snow and how that thinking has evolved. Recent Findings: While migraine is a common comorbidity to visual snow syndrome, evidence points to these conditions being distinct clinical entities, with some overlapping pathophysiological processes. There is increasing structural and functional evidence that visual snow syndrome is due to a widespread cortical dysfunction. Cortical hyperexcitability coupled with changes in thalamocortical pathways and higher-level salience network controls have all shown differences in patients with visual snow syndrome compared to controls. Summary: Further work is needed to clarify the exact mechanisms of visual snow syndrome. Until that time, treatment options will remain limited. Clinicians having a clearer understanding of the basis for visual snow syndrome can appropriately discuss the diagnosis with their patients and steer them towards appropriate management options. [ABSTRACT FROM AUTHOR]

Decelerated resting cortical oscillations, high-frequency activity, and enhanced cross-frequency interactions are features of focal epilepsy. The association between electrophysiological signal properties and neurocognitive function, particularly following resective surgery, is, however, unclear. In the current report, we studied intraoperative recordings from intracranial electrodes implanted in seven children with focal epilepsy and analyzed the spectral dynamics both before and after surgical resection of the hypothesized seizure focus. The associations between electrophysiological spectral signatures and each child’s neurocognitive profiles were characterized using a partial least squares analysis. We find that extent of spectral alteration at the periphery of surgical resection, as indexed by slowed resting frequency and its acceleration following surgery, is associated with baseline cognitive deficits in children. The current report provides evidence supporting the relationship between altered spectral properties in focal epilepsy and neuropsychological deficits in children. In particular, these findings suggest a critical role of disrupted thalamocortical rhythms, which are believed to underlie the spectral alterations we describe, in both epileptogenicity and neurocognitive function. [ABSTRACT FROM AUTHOR]

Treatments for major depressive disorder (MDD) act at different hierarchical levels of biological complexity, ranging from the individual synapse to the brain as a whole. Theories of antidepressant medication action traditionally have focused on the level of cell-to-cell interaction and synaptic neurotransmission. However, recent evidence suggests that modulation of synchronized electrical activity in neuronal networks is a common effect of antidepressant treatments, including not only medications, but also neuromodulatory treatments such as repetitive transcranial magnetic stimulation. Synchronization of oscillatory network activity in particular frequency bands has been proposed to underlie neurodevelopmental and learning processes, and also may be important in the mechanism of action of antidepressant treatments. Here, we review current research on the relationship between neuroplasticity and oscillatory synchrony, which suggests that oscillatory synchrony may help mediate neuroplastic changes related to neurodevelopment, learning, and memory, as well as medication and neuromodulatory treatment for MDD. We hypothesize that medication and neuromodulation treatments may have related effects on the rate and pattern of neuronal firing, and that these effects underlie antidepressant efficacy. Elucidating the mechanisms through which oscillatory synchrony may be related to neuroplasticity could lead to enhanced treatment strategies for MDD.

Major depressive disorder (MDD) is a pleomorphic illness originating from gene x environment interactions. Patients with differing symptom phenotypes receive the same diagnosis and similar treatment recommendations without regard to genomics, brain structure or function, or other physiologic or psychosocial factors. Using this present approach, only one third of patients enter remission with the first medication prescribed, and patients may take longer than 1 year to enter remission with repeated trials. Research to improve treatment effectiveness recently has focused on identification of intermediate phenotypes (IPs) that could parse the heterogeneous population of patients with MDD into subgroups with more homogeneous responses to treatment. Such IPs could be used to develop biomarkers that could be applied clinically to match patients with the treatment that would be most likely to lead to remission. Putative biomarkers include genetic polymorphisms, RNA and protein expression (transcriptome and proteome), neurotransmitter levels (metabolome), additional measures of signaling cascades, oscillatory synchrony, neuronal circuits and neural pathways (connectome), along with other possible physiologic measures. All of these measures represent components of a continuum that extends from proximity to the genome to proximity to the clinical phenotype of depression, and there are many levels along this continuum at which useful IPs may be defined. Because of the highly integrative nature of brain systems and the complex neurobiology of depression, the most useful biomarkers are likely to be those with intermediate proximity both to the genome and the clinical phenotype of MDD. Translation of findings across the spectrum from genotype to phenotype promises to better characterize the complex disruptions in signaling and neuroplasticity that accompany MDD, and ultimately to lead to greater understanding of the causes of depressive illness.

Background and Purpose: Visual Snow (VS) is a disorder characterised by the subjective perception of black-and-white visual static. The aetiology of this condition is not known. In our previous work we suggested that there is a link between short-wave (S or “blue” cone) signals and severity of visual snow symptoms. Therefore we aimed to further characterise this potential link.Methods: Patients (n = 22) with classic VS based on the diagnostic criteria and healthy controls (n = 12), underwent Intuitive Colorimetry (IC) testing (Cerium Visual Technologies). Twelve hue directions (expressed as angle in CIE 1976 LUV space relative to D65) were rated on a five-point scale from preferred (relieving, positive score) to non-preferred (exacerbating, negative score), and overall preferred and non-preferred angles were chosen.Results: A non-preferred violet region near the tritanopic confusion line / S-cone axis (267 deg.) was strongly associated with exacerbation of VS symptoms (range 250–310 deg, mean 276 ± 16, n = 20, Rayleigh p < 0.001). Two subjects with non-preferred region > 90 deg from mean were considered as outliers. Median rank at hue angle 270 deg was significantly lower than at angle 90 (−1.5 vs. 0.0, p < 0.001, Wilcoxon non-parametric rank-sum test). Patients showed preference for one of two spectral regions which relieved VS symptoms: orange-yellow (range 50–110 deg., mean 79 ± 24, n = 14) and turquoise-blue (range (210–250 deg., mean 234 ± 27, n = 8).Conclusion: Our results show that visual snow symptoms are exacerbated by colour modulation that selectively increased levels of S-cone excitation. Because S-cone signals travel on primordial brain pathways that regulate cortical rhythms (koniocellular pathways) we hypothesis that these pathways contribute to the pathogenesis of this disorder.

Background and Purpose: Visual Snow (VS) is a disorder characterised by the subjective perception of black-and-white visual static. The aetiology of this condition is not known. In our previous work we suggested that there is a link between short-wave (S or "blue" cone) signals and severity of visual snow symptoms. Therefore we aimed to further characterise this potential link. Methods: Patients (n = 22) with classic VS based on the diagnostic criteria and healthy controls (n = 12), underwent Intuitive Colorimetry (IC) testing (Cerium Visual Technologies). Twelve hue directions (expressed as angle in CIE 1976 LUV space relative to D65) were rated on a five-point scale from preferred (relieving, positive score) to non-preferred (exacerbating, negative score), and overall preferred and non-preferred angles were chosen. Results: A non-preferred violet region near the tritanopic confusion line / S-cone axis (267 deg.) was strongly associated with exacerbation of VS symptoms (range 250–310 deg, mean 276 ± 16, n = 20, Rayleigh p < 0.001). Two subjects with non-preferred region > 90 deg from mean were considered as outliers. Median rank at hue angle 270 deg was significantly lower than at angle 90 (−1.5 vs. 0.0, p < 0.001, Wilcoxon non-parametric rank-sum test). Patients showed preference for one of two spectral regions which relieved VS symptoms: orange-yellow (range 50–110 deg., mean 79 ± 24, n = 14) and turquoise-blue (range (210–250 deg., mean 234 ± 27, n = 8). Conclusion: Our results show that visual snow symptoms are exacerbated by colour modulation that selectively increased levels of S-cone excitation. Because S-cone signals travel on primordial brain pathways that regulate cortical rhythms (koniocellular pathways) we hypothesis that these pathways contribute to the pathogenesis of this disorder. [ABSTRACT FROM AUTHOR]

• Delta, theta, alpha 1 and gamma sources appeared in the temporal and perirhinal cortex during a Tinnitus-On state. • A network involving the inferior-middle temporal and perirhinal cortex may trigger tinnitus. • Many EEG sources shifted to the opposite hemisphere when tinnitus was switched on. To identify the spectrotemporal changes and sources in patients that could "turn on" tinnitus with multichannel electroencephalography (EEG) system. Multichannel EEG was recorded from six patients during the Tinnitus-On and Tinnitus-Off states. The EEG power spectrum and eLORETA-based sources were measured. There was a global increase in delta and theta during Tinnitus-On plus large changes in alpha 1 and alpha 2. During the Tinnitus-On state, many new sources in delta, theta, alpha 1 and gamma bands emerged in the opposite hemisphere in the inferior temporal gyrus (Brodmann area, BA 20), middle temporal gyrus (BA 21), lateral perirhinal cortex (BA 36), ventral entorhinal cortex (BA 28) and anterior pole of the temporal gyrus (BA 38). The emergence of new delta, theta and gamma band sources in the inferior temporal gyrus (BA 20), middle temporal gyrus (BA 21) and lateral perirhinal cortex (BA 36) plus the appearance of new delta and theta sources in the ventral entorhinal cortex (BA28) and anterior pole of the temporal lobe (BA 38) may comprise a network capable of evoking the phantom sound of tinnitus by simultaneously engaging brain regions involved in memory, sound recognition, and distress which together contribute to tinnitus severity. The sudden appearance of new sources of activity in the opposite hemisphere within the inferior temporal gyrus, middle temporal gyrus and perirhinal cortex may initiate the perception of tinnitus perception. [ABSTRACT FROM AUTHOR]

It has been suggested that there may be an imbalance of excitation and inhibitory processes in the visual areas of the brain in people with migraine aura (MA). One idea is thalamocortical dysrhythmia, characterized by disordered oscillations, and thus disordered communication between the lateral geniculate nucleus and the cortex. Cross-orientation suppression is a visual task thought to rely on inhibitory processing, possibly originating in the lateral geniculate nucleus. We measured both resting-state oscillations and cross-orientation suppression using EEG over occipital areas in people with MA and healthy volunteers. We found evidence of cross-orientation suppression in the SSVEP responses, but no evidence of any group difference. Therefore, inhibitory processes related to cross-orientation suppression do not appear to be impaired in MA.

In this position review, we propose to establish a path for replacing the empirical classification of tinnitus with a taxonomy from precision medicine. The goal of a classification system is to understand the inherent heterogeneity of individuals experiencing and suffering from tinnitus and to identify what differentiates potential subgroups. Identification of different patient subgroups with distinct audiological, psychophysical, and neurophysiological characteristics will facilitate the management of patients with tinnitus as well as the design and execution of drug development and clinical trials, which, for the most part, have not yielded conclusive results. An alternative outcome of a precision medicine approach in tinnitus would be that additional mechanistic phenotyping might not lead to the identification of distinct drivers in each individual, but instead, it might reveal that each individual may display a quantitative blend of causal factors. Therefore, a precision medicine approach towards identifying these causal factors might not lead to subtyping these patients but may instead highlight causal pathways that can be manipulated for therapeutic gain. These two outcomes are not mutually exclusive, and no matter what the final outcome is, a mechanistic-driven precision medicine approach is a win-win approach for advancing tinnitus research and treatment. Although there are several controversies and inconsistencies in the tinnitus field, which will not be discussed here, we will give a few examples, as to how the field can move forward by exploring the major neurophysiological tinnitus models, mostly by taking advantage of the common features supported by all of the models. Our position stems from the central concept that, as a field, we can and must do more to bring studies of mechanisms into the realm of neuroscience. [ABSTRACT FROM AUTHOR]

Electrophysiological and imaging studies from humans suggest that the phantom sound of tinnitus is associated with abnormal thalamocortical neural oscillations (dysrhythmia) and enhanced gamma band activity in the auditory cortex. However, these models have seldom been tested in animal models where it is possible to simultaneously assess the neural oscillatory activity within and between the thalamus and auditory cortex. To explore this issue, we used multichannel electrodes to examine the oscillatory behavior of local field potentials recorded in the rat medial geniculate body (MBG) and primary auditory cortex (A1) before and after administering a dose of sodium salicylate (SS) that reliably induces tinnitus. In the MGB, SS reduced theta, alpha, and beta oscillations and decreased coherence (synchrony) between electrode pairs in theta, alpha, and beta bands but increased coherence in the gamma band. Within A1, SS significantly increased gamma oscillations, decreased theta power, and decreased coherence between electrode pairs in theta and alpha bands but increased coherence in the gamma band. When coherence was measured between one electrode in the MGB and another in A1, SS decreased coherence in beta, alpha, and theta bands but increased coherence in the gamma band. SS also increased cross-frequency coupling between the phase of theta oscillations in the MGB and amplitude of gamma oscillations in A1. Altogether, our results suggest that SS treatment fundamentally alters the manner in which thalamocortical circuits communicate, leading to excessive cortical gamma power and synchronization, neurophysiological changes implicated in tinnitus. Our data provide support for elements of both the thalamocortical dysrhythmia (TD) and synchronization by loss of inhibition (SLIM) models of tinnitus, demonstrating that increased cortical gamma band activity is associated with both enhanced theta-gamma coupling as well as decreases alpha power/coherence between the MGB and A1. NEW & NOTEWORTHY There are no effective drugs to alleviate the phantom sound of tinnitus because the physiological mechanisms leading to its generation are poorly understood. Neural models of tinnitus suggest that it arises from abnormal thalamocortical oscillations, but these models have not been extensively tested. This article identifies abnormal thalamocortical oscillations in a drug-induced tinnitus model. Our findings open up new avenues of research to investigate whether cellular mechanisms underlying thalamocortical oscillations are causally linked to tinnitus. [ABSTRACT FROM AUTHOR]

Highlights • Thalamocortical (TC) pathways encode sensory and emotional aspects of pain. • The experience of pain arises from specific activity patterns in TC pathways. • Chronic pain is linked to functional, anatomical and biochemical changes in TC pathways. • Development of chronic pain treatments aim at altering neural and glial function. Abstract The transmission of noxious stimuli from peripheral receptors to the cortex involves multiple central ascending pathways. While projections to areas in the brainstem and diencephalon are likely involved in mediating the immediate behavioral responses to pain, the assessment of the sensory and emotional/motivational components of pain are likely processed in parallel ascending pathways that relay in the thalamus on their way to the cerebral cortex. In this review we discuss experimental animal and human findings that support the view that a lateral thalamocortical pathway is involved in coding the sensory discriminative aspects of pain, while a medial thalamocortical pathway codes the emotional qualities of pain. In addition, we outline experimental animal and human evidence of functional, anatomical and biochemical alterations in thalamocortical circuits that may be responsible for altered thalamocortical rhythms and the persistent presence of pain following nervous system damage. Finally, we discuss advances in clinical and preclinical development of chronic pain treatments aimed at altering neural and glial function. [ABSTRACT FROM AUTHOR]

Tinnitus is a problem that affects a diverse range of people. One common trait amongst people with tinnitus is the presence of hearing loss, which is apparent in over 90% of the cohort. It is postulated that the remainder of people with tinnitus have hidden hearing loss in the form of cochlear synaptopathy. The loss of hearing sensation is thought to cause a reduction in the bottom-up excitatory signals of the auditory pathway leading to a change in the frequency of thalamocortical oscillations known as thalamocortical dysrhythmia (TCD). The downward shift in oscillatory behavior, characteristic of TCD, has been recorded experimentally but the underlying mechanisms responsible for TCD in tinnitus subjects cannot be directly observed. This paper investigates these underlying mechanisms by creating a biologically faithful model of the auditory periphery and thalamocortical network, called the central auditory processing (CAP) model. The proposed model replicates tinnitus related activity in the presence of hearing loss and hidden hearing loss in the form of cochlear synaptopathy. The results of this paper show that, both the bottom-up and top-down changes are required in the auditory system for tinnitus related hyperactivity to coexist with TCD, contrary to the theoretical model for TCD. The CAP model provides a novel modeling approach to account for tinnitus related activity with and without hearing loss. Moreover, the results provide additional clarity to the understanding of TCD and tinnitus and provide direction for future approaches to treating tinnitus. [ABSTRACT FROM AUTHOR]

Cross-frequency phase-amplitude coupling (cfPAC) subserves an integral role in the hierarchical organization of interregional neuronal communication and is also expressed by epileptogenic cortex during seizures. Here, we sought to characterize patterns of cfPAC expression in the anterior thalamic nuclei during seizures by studying extra-operative recordings in patients implanted with deep brain stimulation electrodes for intractable epilepsy. Nine seizures from two patients were analyzed in the peri-ictal period. CfPAC was calculated using the modulation index and interregional functional connectivity was indexed using the phase-locking value. Statistical analysis was performed within subjects on the basis of nonparametric permutation and corrected with Gaussian field theory. Five of the nine analyzed seizures demonstrated significant cfPAC. Significant cfPAC occurred during the pre-ictal and ictal periods in three seizures, as well as the postictal windows in four seizures. The preferred phase at which cfPAC occurred differed 1) in space, between the thalami of the epileptogenic and nonepileptogenic hemispheres; and 2) in time, at seizure termination. The anterior thalamic nucleus of the epileptogenic hemisphere also exhibited altered interregional phase-locking synchrony concurrent with the expression of cfPAC. By analyzing extraoperative recordings from the anterior thalamic nuclei, we show that cfPAC associated with altered interregional phase synchrony is lateralized to the thalamus of the epileptogenic hemisphere during seizures. Electrophysiological differences in cfPAC, including preferred phase of oscillatory interactions may be further investigated as putative targets for individualized neuromodulation paradigms in patients with drug-resistant epilepsy. [ABSTRACT FROM AUTHOR]

Tinnitus is defined as a phantom sound (ringing in the ears), and can significantly reduce the quality of life for those who suffer its effects. Ten to fifteen percent of the general adult population report symptoms of tinnitus with 1–2% reporting that tinnitus negatively impacts their quality of life. Noise exposure is the most common cause of tinnitus and the military environment presents many challenging high-noise situations. Military noise levels can be so intense that standard hearing protection is not adequate. Recent studies suggest a role for inhibitory neurotransmitter dysfunction in response to noise-induced peripheral deafferentation as a key element in the pathology of tinnitus. The auditory thalamus, or medial geniculate body (MGB), is an obligate auditory brain center in a unique position to gate the percept of sound as it projects to auditory cortex and to limbic structures. Both areas are thought to be involved in those individuals most impacted by tinnitus. For MGB, opposing hypotheses have posited either a tinnitus-related pathologic decrease or pathologic increase in GABAergic inhibition. In sensory thalamus, GABA mediates fast synaptic inhibition via synaptic GABA A receptors (GABA A Rs) as well as a persistent tonic inhibition via high-affinity extrasynaptic GABA A Rs and slow synaptic inhibition via GABA B Rs. Down-regulation of inhibitory neurotransmission, related to partial peripheral deafferentation, is consistently presented as partially underpinning neuronal hyperactivity seen in animal models of tinnitus. This maladaptive plasticity/Gain Control Theory of tinnitus pathology (see Auerbach et al., 2014 ; Richardson et al., 2012) is characterized by reduced inhibition associated with increased spontaneous and abnormal neuronal activity, including bursting and increased synchrony throughout much of the central auditory pathway. A competing hypothesis suggests that maladaptive oscillations between the MGB and auditory cortex, thalamocortical dysrhythmia, predict tinnitus pathology (De Ridder et al., 2015). These unusual oscillations/rhythms reflect net increased tonic inhibition in a subset of thalamocortical projection neurons resulting in abnormal bursting. Hyperpolarizing de-inactivation of T-type Ca2+ channels switches thalamocortical projection neurons into burst mode. Thalamocortical dysrhythmia originating in sensory thalamus has been postulated to underpin neuropathies including tinnitus and chronic pain. Here we review the relationship between noise-induced tinnitus and altered inhibition in the MGB. [ABSTRACT FROM AUTHOR]

1-octanol is a therapeutic candidate for disorders involving the abnormal activation of the T-type calcium current since it blocks this current specifically. Such disorders include essential tremor and a group of neurological and psychiatric disorders resulting from thalamocortical dysrhythmia (TCD). For example, clinically, the observable phenotype in essential tremor is the tremor itself. The differential diagnostic of TCD is not based only on clinical signs and symptoms. Rather, TCD incorporates an electromagnetic biomarker, the presence of abnormal thalamocortical low frequency brain oscillations. The effect of 1-octanol on brain activity has not been tested. As a preliminary step to such a TCD study, we examined the short-term effects of a single dose of 1- octanol on resting brain activity in 32 healthy adults using magnetoencephalograpy. Visual inspection of baseline power spectra revealed that the subjects fell into those with strong low frequency activity (set 2, n D 11) and those without such activity, but dominated by an alpha peak (set 1, n D 22). Cross-validated linear discriminant analysis, using mean spectral density (MSD) in nine frequency bands as predictors, found overall that 82.5% of the subjects were classified as determined by visual inspection. The effect of 1-octanol on the MSD in narrow frequency bands differed between the two subject groups. In set 1 subjects the MSD increased in the 4.5-6.5Hz and 6.5-8.5 Hz bands. This was consistent with a widening of the alpha peak toward lower frequencies. In the set two subjects the MSD decrease in the 2.5-4.5 Hz and 4.5-6.5 Hz bands. This decreased power is consistent with the blocking effect of 1-octanol on T-type calcium channels. The subjects reported no adverse effects of the 1-octanol. Since stronger low frequency activity is characteristic of patients with TCD, 1-octanol and other T-type calcium channel blockers are good candidates for treatment of this group of disorders following a placebo-controlled study. [ABSTRACT FROM AUTHOR]

Recent human neuroimaging studies have suggested that fibromyalgia (FM), a chronic widespread pain disorder, exhibits altered thalamic structure and function. Since the thalamus has extensive reciprocal connection with the cortex, structural and functional thalamic alterations in FM might be linked to aberrant thalamocortical oscillation. This study investigated the presence of abnormal brain rhythmicity in low- and high-frequency bands during resting state in patients with FM and their relationship to clinical pain symptom. Spontaneous magnetoencephalography activity was recorded in 18 females with FM and 18 age- and sex-matched healthy control subjects. The most remarkable finding was that FM patients had general increases in theta, beta and gamma power along with a slowing of the dominant alpha peak. Increased spectral powers in the theta-band were primarily localized to the left dorsolateral prefrontal (DLPFC) and orbitofrontal cortex (OFC). Beta and gamma over-activation were localized to insular, primary motor and primary and secondary somatosensory cortices, as well as the DLPFC and OFC. Furthermore, enhanced high-frequency oscillatory activities in the DLPFC and OFC were associated with higher affective pain scores in patients with FM. Our results demonstrate that FM patients feature enhanced low- and high-frequency oscillatory activity in the brain areas related to cognitive and emotional modulation of pain. Increased low- and high-frequency activity of the prefrontal cortex may contribute to persistent perception of pain in FM. Therapeutic intervention based on manipulating neural oscillation to restore normal thalamocortical rhythmicity may be beneficial to pain relief in FM.

In this paper we review the visual snow (VS) characteristics of a case cohort of 32 patients. History of symptoms and associated co-morbidities, ophthalmic examination, previous investigations and the results of intuitive colourimetry were collected and reviewed. VS symptoms follow a stereotypical description and are strongly associated with palinopsia, migraine and tinnitus, but also tremor. The condition is a chronic one and often results in misdiagnosis with psychiatric disorders or malingering. Colour filters, particularly in the yellow-blue colour spectrum, subjectively reduced symptoms of VS. There is neurobiological evidence for the syndrome of VS that links it with other disorders of visual and sensory processing such as migraine and tinnitus. Colour filters in the blue-yellow spectrum may alter the koniocellular pathway processing, which has a regulatory effect on background electroencephalographic rhythms, and may add weight to the hypothesis that VS is a thalamocortical dysrhythmia of the visual pathway. [ABSTRACT FROM AUTHOR]

A crucial pathophysiological issue concerning central neuropathic pain is the modification of sensory processing by abnormally increased low-frequency brain rhythms. Here we explore the molecular mechanisms responsible for such abnormal rhythmicity and its relation to neuropathic pain syndrome. Toward this aim, we investigated the behavioral and electrophysiological consequences of trigeminal neuropathic pain following infraorbital nerve ligations in CaV3.1 T-type Ca2+ channel knockout and wild-type mice. CaV3.1 knockout mice had decreased mechanical hypersensitivity and reduced low-frequency rhythms in the primary somatosensory cortex and related thalamic nuclei than wild-type mice. Lateral inhibition of gamma rhythm in primary somatosensory cortex layer 4, reflecting intact sensory contrast, was present in knockout mice but severely impaired in wild-type mice. Moreover, cross-frequency coupling between low-frequency and gamma rhythms, which may serve in sensory processing,was pronounced inwild-typemice but not in CaV3.1 knockout mice. Our results suggest that the presence of CaV3.1 channels is a key element in the pathophysiology of trigeminal neuropathic pain. [ABSTRACT FROM AUTHOR]

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Tinnitus is the perception of a sound in the absence of a corresponding external sound source. Pathophysiologically it has been attributed to bottom-up deafferentation and/or top-down noise-cancelling deficit. Both mechanisms are proposed to alter auditory thalamocortical signal transmission, resulting in thalamocortical dysrhythmia (TCD). In deafferentation, TCD is characterized by a slowing down of resting state alpha to theta activity associated with an increase in surrounding gamma activity, resulting in persisting cross-frequency coupling between theta and gamma activity. Theta burst-firing increases network synchrony and recruitment, a mechanism, which might enable long-range synchrony, which in turn could represent a means for finding the missing thalamocortical information and for gaining access to consciousness. Theta oscillations could function as a carrier wave to integrate the tinnitus-related focal auditory gamma activity in a consciousness enabling network, as envisioned by the global workspace model. This model suggests that focal activity in the brain does not reach consciousness, except if the focal activity becomes functionally coupled to a consciousness enabling network, aka the global workspace. In limited deafferentation, the missing information can be retrieved from the auditory cortical neighborhood, decreasing surround inhibition, resulting in TCD. When the deafferentation is too wide in bandwidth, it is hypothesized that the missing information is retrieved from theta-mediated parahippocampal auditory memory. This suggests that based on the amount of deafferentation TCD might change to parahippocampocortical persisting and thus pathological theta-gamma rhythm. From a Bayesian point of view, in which the brain is conceived as a prediction machine that updates its memory-based predictions through sensory updating, tinnitus is the result of a prediction error between the predicted and sensed auditory input. The decrease in sensory updating is reflected by decreased alpha activity and the prediction error results in theta-gamma and beta-gamma coupling. Thus, TCD can be considered as an adaptive mechanism to retrieve missing auditory input in tinnitus. [ABSTRACT FROM AUTHOR]

A consensus is yet to be reached regarding the exact prevalence of epileptic seizures or epilepsy in multiple sclerosis (MS). In addition, the underlying pathophysiological basis of the reciprocal interaction among neuroinflammation, demyelination, and epilepsy remains unclear. Therefore, a better understanding of cellular and network mechanisms linking these pathologies is needed. Cuprizone-induced general demyelination in rodents is a valuable model for studying MS pathologies. Here, we studied the relationship among epileptic activity, loss of myelin, and pro-inflammatory cytokines by inducing acute, generalized demyelination in a genetic mouse model of human absence epilepsy, C3H/HeJ mice. Both cellular and network mechanisms were studied using in vivo and in vitro electrophysiological techniques. We found that acute, generalized demyelination in C3H/HeJ mice resulted in a lower number of spike-wave discharges, increased cortical theta oscillations, and reduction of slow rhythmic intrathalamic burst activity. In addition, generalized demyelination resulted in a significant reduction in the amplitude of the hyperpolarization-activated inward current (Ih) in thalamic relay cells, which was accompanied by lower surface expression of hyperpolarization-activated, cyclic nucleotide-gated channels, and the phosphorylated form of TRIP8b (pS237-TRIP8b). We suggest that demyelination-related changes in thalamic Ih may be one of the factors defining the prevalence of seizures in MS., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The management of chronic neuropathic pain remains a challenge, because pain is subjective, and measuring it objectively is usually out of question. However, neuropathic pain is also a signal provided by maladaptive neuronal activity. Thus, the integral management of chronic neuropathic pain should not only rely on the subjective perception of the patient, but also on objective data that measures the evolution of neuronal activity. We will discuss different objective and subjective methods for the characterization of neuropathic pain. Additionally, the gaps and proposals for an integral management of chronic neuropathic pain will also be discussed. The current management that relies mostly on subjective measures has not been sufficient, therefore, this has hindered advances in pain management and clinical trials. If an integral characterization is achieved, clinical management and stratification for clinical trials could be based on both questionnaires and neuronal activity. Appropriate characterization may lead to an increased effectiveness for new therapies, and a better quality of life for neuropathic pain sufferers. • We integrate subjective and objective methods for characterizing neuropathic pain. • The need for an integral characterization has led to poor pain management. • Maladaptive plasticity and aberrant neural oscillations cause neuropathic pain. • EEG can measure the evoked and spontaneous components of neuropathic pain. • We propose a standardized methodology of three stimuli: tactile, vibration and air. [ABSTRACT FROM AUTHOR]

Abstract: While tinnitus can be interpreted as a simple or elementary form of auditory phantom perception, musical hallucinosis is a more complex auditory phantom phenomenon not only limited to sound perception, but also containing semantic and musical content. It most often occurs in association with hearing loss. To elucidate the relation between simple and complex auditory phantom percepts a source localized electroencephalography (EEG) study is performed. The analyses showed in both simple and complex auditory phantoms an increase in theta–gamma activity and coupling within the auditory cortex that could be associated with the thalamocortical dysrhythmia model. Furthermore increased beta activity within the dorsal anterior cingulate cortex and anterior insula is demonstrated, that might be related to auditory awareness, salience and its attribution to an external sound source. The difference between simple and complex auditory phantoms relies on differential alpha band activity within the auditory cortex and on beta activity in the dorsal anterior cingulate cortex and (para)hippocampal area. This could be related to memory based load dependency, while suppression within the primary visual cortex might be due the presence of a continuous auditory cortex activation inducing an inhibitory signal to the visual system. Complex auditory phantoms further activate the right inferior frontal area (right sided Broca homolog) and right superior temporal pole that might be associated with the musical content. In summary, this study showed for the first time that simple and complex auditory phantoms might share a common neural substrate but differ as complex auditory phantoms are associated with activation in brain areas related to music and language processing. [Copyright &y& Elsevier]

Tinnitus is an auditory phenomenon characterised by the perception of a sound in the absence of an external auditory stimulus. Chronic subjective tinnitus is almost certainly maintained via central mechanisms, and this is consistent with observed measures of altered spontaneous brain activity. A number of putative central auditory mechanisms for tinnitus have been proposed. The influential thalamocortical dysrhythmia model suggests that tinnitus can be attributed to the disruption of coherent oscillatory activity between thalamus and cortex following hearing loss. However, the extent to which this disruption specifically contributes to tinnitus or is simply a consequence of the hearing loss is unclear because the necessary matched controls have not been tested. Here, we rigorously test several predictions made by this model in four groups of participants (tinnitus with hearing loss, tinnitus with clinically normal hearing, no tinnitus with hearing loss and no tinnitus with clinically normal hearing). Magnetoencephalography was used to measure oscillatory brain activity within different frequency bands in a 'resting' state and during presentation of a masking noise. Results revealed that low-frequency activity in the delta band (1-4 Hz) was significantly higher in the 'tinnitus with hearing loss' group compared to the 'no tinnitus with normal hearing' group. A planned comparison indicated that this effect was unlikely to be driven by the hearing loss alone, but could possibly be a consequence of tinnitus and hearing loss. A further interpretative linkage to tinnitus was given by the result that the delta activity tended to reduce when tinnitus was masked. High-frequency activity in the gamma band (25-80 Hz) was not correlated with tinnitus (or hearing loss). The findings partly support the thalamocortical dysrhythmia model and suggest that slow-wave (delta band) activity may be a more reliable correlate of tinnitus than high-frequency activity. [ABSTRACT FROM AUTHOR]