Alterations of the alpha rhythm in visual snow syndrome: a case-control study.

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).

Contemporary clinical neurophysiology applications in dystonia.

The complex phenomenological understanding of dystonia has transcended from the clinics to genetics, imaging and neurophysiology. One way in which electrophysiology will impact into the clinics are cases wherein a dystonic clinical presentation may not be typical or a "forme fruste" of the disorder. Indeed, the physiological imprints of dystonia are present regardless of its clinical manifestation. Underpinnings in the understanding of dystonia span from the peripheral, segmental and suprasegmental levels to the cortex, and various electrophysiological tests have been applied in the course of time to elucidate the origin of dystonia pathophysiology. While loss of inhibition remains to be the key finding in this regard, intricacies and variabilities exist, thus leading to a notion that perhaps dystonia should best be gleaned as network disorder. Interestingly, the complex process has now spanned towards the understanding in terms of networks related to the cerebellar circuitry and the neuroplasticity. What is evolving towards a better and cohesive view will be neurophysiology attributes combined with structural dynamic imaging. Such a sound approach will significantly lead to better therapeutic modalities in the future.

Smell and taste in cervical dystonia.

The pathophysiology of cervical dystonia is not completely understood. Current concepts of the pathophysiology propose that it is a network disorder involving the basal ganglia, cerebellum and sensorimotor cortex. These structures are primarily concerned with sensorimotor control but are also involved in non-motor functioning such as the processing of information related to the chemical senses. This overlap lets us hypothesize a link between cervical dystonia and altered sense of smell and taste. To prove this hypothesis and to contribute to the better understanding of cervical dystonia, we assessed olfactory and gustatory functioning in 40 adults with idiopathic cervical dystonia and 40 healthy controls. The Sniffin Sticks were used to assess odor threshold, discrimination and identification. Furthermore, the Taste Strips were applied to assess the combined taste score. Motor and non-motor deficits of cervical dystonia including neuropsychological and psychiatric alterations were assessed as cofactors for regression analyses. We found that cervical dystonia subjects had lower scores than healthy controls for odor threshold (5.8 ± 2.4 versus 8.0 ± 3.2; p = 0.001), odor identification (11.7 ± 2.3 versus 13.1 ± 1.3; p = 0.001) and the combined taste score (9.5 ± 2.2 versus 11.7 ± 2.7; p < 0.001), while no difference was found in odor discrimination (12.0 ± 2.5 versus 12.9 ± 1.8; p = 0.097). Regression analysis suggests that age is the main predictor for olfactory decline in subjects with cervical dystonia. Moreover, performance in the Montreal Cognitive Assessment is a predictor for gustatory decline in cervical dystonia subjects. Findings propose that cervical dystonia is associated with diminished olfactory and gustatory functioning.

Neuroimaging of memory in frontal lobe epilepsy.

In a large percentage of epilepsies, seizures have focal onset. These epilepsies are associated with a wide range of behavioral and cognitive deficits sometimes limited to the functions encompassed within the ictal onset zone but, more frequently, expanding beyond it. The presence of impairments associated with neuroanatomical areas outside of the ictal onset zone suggests distal propagation of epileptic activity via brain networks and interconnected whole-brain neural circuitry. In patients with frontal lobe epilepsy (FLE), using functional magnetic resonance imaging (fMRI) to identify deficits in working, semantic, and episodic memory may provide a lens through which to understand typical and atypical network organization. A network approach to focal epilepsy is relevant in these patients because of the frequently noted early age of seizure onset. Early seizure-related disruption in healthy brain development may result in a significant brain reorganization, development of compensation-related mechanisms of dealing with function abnormalities and disruptions, and the propagation of epileptic activity from the focus to widespread brain areas (functional deficit zones). Benefits of a network approach in the study of focal epilepsy are discussed along with considerations for future neuroimaging studies of patients with FLE.

Endo-Lysosomal Network Disorder Reprograms Energy Metabolism in SorL1-Null Rat Hippocampus.

Sortilin-related receptor 1 (SorL1) deficiency is a genetic predisposition to familial Alzheimer's disease (AD), but its pathology is poorly understood. In SorL1-null rats, a disorder of the global endosome-lysosome network (ELN) is found in hippocampal neurons. Deletion of amyloid precursor protein (APP) in SorL1-null rats could not completely rescue the neuronal abnormalities in the ELN of the hippocampus and the impairment of spatial memory in SorL1-null young rats. These in vivo observations indicated that APP is one of the cargoes of SorL1 in the regulation of the ELN, which affects hippocampal-dependent memory. When SorL1 is depleted, the endolysosome takes up more of the lysosome flux and damages lysosomal digestion, leading to pathological lysosomal storage and disturbance of cholesterol and iron homeostasis in the hippocampus. These disturbances disrupt the original homeostasis of the material-energy-subcellular structure and reprogram energy metabolism based on fatty acids in the SorL1-null hippocampus, instead of glucose. Although fatty acid oxidation increases ATP supply, it cannot reduce the levels of the harmful byproduct ROS during oxidative phosphorylation, as it does in glucose catabolism. Therefore, the SorL1-null rats exhibit hippocampal degeneration, and their spatial memory is impaired. Our research sheds light on the pathology of SorL1 deficiency in AD.

Clinical Implications of Dystonia as a Neural Network Disorder.

Isolated dystonia is a neurological disorder of diverse etiology, multifactorial pathophysiology, and wide spectrum of clinical presentations. We review the recent neuroimaging advances that led to the conceptualization of dystonia as a neural network disorder and discuss how current knowledge is shaping the identification of biomarkers of dystonia and the development of novel pharmacological therapies.

Function and dysfunction of the dystonia network: an exploration of neural circuits that underlie the acquired and isolated dystonias.

Dystonia is a highly prevalent movement disorder that can manifest at any time across the lifespan. An increasing number of investigations have tied this disorder to dysfunction of a broad "dystonia network" encompassing the cerebellum, thalamus, basal ganglia, and cortex. However, pinpointing how dysfunction of the various anatomic components of the network produces the wide variety of dystonia presentations across etiologies remains a difficult problem. In this review, a discussion of functional network findings in non-mendelian etiologies of dystonia is undertaken. Initially acquired etiologies of dystonia and how lesion location leads to alterations in network function are explored, first through an examination of cerebral palsy, in which early brain injury may lead to dystonic/dyskinetic forms of the movement disorder. The discussion of acquired etiologies then continues with an evaluation of the literature covering dystonia resulting from focal lesions followed by the isolated focal dystonias, both idiopathic and task dependent. Next, how the dystonia network responds to therapeutic interventions, from the "geste antagoniste" or "sensory trick" to botulinum toxin and deep brain stimulation, is covered with an eye towards finding similarities in network responses with effective treatment. Finally, an examination of how focal network disruptions in mouse models has informed our understanding of the circuits involved in dystonia is provided. Together, this article aims to offer a synthesis of the literature examining dystonia from the perspective of brain networks and it provides grounding for the perspective of dystonia as disorder of network function.

Embouchure Dystonia as a Network Disease.

While the pathophysiology of embouchure dystonia, a sub-entity of musician's dystonia, is still not fully understood, recent research has shown that it involves alterations of several brain functions and networks. Maladaptive plasticity in sensorimotor integration, sensory perception, and deficient inhibitory mechanisms at cortical, subcortical, and spinal level seem to contribute to its pathophysiology. Furthermore, functional systems of the basal ganglia and the cerebellum are involved, clearly pointing toward a network disorder. We therefore propose a novel network model, based on electrophysiological and recent neuroimaging studies highlighting embouchure dystonia.

Recent Advances in Neuroimaging of Epilepsy.

Human neuroimaging has had a major impact on the biological understanding of epilepsy and the relationship between pathophysiology, seizure management, and outcomes. This review highlights notable recent advancements in hardware, sequences, methods, analyses, and applications of human neuroimaging techniques utilized to assess epilepsy. These structural, functional, and metabolic assessments include magnetic resonance imaging (MRI), positron emission tomography (PET), and magnetoencephalography (MEG). Advancements that highlight non-invasive neuroimaging techniques used to study the whole brain are emphasized due to the advantages these provide in clinical and research applications. Thus, topics range across presurgical evaluations, understanding of epilepsy as a network disorder, and the interactions between epilepsy and comorbidities. New techniques and approaches are discussed which are expected to emerge into the mainstream within the next decade and impact our understanding of epilepsies. Further, an increasing breadth of investigations includes the interplay between epilepsy, mental health comorbidities, and aberrant brain networks. In the final section of this review, we focus on neuroimaging studies that assess bidirectional relationships between mental health comorbidities and epilepsy as a model for better understanding of the commonalities between both conditions.

Visual Snow Syndrome as a Network Disorder: A Systematic Review.

Aim: By reviewing the existing clinical studies about visual snow (VS) as a symptom or as part of visual snow syndrome (VSS), we aim at improving our understanding of VSS being a network disorder. Background: Patients with VSS suffer from a continuous visual disturbance resembling the view of a badly tuned analog television (i.e., VS) and other visual, as well as non-visual symptoms. These symptoms can persist over years and often strongly impact the quality of life. The exact prevalence is still unknown, but up to 2.2% of the population could be affected. Presently, there is no established treatment, and the underlying pathophysiology is unknown. In recent years, there have been several approaches to identify the brain areas involved and their interplay to explain the complex presentation. Methods: We collected the clinical and paraclinical evidence from the currently published original studies on VS and its syndrome by searching PubMed and Google Scholar for the term visual snow. We included original studies in English or German and excluded all reviews, case reports that did not add new information to the topic of this review, and articles that were not retrievable in PubMed or Google Scholar. We grouped the studies according to the methods that were used. Results: Fifty-three studies were found for this review. In VSS, the clinical spectrum includes additional visual disturbances such as excessive floaters, palinopsia, nyctalopia, photophobia, and entoptic phenomena. There is also an association with other perceptual and affective disorders as well as cognitive symptoms. The studies that have been included in this review demonstrate structural, functional, and metabolic alterations in the primary and/or secondary visual areas of the brain. Beyond that, results indicate a disruption in the pre-cortical visual pathways and large-scale networks including the default mode network and the salience network. Discussion: The combination of the clinical picture and widespread functional and structural alterations in visual and extra-visual areas indicates that the VSS is a network disorder. The involvement of pre-cortical visual structures and attentional networks might result in an impairment of "filtering" and prioritizing stimuli as top-down process with subsequent excessive activation of the visual cortices when exposed to irrelevant external and internal stimuli. Limitations of the existing literature are that not all authors used the ICHD-3 definition of the VSS. Some were referring to the symptom VS, and in many cases, the control groups were not matched for migraine or migraine aura.

A Neural Substrate for Mirror Agnosia and Mirror Image Agnosia - Is it a Network disorder?

BACKGROUND: Reflected image processing is a unique brain function and its abnormalities result in problems of localizing, recognizing the images, and utilizing this information in everyday life. OBJECTIVES: The aim of this study was to characterize clinical and neuropsychological profiles and to identify the probable neural substrate for this phenomenon in major cognitive disorder. MATERIALS AND METHODS: We conducted a prospective study from February 2015 to May 2017 in patients with Major Cognitive Disorder (MCD, DSM-5 criteria). All patients were tested for problems in reflected image processing using the detailed protocol after ethical approval of the institute and consent. They also underwent a detailed neuropsychological evaluation, biochemical tests and neuroimaging (structural, diffusion, and resting-state functional MRI) as per established protocol. RESULTS: Of the 18 patients, 11 had mirror agnosia (MA), 5 had mirror image agnosia (MIA) and 2 had both. MRI of MA patients showed parietal atrophy and whereas diffuse pattern of atrophy was seen with MIA. In the MA group, the left superior longitudinal fasciculus showed significantly greater fractional anisotropy and the left angular gyrus showed increased functional connectivity with left anterior cingulate, left dorsolateral prefrontal and bilateral posterior cingulate regions. CONCLUSION: Mirror image processing defects were not related to the type of MCD, severity or pattern of neuropsychological dysfunction. There are structural and functional alterations in localized regions as well as both hemispheres. Therefore, it is more likely to be a network disorder, irrespective of the MCD type or severity.

Abnormal effective connectivity in the sensory network in writer's cramp.

BACKGROUND: Writer's cramp (WC), a task specific form of dystonia, is considered to be a motor network disorder, but abnormal sensory tactile processing has also been acknowledged. The sensory spatial discrimination threshold (SDT) can be determined with a spatial acuity test (JVP domes). In addition to increased SDT, patients with WC exhibited dysfunctional sensory processing in the sensory cortex, insula, basal ganglia and cerebellum in a functional magnetic resonance imaging (fMRI) study while performing the spatial acuity test. OBJECTIVES: To assess whether effective connectivity (EC) in the sensory network including cortical, basal ganglia, thalamic and cerebellar regions of interest in WC patients is abnormal. METHODS: We used fMRI and applied a block design, while 19 WC patients and 13 age-matched healthy controls performed a spatial discrimination task. Before we assessed EC using dynamic causal modelling, we compared three model structures based on the current literature. We enclosed regions of interest that are established for sensory processing during right hand stimulation: Left thalamus, somatosensory, parietal and insular cortex, posterior putamen, and right cerebellum. RESULTS: The EC analysis revealed task-dependent decreased unidirectional connectivity between the insula and the posterior putamen. The connectivity involving the primary sensory cortex, parietal cortex and cerebellum were not abnormal in WC. The two groups showed no differences in their behavioural data. CONCLUSIONS: Perception and integration of sensory information requires the exchange of information between the insula cortex and the putamen, a sensory process that was disturbed in WC patients.

Dynamic causal modeling revealed dysfunctional effective connectivity in both, the cortico-basal-ganglia and the cerebello-cortical motor network in writers' cramp.

Writer's cramp (WC) is a focal task-specific dystonia characterized by sustained or intermittent muscle contractions while writing, particularly with the dominant hand. Since structural lesions rarely cause WC, it has been assumed that the disease might be caused by a functional maladaptation within the sensory-motor system. Therefore, our objective was to examine the differences between patients suffering from WC and a healthy control (HC) group with regard to the effective connectivity that describes causal influences one brain region exerts over another within the motor network. The effective connectivity within a network including contralateral motor cortex (M1), supplementary motor area (SMA), globus pallidus (GP), putamen (PU) and ipsilateral cerebellum (CB) was investigated using dynamic causal modeling (DCM) for fMRI. Eight connectivity models of functional motor systems were compared. Fifteen WC patients and 18 age-matched HC performed a sequential, five-element finger-tapping task with the non-dominant and non-affected left hand within a 3 T MRI-scanner as quickly and accurately as possible. The task was conducted in a fixed block design repeated 15 times and included 30 s of tapping followed by 30 s of rest. DCM identified the same model in WC and HC as superior for reflecting basal ganglia and cerebellar motor circuits of healthy subjects. The M1-PU, as well as M1-CB connectivity, was more strongly influenced by tapping in WC, but the intracortical M1-SMA connection was more facilitating in controls. Inhibiting influences originating from GP to M1 were stronger in controls compared to WC patients whereby facilitating influences the PU exerts over CB and CB exerts over M1 were not as strong. Although the same model structure explains the given data best, DCM confirms previous research demonstrating a malfunction in effective connectivity intracortically (M1-SMA) and in the cortico-basal ganglia circuitry in WC. In addition, DCM analysis demonstrates abnormal reciprocal excitatory connectivity in the cortico-cerebellar circuitry. These results highlight the dysfunctional cerebello-cortical as well as basalganglio-cortical interaction in WC.

Neonatal capsaicin treatment in rats affects TRPV1-related noxious heat sensation and circadian body temperature rhythm.

The transient receptor potential vanilloid 1 (TRPV1) is a cation channel that serves as a polymodal detector of noxious stimuli such as capsaicin. Therefore, capsaicin treatment has been used to investigate the physiological function of TRPV1. Here, we report physiological changes induced by treating neonatal rats with capsaicin. Capsaicin (50mg/kg) (cap-treated) or vehicle (vehicle-treated) was systemically administered to newborn SD rat pups within 48 h after birth. TRPV1 expression, intake volume of capsaicin water, and noxious heat sensation were measured 6 weeks after capsaicin treatment. Circadian body temperature and locomotion were recorded by biotelemetry. Expression of Per1, Per2, Bmal1 and Hsf1 (clock genes) was also investigated. Neonatal capsaicin treatment not only decreased TRPV1 expression but also induced desensitization to noxious heat stimuli. Circadian body temperature of cap-treated rats increased significantly compared with that of vehicle-treated rats. Additionally, the amplitude of the circadian body temperature was reversed in cap-treated rats. Expression of the hypothalamic Hsf1 and liver Per2 clock genes followed a similar trend. Therefore, we suggest that these findings will be useful in studying various physiological mechanisms related to TRPV1.