Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements, postures, or both. Although dystonia is traditionally associated with basal ganglia dysfunction, recent evidence has been pointing to a role of the cerebellum, a brain area involved in motor control and learning. Cerebellar abnormalities have been correlated with dystonia but their potential causative role remains elusive. Here, we simulated the cerebellar input-output relationship with high-resolution computational modeling. We used a data-driven cerebellar Spiking Neural Network and simulated a cerebellum-driven associative learning task, Eye-Blink Classical Conditioning (EBCC), which is characteristically altered in relation to cerebellar lesions in several pathologies. In control simulations, input stimuli entrained characteristic network dynamics and induced synaptic plasticity along task repetitions, causing a progressive spike suppression in Purkinje cells with consequent facilitation of deep cerebellar nuclei cells. These neuronal processes caused a progressive acquisition of eyelid Conditioned Responses (CRs). Then, we modified structural or functional local neural features in the network reproducing alterations reported in dystonic mice. Either reduced olivocerebellar input or aberrant Purkinje cell burst-firing resulted in abnormal learning curves imitating the dysfunctional EBCC motor responses (in terms of CR amount and timing) of dystonic mice. These behavioral deficits might be due to altered temporal processing of sensorimotor information and uncoordinated control of muscle contractions. Conversely, an imbalance of excitatory and inhibitory synaptic densities on Purkinje cells did not reflect into significant EBCC deficit. The present work suggests that only certain types of alterations, including reduced olivocerebellar input and aberrant PC burst-firing, are compatible with the EBCC changes observed in dystonia, indicating that some cerebellar lesions can have a causative role in the pathogenesis of symptoms.
Activity in the gamma range is related to many sensory and cognitive processes that are impaired in neuropsychiatric conditions. Therefore, individualized measures of gamma-band activity are considered to be potential markers that reflect the state of networks within the brain. Relatively little has been studied in respect of the individual gamma frequency (IGF) parameter. The methodology for determining the IGF is not well established. In the present work, we tested the extraction of IGFs from electroencephalogram (EEG) data in two datasets where subjects received auditory stimulation consisting of clicks with varying inter-click periods, covering a 30–60 Hz range: in 80 young subjects EEG was recorded with 64 gel-based electrodes; in 33 young subjects, EEG was recorded using three active dry electrodes. IGFs were extracted from either fifteen or three electrodes in frontocentral regions by estimating the individual-specific frequency that most consistently exhibited high phase locking during the stimulation. The method showed overall high reliability of extracted IGFs for all extraction approaches; however, averaging over channels resulted in somewhat higher reliability scores. This work demonstrates that the estimation of individual gamma frequency is possible using a limited number of both the gel and dry electrodes from responses to click-based chirp-modulated sounds.
In recent years, the concept of individualized measures of electroencephalographic (EEG) activity has emerged. Gamma-band activity plays an important role in many sensory and cognitive processes. Thus, peak frequency in the gamma range has received considerable attention. However, peak or individual gamma frequency (IGF) is rarely used as a primary measure of interest; consequently, little is known about its nature and functional significance. With this review, we attempt to comprehensively overview available information on the functional properties of peak gamma frequency, addressing its relationship with certain processes and/or modulation by various factors. Here, we show that IGFs seem to be related to various endogenous and exogenous factors. Broad functional aspects that are related to IGF might point to the differences in underlying mechanisms. Therefore, research utilizing different types of stimulation for IGF estimation and covering several functional aspects in the same population is required. Moreover, IGFs span a wide range of frequencies (30–100 Hz). This could be partly due to the variability of methods used to extract the measures of IGF. In order to overcome this issue, further studies aiming at the optimization of IGF extraction would be greatly beneficial.
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