Cerebello-Cortical Coherence of Local Field Potentials following Patterned Stimulation of the Cerebellar Vermis

The cerebellum is involved in sensorimotor, cognitive, and emotional functions through cerebello- cerebral connectivity. Non-invasive cerebellar neurostimulation has been used to treat neurological disorders and has positive effects on cognition and mood, which have been related to modulation in frontal oscillations. To explore the mechanisms, we studied the effects of cerebellar stimulation at various frequencies on oscillations and coherence across a cerebello-cortical network, in the anesthetized rat. Local field potentials were recorded continuously with monopolar and bipolar electrodes in the lateral cerebellum (crus I/II), and in the prefrontal cortex (FrA), in six adult male Sprague-Dawley rats anesthetized with urethane. Stimulation patterns were delivered to the cerebellar vermis (lobule VII) in a randomized order: single pulses (0.2 Hz for 60 s), and repeated pulses at 1 Hz (30 s), 5 Hz (10 s), 25 Hz (2 s), and 50 Hz (1 s). Low frequency stimulation (1 Hz and 5 Hz) enhanced coherence in the cerebello-cortical network in theta and alpha, while high frequency stimulation (50 Hz) had an enhancing effect on beta and low gamma coherence. Stimulation effects were influenced by the initial oscillatory state, perhaps due to cyclic stages under urethane anesthesia. Low frequency stimulation was more efficient when delivered in a state dominated by slow waves, while high frequency stimulation showed the opposite relationship. We have found here that cerebellar stimulation can drive synchronization of cerebello-cortical and cortico-cortical networks. The present results could provide basic mechanisms underlying the therapeutic effects of cerebellar stimulation by promoting large-scale synchronization of neural networks

Atypical EEG in autism spectrum disorder: Comparing a dimensional and a categorical approach

Myriad studies have found group differences in neural dynamics between people with and without autism spectrum disorder (ASD). However, the extent to which variation in neural dynamics is related to variation in the autism phenotype across the population is not known. Here we measured behavioral characteristics of autism alongside intertrial phase coherence (ITC) and multiscale entropy (MSE) computed from EEG in order to address this question. Data were obtained from 99 adults, 38 of whom had an ASD diagnosis. Phenotypic information was obtained from the Social Responsiveness Scale (Revised), the Repetitive Behavior Questionnaire, the WHO Adult ADHD Self-Report Scale Screener, and the Beck Anxiety Inventory (Trait version). ITC and MSE were computed from EEG recorded during visual stimulation and eyes-closed rest. We found no evidence to suggest that population variance in autistic traits is underpinned by variance in neural dynamics, despite finding that ITC and MSE are more likely to be reduced in people with ASD than in those without. We conclude that there are likely to be multiple neural profiles underpinning ASD, and suggest that while individual differences in the autism phenotype exist across the population, their distribution is not underpinned by individual differences in neural dynamics

An investigation into memory control: neuromodulatory approaches and potential clinical target populations

The present doctoral dissertation is composed of six studies investigating various aspects of cognitive control, with a focus on selective memory retrieval: The brain areas that support this ability, the possibility of modulating its behavioural manifestations with transcranial Direct Current Stimulation (tDCS), its relationship with motor stopping, and its integrity in two clinical populations. Results provided by these experiments highlight four major achievements of this line of research: Firstly, we provided causal evidence for the involvement of right PFC in supporting the cognitive processes underlying memory control, because interfering with the activity of this region was sufficient to disrupt the RIF effect. Secondly, we demonstrated the effectiveness and viability of tDCS as a tool to modulate this peculiar effect. Thirdly, we provided compelling evidence for the advantages of analysing RPP data with a statistical approach that is more consistent with the nature of the data, as well as informative in respect of the different dimensions of the data that contribute to the results. Last, but not least, we contributed to the characterization of the cognitive profile of patients affected by substance-related and addictive disorders and EDs, paving the way to future research that could further investigate the extents and specificity of the previously unexplored memory control deficits that we unveiled in these patients

Neural Activity of 16p11.2 CNV Human and Mouse

Although rare in the population, individuals affected by deletions or duplications of DNA material at 16p11.2 chromosomal region (within the region ’11.2’ in the short arm of chromosome 16) are at higher risk of myriad clinical features and neurodevelopmental disorders including intellectual disability, developmental delays, and autism spectrum disorder. Whether inherited or appearing for the first time in the family, this 16p11.2 copy number variation (CNV) seems to impact on brain structure and function that may, in turn, drive the profile and severity of 16p11.2 associated phenotypes. As studies of 16p11.2 CNV brain function are scarce, the aim of this thesis is to investigate EEG activity in (human) 16p11.2 CNV carriers and parallel in-vivo electrophysiological activity in 16p11.2 deletion mouse model. Data-sharing platforms and collaborative efforts made it possible to access datasets of this rare population and analyse it for the purpose of this thesis. The thesis is comprised of three studies: 1) an investigation of visual-evoked neural variability, as measured by variability of intra-participant ERP and spectral power, and signal-to-noise ratio, in 16p11.2 CNV carriers; 2) a study of spontaneous neural activity, as measured by multi-scale entropy and conventional spectral power, in 16p11.2 deletion carriers; and 3) a study of spontaneous neural activity in 16p11.2 deletion mouse model. Neural variability was mostly higher in 16p11.2 deletion carriers relative to typical controls and 16p11.2 duplication carriers. Compared to typical controls, higher entropy was found in 16p11.2 deletion carriers and this was associated with certain psychiatric and behavioural traits, e.g., anxiety problems. The 16p11.2 deletion mice showed no group differences in neural activity compared to wild-type control mice. In conclusion, despite the lack of converging evidence from the mouse model, the collective 16p11.2 CNV human findings indicated that neural activity in 16p11.2 deletion carriers, especially, was altered and related to psychiatric traits found in 16p11.2 deletion carriers

Obsessive-Compulsive Disorder

Although Obsessive-Compulsive Disorder (OCD) has been known since the ancient times, the exact etiology and pathogenesis of OCD unfortunately still remain unknown. In addition, the therapeutic approaches elaborated for the treatment of OCD as a whole are not perfect, and this disorder as a rule is characterized by unfavorable course and lack of full therapeutic response. In the current book some modern data on pathogenesis, phenomenology and treatment of OCD are presented. Besides, the data on co-morbidity of OCD with other neurological and psychiatric disorders are also included. This book is intended for broad circle of readers, but mostly for psychiatrists, psychologists and neurologists

Eye quietness and quiet eye in expert and novice golf performance: an electrooculographic analysis

Quiet eye (QE) is the final ocular fixation on the target of an action (e.g., the ball in golf putting). Camerabased eye-tracking studies have consistently found longer QE durations in experts than novices; however, mechanisms underlying QE are not known. To offer a new perspective we examined the feasibility of measuring the QE using electrooculography (EOG) and developed an index to assess ocular activity across time: eye quietness (EQ). Ten expert and ten novice golfers putted 60 balls to a 2.4 m distant hole. Horizontal EOG (2ms resolution) was recorded from two electrodes placed on the outer sides of the eyes. QE duration was measured using a EOG voltage threshold and comprised the sum of the pre-movement and post-movement initiation components. EQ was computed as the standard deviation of the EOG in 0.5 s bins from –4 to +2 s, relative to backswing initiation: lower values indicate less movement of the eyes, hence greater quietness. Finally, we measured club-ball address and swing durations. T-tests showed that total QE did not differ between groups (p = .31); however, experts had marginally shorter pre-movement QE (p = .08) and longer post-movement QE (p < .001) than novices. A group × time ANOVA revealed that experts had less EQ before backswing initiation and greater EQ after backswing initiation (p = .002). QE durations were inversely correlated with EQ from –1.5 to 1 s (rs = –.48 - –.90, ps = .03 - .001). Experts had longer swing durations than novices (p = .01) and, importantly, swing durations correlated positively with post-movement QE (r = .52, p = .02) and negatively with EQ from 0.5 to 1s (r = –.63, p = .003). This study demonstrates the feasibility of measuring ocular activity using EOG and validates EQ as an index of ocular activity. Its findings challenge the dominant perspective on QE and provide new evidence that expert-novice differences in ocular activity may reflect differences in the kinematics of how experts and novices execute skills