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    Rothwell, J

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    Cerebellar Theta-Burst Stimulation Impairs Memory Consolidation in Eyeblink Classical Conditioning

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    Associative learning of sensorimotor contingences, as it occurs in eyeblink classical conditioning (EBCC), is known to involve the cerebellum, but its mechanism remains controversial. EBCC involves a sequence of learning processes which are thought to occur in the cerebellar cortex and deep cerebellar nuclei. Recently, the extinction phase of EBCC has been shown to be modulated after one week by cerebellar continuous theta-burst stimulation (cTBS). Here, we asked whether cerebellar cTBS could affect retention and reacquisition of conditioned responses (CRs) tested immediately after conditioning. We also investigated a possible lateralized cerebellar control of EBCC by applying cTBS on both the right and left cerebellar hemispheres. Both right and left cerebellar cTBSs induced a statistically significant impairment in retention and new acquisition of conditioned responses (CRs), the disruption effect being marginally more effective when the left cerebellar hemisphere was stimulated. These data support a model in which cTBS impairs retention and reacquisition of CR in the cerebellum, possibly by interfering with the transfer of memory to the deep cerebellar nuclei

    Effects of paired pulse TMS of primary somatosensory cortex on perception of a peripheral electrical stimulus

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    Paired pulse transcranial magnetic stimulation (paired TMS) was introduced to study local inhibitory or facilitatory intracortical circuits of the primary motor cortex. However, similar interactions can be shown in other areas of cortex. The current study tests the effects of paired pulse TMS of the right primary somatosensory cortex (S1) on the sensory perception of electrical stimuli applied on the contralateral thumb finger. In the main experiment a subthreshold conditioning stimulus (CS) preceded a suprathreshold test stimulus (TS) at different inter-stimulus intervals. We found that perception of a peripheral electrical stimulus was markedly attenuated by paired TMS in comparison to single pulse TMS when the ISIs was 10 or 15 ms, while there was no effect at shorter ISIs. There was no additional effect of the CS pulse if the intensity of the TS was subthreshold. In control experiments we observed that the effect vanished when the delay between the peripheral stimulus and the TS was 10 or 30 ms rather than 20 ms or if the pairs of pulses were applied over the vertex rather than the hand area. Furthermore, there was no change at longer ISIs when paired TMS was applied over the posterior parietal cortex of the same hemisphere. These results demonstrate that paired pulse TMS is able to probe intracortical circuits in S1 and that the intrinsic properties of these circuits differ even between closely adjacent areas of the cortex

    Effect of donepezil on transcranial magnetic stimulation parameters in Alzheimer's disease

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    Introduction: There is a need for a reliable, noninvasive biomarker for Alzheimer's disease (AD). We assessed whether short-latency afferent inhibition (SAI), a transcranial magnetic stimulation paradigm that assesses cholinergic circuits of the brain, could become such a biomarker. Methods: Nineteen patients with AD underwent four SAI testing sessions. The timing of their usual donepezil dose was altered to create different cholinergic states for each session. This was compared to the SAI results from 20 healthy subjects. Results: SAI was not able to distinguish the different cholinergic states assessed in our study. There appeared to be a diurnal variation in cholinergic function in the control group, which was not present in the AD cohort. Discussion: SAI does not appear to have a role in diagnosis and assessment of AD patients. The loss of diurnal variation, however, warrants further investigation as it may provide further biochemical insights about AD

    High frequency somatosensory stimulation in dystonia: Evidence for defective inhibitory plasticity

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    Background: Apart from motor symptoms, multiple deficits of sensory processing have been demonstrated in dystonia. The most consistent behavioural measure of this is abnormal somatosensory temporal discrimination threshold, which has recently been associated with physiological measures of reduced inhibition within the primary somatosensory area. High-frequency repetitive sensory stimulation is a patterned electric stimulation applied to the skin through surface electrodes that has been recently reported to shorten somatosensory temporal discrimination in healthy subjects and to increase the resting level of excitability in several different types of inhibitory interaction in the somatosensory and even motor areas. Objectives: We tested whether high-frequency repetitive sensory stimulation could augment cortical inhibition and, in turn, ameliorate somatosensory temporal discrimination in cervical dystonia. Methods: Somatosensory temporal discrimination and a number of electrophysiological measures of sensorimotor inhibition and facilitation were measured before and after 45 minutes of high-frequency repetitive sensory stimulation. Results: As compared with a group of healthy volunteers of similar age, in whom high-frequency repetitive sensory stimulation increased inhibition and shortened somatosensory temporal discrimination, patients with cervical dystonia showed a consistent, paradoxical response: they had reduced suppression of paired-pulse somatosensory evoked potentials, as well as reduced high-frequency oscillations, lateral inhibition, and short interval intracortical inhibition. Somatosensory temporal discrimination deteriorated after the stimulation protocol, and correlated with reduced measures of inhibition within the primary somatosensory cortex. Conclusions: We suggest that patients with dystonia have abnormal homeostatic inhibitory plasticity within the sensorimotor cortex and that this is responsible for their paradoxical response to high-frequency repetitive sensory stimulation

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Frequency-dependent modulation of cerebellar excitability during the application of non-invasive alternating current stimulation

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    Background: it is well-known that the cerebellum is critical for the integrity of motor and cognitive actions. Applying non-invasive brain stimulation techniques over this region results in neurophysiological and behavioural changes, which have been associated with the modulation of cerebellar-cerebral cortex connectivity. Here, we investigated whether online application of cerebellar transcranial alternating current stimulation (tACS) results in changes to this pathway. Methods: thirteen healthy individuals participated in two sessions of cerebellar tACS delivered at different frequencies (5Hz and 50Hz). We used transcranial magnetic stimulation to measure cerebellar-motor cortex (M1) inhibition (CBI), short-intracortical inhibition (SICI) and short-afferent inhibition (SAI) before, during and after the application of tACS. Results: we found that CBI was specifically strengthened during the application of 5Hz cerebellar tACS. No changes were detected immediately following the application of 5Hz stimulation, nor at any time point with 50Hz stimulation. We also found no changes to M1 intracortical circuits (i.e. SICI) or sensorimotor interaction (i.e. SAI), indicating that the effects of 5Hz tACS over the cerebellum are site-specific. Conclusions: cerebellar tACS can modulate cerebellar excitability in a time- and frequency-dependent manner. Additionally, cerebellar tACS does not appear to induce any long-lasting effects (i.e. plasticity), suggesting that stimulation enhances oscillations within the cerebellum only throughout the stimulation period. As such, cerebellar tACS may have significant implications for diseases manifesting with abnormal cerebellar oscillatory activity and also for future behavioural studies
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