Abstract In humans, execution of unimanual motor tasks requires a neural network that is capable of restricting neuronal motor output activity to the primary motor cortex (M1) contralateral to the ...voluntary movement by counteracting the default propensity to produce mirror-symmetrical bimanual movements. The motor command is transmitted from the M1 to the contralateral spinal motoneurons by a largely crossed system of fast-conducting corticospinal neurons. Alteration or even transient dysfunction of the neural circuits underlying movement lateralization may result in involuntary mirror movements (MM). Different models exist, which have attributed MM to unintended motor output from the M1 ipsilateral to the voluntary movement, functionally active uncrossed corticospinal projections, or on a combination of both. Over the last two decades, transcranial magnetic stimulation (TMS) proved as a valuable, non-invasive neurophysiological tool to investigate motor control in healthy volunteers and neurological patients. The contribution of TMS and other non-invasive electrophysiological techniques to characterize the neural network responsible for the so-called ‘non-mirror transformation’ of motor programs and the various mechanisms underlying ‘physiological’ mirroring, and congenital or acquired pathological MM are the focus of this review.
The caudate nucleus is commonly active when learning relationships between stimuli and responses or categories. Previous research has not differentiated between the contributions to learning in the ...caudate and its contributions to executive functions such as feedback processing. We used event-related functional magnetic resonance imaging while participants learned to categorize visual stimuli as predicting "rain" or "sun." In each trial, participants viewed a stimulus, indicated their prediction via a button press, and then received feedback. Conditions were defined on the bases of stimulus-outcome contingency (deterministic, probabilistic, and random) and feedback (negative and positive). A region of interest analysis was used to examine activity in the head of the caudate, body/tail of the caudate, and putamen. Activity associated with successful learning was localized in the body and tail of the caudate and putamen; this activity increased as the stimulus-outcome contingencies were learned. In contrast, activity in the head of the caudate and ventral striatum was associated most strongly with processing feedback and decreased across trials. The left superior frontal gyrus was more active for deterministic than probabilistic stimuli; conversely, extrastriate visual areas were more active for probabilistic than deterministic stimuli. Overall, hippocampal activity was associated with receiving positive feedback but not with correct classification. Successful learning correlated positively with activity in the body and tail of the caudate nucleus and negatively with activity in the hippocampus.
Convergent evidence from functional imaging and from neuropsychological studies of basal ganglia disorders indicates that the striatum is involved in learning to categorize visual stimuli with ...feedback. However, it is unclear which cognitive process or processes involved in categorization is or are responsible for striatal recruitment; different regions of the striatum have been linked to feedback processing and to acquisition of stimulus-category associations. We examined the effect of the presence of feedback during learning on striatal recruitment by comparing feedback learning with observational learning of an information integration task. In the feedback task, participants were shown a stimulus, made a button press response, and then received feedback as to whether they had made the correct response. In the observational task, participants were given the category label before the stimulus appeared and then made a button press indicating the correct category membership. A region-of-interest analysis was used to examine activity in three regions of the striatum: the head of the caudate, body and tail of the caudate, and the putamen. Activity in the left head of the caudate was modulated by the presence of feedback: The magnitude of activation change was greater during feedback learning than during observational learning. In contrast, the bilateral body and tail of the caudate and the putamen were active to a similar degree in both feedback and observational learning. This pattern of results supports a functional dissociation between regions of the striatum, such that the head of the caudate is involved in feedback processing, whereas the body and tail of the caudate and the putamen are involved in learning stimulus-category associations. The hippocampus was active bilaterally during both feedback and observational learning, indicating potential parallel involvement with the striatum in information integration category learning.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and purpose
To identify adverse events (AEs) significantly associated with perampanel treatment in double‐blind clinical studies (RCTs). Serious AEs, study withdrawals due to AEs and ...dose–effect responses of individual AEs were also investigated.
Methods
All placebo controlled, double‐blind RCTs investigating therapeutic effects of oral perampanel were searched. AEs were assessed for their association with perampanel after exclusion of synonyms, rare AEs and non‐assessable AEs. Risk difference (RD) was used to evaluate the association of any AE (99% confidence intervals) and withdrawals or serious AEs (95% confidence intervals) with perampanel.
Results
Nine RCTs (five in pharmacoresistant epilepsy and four in Parkinson's disease) were included in our study. Almost 4000 patients had been recruited, 2627 of whom were randomized to perampanel and treated with drug doses of 0.5 mg/day (n = 68), 1 mg/day (n = 65), 2 mg/day (n = 753), 4 mg/day (n = 1017), 8 mg/day (n = 431) or 12 mg/day (n = 293). Serious AEs were not significantly associated with perampanel treatment. The experimental drug was significantly associated with an increased risk of AE‐related study withdrawals at 4 mg/day RD (95% confidence interval) 0.03 (0.00, 0.06) and 12 mg/day RD (95% confidence interval) 0.13 (0.07, 0.18). Of 15 identified AEs, five (dizziness, ataxia, somnolence, irritability and weight increase) were found to be significantly associated with perampanel and one (seizure worsening) was significantly associated with placebo.
Conclusions
Vestibulocerebellar AEs (dizziness, ataxia), sedative effects (somnolence), irritability and weight increase were significantly associated with perampanel treatment.
•Readiness Potential (RP) dynamics have been studied during Libet’s clock task.•Impulsivity traits assessed by the Barratt Impulsiveness Scale (BIS-11).•RP shows an earlier rising and a greater ...amplitude for higher BIS-11 scores.•Trait impulsivity positively correlates with motor system excitability.•We hypothesize less effective preparatory inhibition in trait impulsivity.
Electrophysiological and neuroimaging studies suggest that our actions are initiated by unconscious mental processes long before awareness of intention to act. The time window between the awareness of the intention to move and the movement onset, which normally permits to exert a conscious “veto” on the impending action, is modulated by individual differences in trait impulsivity. In particular, trait impulsive people show a delayed awareness of the intention to act, probably exceeding the “point of no return”, after which the action can no longer be inhibited. In order to investigate if individual differences in the “veto” interval might be explained by differences in the readiness potential (RP) dynamics, nineteen healthy participants underwent an impulsivity trait assessment using the Barratt Impulsiveness Scale (BIS-11) and performed a task based on Libet’s clock paradigm, during EEG recordings of pre-movement neural activity. We observed a positive relationship between impulsive personality trait and motor system excitability during the preparation of self-initiated movements. In particular, the RP showed an earlier negative rising phase and a greater amplitude, with the increasing of BIS-11 scores. Based on present results, we conclude hypothesizing that trait impulsivity might be characterized by less effective preparatory inhibition mechanisms, which have a fundamental role in the control of behavior.
We show that diffusion due to chaotic mixing in the neighbourhood of the Sun may not be as relevant as previously suggested in erasing phase space signatures of past Galactic accretion events. For ...this purpose, we analyse solar neighbourhood-like volumes extracted from cosmological simulations that naturally account for chaotic orbital behaviour induced by the strongly triaxial and cuspy shape of the resulting dark matter haloes, among other factors. In the approximation of an analytical static triaxial model, our results show that a large fraction of stellar halo particles in such local volumes have chaos onset times (i.e. the time-scale at which stars commonly associated with chaotic orbits will exhibit their chaotic behaviour) significantly larger than a Hubble time. Furthermore, particles that do present a chaotic behaviour within a Hubble time do not exhibit significant diffusion in phase space.
In healthy subjects (HS), transcranial magnetic stimulation (TMS) applied during ‘linguistic’ tasks discloses excitability changes in the dominant hemisphere primary motor cortex (M1). We ...investigated ‘linguistic’ task‐related cortical excitability modulation in patients with adductor‐type spasmodic dysphonia (ASD), a speech‐related focal dystonia. We studied 10 ASD patients and 10 HS. Speech examination included voice cepstral analysis. We investigated the dominant/non‐dominant M1 excitability at baseline, during ‘linguistic’ (reading aloud/silent reading/producing simple phonation) and ‘non‐linguistic’ tasks (looking at non‐letter strings/producing oral movements). Motor evoked potentials (MEPs) were recorded from the contralateral hand muscles. We measured the cortical silent period (CSP) length and tested MEPs in HS and patients performing the ‘linguistic’ tasks with different voice intensities. We also examined MEPs in HS and ASD during hand‐related ‘action‐verb’ observation. Patients were studied under and not‐under botulinum neurotoxin‐type A (BoNT‐A). In HS, TMS over the dominant M1 elicited larger MEPs during ‘reading aloud’ than during the other ‘linguistic’/‘non‐linguistic’ tasks. Conversely, in ASD, TMS over the dominant M1 elicited increased‐amplitude MEPs during ‘reading aloud’ and ‘syllabic phonation’ tasks. CSP length was shorter in ASD than in HS and remained unchanged in both groups performing ‘linguistic’/‘non‐linguistic’ tasks. In HS and ASD, ‘linguistic’ task‐related excitability changes were present regardless of the different voice intensities. During hand‐related ‘action‐verb’ observation, MEPs decreased in HS, whereas in ASD they increased. In ASD, BoNT‐A improved speech, as demonstrated by cepstral analysis and restored the TMS abnormalities. ASD reflects dominant hemisphere excitability changes related to ‘linguistic’ tasks; BoNT‐A returns these excitability changes to normal.
In healthy subjects, magnetic stimulation over dominant primary motor area elicited larger MEPs during loud reading compared to other linguistic and non linguistic tasks, while in spasmodic dysphonia (ASD) it elicited MEPs of increased amplitude also during syllabic phonation. In ASD, BoNT‐A improved speech as demonstrated by cepstral analysis and restored the TMS abnormalities. We conclude that spasmodic dysphonia is characterized by abnormal dominant speech‐related network activation.
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