0000000000020908
AUTHOR
Sara Torriero
Cerebellar magnetic stimulation decreases levodopa-induced dyskinesias in Parkinson disease
BACKGROUND: The neural mechanisms and the circuitry involved in levodopa-induced dyskinesia (LID) are still partially obscure. LID can be considered the consequence of an abnormal pattern or code of activity that originates and is conveyed from the basal ganglia to the thalamus and the cortical motor areas. However, not only striatothalamocortical motor circuits but also other interconnected pathways could be implicated in its pathogenesis. METHODS: In a series of experiments, we applied repetitive transcranial magnetic stimulation (rTMS) over the lateral cerebellum in a group of patients with advanced Parkinson disease, to investigate whether modulation of cerebellothalamocortical circuits…
The influence of rTMS over prefrontal and motor areas in a morphological task: grammatical vs. semantic effects
We investigated the differential role of two frontal regions in the processing of grammatical and semantic knowledge. Given the documented specificity of the prefrontal cortex for the grammatical class of verbs, and of the primary motor cortex for the semantic class of action words, we sought to investigate whether the prefrontal cortex is also sensitive to semantic effects, and whether the motor cortex is also sensitive to grammatical class effects. We used repetitive transcranial magnetic stimulation (rTMS) to suppress the excitability of a portion of left prefontal cortex (first experiment) and of the motor area (second experiment). In the first experiment we found that rTMS applied to t…
Cortical networks of procedural learning: Evidence from cerebellar damage
The lateral cerebellum plays a critical role in procedural learning that goes beyond the strict motor control functions attributed to it. Patients with cerebellar damage show marked impairment in the acquisition of procedures, as revealed by their performance on the serial reaction time task (SRTT). Here we present the case of a patient affected by ischemic damage involving the left cerebellum who showed a selective deficit in procedural learning while performing the SRTT with the left hand. The deficit recovered when the cortical excitability of an extensive network involving both cerebellar hemispheres and the dorsolateral prefrontal cortex (DLPFC) was decreased by low-frequency repetitiv…
rTMS evidence of different delay and decision processes in a fronto-parietal neuronal network activated during spatial working memory.
The existence of a specific and widely distributed network for spatial working memory (WM) in humans, involving the posterior parietal cortex and the prefrontal cortex, is supported by a number of neuroimaging studies. We used a repetitive transcranial magnetic stimulation (rTMS) approach to investigate the temporal dynamics and the reciprocal interactions of the different areas of the parieto-frontal network in normal subjects performing a spatial WM task, with the aim to compare neural activity of the different areas in the delay and decision phases of the task. Trains of rTMS at 25 Hz were delivered over the posterior parietal cortex (PPC), the premotor cortex (SFG) and the dorsolateral …
Modulation of excitatory and inhibitory circuits for visual awareness in the human right parietal cortex.
The balance of specific patterns of excitation and inhibition in critical regions of both hemispheres could be relevant in orienting attention over the extrapersonal space. In the present study a group of normal subjects had to detect small rectangular stimuli presented briefly on a computer screen in three different conditions: unilateral presentation either to left or right visual periphery or bilateral simultaneous presentation. Paired transcranial magnetic stimulation (TMS), was applied over the right parietal cortex 150 ms after the presentation of the visual stimuli with different inter-stimulus intervals (ISIs: 1, 3,5 and 10 ms). When paired TMS was applied 150 ms, but not 100 ms, af…
Keeping memory for intentions: A cTBS investigation of the frontopolar cortex
The present study aimed to investigate the role of frontopolar cortex in prospective memory (PM) by means of inhibitory theta-burst stimulation (cTBS). "Experiment 1"-8 volunteers were evaluated after inhibitory cTBS over left Brodmann area (BA) 10, right BA10, and Cz. In the PM procedure, sequences of 4 words each were presented. During the intersequence delay, subjects had to repeat the sequence in the observed order (ongoing task forward) or in the reverse order (backward). At the occurrence of a target word, subjects had to press a key on the keyboard (PM task). Recall and recognition of the target words were also tested. PM accuracy was lower after cTBS over left BA10 compared with Cz …
Prefrontal and temporo-parietal involvement in taking others' perspective: TMS evidence.
INTRODUCTION: Understanding the mental states of others entails a number of cognitive processes known as Theory of Mind (ToM). Behavioural and functional neuroimaging evidence suggests that prefrontal and temporo-parietal cortices are involved in these abilities. The present study was aimed at investigating the role of the dorsolateral prefrontal cortex and temporo-parietal junction in ToM by using a repetitive transcranial magnetic stimulation (rTMS) paradigm. MATERIAL AND METHODS: Eleven healthy subjects participated in the study. The experimental ToM procedure was constituted by false belief and faux-pas written stories. Subjects were evaluated in baseline condition (Sham) and after 1Hz …
Changes in intracortical circuits of the human motor cortex following theta burst stimulation of the lateral cerebellum
Objective: The cerebellum takes part in several motor functions through its influence on the motor cortex (M1). Here, we applied the theta burst stimulation (TBS) protocol, a novel form of repetitive Transcranial Magnetic Stimulation (rTMS) over the lateral cerebellum. The aim of this study was to test whether TBS of the lateral cerebellum could be able to modulate the excitability of the contralateral M1 in healthy subjects. Methods: Motor-evoked potentials (MEPs) amplitude, short intracortical inhibition (SICI), long intracortical inhibition (LICI) and short intracortical facilitation (SICF) were tested in the M1 before and after cerebellar continuous TBS (cTBS) or intermittent TBS (iTBS)…
High-frequency rTMS improves time perception in Parkinson disease.
Patients with Parkinson disease (PD) are impaired in time processing. The authors investigated the effects of high-frequency (5 Hz) repetitive transcranial magnetic stimulation (rTMS) in patients with PD performing a time reproduction task. The authors found significant improvement in time processing induced by rTMS when trains were applied over the right dorsolateral prefrontal cortex (DLPFC) but not over the supplementary motor area, suggesting that the circuit involving the basal ganglia and the DLPFC might constitute the neural network subserving time perception.
Repetitive TMS of cerebellum interferes with millisecond time processing
Time processing is important in several cognitive and motor functions, but it is still unclear how the human brain perceives time intervals of different durations. Processing of time in millisecond and second intervals may depend on different neural networks and there is now considerable evidence to suggest that these intervals are possibly measured by independent brain mechanisms. Using repetitive transcranial magnetic stimulation (rTMS), we determined that the cerebellum is essential in explicit temporal processing of millisecond time intervals. In the first experiment, subjects' performance in a time reproduction task of short (400-600 ms) and long (1,600-2,400 ms) intervals, were evalua…
Changes in Cerebello-motor Connectivity during Procedural Learning by Actual Execution and Observation
Abstract The cerebellum is involved in motor learning of new procedures both during actual execution of a motor task and during observational training. These processes are thought to depend on the activity of a neural network that involves the lateral cerebellum and primary motor cortex (M1). In this study, we used a twin-coil TMS technique to investigate whether execution and observation of a visuomotor procedural learning task is related to modulation of cerebello-motor connectivity. We observed that, at rest, a magnetic conditioning pulse applied over the lateral cerebellum reduced the motor-evoked potentials obtained by stimulating the contralateral M1, indicating activation of a cerebe…
Representation of time intervals in the right posterior parietal cortex: implications for a mental time line
Space and time interact with each other in the cognitive system. Recent studies indicate the posterior parietal cortex (PPC) as the neural correlate of spatial-temporal interactions. We studied whether the contribution of the PPC becomes critical in tasks requiring the performance of spatial computations on time intervals. We adopted an integrated neuropsychological and transcranial magnetic stimulation (rTMS) approach, presenting behavioural timing tasks to both healthy subjects and right-brain-damaged patients with and without evidence of spatial neglect. rTMS of the right PPC of healthy subjects induced a lateralised bias during a task requiring setting the midpoint of a time interval. T…
Impaired reproduction of second but not millisecond time intervals in Parkinson's disease
The basal ganglia have been associated with temporal processing in ranges of milliseconds and seconds. However, results from PD patient studies are elusive. Time perception in these patients has been tested with different approaches including repetitive movement tasks (i.e. finger tapping) and cognitive tasks (i.e. time reproduction), and both abnormal and normal performances have been reported for different time intervals. Furthermore, when PD patients were required to learn two target durations in the same session when they were off medication, they overestimated the short duration and underestimated the long duration in the seconds range. This pattern of temporal accuracy was described a…
The what and how of observational learning
Abstract Neuroimaging evidence increasingly supports the hypothesis that the same neural structures subserve the execution, imagination, and observation of actions. We used repetitive transcranial magnetic stimulation (rTMS) to investigate the specific roles of cerebellum and dorsolateral prefrontal cortex (DLPFC) in observational learning of a visuomotor task. Subjects observed an actor detecting a hidden sequence in a matrix and then performed the task detecting either the previously observed sequence or a new one. rTMS applied over the cerebellum before the observational training interfered with performance of the new sequence, whereas rTMS applied over the DLPFC interfered with performa…
TMS activation of interhemispheric pathways between the posterior parietal cortex and the contralateral motor cortex
Using a twin coil transcranial magnetic stimulation (tc-TMS) approach we have previously demonstrated that facilitation may be detected in the primary motor cortex (M1) following stimulation over the ipsilateral caudal intraparietal sulcus (cIPS). Here we tested the interhemispheric interactions between the IPS and the contralateral motor cortex (M1). We found that conditioning the right cIPS facilitated contralateral M1 when the conditioning stimulus had an intensity of 90% resting motor threshold (RMT) but not at 70% or 110% RMT. Facilitation was maximal when the interstimulus interval (ISI) between cIPS and M1 was 6 or 12 ms. These facilitatory effects were mediated by interactions with …
Increased facilitation of the primary motor cortex following 1 Hz repetitive transcranial magnetic stimulation of the contralateral cerebellum in normal humans.
Connections between the cerebellum and the contralateral motor cortex are dense and important, but their physiological significance is difficult to measure in humans. We have studied a group of 10 healthy subjects to test whether a modulation of the excitability of the left cerebellum can affect the excitability of the contralateral motor cortex. We used repetitive transcranial magnetic stimulation (rTMS) at 1 Hz frequency to transiently depress the excitability of the left cerebellar cortex and paired-pulse TMS testing of intracortical inhibition (ICI) and intracortical facilitation (ICF) to probe the excitability of cortico-cortical connections in the right motor cortex. The cortical sile…
Motor and linguistic linking of space and time in the cerebellum
Background: Recent literature documented the presence of spatial-temporal interactions in the human brain. The aim of the present study was to verify whether representation of past and future is also mapped onto spatial representations and whether the cerebellum may be a neural substrate for linking space and time in the linguistic domain. We asked whether processing of the tense of a verb is influenced by the space where response takes place and by the semantics of the verb. Principal Findings: Responses to past tense were facilitated in the left space while responses to future tense were facilitated in the right space. Repetitive transcranial magnetic stimulation (rTMS) of the right cereb…
The role of transcranial magnetic stimulation in the study of cerebellar cognitive function.
Transcranial magnetic stimulation (TMS) allows non-invasive stimulation of brain structures. This technique can be used either for stimulating the motor cortex, recording motor evoked potentials from peripheral muscles, or for modulating the excitability of other non-motor areas in order to establish their necessity for a given task. TMS of the cerebellum can give interesting insights on the cerebellar functions. Paired-TMS techniques, delivering stimuli over the cerebellum followed at various interstimulus intervals by stimuli over the motor cortex, allow studying the pattern of connectivity between the cerebellum and the contralateral motor cortex in physiological as well as in pathologic…
Overestimation of numerical distances in the left side of space
Normal subjects presented with a middle number and two left- and right-sided outer numbers overestimate the numerical distance between the middle number and that positioned at its left side. Repetitive transcranial magnetic stimulation (rTMS) of the right posterior parietal cortex specifically counteracts this bias, suggesting that the mental representation of space defined by numbers is shifted toward the left side depending on a greater activity of the right hemisphere.
Hyperexcitability of parietal-motor functional connections in the intact left-hemisphere of patients with neglect
Hemispatial neglect is common after unilateral brain damage, particularly to perisylvian structures in the right-hemisphere (RH). In this disabling syndrome, behaviour and awareness are biased away from the contralesional side of space towards the ipsilesional side. Theoretical accounts of this in terms of hemispheric rivalry have speculated that the intact left-hemisphere (LH) may become hyper-excitable after a RH lesion, due to release of inhibition from the damaged hemisphere. We tested this directly using a novel twin-coil transcranial magnetic stimulation (TMS) approach to measure excitability within the intact LH of neglect patients. This involved applying a conditioning TMS pulse ove…
Interference of left and right cerebellar rTMS with procedural learning.
Abstract Increasing evidence suggests cerebellar involvement in procedural learning. To further analyze its role and to assess whether it has a lateralized influence, in the present study we used a repetitive transcranial magnetic stimulation interference approach in a group of normal subjects performing a serial reaction time task. We studied 36 normal volunteers: 13 subjects underwent repetitive transcranial magnetic stimulation on the left cerebellum and performed the task with the right (6 subjects) or left (7 subjects) hand; 10 subjects underwent repetitive transcranial magnetic stimulation on the right cerebellum and performed the task with the hand ipsilateral (5 subjects) or contral…