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Further insights into the effect of BDNF genotype on Non-invasive Brain Stimulation
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Transcranial magnetic stimulation: From neurophysiology to pharmacology, molecular biology and genomics
Noninvasive plasticity paradigms, both physiologically induced and artificially induced, have come into their own in the
study of the effects of genetic variation on human cortical plasticity. These techniques have the singular advantage that
they enable one to study the effects of genetic variation in its natural and most relevant context, that of the awake
intact human cortex, in both health and disease. This review aims to introduce the currently available artificially induced
plasticity paradigms, their putative mechanisms—both in the traditional language of the systems neurophysiologist and
in the evolving (and perhaps more relevant for the purposes of stimulation genomics) reinterpretation in terms of
molecular neurochemistry, and highlights recent studies employing these techniques by way of examples of applications.Noninvasive plasticity paradigms, both physiologically induced and artificially induced, have come into their own in the study of the effects of genetic variation on human cortical plasticity. These techniques have the singular advantage that they enable one to study the effects of genetic variation in its natural and most relevant context, that of the awake intact human cortex, in both health and disease. This review aims to introduce the currently available artificially induced plasticity paradigms, their putative mechanismsĝ€"both in the traditional language of the systems neurophysiologist and in the evolving (and perhaps more relevant for the purposes of stimulation genomics) reinterpretation in terms of molecular neurochemistry, and highlights recent studies employing these techniques by way of examples of applications. © The Author(s) 2010
Role of the cerebellum in externally paced rhythmic finger movements
Several studies have suggested that the
cerebellum has an important role in timing of subsecond intervals.
Previous studies using transcranial magnetic stimulation (TMS) to test
this hypothesis directly have produced inconsistent results. Here we
used 1-Hz repetitive TMS (rTMS) for 10 min over the right or left
cerebellar hemisphere to interfere transiently with cerebellar processing to assess its effect on the performance of a finger-tapping task.
Subjects tapped with their right index finger for 1 min (synchronization phase) with an auditory or visual cue at 0.5, 1, or 2 Hz; they
continued for a further 1 min at the same rate with no cues (continuation phase). The blocks of trials were performed in a random order.
rTMS of the cerebellum ipsilateral to the movement increased the
variability of the intertap interval but only for movements at 2 Hz that
were made while subjects were synchronizing with an auditory cue.
There was no effect on the continuation phase of the task when the
cues were no longer present or on synchronization with a visual cue.
Similar results were seen after stimulation over the contralateral
dorsal premotor cortex but not after rTMS over supplementary motor
area. There was no effect after rTMS over the ipsilateral right cervical
nerve roots or over the ipsilateral primary motor cortex. The results
support the hypothesis of neural network for event-related timing in
the subsecond range that involves a cerebellar-premotor network
Variability in non-invasive brain stimulation studies: Reasons and results
Non-invasive brain stimulation techniques (NIBS), such as Theta Burst Stimulation (TBS), Paired Associative Stimulation (PAS) and transcranial Direct Current Stimulation (tDCS), are widely used to probe plasticity in the human motor cortex (M1). Although TBS, PAS and tDCS differ in terms of physiological mechanisms responsible for experimentally-induced cortical plasticity, they all share the ability to elicit long-term potentiation (LTP) and depression (LTD) in M1. However, NIBS techniques are all affected by relevant variability in intra- and inter-subject responses. A growing number of factors contributing to NIBS variability have been recently identified and reported. In this review, we have readdressed the issue of variability in human NIBS studies. We have first briefly discussed the physiological mechanisms responsible for TBS, PAS and tDCS-induced cortical plasticity. Then, we have provided statistical measures of intra- and inter-subject variability, as calculated in previous studies. Finally, we have reported in detail known sources of variability by categorizing them into physiological, technical and statistical factors. Improving knowledge about sources of variability could lead to relevant advances in designing new tailored NIBS protocols in physiological and pathological conditions
Solutions for managing variability in non-invasive brain stimulation studies
In the last three decades, a number of non-invasive brain stimulation (NIBS) protocols, capable of assessing and modulating plasticity in the human motor cortex (M1), have been described. For almost as long, NIBS has delivered the tantalising prospect of non-invasive neuromodulation as a therapeutic intervention for neurorehabilitation, psychiatry, chronic pain and other disease states. Apart from modest effects in depression, this early promise has not been realised since the symptomatic improvements produced by NIBS are generally weak. One key factor explaining this lack of clinical translation concerns variability in response to NIBS. Several studies have demonstrated a number of physiological, technical and statistical factors accounting for intra- and inter-subject variability. However, solutions to overcome this problem are still under debate. In the present review, we have provided a detailed description of methodological and technical solutions to control known factors influencing variability. We have also suggested potential strategies to strengthen and stabilize NIBS-induced after-effects. Finally, we propose new possible outcome variables which better reflect intrinsic cortical activity, allowing a more sensitive measurement and valid interpretation of responses to NIBS
Time course of functional connectivity between dorsal premotor and contralateral motor cortex during movement selection
The left dorsal premotor cortex (PMd) is thought to play a dominant role in the selection of movements made by either hand. We used
transcranial magnetic stimulation to study the functional connectivity of the left PMd and right primary motor cortex (M1) during an
acoustic choice reaction time (RT) task involving contraction of the thumb and forefinger. The facilitatory and inhibitory pathways that
can be demonstrated between left PMd and right M1 at rest were suppressed during most of the reaction period. However, they were
activated briefly at the start of the reaction period, depending on whether the cue indicated that the forthcoming movement had to be
made withthe left orthe right hand. Thefacilitatory pathway was active at 75msinthosetrialsin whichthe subjects were requiredtomove
the left hand, whereastheinhibitory pathway was active at 100 msintrialsin whichthe subjects hadto movethe right hand. These changes
in excitability did not occur in hand muscles not used in the task. There were no significant changes in the excitability of intracortical
circuits [short intracortical inhibition (SICI) and intracortical facilitation (ICF)] in the right M1. Interhemispheric interactions between
the right PMd and left M1 were mainly inhibitory at rest and showed the same temporal profile of interhemispheric inhibition as for left
PMd–right M1, although no evidence was found for facilitatory interactions. The results illustrate the importance of PMd not only in
facilitating cued movements but also in suppressing movements that have been prepared but are not use
Functional interplay between posterior parietal and ipsilateral motor cortex revealed by twin-coil transcranial magnetic stimulation during reach planning toward contralateral space
Posterior parietal cortex (PPC) has connections with motor and premotor cortex, thought to transfer information relevant for planning
movements in space. We used twin-coil transcranial magnetic stimulation (tcTMS) methods to show that the functional interplay
between human right PPC and ipsilateral motor cortex (M1) varies with current motor plans. tcTMS during the reaction time of a reach
task revealed facilitatory influences of right PPC on right M1 only when planning a (contralateral) leftward rather than rightward reach,
attwo specifictime intervals (50 and 125 ms) after an auditory cue. The earlier reach-direction-specificfacilitatory influencefrom PPC on
M1 occurred when subjects were blindfolded or when the targets were presented briefly, so that visual feedback corrections could not
occur. PPC–M1 interplay was similar withinthe left hemisphere but was specificto (contralateral) rightward planned reaches, with peaks
at 50 and 100 ms. Functional interplay between human parietal and motor cortex is enhanced during early stages of planning a reach in
the contralateral directio
Focal stimulation of the posterior parietal cortex increases the excitability of the ipsilateral motor cortex
Paired-pulse transcranial magnetic stimulation (TMS) has been applied as a probe to test functional connectivity within distinct cortical
areas ofthe human motor system. Here, wetestedthe interaction betweenthe posterior parietal cortex (PPC) and ipsilateral motor cortex
(M1). A conditioning TMS pulse over the right PPC potentiates motor evoked-potentials evoked by a test TMS pulse over the ipsilateral
motor cortex, with a time course characterized by two phases: an early peak at 4 ms interstimulus interval (ISI) and a late peak at 15 ms
ISI. Activation of this facilitatory pathway depends on the intensity of stimulation, because the effects are induced with a conditioning
stimulus of 90% resting motor threshold but not at lower or higher intensities. Similar results were obtained testing the ipsilateral
interaction inthe left hemisphere with a slightly differenttime course. In control experiments, wefoundthat activation ofthisfacilitatory
pathway depends on the direction of induced current in the brain and is specific for stimulation of the caudal part of the inferior parietal
sulcus (cIPS) site, because it is not observed for stimulation of adjacent scalp sites. Finally, we found that by using poststimulus time
histogram analysis of single motor unit firing, the PPC conditioning increases the excitability of ipsilateral M1, enhancing the relative
amount of late I wave input recruited by the test stimulus over M1, suggesting that such interaction is mediated by specific interneurons
in the motor cortex. The described facilitatory connections between cIPS and M1 may be important in a variety of motor tasks and
neuropsychiatric disorder
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