Priming the right motor cortex (M1) influences the effect of intermittent theta burst stimulation on excitability over left M1

Priming the right motor cortex (M1) influences the effect of intermittent theta burst stimulation on excitability over left M1

264 Abstracts 1. Stagg et al, 2008 Submitted. 2. Brand et al, 1993 Dev Neurosci. 3. Yousry et al, 1997 Brain. Physiology Poster Only 77 dosing, af...

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264

Abstracts

1. Stagg et al, 2008 Submitted. 2. Brand et al, 1993 Dev Neurosci. 3. Yousry et al, 1997 Brain.

Physiology Poster Only 77

dosing, after drug dosing and after practice of a ballistic motor task. Changes in these measures after the drug dosing were compared with the changes in amplitude of motor-evoked potentials (MEP) after the ballistic motor task. Result: Lorazepam increased SICI and decreased SAI, while zolpidem only decreased SAI. Practice-dependent plasticity of MEPs was impaired by lorazepam but not zolpidem. The increase in SICI produced by lorazepam was negatively correlated with practice-dependent plasticity (Figure 1), but there was no correlation with lorazepam-induced SAI change.

Oculo-manual coupling during visually-guided saccades: A transcranial magnetic stimulation study

Falciati L, Gianesini T, Maioli C, University of Brescia (Brescia, IT) Hand pointing of objects under visual guidance is one of the most common motor behaviour in everyday life. In natural conditions gaze and arm movements are commonly aimed at the same target and the accuracy of both systems is considerably enhanced if eye and hand move together. Evidence supports the viewpoint that gaze and limb control systems are not independent, but share at least partially a common neural controller. The present study was aimed at verifying whether a saccade execution induces excitability changes in the upper-limb corticospinal system (CSS), even in the absence of a manual response, demonstrating the existence of a common drive to ocular and arm motor systems during fast aiming movements. Nineteen right-handed healthy subjects (mean age 20.7 years, range: 20-23) were tested. By applying a single-pulse TMS to the left motor cortex during a saccadic eye movement task, we recorded motor evoked potentials (MEPs) induced in hand and wrist muscles of the contralateral relaxed arm (first dorsal interosseous, abductor digiti minimi, extensor carpi radialis and flexor carpi ulnaris). Subjects had to made visually-guided saccades to one of 6 positions along the horizontal meridian (65 , 610 or 615 ). During each trial, TMS was randomly delivered at one of 3 different time delays: shortly after the end of the saccade, 300 ms, or 540 ms after saccade onset. Results demonstrate that a fast eye movement toward a peripheral target is linked to changes in the CSS excitability of the relaxed upper-limb, as estimated by the amplitude of the recorded MEPs. MEP amplitude increases immediately after the saccade onset and gradually decreases at longer TMS delays. Moreover, on top of the decrease in the overall CSS excitability, MEP amplitudes are modulated in a highly specific manner in the different muscles, depending on the target position of the visually-guided saccade and on the timing of TMS stimulation. By applying a simple model of a manual aiming movement, it is possible to demonstrate that the experimentally observed changes in CSS excitability are in principle compatible with the facilitation of an arm motor program, whose goal is to direct the hand toward the same target of the gaze movement. Our data provide strong evidence in favour of the existence of a common drive to both eye and limb motor systems. Making a visually-guided saccade entails a motor plan also for a covert hand movement, aiming at the same target of gaze.

TMS Poster Only 78

Differences in intracortical circuits that inhibit practice-dependent plasticity

Teo JTH, Terranova C, Swayne OB, Greenwood RJ, Rothwell JC, Institute of Neurology (London, UK) Introduction: Practice of a motor task leads to an increase in amplitude of motor-evoked potentials (MEP) in the exercised muscle. This is termed practice-dependent plasticity, and is abolished by the NMDA antagonist dextromethorphan or the GABAA agonist lorazepam. Objective: Here, we sought to determine whether specific GABAA circuits are responsible for the inhibition of practice-dependent plasticity. Method: A randomised double-blind trial was performed consisting of two drug arms: the non-specific GABAA agonist, lorazepam, or the specific GABAAalpha1-agonist, zolpidem. Short-interval intracortical inhibition (SICI), shortinterval afferent inhibition (SAI) and long-interval intracortical inhibition (LICI) were measured using transcranial magnetic stimulation (TMS) before drug

Conclusion: This suggests that neurons expressing GABAA-alpha1 receptor subunits may not be involved in modulating practice-dependent plasticity, and the SICI intracortical circuit is the predominant inhibitor of practice-dependent plasticity.

rTMS Poster Only 79

Priming the right motor cortex (M1) influences the effect of intermittent theta burst stimulation on excitability over left M1

Ragert P1, Camus M2, Vandermeeren Y2, Cohen L2, 1MPI Leipzig (Leipzig, DE); 2NINDS (Bethesda, US) Introduction: Theta Burst Stimulation (TBS) is a novel non-invasive method of conditioning the human motor cortex (M1) that can induce bidirectional changes in corticospinal excitability depending on the choice of stimulus parameters. However, several previous human studies provided evidence that the outcome of non-invasive brain stimulation depends on the previous history of neural activity. These findings indicate that homeostatic plasticity in human M1 might be one important physiological mechanism for the regulation of corticospinal excitability. While homeostatic plasticity has been demonstrated within M1 of one hemisphere, little is known to which extent it operates across the two hemispheres. Methods: Using two subsequent brain stimulation protocols, we sought to determine whether preconditioning of the right M1 by means of lowfrequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) influences the effect of iTBS on corticospinal excitability over left M1. Subjects were randomly allocated to one of four experimental groups in a sham-controlled parallel design. The only difference between each group was the type of the brain stimulation protocol (real/sham) applied to the right and left M1. In general, right M1 stimulation using 1 Hz rTMS or sham preceded left M1 stimulation (iTBS or sham) by approximately 10 minutes. Changes in corticospinal excitability of the ipsilateral (left) MI were assessed by recruitment curves (RCs) to TMS. Additionally, pinch force, simple reaction time and tapping speed were assessed in the right hand. Results: When applied alone, 1Hz rTMS over right M1 and iTBS over left M1 increased RCs in the left M1 relative to sham. However, the effect of iTBS on

Abstracts RCs was diminished when the right M1 was preconditioned with 1 Hz rTMS. Motor performance of the right hand remained unchanged under all conditions. Significance: The present findings suggest that homeostatic mechanisms might contribute to regulate plasticity across human motor cortices.

rTMS Poster Only 81

TMS: increase of neural noise or reduction of signal strength?

Ruzzoli M1, Marzi CA1, Miniussi C2, 1University of Verona (Verona, IT); 2 University of Brescia, IRCCS San Giovanni di Dio (Brescia, IT) TMS has become a popular tool in neuroscience for mapping perceptual and cognitive processes in the human cortex. In this respect TMS is often considered as ‘‘virtual lesion’’ method because it induces a transitory disruption of cognitive activity (Pascual-Leone et al., 2000). An alternative hypothesis suggests that TMS impairs performance by inducing random neuronal activity (Amassian et al., 1994; Stewart et al., 2001; Harris et al., 2008). The aim of the present study is to highlight the mechanisms of action of TMS by observing its effects with respect to the strength of a visual signal. We tested 9 healthy subjects (mean age 5 22, SD 5 2.99) during a moving dots direction discrimination task (2forced-choice response). We considered 5 levels of motion coherence with respect to the individual threshold perceptual level (methods of constant stimuli). The TMS protocol included repetitive TMS 15Hz (at 50-150 ms) on left V5/MT, left V1 and a SHAM condition. Our predictions were as follows: a) if TMS acts by adding random neural noise it should modify the psychometric curve, shifting it toward left, and therefore indicating a drop of performance when applied to V5 unrelated to the strength of visual signal. b) If TMS acts selectively on the processing of relevant information rather than on visual noise, the impairment of performance should be evident only when the strength of the visual signal is high. We performed an ANOVA with repetitive measures on d-prime variables: the results indicate an interaction between Site of TMS Application (V5, V1, Sham) and Motion Strength (5 levels), (F 5 2.45, df 5 8, p 5 0.02). Post hoc analysis showed that TMS of V5 affects performance only when the visual motion strength is high (p , 0.05).There was no statistical difference between the V1 and the Sham condition. We interpret these results as evidence that rTMS on line does not induce neural noise interfering with the processing of relevant information, but decreases the strength of the neural signal carrying information about the stimulus.

rTMS Poster Only 82

Effects of unilateral 10Hz repetitive transcranial magnetic stimulation (rTMS) on the excitability of corticospinal and inter-hemispheric pathways in humans

Kuppuswamy A, Ellaway P, Imperial College (London, UK) Repetitive transcranial magnetic stimulation (rTMS) induces plasticity in the motor cortex revealed as short term changes in the excitability of corticospinal pathways. The action appears dependent on the pattern and duration of rTMS. This study is designed to investigate the effect of short trains of 10Hz rTMS on the corticospinal and inter-hemispheric pathways. With informed consent 15 normal healthy volunteers were studied. Surface Ag-AgCl electrodes were used to record EMG from the right and left first dorsal interosseous (FDI) muscles. A 70mm fig-of-8 coil attached to a Rapid2 Magstim stimulator was used to deliver TMS. The cranial hotspot and resting motor threshold (RMT) was determined for both left and right motor cortices for motor evoked potentials (MEP) in the contralateral FDI. Contralateral MEPs were then elicited at 120% RMT for both cortices with the FDI muscle at rest. Ipsilateral cortical silent periods (iCSP) were recorded in response to ipsilateral cortex stimulation at 120% RMT (for the contralateral muscle) during a 50% maximum voluntary contraction. Rectified and averaged traces were used to determine magnitude of the MEPs and iCSPs.

265 rTMS was delivered as 1s trains at 10Hz every 10s at RMT to the left motor cortex. Following rTMS, MEPs and iCSPs were reassessed. The MEP and iCSP responses in the right FDI muscle did not show any significant changes (P . 0.05, paired t-tests). MEPs in the relaxed left FDI muscle were smaller and iCSP in left FDI was significantly larger following rTMS (P , 0.05, paired t-tests). A short train of 10Hz rTMS stimulation over the left motor cortex increased inter-hemispheric inhibition evident as a reduction of MEP size in the left FDI and an increase in the ipsilateral cortical silent period of left FDI. A small number of rTMS pulses at 10Hz appear to enhance selectively the activity of inter-hemispheric inhibitory circuits, presumably via a transcallosal pathway.

rTMS Poster Only 83

Interhemispheric balance of attention: A theta burst stimulation study

Nyffeler T, Cazzoli D, Wurtz P, von Wartburg R, Chaves S, Lu¨thi M, De´ruaz A, Hess C, Mu¨ri R, Perception and Eye Movement Laboratory (Bern, CH) Objective: Interhemispheric imbalance is discussed as a pathophysiological mechanism in visuospatial neglect. It is suggested that after a lesion of the right hemisphere, the mutual transcallosal inhibition is impaired resulting in an increased activity of the left hemisphere. We investigated interhemispheric balance of attention in healthy subjects using a free visual exploration task and by interfering with the neural activity of the posterior parietal cortex (PPC) of either hemisphere by means of theta burst stimulation (TBS). Method: Subjects explored colour photographs of real-life scenes presented on a computer screen under four conditions: 1) without TBS; 2) after TBS over right PPC; 3) after TBS over left PPC; 4) after TBS over right PPC and – after the first half of the task - over left PPC. Eye movements were measured, and the distribution of mean cumulative fixation duration over screen halves was analyzed. In addition, a symmetry index (SI) with percentage of change over conditions was calculated. Result: TBS over the right PPC resulted in a significant rightward shift of mean cumulative fixation duration over thirty minutes. This shift could be reversed when a subsequent train of TBS was applied over the left PPC. However, left PPC stimulation alone had no significant effect on visual exploration behaviour. A stronger TBS effect over left PPC in the bilateral stimulation condition was also reflected in the percentage of change of the SI: Compared to stimulation over the left PPC alone, TBS effects were about four times greater if the right PPC was stimulated beforehand. Conclusion: The present study shows that the effect of TBS on the PPC critically depends on which hemisphere is stimulated and on the state of the contralateral homologue area. The effect of TBS over the left PPC was more pronounced after prior disruption of the interhemispheric balance by means of right PPC stimulation. Such a finding is in accordance with the predictions of the interhemispheric imbalance model. The finding of stronger effects after right vs. left PPC stimulation are in line with the well known right hemispheric dominance for visuospatial attention.

rTMS Poster Only 84

Visuospatial attention and theta burst stimulation: does gender play a role?

Cazzoli D, Nyffeler T, Wurtz P, von Wartburg R, Chaves S, De´ruaz A, Lu¨thi M, Hess C, Mu¨ri R, Perception and Eye Movement Laboratory (Bern, CH) Objective: Literature concerning gender differences in visuospatial attention is inconsistent. Furthermore, only few transcranial magnetic stimulation (TMS) studies investigated gender differences. By means of a free visual exploration task, the present study aimed at investigating gender