Milan B. Jelić

Transcranial application of near-infrared low-level laser can modulate cortical excitability

Near‐infrared low‐level laser (NIR‐LLL) irradiation penetrates scalp and skull and can reach superficial layers of the cerebral cortex. It was shown to improve the outcome of acute stroke in both animal and human studies. In this study we evaluated whether transcranial laser stimulation (TLS) with NIR‐LLL can modulate the excitability of the motor cortex (M1) as measured by transcranial magnetic stimulation (TMS).

Improvement of language functions in a chronic non-fluent post-stroke aphasic patient following bilateral sequential theta burst magnetic stimulation

In chronic non-fluent aphasia patients, inhibition of the intact right hemisphere (RH), by transcranial magnetic stimulation (TMS) or similar methods, can induce improvement in language functions. The supposed mechanism behind this improvement is a release of preserved left hemisphere (LH) language networks from RH transcallosal inhibition. Direct stimulation of the damaged LH can sometimes bring similar results too. Therefore, we developed a novel treatment approach that combined direct LH (Broca’s area (BA)) stimulation, by intermittent theta burst stimulation (TBS), with homologue RH area’s inhibition, by continuous TBS. We present the results of application of 15 daily sessions of the described treatment approach in a right-handed patient with chronic post-stroke non-fluent aphasia. The intervention appeared to improve several language functions, but most notably propositional speech, semantic fluency, short-term verbal memory, and verbal learning. Bilateral TBS modulation of activation of the language-related areas of both hemispheres seems to be a feasible and promising way to induce recovery in chronic aphasic patients. Due to potentially cumulative physiological effects of bilateral stimulation, the improvements may be even greater than following unilateral interventions.

Transcranial magnetic stimulation has no placebo effect on motor learning

OBJECTIVE Motor learning is the core cognitive function in neurorehabilitation and in various other skill-training activities (e.g. sport, music). Therefore, there is an increasing interest in the use of transcranial magnetic stimulation (TMS) methods for its enhancement. However, although usually assumed, a potential placebo effect of TMS methods on motor learning has never been systematically investigated. METHODS Improvement of performance on the Purdue Pegboard Task over three test-blocks (T0, T1, and T2), separated by >20 min, was used to evaluate motor learning. In Experiment-1, two groups of 10 participants each were compared: one group immediately before T1 received a sham intermittent theta burst stimulation procedure (P-iTBS group), while another did not have any intervention at all (control - CON group). In Experiment-2, a third group of participants (six subjects) who received sham high-frequency repetitive TMS procedure before T1 (P-rTMS group) was compared with P-iTBS group. RESULTS All three groups showed significant learning over time, but without any difference between them, either in Experiment-1 between P-iTBS and CON, or in Experiment-2 between P-rTMS and P-iTBS. CONCLUSION The results suggest lack of any placebo effect of TMS on motor learning. SIGNIFICANCE The results may help in designing further TMS-motor learning studies and in interpreting their results.

Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning.

OBJECTIVE To evaluate the differential effects on motor learning of two types of theta burst stimulation (TBS), the excitatory intermittent TBS (iTBS) and inhibitory continuous TBS (cTBS), if TBS is applied in an early stage of learning process. METHODS Thirty right handed healthy people were randomly allocated into one of the three groups according to the intervention applied, iTBS, cTBS or placebo. The interventions and measurements targeted the non-dominant side. The reaction time task (RTT) and Purdue pegboard task (PPT) were used. Measurements and motor tasks were carried out at baseline (T0), immediately after the intervention (T1), and 30 min later (T2). RESULTS Compared to placebo, following cTBS M1 excitability went down and PPT learning was slowed. Following iTBS M1 excitability increased temporarily and PPT learning pattern changed, but learning was not improved. The MEP and PPT changes induced during the T0-T1 time interval correlated significantly. CONCLUSIONS The early consolidation of the learned material was much more influenced by the TBS induced promotion/suppression of the M1 functional plasticity reserves than by the absolute level of the M1 activation. SIGNIFICANCE The results may help to better define the use of TBS in promotion of motor learning in neurorehabilitation and cognitive enhancement.

Bilateral sequential motor cortex stimulation and skilled task performance with non-dominant hand

OBJECTIVE To check whether bilateral sequential stimulation (BSS) of M1 with theta burst stimulation (TBS), using facilitatory protocol over non-dominant M1 followed by inhibitory one over dominant M1, can improve skilled task performance with non-dominant hand more than either of the unilateral stimulations do. Both, direct motor cortex (M1) facilitatory non-invasive brain stimulation (NIBS) and contralateral M1 inhibitory NIBS were shown to improve motor learning. METHODS Forty right-handed healthy subjects were divided into 4 matched groups which received either ipsilateral facilitatory (intermittent TBS [iTBS] over non-dominant M1), contralateral inhibitory (continuous TBS [cTBS] over dominant M1), bilateral sequential (contralateral cTBS followed by ipsilateral iTBS), or placebo stimulation. Performance was evaluated by Purdue peg-board test (PPT), before (T0), immediately after (T1), and 30min after (T2) an intervention. RESULTS In all groups and for both hands, the PPT scores increased at T1 and T2 in comparison to T0, showing clear learning effect. However, for the target non-dominant hand only, immediately after BSS (at T1) the PPT scores improved significantly more than after either of unilateral interventions or placebo. CONCLUSION M1 BSS TBS is an effective intervention for improving motor performance. SIGNIFICANCE M1 BSS TBS seems as a promising tool for motor learning improvement with potential uses in neurorehabilitation.

P 229. Transcranial Laser Stimulation-A New Method for Non-Invasive Modulation of Cortical Excitability

Question: Near infrared low-level laser (nirLLL) irradiation penetrates scalp and skull. It was shown to be able to reduce damage from experimentally induced stroke in animals and to improve memory in middle-aged mice. It was also reported to improve the outcome in human cases of acute stroke. In this study we evaluated whether transcranial application of the nirLLL (transcranial laser stimulation-TLS) can modulate the excitability of the motor cortex (M1) as measured by transcranial magnetic stimulation (TMS). Methods: In the 1st part of the study, motor evoked potentials (MEPs) from the right abductor pollicis brevis (APB) muscle, elicited by single-pulse TMS applied to the left M1 (intensity 120% of the resting motor threshold, rMT) were measured at baseline and every 5 min (up to 30 min) after the TLS, in 18 healthy subjects. For TLS, the nirLLL (wavelength 905 nm, pulse frequency 3 kHz, power density of 50 mW/cm 2 , single dose of 3 J/cm 2 ) was applied for 60 s over a circular area 3 cm in diameter cantered at left M1 APB hot-spot. In the 2 nd part of the study, the MEPs were recorded in the same way in 6 subjects who were found to have very high rMT and poor response to TLS in the Exp1. The TLS parameters were the same except pulse frequency that was increased to 5 kHz which increased total nirLLL delivered (single dose of 4.5 J/cm 2 ). All applied dosed were within the recommended safety limits for human application of nirLLL in physical medicine. The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee. Results: In the 1st part, the most prominent MEP suppression was within time-window 10–25 min following TLS (Fig. 1A). Total of 12 subjects (66.7%) had MEP sizes below baseline level in at least 4 out of 7 (i.e. >50%) post-TLS time points-Responders. ANOVA and post hoc pair-wise analyses showed significant reduction of post-TLS MEP sizes related to baseline in Responders (Fig. 1B). The only difference between Responders and Non-Responders was in rMT (54.9 ± 5.8, and 63.2 ± 8.7, respectively; t(16) = 2.41, p = 0.029). For all subjects together, average post-TLS MEP size correlated significantly with rMT (Spearman R = 0.499, p = 0.035). In the 2nd part, with higher intensity of TLS, 5 subjects were Responders, 4 of them who were Non-Responders in the 1st part, and 1 who was Responder from the beginning but had much larger MEP suppression in the 2nd part. Average post-TLS MEP sizes in these 5 Responders dropped significantly(t(4) = 5.105, p = 007) in comparison to the 1st part. Conclusions: The M1 excitability was found to be reduced after TLS in dose dependent manner. These findings may give insight into the mechanisms of nirLLL effects in the human cerebral cortex, also suggesting more suitable applications of TLS in clinical settings.