Theta burst TMS increases cerebral blood flow in the primary motor cortex during motor performance as assessed by arterial spin labeling (ASL)

Theta burst stimulation (TBS) is a novel variant of repetitive transcranial magnetic stimulation (rTMS), which induces changes in neuronal excitability persisting up to 1h. When elicited in the primary motor cortex, such physiological modulations might also have an impact on motor behavior. In the present study, we applied TBS in combination with pseudo continuous arterial spin labeling (pCASL) in order to address the question of whether TBS effects are measurable by means of changes in physiological parameters such as cerebral blood flow (CBF) and if TBS-induced plasticity can modify motor behavior. Twelve right-handed healthy subjects were stimulated using an inhibitory TBS protocol at subthreshold stimulation intensity targeted over the right motor cortex. The control condition consisted of within-subject Sham treatment in a crossover design. PCASL was performed before (pre TBS/pre Sham) and immediately after treatment (post TBS/post Sham). During the pCASL runs, the subjects performed a sequential fingertapping task with the left hand at individual maximum speed. There was a significant increase of CBF in the primary motor cortex after TBS, but not after Sham. It is assumed that inhibitory TBS induced a "local virtual lesion" which leads to the mobilization of more neuronal resources. There was no TBS-specific modulation in motor behavior, which might indicate that acute changes in brain plasticity caused by TBS are immediately compensated. This compensatory reaction seems to be observable at the metabolic, but not at the behavioral level.

Synthesis and two-photon photolysis of 6-(ortho-nitroveratryl)-caged IP3 in living cells

The synthesis of a photolabile derivative of inositol-1,4,5-trisphosphate (IP3) is described. This new caged second messenger (6-ortho-nitroveratryl)-IP3 (6-NV-IP3) has an extinction coefficient of 5000 M(-1) cm(-1) at 350 nm, and a quantum yield of photolysis of 0.12. Therefore, 6-NV-IP3 is photolyzed with UV light about three times more efficiently than the widely used P(4(5))-1-(2-nitrophenyl)ethyl-caged IP3 (NPE-IP3). 6-NV-IP3 has a two-photon cross-section of about 0.035 GM at 730 nm. This absorbance is sufficiently large for effective two-photon excitation in living cells at modest power levels. Using near-IR light (5 mW, 710 nm, 80 MHz, pulse-width 70 fs), we produced focal bursts of IP3 in HeLa cells, as revealed by laser-scanning confocal imaging of intracellular Ca2+ concentrations. Therefore, 6-NV-IP3 can be used for efficient, subcellular photorelease of IP3, not only in cultured cells but also, potentially, in vivo. It is in the latter situation that two-photon photolysis should reveal its true forte.

Benefit of pulmonary vein isolation guided by loss of pace capture on the ablation line: results from a prospective 2-center randomized trial.

OBJECTIVES This study was conducted to determine if an additional procedural endpoint of unexcitability (UE) to pacing along the ablation line reduces recurrence of atrial fibrillation (AF) or atrial tachycardia (AT) after radiofrequency catheter ablation. BACKGROUND AF/AT recurrence is common after pulmonary vein isolation (PVI). METHODS We included 102 patients from 2 centers (age 63 ± 10 years; 33 women; left atrium 38 ± 7 mm; left ventricular ejection fraction 61 ± 6%) with symptomatic paroxysmal AF. A 3-dimensional mapping system and circumferential mapping catheter were used in all patients for PVI. In group 1 (n = 50), the procedural endpoint was bidirectional block across the ablation line. In group 2 (n = 52), additional UE to bipolar pacing at an output of 10 mA and 2-ms pulse width was required. The primary endpoint was freedom from any AF/AT (>30 s) after discontinuation of antiarrhythmic drugs. RESULTS Procedural endpoints were successfully achieved in all patients. Procedure duration was significantly longer in group 2 (185 ± 58 min vs. 139 ± 57 min; p < 0.001); however, fluoroscopy times were not different (23 ± 9 min vs. 23 ± 9 min; p = 0.49). After a follow-up of 12 months in all patients, 26 patients (52%) in group 1 versus 43 (82.7%) in group 2 were free from any AF/AT (p = 0.001) after a single procedure. No major complications occurred. CONCLUSIONS The use of pacing to ensure UE along the PVI line markedly improved near-term single-procedure success, compared with demonstration of bidirectional block alone. This additional endpoint significantly improved patient outcomes after PVI. (Unexcitability Along the Ablation as an Endpoint for Atrial Fibrillation Ablation; NCT01724437).

Space-qualified laser system for the BepiColombo Laser Altimeter

The space-qualified design of a miniaturized laser for pulsed operation at a wavelength of 1064 nm and at repetition rates up to 10 Hz is presented. This laser consists of a pair of diode-laser pumped, actively q-switched Nd:YAG rod oscillators hermetically sealed and encapsulated in an environment of dry synthetic air. The system delivers at least 300 million laser pulses with 50 mJ energy and 5 ns pulse width (FWHM). It will be launched in 2017 aboard European Space Agency’s Mercury Planetary Orbiter as part of the BepiColombo Laser Altimeter, which, after a 6-years cruise, will start recording topographic data from orbital altitudes between 400 and 1500 km above Mercury’s surface.

Estimating the number of motor units using random sums with independently thinned terms

The problem of estimating the numbers of motor units N in a muscle is embedded in a general stochastic model using the notion of thinning from point process theory. In the paper a new moment type estimator for the numbers of motor units in a muscle is denned, which is derived using random sums with independently thinned terms. Asymptotic normality of the estimator is shown and its practical value is demonstrated with bootstrap and approximative confidence intervals for a data set from a 31-year-old healthy right-handed, female volunteer. Moreover simulation results are presented and Monte-Carlo based quantiles, means, and variances are calculated for N in{300,600,1000}.

Modulation of parvalbumin expression in the motor cortex of parkinsonian rats

Dopamine deficiency in Parkinson's disease leads to numerous molecular changes in basal ganglia. However, the consequences of these changes on the motor cortex remain unclear. Here we show that the immunoreactivity of parvalbumin, which is expressed in GABAergic interneurons, increases in the primary motor cortex of parkinsonian rats. This increase can be reversed by a subsequent lesion of the subthalamic nucleus. These results suggest that dopamine deficiency induces reversible changes in GABAergic cortical cells, which might be linked with parkinsonian symptoms.

Semantic, perceptual and number space: relations between category width and spatial processing.

Coarse semantic encoding and broad categorization behavior are the hallmarks of the right cerebral hemisphere's contribution to language processing. We correlated 40 healthy subjects' breadth of categorization as assessed with Pettigrew's category width scale with lateral asymmetries in perceptual and representational space. Specifically, we hypothesized broader category width to be associated with larger leftward spatial biases. For the 20 men, but not the 20 women, this hypothesis was confirmed both in a lateralized tachistoscopic task with chimeric faces and a random digit generation task; the higher a male participant's score on category width, the more pronounced were his left-visual field bias in the judgement of chimeric faces and his small-number preference in digit generation ("small" is to the left of "large" in number space). Subjects' category width was unrelated to lateral displacements in a blindfolded tactile-motor rod centering task. These findings indicate that visual-spatial functions of the right hemisphere should not be considered independent of the same hemisphere's contribution to language. Linguistic and spatial cognition may be more tightly interwoven than is currently assumed.

The latency distribution of motor evoked potentials in patients with multiple sclerosis

OBJECTIVE: To compare the individual latency distributions of motor evoked potentials (MEP) in patients with multiple sclerosis (MS) to the previously reported results in healthy subjects (Firmin et al., 2011). METHODS: We applied the previously reported method to measure the distribution of MEP latencies to 16 patients with MS. The method is based on transcranial magnetic stimulation and consists of a combination of the triple stimulation technique with a method originally developed to measure conduction velocity distributions in peripheral nerves. RESULTS: MEP latency distributions in MS typically showed two peaks. The individual MEP latency distributions were significantly wider in patients with MS than in healthy subjects. The mean triple stimulation delay extension at the 75% quantile, a proxy for MEP latency distribution width, was 7.3ms in healthy subjects and 10.7ms in patients with MS. CONCLUSIONS: In patients with MS, slow portions of the central motor pathway contribute more to the MEP than in healthy subjects. The bimodal distribution found in healthy subjects is preserved in MS. SIGNIFICANCE: Our method to measure the distribution of MEP latencies is suitable to detect alterations in the relative contribution of corticospinal tract portions with long MEP latencies to motor conduction.

Abnormality of motor cortex excitability in peripherally induced dystonia

It is widely accepted that peripheral trauma such as soft tissue injuries can trigger dystonia, although little is known about the underlying mechanism. Because peripheral injury only rarely appears to elicit dystonia, a predisposing vulnerability in cortical motor areas might play a role. Using single and paired-pulse pulse transcranial magnetic stimulation, we evaluated motor cortex excitability of a hand muscle in a patient with peripherally induced foot dystonia, in her brother with craniocervical dystonia, and in her unaffected sister, and compared their results to those from a group of normal subjects. In the patient with peripherally induced dystonia, we found a paradoxical intracortical facilitation at short interstimulus intervals of 3 and 5 milliseconds, at which regular intracortical inhibition (ICI) occurred in healthy subjects. These findings suggest that the foot dystonia may have been precipitated as the result of a preexisting abnormality of motor cortex excitability. Furthermore, the abnormality of ICI in her brother and sister indicates that altered motor excitability may be a hereditary predisposition. The study demonstrates that the paired-pulse technique is a useful tool to assess individual vulnerability, which can be particularly relevant when the causal association between trauma and dystonia is less evident.

Interference during the implicit learning of two different motor sequences

It has been demonstrated that learning a second motor task after having learned a first task may interfere with the long-term consolidation of the first task. However, little is known about immediate changes in the representation of the motor memory in the early acquisition phase within the first minutes of the learning process. Therefore, we investigated such early interference effects with an implicit serial reaction time task in 55 healthy subjects. Each subject performed either a sequence learning task involving two different sequences, or a random control task. The results showed that learning the first sequence led to only a slight, short-lived interference effect in the early acquisition phase of the second sequence. Overall, learning of neither sequence was impaired. Furthermore, the two processes, sequence-unrelated task learning (i.e. general motor training) and the sequence learning itself did not appear to interfere with each other. In conclusion, although the long-term consolidation of a motor memory has been shown to be sensitive to other interfering memories, the present study suggests that the brain is initially able to acquire more than one new motor sequence within a short space of time without significant interference.

Hemispheric asymmetry in visuospatial attention assessed with transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) was used to study visuospatial attention processing in ten healthy volunteers. In a forced choice recognition task the subjects were confronted with two symbols simultaneously presented during 120 ms at random positions, one in the left and the other in the right visual field. The subject had to identify the presented pattern out of four possible combinations and to press the corresponding response key within 2 s. Double-pulse TMS (dTMS) with a 100-ms interstimulus interval (ISI) and an intensity of 80% of the stimulator output (corresponding to 110-120% of the motor threshold) was applied by a non-focal coil over the right or left posterior parietal cortex (PPC, corresponding to P3/P4 of the international 10-20 system) at different time intervals after onset of the visual stimulus (starting at 120 ms, 270 ms and 520 ms). Double-pulse TMS over the right PPC starting at 270 ms led to a significant increase in percentage of errors in the contralateral, left visual field (median: 23% with TMS vs 13% without TMS, P=0.0025). TMS applied earlier or later showed no effect. Furthermore, no significant increase in contra- or ipsilateral percentage of errors was found when the left parietal cortex was stimulated with the same timing. These data indicate that: (1) parietal influence on visuospatial attention is mainly controlled by the right lobe since the same stimulation over the left parietal cortex had no significant effect, and (2) there is a vulnerable time window to disturb this cortical process, since dTMS had a significant effect on the percentage of errors in the contralateral visual hemifield only when applied 270 ms after visual stimulus presentation.

Low-threshold monopolar motor mapping for resection of lesions in motor eloquent areas in children and adolescents

Object Resection of lesions close to the primary motor cortex (M1) and the corticospinal tract (CST) is generally regarded as high-risk surgery due to reported rates of postoperative severe deficits of up to 50%. The authors' objective was to determine the feasibility and safety of low-threshold motor mapping and its efficacy for increasing the extent of lesion resection in the proximity of M1 and the CST in children and adolescents. Methods The authors analyzed 8 consecutive pediatric patients in whom they performed 9 resections for lesions within or close (≤ 10 mm) to M1 and/or the CST. Monopolar high-frequency motor mapping with train-of-five stimuli (pulse duration 500 μsec, interstimulus interval 4.0 msec, frequency 250 Hz) was used. The motor threshold was defined as the minimal stimulation intensity that elicited motor evoked potentials (MEPs) from target muscles (amplitude > 30 μV). Resection was performed toward M1 and the CST at sites negative to 1- to 3-mA high-frequency train-of-five stimulation. Results The M1 was identified through high-frequency train-of-five via application of varying low intensities. The lowest motor thresholds after final resection ranged from 1 to 9 mA in 8 cases and up to 18 mA in 1 case, indicating proximity to motor neurons. Intraoperative electroencephalography documented an absence of seizures during all surgeries. Two transient neurological deficits were observed, but there were no permanent deficits. Postoperative imaging revealed complete resection in 8 patients and a very small remnant (< 0.175 cm(3)) in 1 patient. Conclusions High-frequency train-of-five with a minimal threshold of 1-3 mA is a feasible and safe procedure for resections in the proximity of the CST. Thus, low-threshold motor mapping might help to expand the area for safe resection in pediatric patients with lesions located within the precentral gyrus and close to the CST, and may be regarded as a functional navigational tool. The additional use of continuous MEP monitoring serves as a safety feedback for the functional integrity of the CST, especially because the true excitability threshold in children is unknown.

Modulation of corticospinal activity by strong emotions evoked by pictures and classical music: a transcranial magnetic stimulation study.

Using transcranial magnetic stimulation and skin conductance responses, we sought to clarify if, and to what extent, emotional experiences of different valences and intensity activate the hand-motor system and the associated corticospinal tract. For that purpose, we applied a newly developed method to evoke strong emotional experiences by the simultaneous presentation of musical and pictorial stimuli of congruent emotional valence. We uncovered enhanced motor-evoked potentials, irrespective of valence, during the simultaneous presentation of emotional music and picture stimuli (Combined conditions) compared with the single presentation of the two modalities (Picture/Music conditions). In contrast, vegetative arousal was enhanced during both the Combined and Music conditions, compared with the Picture conditions, again irrespective of emotional valence. These findings strongly indicate that arousal is a necessary, but not sufficient, prerequisite for triggering the motor system of the brain. We offer a potential explanation for this discrepant, but intriguing, finding in the paper.

Intraoperative monopolar mapping during 5-ALA-guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome.

OBJECT Resection of glioblastoma adjacent to motor cortex or subcortical motor pathways carries a high risk of both incomplete resection and postoperative motor deficits. Although the strategy of maximum safe resection is widely accepted, the rates of complete resection of enhancing tumor (CRET) and the exact causes for motor deficits (mechanical vs vascular) are not always known. The authors report the results of their concept of combining monopolar mapping and 5-aminolevulinic acid (5-ALA)-guided surgery in patients with glioblastoma adjacent to eloquent tissue. METHODS The authors prospectively studied 72 consecutive patients who underwent 5-ALA-guided surgery for a glioblastoma adjacent to the corticospinal tract (CST; < 10 mm) with continuous dynamic monopolar motor mapping (short-train interstimulus interval 4.0 msec, pulse duration 500 μsec) coupled to an acoustic motor evoked potential (MEP) alarm. The extent of resection was determined based on early (< 48 hours) postoperative MRI findings. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. RESULTS Five patients were excluded because of nonadherence to protocol; thus, 67 patients were evaluated. The lowest motor threshold reached during individual surgery was as follows (motor threshold, number of patients): > 20 mA, n = 8; 11-20 mA, n = 13; 6-10 mA, n = 10; 4-5 mA, n = 13; and 1-3 mA, n = 23. Motor deterioration at postsurgical Day 1 and at discharge occurred in 30% (n = 20) and 10% (n = 7) of patients, respectively. At 3 months, 3 patients (4%) had a persisting postoperative motor deficit, 2 caused by vascular injury and 1 by mechanical injury. The rates of intra- and postoperative seizures were 1% and 0%, respectively. Complete resection of enhancing tumor was achieved in 73% of patients (49/67) despite proximity to the CST. CONCLUSIONS A rather high rate of CRET can be achieved in glioblastomas in motor eloquent areas via a combination of 5-ALA for tumor identification and intraoperative mapping for distinguishing between presumed and actual motor eloquent tissues. Continuous dynamic mapping was found to be a very ergonomic technique that localizes the motor tissue early and reliably.