Everyday problem solving requires the ability to go beyond experience by efficiently encoding and manipulating new information, i.e., fluid intelligence (Gf) [1]. Performance in tasks involving Gf, such as logical and abstract reasoning, has been shown to rely on distributed neural networks, with a crucial role played by prefrontal regions [2]. Synchronization of neuronal activity in the gamma band is a ubiquitous phenomenon within the brain; however, no evidence of its causal involvement in cognition exists to date [3]. Here, we show an enhancement of Gf ability in a cognitive task induced by exogenous rhythmic stimulation within the gamma band. Imperceptible alternating current [4] delivered through the scalp over the left middle frontal gyrus resulted in a frequency-specific shortening of the time required to find the correct solution in a visuospatial abstract reasoning task classically employed to measure Gf abilities (i.e., Raven's matrices) [5]. Crucially, gamma-band stimulation (γ-tACS) selectively enhanced performance only on more complex trials involving conditional/logical reasoning. The present finding supports a direct involvement of gamma oscillatory activity in the mechanisms underlying higher-order human cognition.

Brief interruption of voluntary EMG in a handAbbreviations BB, biceps brachii; CSP, cortical silent period; ECR, extensor carpi radialis; EIP, extensor indicis proprius; EMG, electromyographic; FDI, first dorsal interosseous; IHI, interhemispheric inhibition; ISP, ipsilateral silent period; L-IHI, long-interval interhemispheric inhibition; M1, primary motor cortex; MEP, motor-evoked potential; MSO, maximum stimulator output; RMS, root mean squares; RMT, resting motor threshold; RT, reaction time; S-IHI, short-interval interhemispheric inhibition; TA, tibialis anterior; TMS, transcranial magnetic stimulation. IntroductionIn humans, intricate and independent finger movements are enabled by a largely crossed system of fast-conducting axons that provides mono-synaptic connections between primary motor cortex (M1) and contralateral spinal motoneurones (Porter & Lemon, 1993). Execution of unimanual or asymmetric bilateral movements relies on a neural network that is capable of lateralising motor cortical output (Carson, 2005;Cincotta & Ziemann, 2008). While a full characterisation of this distributed network is still lacking, data from lesioned monkeys (Brinkman, 1984) and human patients (Chan & Ross, 1988) are in keeping with the view that it probably includes the supplementary motor area and the cingulate gyrus. Positron emission tomography (PET) findings (Sadato et al. 1997) transcranial magnetic stimulation (TMS) data in healthy human subjects (Meyer-Lindenberg et al. 2002;Cincotta et al. 2004;Giovannelli et al. 2006) suggest that the dorsal premotor cortex is also involved. This notion of a neuronal network for movement lateralisation upstream of M1 by no means rules out the possibility that movement lateralisation is supported, in addition, by active inhibition from the voluntarily active M1 to the opposite M1. TMS studies that examined interhemispheric inhibition (IHI) by a paired-pulse protocol with the conditioning stimulus delivered to one M1 and the test stimulus delivered to the other M1 support this hypothesis (Ferbert et al. 1992;Mochizuki et al. 2004;Duque et al. 2007;Hübers et al. 2008). In particular, volitional activity in the M1 receiving the conditioning pulse, e.g. slight unilateral contraction of the contralateral hand, facilitates inhibition of the motor-evoked potential (MEP) elicited by a test stimulus delivered 10 ms later to the opposite M1 (interhemispheric inhibition at short-interstimulus interval, S-IHI) when compared to the rest condition (Ferbert et al. 1992;Mochizuki et al. 2004;Talelli et al. 2008).Besides S-IHI of the MEP, interhemispheric inhibition can also be studied by a short attenuation or interruption of ongoing voluntary electromyographic (EMG) activity in hand muscles induced by focal TMS of the ipsilateral M1 (Wassermann et al. 1991;Ferbert et al. 1992;Meyer et al. 1995;Trompetto et al. 2004;Cincotta et al. 2006). This ipsilateral silent period (ISP) begins 30-40 ms after a single magnetic pulse and lasts, on average, 25 ms (Meyer et al. 1995). Studies in patients with ca...

Differential diagnoses between vegetative and minimally conscious states (VS and MCS, respectively) are frequently incorrect. Hence, further research is necessary to improve the diagnostic accuracy at the bedside. The main neuropathological feature of VS is the diffuse damage of cortical and subcortical connections. Starting with this premise, we used electroencephalography (EEG) recordings to evaluate the cortical reactivity and effective connectivity during transcranial magnetic stimulation (TMS) in chronic VS or MCS patients. Moreover, the TMS-EEG data were compared with the results from standard somatosensory-evoked potentials (SEPs) and event-related potentials (ERPs). Thirteen patients with chronic consciousness disorders were examined at their bedsides. A group of healthy volunteers served as the control group. The amplitudes (reactivity) and scalp distributions (connectivity) of the cortical potentials evoked by TMS (TEPs) of the primary motor cortex were measured. Short-latency median nerve SEPs and auditory ERPs were also recorded. Reproducible TEPs were present in all control subjects in both the ipsilateral and the contralateral hemispheres relative to the site of the TMS. The amplitudes of the ipsilateral and contralateral TEPs were reduced in four of the five MCS patients, and the TEPs were bilaterally absent in one MCS patient. Among the VS patients, five did not manifest ipsilateral or contralateral TEPs, and three of the patients exhibited only ipsilateral TEPs with reduced amplitudes. The SEPs were altered in five VS and two MCS patients but did not correlate with the clinical diagnosis. The ERPs were impaired in all patients and did not correlate with the clinical diagnosis. These TEP results suggest that cortical reactivity and connectivity are severely impaired in all VS patients, whereas in most MCS patients, the TEPs are preserved but with abnormal features. Therefore, TEPs may add valuable information to the current clinical and neurophysiological assessment of chronic consciousness disorders.

Objective: There is growing interest in neuropsychiatry for repetitive transcranial magnetic stimulation (rTMS) as a neuromodulatory treatment. However, there are limitations in interpreting rTMS effects as a real consequence of physiological brain changes or as placebo-mediated unspecific effects, which may be particularly strong in psychiatric patients. This is due to the fact that existing sham rTMS procedures are less than optimal. A new placebo tool is introduced here, called real electro-magnetic placebo (REMP) device, which can simulate the scalp sensation induced by the real TMS, while leaving both the visual impact and acoustic sensation of real TMS unaltered. Methods: Physical, neurophysiological and behavioural variables of monophasic and biphasic single-pulse TMS and biphasic 1 Hz and 20 Hz rTMS procedures (at different intensities) were tested in subjects who were expert or naïve of TMS. Results of the real TMS were compared with those induced by the REMP device and with two other currently used sham procedures, namely the commercially available Magstim sham coil and tilting the real coil by 90°. Results: The REMP device, besides producing scalp sensations similar to the real TMS, attenuated the TMS-induced electric field (as measured by a dipole probe) to a biologically inactive level. Behaviourally, neither expert nor naïve TMS subjects identified the ''coil at 90°'' or the ''Magstim sham coil'' as a real TMS intervention, whilst naïve subjects were significantly more likely to identify the REMP-attenuated TMS as real. Conclusions: The ''goodness of sham'' of the REMP device is demonstrated by physical, neurophysiological, and behavioural results. Significance: Such placebo TMS is superior to the available sham procedures when applied on subjects naïve to TMS, as in case of patients undergoing a clinical rTMS trial.

DCC has a crucial role in the development of corticospinal tracts in humans. Congenital MM is genetically heterogeneous, despite its clinical homogeneity.

Second and third generation AEDs have been directly compared to controlled-release carbamazepine (CBZ-CR) as initial monotherapy for new-onset focal epilepsy. Conversely, no head-to-head trials have been performed. The aim of this study was to estimate the comparative efficacy and tolerability of the antiepileptic monotherapies in adults with newly diagnosed focal epilepsy through a network meta-analysis (NMA). Randomized, double-blinded, parallel group, monotherapy studies comparing any AED to CBZ-CR in adults with newly diagnosed untreated epilepsy with focal-onset seizures was identified. The outcome measures were the seizure freedom for 6 and 12 months, the occurrence of treatment-emergent adverse events (TEAEs), and the treatment withdrawal due to TEAEs. Mixed treatment comparisons were conducted by a Bayesian NMA using the Markov chain Monte Carlo methods. Effect sizes were calculated as odds ratios (ORs) with 95% credible intervals (CrIs). Four trials were included involving 2856 participants, 1445 for CBZ-CR and 1411 for the comparative AEDs. Monotherapy AEDs compared to CBR-CR were levetiracetam (LEV), zonisamide (ZNS), lacosamide (LCM), and eslicarbazepine acetate (ESL). There were no statistical differences in the 6- and 12-month seizure freedom and TEAEs occurrence between LEV, ZNS, LCM, ESL, and CBZ-CR In the analysis of drug withdrawal due to TEAEs, LCM treatment was associated with a significantly lower discontinuation rate than CBZ-CR (OR 0.659, 95% CrI 0.428-0.950). LEV, ZNS, LCM, and ESL are effective initial monotherapy treatments in adult patients with newly diagnosed focal epilepsy and represent suitable alternatives to CBZ-CR.

The neural mechanisms underlying unintended mirror movements (MMs) of one hand during unimanual movements of the other hand in patients with Parkinson's disease (PD) are largely unexplored. Here we used surface electromyographic (EMG) analysis and focal transcranial magnetic stimulation (TMS) to investigate the pathophysiological substrate of MMs in four PD patients. Surface EMG was recorded from both abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles. Cross-correlation EMG analysis revealed no common motor drive to the two APBs during intended unimanual tasks. Focal TMS of either primary motor cortex (M1) elicited normal motor-evoked potentials (MEPs) in the contralateral APB, whereas MEPs were not seen in the ipsilateral hand. During either mirror or voluntary APB contraction, focal TMS of the contralateral M1 produced a long-lasting silent period (SP), whereas stimulation of the ipsilateral M1 produced a short-lasting SP. During either mirror or voluntary finger tapping, 5 Hz repetitive TMS (rTMS) of the contralateral M1 disrupted EMG activity in the target FDI, whereas the effects of rTMS of the ipsilateral M1 were by far slighter. During either mirror or voluntary APB contraction, paired-pulse TMS showed a reduction of short-interval intracortical inhibition in the contralateral M1. These findings provide converging evidence that, in PD, MMs do not depend on unmasking of ipsilateral projections but are explained by motor output along the crossed corticospinal projection from the mirror M1.

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