Fragile-X syndrome (FXS) is characterized by neurological and psychiatric problems symptomatic of cortical hyperexcitability. Recent animal studies identified deficient γ-aminobutyricacid (GABA) inhibition as a key mechanism for hyperexcitability in FXS, but the GABA system remains largely unexplored in humans with the disorder. The primary objective of this study was to assess GABA-mediated inhibition and its relationship with hyperexcitability in patients with FXS. Transcranial magnetic stimulation (TMS) was used to assess cortical and corticospinal inhibitory and excitatory mechanisms in 18 patients with a molecular diagnosis of FXS and 18 healthy controls. GABA-mediated inhibition was measured with short-interval intracortical inhibition (GABAA), long-interval intracortical inhibition (GABAB), and the corticospinal silent period (GABAA+B). Net intracortical facilitation involving glutamate was assessed with intracortical facilitation, and corticospinal excitability was measured with the resting motor threshold. Results showed that FXS patients had significantly reduced short-interval intracortical inhibition, increased long-interval intracortical inhibition, and increased intracortical facilitation compared to healthy controls. In the FXS group, reduced short-interval intracortical inhibition was associated with heightened intracortical facilitation. Taken together, these results suggest that reduced GABAA inhibition is a plausible mechanism underlying cortical hyperexcitability in patients with FXS. These findings closely match those observed in animal models, supporting the translational validity of these markers for clinical research.

Static magnetic fields (SMFs) are known to alter neural activity, but evidence of their ability to modify learning-related neuroplasticity is lacking. The present study tested the hypothesis that application of static magnetic stimulation (SMS), an SMF applied transcranially via a neodymium magnet, over the primary motor cortex (M1) would alter learning of a serial reaction time task (SRTT). Thirty-nine participants took part in two experimental sessions separated by 24 h where they had to learn the SRTT with their right hand. During the first session, two groups received SMS either over contralateral (i.e., left) or ipsilateral (i.e., right) M1 while a third group received sham stimulation. SMS was not applied during the second session. Results of the first session showed that application of SMS over contralateral M1 impaired online learning as compared to both ipsilateral and sham groups, which did not differ. Results further revealed that application of SMS did not impair offline learning or relearning. Overall, these results are in line with those obtained using other neuromodulatory techniques believed to reduce cortical excitability in the context of motor learning and suggest that the ability of SMS to alter learning-related neuroplasticity is temporally circumscribed to the duration of its application.

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It has been shown that when incentives are provided during movement preparation, activity in parieto-frontal regions reflects both expected value and motivational salience. Yet behavioral work suggests that the processing of rewards is faster than for punishments, raising the possibility that expected value and motivational salience manifest at different latencies during movement planning. Given the role of beta oscillations (13-30 Hz) in movement preparation and in communication within the reward circuit, this study investigated how beta activity is modulated by positive and negative monetary incentives during reach planning, and in particular whether it reflects expected value and motivational salience at different latencies. Electroencephalography was recorded while male and female humans performed a reaching task in which reward or punishment delivery depended on movement accuracy. Before a preparatory delay period, participants were informed of the consequences of hitting or missing the target, according to four experimental conditions: Neutral (hit/miss:ϩ0/Ϫ0¢), Reward (hit/miss:ϩ5/Ϫ0¢), Punish (hit/miss:ϩ0/Ϫ5¢) and Mixed (hit/miss:ϩ5/Ϫ5¢). Results revealed that beta power over parieto-frontal regions was strongly modulated by incentives during the delay period, with power positively correlating with movement times. Interestingly, beta power was selectively sensitive to potential rewards early in the delay period, after which it came to reflect motivational salience as movement onset neared. These results demonstrate that beta activity reflects expected value and motivational salience on different time scales during reach planning. They also provide support for models that link beta activity with basal ganglia and dopamine for the allocation of neural resources according to behavioral salience.The present work demonstrates that pre-movement parieto-frontal beta power is modulated by monetary incentives in a goaldirected reaching task. Specifically, beta power transiently scaled with the availability of rewards early in movement planning, before reflecting motivational salience as movement onset neared. Moreover, pre-movement beta activity correlated with the vigor of the upcoming movement. These findings suggest that beta oscillations reflect neural processes that mediate the invigorating effect of incentives on motor performance, possibly through dopamine-mediated interactions with the basal ganglia.