Late cortical disinhibition in focal hand dystonia.

In writer's cramp (WC), a form of focal hand dystonia, cortical GABAergic inhibitory mechanisms are altered and may cause involuntary tonic contractions while writing. The objective of this study was to explore the time course of long-interval intracortical inhibition (LICI) that involves gamma-amino butyric acid (GABA)-B transmission and late cortical disinhibition (LCD) (that combines GABA-A and GABA-B mechanisms) in patients with WC and in control subjects. A double pulse transcranial magnetic stimulation protocol was used to evoke LICI and LCD while the subjects either gripped a cylinder between their thumb and index fingers or relaxed all their upper limb muscles. We measured the ratio between primed and unprimed motor evoked potential in the first dorsal interosseous at interstimulus intervals ranging between 60 and 300 ms. Though the cortical silent period was not different between the groups, LICI lasted longer in patients with WC, that is, LCD was delayed for more than 30 ms and reached a higher level. In addition to the alteration of inhibitory mechanism mediated by GABA-B transmission, LCD which probably involves presynaptic inhibition is also modified in patients with WC with possible consequences on the activity of primary motor cortex inhibitory and excitatory circuits which control the hand muscles.caus.

Parietomotor connectivity in the contralesional hemisphere after stroke: A paired-pulse TMS study.

OBJECTIVES: To assess the contralesional connectivity between the posterior parietal cortex (PPC) and the motor cortex (M1) in stroke patients, and to probe putative relationships with spatial neglect and motor impairment. METHODS: In 12 right-side stroke patients and 12 age-matched healthy controls, we used paired-pulse transcranial magnetic stimulation to assess the contralesional connectivity between three left-side PPC sites (the anterior intraparietal sulcus (aIPS), the posterior intraparietal sulcus and the superior parieto-occipital cortex (SPOC)) and M1. The interstimulus interval (ISI) was set to 4 or 6ms. RESULTS: Although there were no differences between the stroke patient group and the controls, a subgroup analysis showed that stimulation over the SPOC with an ISI of 6ms facilitated motor-evoked potential responses in patients with neglect (and especially those with severe peripersonal neglect), relative to non-neglect patients. With an ISI of 4ms, the aIPS exerted an inhibitory influence on M1 in all subjects. The severity of motor impairment was not associated with PPC-M1 connectivity. CONCLUSIONS: aIPS-M1 connectivity seems to be unaffected in stroke patients, whereas connectivity from the most posterior parts of the parietal cortex depends on the patient's neglect status. SIGNIFICANCE: These results provide insight into post-stroke changes in contralesional PPC-M1 connectivity.

Influence of repetitive transcranial magnetic stimulation on tibialis anterior activity during walking in humans.

OBJECTIVE: To determine whether or not modulation of the excitability of the M1 region controlling the lower limb (using repetitive transcranial magnetic stimulation; TMS) would change the TA's activity during gait and the effect of aging on this change. METHODS: In three separate sessions, participants underwent different repetitive TMS (rTMS) protocols (sham stimulation, intermittent theta-burst stimulation (TBS) and continuous TBS) delivered over the M1 region controlling the lower limb muscles, using a focal, figure-of-eight coil. Before and after rTMS, the TA's activity was recorded using surface electrodes while participants walked at a freely chosen speed and at an imposed speed on a treadmill. Cortical excitability was assessed by characterizing input-output (IO) curves, after fitting the relationship between motor evoked potential amplitude and stimulus intensity with a Boltzmann sigmoidal equation. RESULTS: We did not observe any effects of rTMS in terms of TA activation during locomotion, gait parameters or IO curves in either healthy young adults or elderly adults. Elderly patients presented lower excitability of cortical TA representation area. CONCLUSION: Modulation of TA activity by TBS was ineffective contrary to what is observed for upper limbs. Interindividual variability in the effects of rTMS on TA activation, activation of the TA before the rTMS and/or differences in the depth of the cortical representation of the TA could have influenced the results and should be taken into account for further studies.

Task-dependent changes in late inhibitory and disinhibitory actions within the primary motor cortex in humans.

The objective of the present study was to investigate the time course of long-interval intracortical inhibition (LICI) and late cortical disinhibition (LCD) as a function of the motor task (index abduction, thumb-index precision grip). Motor-evoked potentials were recorded from the first dorsal interosseus (FDI) muscle of the dominant limb in 13 healthy subjects. We used paired-pulse transcranial magnetic stimulation (TMS) paradigms in which a test pulse was preceded by a suprathreshold priming pulse (130% of the resting motor threshold) with varying interstimulus intervals (ISIs). In each task, double pulses were delivered with ISIs ranging from 30% of the corresponding silent period (SP; ~ 45 ms) to 220% of the SP (~ 330 ms). In both tasks, we found that LICI was followed by LCD (namely a period of increased cortical excitability lasting until ~ 200% of the SP). The time-dependent modulation of LICI and LCD differed in the two tasks; LICI was shorter (i.e. disinhibition occurred earlier) and LCD was more intense during precision grip than during index abduction. Long-interval intracortical inhibition disappeared well before the end of the SP in the precision grip task, suggesting that the mechanisms underlying these two inhibitory phenomena are distinct. Our data suggest that disinhibition might reflect adaptation of neural circuit excitability to the functional requirements of the motor task.