To identify the changes in motor cortical facilitatory and inhibitory circuits in Parkinson disease (PD) by detailed studies of their time courses and interactions.
Short-interval intracortical ...facilitation (SICF) and short-interval intracortical inhibition (SICI) were measured with a paired-pulse paradigm using transcranial magnetic stimulation. Twelve patients with PD in both ON and OFF medication states and 12 age-matched healthy controls were tested. The first experiment tested the time course of SICF in PD and controls. The second experiment tested SICI at different times corresponding to SICF peaks and troughs to investigate whether SICI was affected by SICF.
SICF was increased in PD OFF state and was reduced by dopaminergic medications. The reduction in SICF from the OFF to ON state correlated with the improvement in PD motor signs. SICI was reduced in PD OFF state and was only partially normalized by dopaminergic medications. At SICF peaks, improvement in SICI with medication correlated with improvement in PD motor sign. Principal component analysis showed that variations of SICF and SICI were explained by the same principal component only in the PD OFF group, suggesting that decreased SICI in the OFF state is related to increased SICF.
Motor cortical facilitation is increased and inhibition is decreased in PD. Increased cortical facilitation partly accounts for the decreased inhibition, but there is also impairment in synaptic inhibition in PD. Increased cortical facilitation may be a compensatory mechanism in PD.
The rubber hand illusion (RHI) paradigm experimentally produces an illusion of rubber hand ownership and arm shift by simultaneously stroking a rubber hand in view and a participant's visually ...occluded hand. It involves visual, tactile, and proprioceptive multisensory integration and activates multisensory areas in the brain, including the posterior parietal cortex (PPC). Multisensory inputs are transformed into outputs for motor control in association areas such as PPC. A behavioral study reported decreased motor performance after RHI. However, it remains unclear whether RHI modifies the interactions between sensory and motor systems and between PPC and the primary motor cortex (M1). We used transcranial magnetic stimulation (TMS) and examined the functional connections from the primary somatosensory and association cortices to M1 and from PPC to M1 during RHI. In experiment 1, short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) were measured before and immediately after a synchronous (RHI) or an asynchronous (control) condition. In experiment 2, PPC-M1 interaction was measured using two coils. We found that SAI and LAI were reduced in the synchronous condition compared with baseline, suggesting that RHI decreased somatosensory processing in the primary sensory and the association cortices projecting to M1. We also found that greater inhibitory PPC-M1 interaction was associated with stronger RHI assessed by questionnaire. Our findings suggest that RHI modulates both the early and late stages of processing of tactile afferent, which leads to altered M1 excitability by reducing the gain of somatosensory afferents to resolve conflicts among multisensory inputs. NEW & NOTEWORTHY Perception of one's own body parts involves integrating different sensory information and is important for motor control. We found decreased effects of cutaneous stimulation on motor cortical excitability during rubber hand illusion (RHI), which may reflect decreased gain of tactile input to resolve multisensory conflicts. RHI strength correlated with the degree of inhibitory posterior parietal cortex-motor cortex interaction, indicating that parietal-motor connection is involved in resolving sensory conflicts and body ownership during RHI.
Objective
Internal globus pallidus (GPi) deep brain stimulation (DBS) relieves symptoms in dystonia patients. However, the physiological effects produced by GPi DBS are not fully understood. In ...particular, how a single‐pulse GPi DBS changes cortical circuits has never been investigated. We studied the modulation of motor cortical excitability and plasticity with single‐pulse GPi DBS in dystonia patients with bilateral implantation of GPi DBS.
Methods
The cortical evoked potentials from DBS were recorded with electroencephalography. Transcranial magnetic stimulation with a conditioning test paired‐pulse paradigm was used to investigate the effect of GPi DBS on the primary motor cortex. How GPi DBS might modulate the motor cortical plasticity was tested using a paired associative stimulation paradigm with repetitive pairs of GPi DBS and motor cortical stimulation at specific time intervals.
Results
GPi stimulation produced 2 peaks of cortical evoked potentials with latencies of ∼10 and ∼25 milliseconds in the motor cortical area. Cortical facilitation was observed at ∼10 milliseconds after single‐pulse GPi DBS, and cortical inhibition was observed after a ∼25‐millisecond interval. Repetitive pairs of GPi stimulation with cortical stimulation at these 2 time intervals produced long‐term potentiation‐like effects in the motor cortex.
Interpretation
Single‐pulse DBS modulates cortical excitability and plasticity at specific time intervals. These effects may be related to the mechanism of action of DBS. Combination of DBS with cortical stimulation with appropriate timing has therapeutic potential and could be explored in the future as a method to enhance the effects of neuromodulation for neurological and psychiatric diseases. Ann Neurol 2018;83:352–362
Key points
In the human, sensorimotor integration can be investigated using combined sensory and transcranial magnetic stimulation (TMS).
Short latency afferent inhibition (SAI) refers to motor ...cortical inhibition 20–25ms after median nerve stimulation.
We investigated the influence of SAI on a local excitatory interneuronal motor cortical circuit known as short‐interval intracortical facilitation (SICF) and found that, contrary to expectations, SICF was facilitated in the presence of SAI (SICFSAI); this effect is specific to SICF since there was no effect in control conditions in which SICF was not elicited, and the facilitatory SICFSAI interaction increased with increasing strength of SICF or SAI.
The influence of sensory input on excitatory motor cortical circuitry was similar across different bodily regions, different circuits within motor cortex and across functional states, suggesting that this interaction may have general applicability in sensorimotor integration and motor control.
SAI and SICF were found to correlate between individuals in that those with high SAI were found to have high SICF, and this relationship was maintained when SICF was delivered in the presence of SAI, suggesting an intrinsic relationship between SAI and SICF; these findings are compatible with brain‐slice studies of sensorimotor circuitry and add to our understanding of sensorimotor integration.
In human, sensorimotor integration can be investigated by combining sensory input and transcranial magnetic stimulation (TMS). Short latency afferent inhibition (SAI) refers to motor cortical inhibition 20–25 ms after median nerve stimulation. We investigated the interaction between SAI and short‐interval intracortical facilitation (SICF), an excitatory motor cortical circuit. Seven experiments were performed. Contrary to expectations, SICF was facilitated in the presence of SAI (SICFSAI). This effect is specific to SICF since there was no effect at SICF trough 1 when SICF was absent. Furthermore, the facilitatory SICFSAI interaction increased with stronger SICF or SAI. SAI and SICF correlated between individuals, and this relationship was maintained when SICF was delivered in the presence of SAI, suggesting an intrinsic relationship between SAI and SICF in sensorimotor integration. The interaction was present at rest and during muscle contraction, had a broad degree of somatotopic influence and was present in different interneuronal SICF circuits induced by posterior–anterior and anterior–posterior current directions. Our results are compatible with the finding that projections from sensory to motor cortex terminate in both superficial layers where late indirect (I‐) waves are thought to originate, as well as deeper layers with more direct effect on pyramidal output. This interaction is likely to be relevant to sensorimotor integration and motor control.
Objective
The pathophysiology of psychogenic dystonia has not been examined, but a growing body of literature suggests that abnormal sensory input from repetitive movements can lead to plastic ...cortical changes. Reduced cortical and spinal inhibition is well documented in organic dystonia. We tested the hypothesis that aberrant sensory input associated with abnormal posture may cause similar abnormalities by testing patients with psychogenic dystonia.
Methods
We assessed cortical and spinal inhibitory circuits and cortical activity associated with voluntary movement in 10 patients with clinically definite psychogenic dystonia, 8 patients with organic dystonia, and 12 age‐matched healthy control subjects.
Results
Three measures of cortical inhibition, resting short‐ and long‐interval intracortical inhibition and cortical silent period, were reduced in both psychogenic dystonia and organic dystonia. Cutaneous silent period mediated by spinal circuitries was increased in psychogenic and organic dystonia. Forearm spinal reciprocal inhibition was reduced in psychogenic dystonia.
Interpretation
Psychogenic and organic dystonia share similar physiological abnormalities. Previous findings of abnormal cortical and spinal excitability in organic dystonia may, in part, be a consequence rather than a cause of dystonia. Alternatively, these findings may represent endophenotypic abnormalities that predispose to both types of dystonia. Ann Neurol 2006;59:825–834
Short interval intracortical facilitation (SICF) can be elicited by transcranial magnetic stimulation (TMS) of the motor cortex
(M1) with a suprathreshold first stimulus (S1) followed by a ...subthreshold second stimulus (S2). SICF occurs at three distinct
phases and is likely to be related to the generation of indirect (I) waves. Short interval intracortical inhibition (SICI)
is an inhibitory phenomenon and intracortical facilitation (ICF) is an excitatory phenomenon occurring in the M1 that can
be studied with TMS. We studied the interactions between SICI/ICF and SICF in 17 healthy subjects. Six experiments were conducted.
The first experiment examined the effects of different S1 intensities on SICI, ICF and SICF at three peaks. The effects of
SICI on SICF were tested by a triple-pulse TMS protocol in the second experiment. We performed Experiments 3â5 to further
test the interactions between SICI and SICF with various strengths of SICI, at SICF peaks and troughs, and with SICF generated
by different current direction which preferentially generates late I waves. The effects of ICF on SICF were examined in Experiment
6. The results showed that ICF and SICF decreased whereas SICI increased with higher S1 intensities. SICI facilitated SICF
mediated by late I waves both at the peaks and the troughs of SICF. The increase of SICF in the presence of SICI correlated
to the strength of SICI. ICF decreased the third peak of SICF. We conclude that SICI facilitates SICF at neuronal circuits
responsible for generating late I waves through disinhibition, while ICF may have the opposite effects.
We studied the effects of 1-Hz repetitive transcranial magnetic stimulation (rTMS) on the excitability of interhemispheric connections in 13 right-handed healthy volunteers. TMS was performed using ...figure-eight coils, and surface electromyography (EMG) was recorded from both first dorsal interosseous (FDI) muscles. A paired-pulse method with a conditioning stimulus (CS) to the motor cortex (M1) followed by a test stimulus to the opposite M1 was used to study the interhemispheric inhibition (ppIHI). Both CS and TS were adjusted to produce motor-evoked potentials of approximately 1 mV in the contralateral FDI muscles. After baseline measurement of right-to-left IHI (pre-RIHI) and left-to-right IHI (pre-LIHI), rTMS was applied over left M1 at 1 Hz with 900 stimuli at 115% of resting motor threshold. After rTMS, ppIHI was studied using both the pre-rTMS CS (post-RIHI and post-LIHI) and an adjusted post-rTMS CS set to produce 1-mV motor evoked potentials (MEPs; post-RIHI(adj) and post-LIHI(adj)). The TS was set to produce 1-mV MEPs. There was a significant reduction in post-LIHI (P = 0.0049) and post-LIHI(adj) (P = 0.0169) compared with pre-LIHI at both interstimulus intervals of 10 and 40 ms. Post-RIHI was significantly reduced compared with pre-RIHI (P = 0.0015) but pre-RIHI and post-RIHI(adj) were not significantly different. We conclude that 1-Hz rTMS reduces IHI in both directions but is predominantly from the stimulated to the unstimulated hemisphere. Low-frequency rTMS may be used to modulate the excitability of IHI circuits. Treatment protocols using low-frequency rTMS to reduce cortical excitability in neurological and psychiatric conditions need to take into account their effects on IHI.
Whether there is a projection from the primary motor cortex (M1) to upper facial muscles and how the facial M1 area is modulated
by intracortical inhibitory and facilitatory circuits remains ...controversial. To assess these issues, we applied transcranial
magnetic stimulation (TMS) to the M1 and recorded from resting and active contralateral (C-OOc) and ipsilateral orbicularis
oculi (I-OOc), and contralateral (C-Tr) and ipsilateral triangularis (I-Tr) muscles in 12 volunteers. In five subjects, the
effects of stimulating at different scalp positions were assessed. Paired TMS at interstimulus intervals (ISIs) of 2 ms were
used to elicit short interval intracortical inhibition (SICI) and ISI of 10 ms for intracortical facilitation (ICF). Long
interval intracortical inhibition (LICI) was evaluated at ISIs between 50 and 200 ms, both at rest and during muscle activation.
The silent period (SP) was also determined. C-OOc and I-OOc responses were recorded in all subjects. The optimal position
for eliciting C-OOc responses was lateral to the hand representation in all subjects and MEP amplitude markedly diminished
when the coil was placed 2 cm away from the optimal position. For the I-OOc, responses were present in more scalp sites and
the latency decreased with more anterior placement of the coil. C-Tr response was recorded in 10 out of 12 subjects and the
I-Tr muscle showed either no response or low amplitude response, probably due to volume conduction. SICI and ICF were present
in the C-OOc and C-Tr, but not in the I-OOc muscle. Muscle activation attenuated SICI and ICF. LICI at rest showed facilitation
at 50 ms ISI in all muscles, but there was no significant inhibition at other ISIs. There was no significant inhibition or
facilitation with the LICI protocol during muscle contraction. The SP was present in the C-OOc, C-Tr and I-OOc muscles and
the mean durations ranged from 92 to 104 ms. These findings suggest that the I-OOc muscle response is probably related to
the first component (R1) of the blink reflex. There is M1 projection to the contralateral upper and lower facial muscles in
humans and the facial M1 area is susceptible to cortical inhibition and facilitation, similar to limb muscles.
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