Decrease In Intracortical Facilitation Research Articles

Neurochemical mechanisms underlying serotonergic modulation of neuroplasticity in humans

BackgroundStudies in animals and humans have shown that cortical neuroplasticity can be modulated by increasing serotonin levels by administering selective serotonin reuptake inhibitors (SSRI). However, little is known about the mechanistic background, especially the contribution of intracortical inhibition and facilitation, which depend on gamma-aminobutyric acid (GABA) and glutamate. ObjectiveWe aimed to explore the relevance of drivers of plasticity (glutamate- and GABA-dependent processes) for the effects of serotonin enhancement on tDCS-induced plasticity in healthy humans. MethodsA crossover, partially double-blinded, randomized, and sham-controlled study was conducted in 21 healthy right-handed individuals. In each of the 7 sessions, plasticity was induced via transcranial direct current stimulation (tDCS). Anodal, cathodal, and sham tDCS were applied to the left motor cortex under SSRI (20 mg/40 mg citalopram) or placebo. Short-interval cortical inhibition (SICI) and intracortical facilitation (ICF) were monitored by paired-pulse transcranial magnetic stimulation for 5–6 h after intervention. ResultsUnder placebo, anodal tDCS-induced LTP-like plasticity decreased SICI and increased ICF. In contrast, cathodal tDCS-elicited LTD-like plasticity induced the opposite effect. Under 20 mg and 40 mg citalopram, anodal tDCS did not affect SICI largely, while ICF was enhanced and prolonged. For cathodal tDCS, citalopram converted the increase of SICI and decrease of ICF into antagonistic effects, and this effect was dosage-dependent since it lasted longer under 40 mg when compared to 20 mg. ConclusionWe speculate that the main effects of acute serotonergic enhancement on tDCS-induced plasticity, the increase and prolongation of LTP-like plasticity effects, involves mainly the glutamatergic system.

A Feasibility Study Assessing Cortical Plasticity in Chronic Neuropathic Pain Following Burn Injury

The aim of this article is to evaluate the neuroplastic changes associated with chronic neuropathic pain following burn injury and modulation feasibility using transcranial direct current stimulation (tDCS). This is a crossover, double-blinded case series involving three patients with chronic neuropathic pain following burn injury. Participants were randomly assigned to undergo single sessions of both sham and active anodal tDCS over the primary motor cortex, contralateral to the most painful site. Excitability of the motor cortex was assessed before and after each stimulation session with the use of transcranial magnetic stimulation. An overall decrease in cortical excitability was seen after active tDCS only, as characterized by a decrease in intracortical facilitation and amplitude of motor evoked potentials and an increase in intracortical inhibition. Clinical outcomes did not change after a single session of tDCS. Results are consistent with previous studies showing that patients with chronic neuropathic pain have defective intracortical inhibition. This case series shows early evidence that chronic pain following burn injury may share similar central neural mechanisms, which could be modulated using tDCS.

The dynamic regulation of cortical excitability is altered in episodic ataxia type 2

Episodic ataxia type 2 and familial hemiplegic migraine are two rare hereditary disorders that are linked to dysfunctional ion channels and are characterized clinically by paroxysmal neurological symptoms. Impaired regulation of cerebral excitability is thought to play a role in the occurrence of these paroxysms, but the underlying mechanisms are poorly understood. Normal ion channels are crucial for coordinating neuronal firing in response to facilitatory input. Thus, we hypothesized that channel dysfunction in episodic ataxia type 2 and familial hemiplegic migraine may impair the ability to adjust cerebral excitability after facilitatory events. We tested this hypothesis in patients with episodic ataxia type 2 (n = 6), patients with familial hemiplegic migraine (n = 7) and healthy controls (n = 13). All subjects received a high-frequency burst (10 pulses at 20 Hz) of transcranial magnetic stimulation to transiently increase the excitability of the motor cortex. Acute burst-induced excitability changes were probed at 50, 250, 500 and 1000 ms after the end of the burst. This was done using single-pulse transcranial magnetic stimulation to assess corticospinal excitability, and paired-pulse transcranial magnetic stimulation at an interstimulus interval of 2 and 10 ms to assess intracortical inhibition and facilitation, respectively. The time course of burst-induced excitability changes differed between groups. Healthy controls showed a short-lived increase in excitability that was only present 50 ms after the burst. In contrast, patients with episodic ataxia type 2 showed an abnormally prolonged increase in corticospinal excitability that was still present 250 ms after the transcranial magnetic stimulation burst. Furthermore, while controls showed a decrease in intracortical facilitation during the 1 s period following the transcranial magnetic stimulation burst, patients with episodic ataxia type 2 had increased intracortical facilitation 1000 ms after the burst. Intracortical inhibition was unaltered between groups. Patients with familial hemiplegic migraine were not significantly different from either controls or patients with episodic ataxia type 2. Together, these findings indicate that patients with episodic ataxia type 2 have an excessive increase in motor cortex excitability following a strong facilitatory input. We argue that this deficient control of cortical excitability may set the stage for the emergence of paroxysmal neural dysfunction in this disorder.

Effects of intravenous antidepressant drugs on the excitability of human motor cortex: a study with paired magnetic stimulation on depressed patients

The effect of various drugs was investigated by using transcranial magnetic stimulation (TMS) both in healthy subjects and patients, and the results indicated an influence of antidepressant drugs (ADs) on motor excitability. The aim of our study was to analyze the effects of two ADs, the tricyclic (TCA) clomipramine and the serotoninergic antidepressant (SSRI) citalopram on the motor cortex excitability in major depressed patients with TMS. Thirty affected subjects were placed into three groups: two received an intravenous dose of 25 mg clomipramine or 40 mg citalopram, and one received an injection of a placebo. Motor cortex excitability was studied by single and paired TMS before and after 3.5, 8, and 24 hours from administration of the drugs and placebo. Motor cortical excitability was measured using different TMS parameters: resting motor threshold (RMT), motor-evoked potential (MEP) amplitude, intracortical inhibition (ICI), and intracortical facilitation (ICF). The results indicated a temporary but significant increase of RMT and ICI and a decrease of ICF after the administration of both drugs, with a longer inhibition for the clomipramine rather than the citalopram. MEP amplitude was not significantly affected by the antidepressant injections. Our findings highlight that a single intravenous dose of clomipramine or citalopram exerts a significant but transitory suppression of motor cortex excitability in depressed patients. TMS represents a useful research tool in assessing the effects of motor cortical excitability of drugs used in the treatment of mental disorders.

Reduced intracortical facilitation in patients with cerebellar degeneration.

Transcranial magnetic stimulation (TMS) was used to study intracortical inhibitory and excitatory phenomena in patients with cerebellar ataxia. Motor evoked potentials (MEP) following single and paired TMS were recorded from the first dorsal interosseus muscle (FDI) in 15 patients with autosomal-dominant or idiopathic cerebellar ataxia and 15 age matched normal controls. MEP amplitudes after paired TMS with short interstimulus intervals (1-4 ms) showing intracortical inhibition in the control group were not significantly different in the patient group. In contrast, with longer interstimulus intervals (8-20 ms) mean MEP amplitudes were significantly reduced in the patient group, indicating a decrease of intracortical facilitation. The mean postexcitatory inhibition after TMS was also significantly prolonged in the patient group. Our findings support the idea that the cerebellum physiologically exerts a facilitatory influence on the motor cortex which is decreased in patients with a cerebellar degeneration.

Changes in corticomotor excitability of forearm muscles in relation to static shoulder positions

We examined whether the recruitment properties of the corticospinal pathway to forearm muscles are influenced by variations of the shoulder joint angle. Flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles motor evoked potentials (MEPs) in response to transcranial magnetic stimulation were examined during different static positions of shoulder joint in the horizontal plane: from 30° abduction to 30° adduction. We found that at 30° shoulder adduction, maximum slope and plateau phase of the ECR and FCR input–output relationship (i.e., relation between MEP size and stimulus intensity) were significantly higher and lower than at 30° abduction of the shoulder joint, respectively. Intracortical inhibition (ICI) and intracortical facilitation (ICF) of the FCR were assessed using a paired-magnetic pulse paradigm. A significant decrease in ICF was observed after changing shoulder position from 30° abduction to 30° adduction. On the contrary, no variation in the amount of ICI occurred in relation to the same changes in shoulder position. FCR H-reflex to electrical stimulation of median nerve at elbow did not differ significantly between the two shoulder positions. We conclude that shoulder position influences the recruitment efficiency (gain) of the corticospinal volleys to motoneurones of forearm muscles. It is proposed that activity of peripheral receptors signaling static shoulder position influences corticomotor excitability of forearm muscles mainly at cortical level, although C3–C4 propriospinal system could be also involved. It is proposed that the above changes in corticomotoneuronal excitability to forearm muscles as function of shoulder joint position are part of a global proximal–distal synergy operating throughout reaching movements.

Changes in corticomotor excitability of hand muscles in relation to static shoulder positions

We examined whether the recruitment properties of the corticospinal pathway to intrinsic hand muscles are influenced by variations of the shoulder joint angle. Abductor digiti minimi (ADM) motor evoked potentials (MEPs) in response to transcranial magnetic stimulation were examined during different static positions of the shoulder joint in the horizontal plane from 30 degrees adduction to 30 degrees abduction with respect to the neutral position at 0 degrees, while elbow and wrist joints were constrained statically at 90 degrees and 180 degrees respectively. We found that 30 degrees abduction of the shoulder significantly depressed MEP size and prolonged MEP latency in comparison with 30 degrees shoulder adduction. The neutral shoulder angle position (at 0 degrees ) significantly reduced MEP size but had no effect on MEP latency in comparison with 30 degrees shoulder abduction. The input-output relationship between MEP size and stimulus intensity was sigmoidal. The plateau value and maximum slope were significantly lower at 30 degrees abduction than at 30 degrees adduction of the shoulder. However, the threshold value did not differ significantly between the two positions. To differentiate excitability changes at cortical versus subcortical sites, intracortical inhibition (ICI) and intracortical facilitation (ICF) were assessed using a paired-magnetic pulse paradigm. A significant decrease in ICF was observed after changing shoulder position from 30 degrees adduction to 30 degrees abduction. In contrast, no variation in the amount of ICI occurred in relation to the same changes in shoulder position. ADM F-waves elicited by electrical stimulation of the ulnar nerve at the wrist were significantly decreased at 30 degrees shoulder abduction in comparison with 30 degrees adduction. A similar pattern was observed in one subject in whom the H-reflex could be exceptionally elicited in ADM. We conclude that shoulder position influences the recruitment efficiency (gain) of the corticospinal volleys to motoneurons of intrinsic hand muscles. It is proposed that activity of peripheral receptors signalling static shoulder position influences corticomotor excitability of hand muscles both at the cortical and at the spinal level. This modulation may be functionally relevant when reaching to grasp objects.

Subthreshold low frequency repetitive transcranial magnetic stimulation selectively decreases facilitation in the motor cortex

Objective: To investigate the modulatory effect of a subthreshold low frequency repetitive transcranial magnetic stimulation (rTMS) train on motor cortex excitability.Methods: The study consisted of two separate experiments. Subjects received a 10min long subthreshold 1Hz rTMS train. In the first experiment, (single pulse paradigm), cortical excitability was assessed by measuring the amplitude of motor evoked potentials (MEPs) before and after the rTMS train. In the second experiment, a paired pulse paradigm was employed.Results: Corticospinal excitability, as measured by the MEP amplitude, was reduced by the rTMS train (experiment 1), with a significant effect lasting for about 10min after the train completion. There was notable inter-individual as well as intra-individual variability in the effect. rTMS produced a significant decrease in intra-cortical facilitation as measured by the paired pulse paradigm (experiment 2). This effect lasted for up to 15min following the train. Intra-cortical inhibition was not significantly affected.Conclusions: Subthreshold low frequency rTMS depresses cortical excitability beyond the duration of the train. This effect seems primarily due to cortical dysfacilitation. These results have implications on the therapeutic use of rTMS.

Intravenous clomipramine decreases excitability of human motor cortex. A study with paired magnetic stimulation

Several recent reports suggest the possibility of monitoring pharmacological effects on brain excitability through transcranial magnetic stimulation (TMS). In these studies, paired magnetic stimulation has been used in normal subjects and on patients who were taking different antiepileptic drugs. The aim of our study was to investigate motor area excitability on depressed patients after intravenous administration of a single dose of clomipramine, a tricyclic antidepressant. Motor cortex excitability was studied by single and paired transcranial magnetic stimulation (TMS) before and after 4, 8 and 24 h from intravenous administration of 25 mg of clomipramine. Cortical excitability was measured using different TMS parameters: motor threshold (MT), motor evoked potential (MEP) amplitude, duration of cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF). Spinal excitability and peripheral nerve conduction was measured by F response and M wave. A temporary but significant increase of motor threshold and intracortical inhibition and a decrease of intracortical facilitation were observed 4 h following drug administration. MEP amplitude, cortical silent period, F response and M wave were not significantly affected by drug injection. Our findings suggest that a single intravenous dose of clomipramine can exert a significant but transitory suppression of motor cortex excitability in depressed patients. TMS represents a useful research tool in assessing the effects of motor cortical excitability of neuropsychiatric drugs used in psychiatric disease.

PS-10-3 Intracortical and spinal facilitation mechanism in magnetic cortical stimulation

We examined whether the recruitment properties of the corticospinal pathway to forearm muscles are influenced by variations of the shoulder joint angle. Flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles motor evoked potentials (MEPs) in response to transcranial magnetic stimulation were examined during different static positions of shoulder joint in the horizontal plane: from 30° abduction to 30° adduction. We found that at 30° shoulder adduction, maximum slope and plateau phase of the ECR and FCR input–output relationship (i.e., relation between MEP size and stimulus intensity) were significantly higher and lower than at 30° abduction of the shoulder joint, respectively. Intracortical inhibition (ICI) and intracortical facilitation (ICF) of the FCR were assessed using a paired-magnetic pulse paradigm. A significant decrease in ICF was observed after changing shoulder position from 30° abduction to 30° adduction. On the contrary, no variation in the amount of ICI occurred in relation to the same changes in shoulder position. FCR H-reflex to electrical stimulation of median nerve at elbow did not differ significantly between the two shoulder positions. We conclude that shoulder position influences the recruitment efficiency (gain) of the corticospinal volleys to motoneurones of forearm muscles. It is proposed that activity of peripheral receptors signaling static shoulder position influences corticomotor excitability of forearm muscles mainly at cortical level, although C3–C4 propriospinal system could be also involved. It is proposed that the above changes in corticomotoneuronal excitability to forearm muscles as function of shoulder joint position are part of a global proximal–distal synergy operating throughout reaching movements.

Effect of the intrathecal injection of neuropeptide y (NPY) on the tail flick and cardiovascular responses to a noxious thermal stimulus

We examined whether the recruitment properties of the corticospinal pathway to forearm muscles are influenced by variations of the shoulder joint angle. Flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles motor evoked potentials (MEPs) in response to transcranial magnetic stimulation were examined during different static positions of shoulder joint in the horizontal plane: from 30° abduction to 30° adduction. We found that at 30° shoulder adduction, maximum slope and plateau phase of the ECR and FCR input–output relationship (i.e., relation between MEP size and stimulus intensity) were significantly higher and lower than at 30° abduction of the shoulder joint, respectively. Intracortical inhibition (ICI) and intracortical facilitation (ICF) of the FCR were assessed using a paired-magnetic pulse paradigm. A significant decrease in ICF was observed after changing shoulder position from 30° abduction to 30° adduction. On the contrary, no variation in the amount of ICI occurred in relation to the same changes in shoulder position. FCR H-reflex to electrical stimulation of median nerve at elbow did not differ significantly between the two shoulder positions. We conclude that shoulder position influences the recruitment efficiency (gain) of the corticospinal volleys to motoneurones of forearm muscles. It is proposed that activity of peripheral receptors signaling static shoulder position influences corticomotor excitability of forearm muscles mainly at cortical level, although C3–C4 propriospinal system could be also involved. It is proposed that the above changes in corticomotoneuronal excitability to forearm muscles as function of shoulder joint position are part of a global proximal–distal synergy operating throughout reaching movements.