Maryam Zoghi

Differential Modulation of Intracortical Inhibition in Human Motor Cortex during Selective Activation of an Intrinsic Hand Muscle

Paired‐pulse transcranial magnetic stimulation (TMS) was used to assess the effectiveness of intracortical inhibition (ICI) acting on corticospinal neurons controlling three intrinsic hand muscles in humans. We hypothesised that the suppression of ICI with selective activation of a muscle would be restricted to corticospinal neurons controlling the muscle targeted for activation. Surface EMG was recorded from abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles of the left hand. Subjects were tested at rest and during weak selective activation of APB or ADM, while they attempted to keep the other muscles relaxed using visual feedback. Paired‐pulse TMS was applied with a circular coil oriented to produce antero‐posterior (AP) current flow in the right motor cortex (to preferentially evoke I3 waves in corticospinal neurons) and with postero‐anterior (PA) currents (to preferentially evoke I1 waves). Paired‐pulse TMS was less effective in suppressing the muscle evoked potential (MEP) when the muscle was targeted for selective activation, with both AP and PA stimulation. The mechanism for this includes effects on late I waves, as it was evident with a weak AP test TMS pulse that elicited negligible I1 waves in corticospinal neurons. ICI circuits activated by TMS, which exert their effects on late I waves but do not affect I1 waves, are strongly implicated in this modulation. With AP stimulation, paired‐pulse inhibition was not significantly altered for corticospinal neurons controlling other muscles of the same hand which were required to be inactive during the selective activation task. This differential modulation was not seen with PA stimulation, which preferentially activates I1 waves and evokes a MEP that is less influenced by ICI. The observations with AP stimulation suggest that selective activation of a hand muscle is accompanied by a selective suppression of ICI effects on the corticospinal neurons controlling that muscle. The pattern of differential modulation of ICI effectiveness with voluntary activation suggests that the ICI circuits assist the corticospinal system in producing fractionated activity of intrinsic hand muscles.

Does anodal transcranial direct current stimulation modulate sensory perception and pain? A meta-analysis study

OBJECTIVE The primary aim of this systematic review was to evaluate the effects of anodal transcranial direct current stimulation (a-tDCS) on sensory (STh) and pain thresholds (PTh) in healthy individuals and pain levels (PL) in patients with chronic pain. METHODS Electronic databases were searched for a-tDCS studies. Methodological quality was examined using the PEDro and Downs and Black (D&B) assessment tools. RESULTS a-tDCS of the primary motor cortex (M1) increases both STh (P<0.005, with the effect size of 22.19%) and PTh (P<0.001, effect size of 19.28%). In addition, STh was increased by a-tDCS of the primary sensory cortex (S1) (P<0.05 with an effect size of 4.34). Likewise, PL decreased significantly in the patient group following application of a-tDCS to both the M1 and dorsolateral prefrontal cortex (DLPFC). The average decrease in visual analogue score was 14.9% and 19.3% after applying a-tDCS on the M1 and DLPFC. Moreover, meta-analysis showed that in all subgroups (except a-tDCS of S1) active a-tDCS and sham stimulation produced significant differences. CONCLUSIONS This review provides evidence for the effectiveness of a-tDCS in increasing STh/PTh in healthy group and decreasing PL in patients. However, due to small sample sizes in the included studies, our results should be interpreted cautiously. Given the level of blinding did not considered in inclusion criteria, the result of current study should be interpreted with caution. SIGNIFICANCE Site of stimulation should have a differential effect over pain relief.

The effect of anodal transcranial direct current stimulation on motor sequence learning in healthy individuals: A systematic review and meta-analysis

A large number of studies have indicated the effect of anodal transcranial direct current stimulation (a-tDCS) on the primary motor cortex (M1) during motor skill training. The effects of a-tDCS on different stages of motor sequence learning are not yet completely understood. The purpose of this meta-analysis was to determine the effects of single and multiple sessions of a-tDCS on two different tasks: the sequential finger tapping task/serial reaction time task (SEQTAP/SRTT) and the sequential visual isometric pinch task (SVIPT). We searched electronic databases for M1 a-tDCS studies. Thirteen studies met the inclusion criteria. The results indicate that application of multiple sessions of a-tDCS, compared to single session a-tDCS induced a significant improvement in skill in both SEQTAP/SRTT and SVIPT. Retention after a single day and multiple days of a-tDCS was statistically significant for the SEQTAP/SRTT task but not for SVIPT. Therefore, our findings suggest that application of M1 a-tDCS across the three or five consecutive days can be helpful to improve motor sequence learning.

Different Current Intensities of Anodal Transcranial Direct Current Stimulation Do Not Differentially Modulate Motor Cortex Plasticity

Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates the excitability of neurons within the motor cortex (M1). Although the aftereffects of anodal tDCS on modulating cortical excitability have been described, there is limited data describing the outcomes of different tDCS intensities on intracortical circuits. To further elucidate the mechanisms underlying the aftereffects of M1 excitability following anodal tDCS, we used transcranial magnetic stimulation (TMS) to examine the effect of different intensities on cortical excitability and short-interval intracortical inhibition (SICI). Using a randomized, counterbalanced, crossover design, with a one-week wash-out period, 14 participants (6 females and 8 males, 22–45 years) were exposed to 10 minutes of anodal tDCS at 0.8, 1.0, and 1.2 mA. TMS was used to measure M1 excitability and SICI of the contralateral wrist extensor muscle at baseline, immediately after and 15 and 30 minutes following cessation of anodal tDCS. Cortical excitability increased, whilst SICI was reduced at all time points following anodal tDCS. Interestingly, there were no differences between the three intensities of anodal tDCS on modulating cortical excitability or SICI. These results suggest that the aftereffect of anodal tDCS on facilitating cortical excitability is due to the modulation of synaptic mechanisms associated with long-term potentiation and is not influenced by different tDCS intensities.

Focal transcranial magnetic stimulation of motor cortex evokes bilateral and symmetrical silent periods in human masseter muscles.

OBJECTIVE To determine whether a single hemisphere exerts distinct inhibitory influences over masseter muscles on each side, and to compare features of the masseter cortical silent period (CSP) evoked by transcranial magnetic stimulation (TMS) with previous reports from limb and other cranial muscles. METHODS Focal TMS was applied over the motor cortex jaw area in 14 normal subjects. In one experiment, TMS intensity was constant (1.1 or 1.3x active motor threshold, T) and masseter muscle activation varied from 10% to 100% of maximal. In another experiment, muscle activation was constant (20% maximal) and TMS intensity varied from 0.7 to 1.3T. RESULTS In all subjects, TMS evoked a silent period of similar duration in masseter muscles on both sides. Masseter CSP duration increased at higher TMS intensities, but was not affected by muscle activation level or the size of the excitatory response evoked by TMS. Weak TMS produced a bilateral CSP without short-latency excitation. The masseter CSP was short ( approximately 100ms at 1.3T), yet this was not due to maintenance of excitatory drive from the unstimulated hemisphere, as the masseter CSP was not prolonged with dual-hemisphere TMS. CONCLUSIONS Intracortical inhibitory circuits activated by TMS have a relatively weak effect on corticotrigeminal neurons supplying masseter, and effects are equivalent for corticobulbar efferents directed to contralateral and ipsilateral masseter motoneuron pools. SIGNIFICANCE Trigeminally innervated masseter muscles exhibit weak, bilaterally symmetric inhibition following focal TMS. This method can be used to investigate abnormalities of intracortical inhibition in movement disorders or focal lesions affecting the masticatory muscles in humans.

Anodal transcranial pulsed current stimulation: A novel technique to enhance corticospinal excitability.

OBJECTIVE We aimed to compare the effects of anodal-transcranial pulsed current stimulation (a-tPCS) with conventional anodal transcranial direct current stimulation (a-tDCS) on corticospinal excitability (CSE) in healthy individuals. METHODS CSE of the dominant primary motor cortex of the resting right extensor carpi radialis muscle was assessed before, immediately, 10, 20 and 30min after application of four experimental conditions: (1) a-tDCS, (2) a-tPCS with short inter-pulse interval (a-tPCSSIPI, 50ms), (3) a-tPCS with long inter-pulse interval (a-tPCSLIPI., 650ms) and (4) sham a-tPCS. The total charges were kept constant in all experimental conditions except sham condition. The outcome measure in this study was motor evoked potentials. RESULTS Only a-tDCS and a-tPCSSIPI (P<0.05) induced significant increases in CSE, lasted for at least 30min. Post-hoc tests indicated that this increase was larger in a-tPCSSIPI (P<0.05). There were no significant changes following application of a-tPCSLIPI and sham a-tPCS. All participants tolerated the applied currents in all experimental conditions very well. CONCLUSIONS Compared to a-tDCS, a-tPCSSIPI is a better technique for enhancement of CSE. There were no sham effects for application of a-tPCS. However, unlike a-tDCS which modifies neuronal excitability by tonic depolarization of the resting membrane potential, a-tPCS modifies neuronal excitability by a combination of tonic and phasic effects. SIGNIFICANCE a-tPCS could be considered as a promising neuromodulatory tool in basic neuroscience and as a therapeutic technique in neurorehabilitation.

A Meta-Analysis of Site-Specific Effects of Cathodal Transcranial Direct Current Stimulation on Sensory Perception and Pain

The primary aim of our meta-analysis was to evaluate the effects of cathodal transcranial direct current stimulation (c-tDCS) on sensory and pain thresholds (STh and PTh) in healthy individuals and pain level (PL) in patients with chronic pain. Electronic databases were searched for c-tDCS studies. Methodological quality was evaluated using the PEDro and Downs and Black (D&B) assessment tools. C-tDCS of the primary motor cortex (S1) increases both STh (P<0.001, effect size of 26.84%) and PTh (P<0.001, effect size of 11.62%). In addition, c-tDCS over M1 led to STh increase (P<0.005, effect size of 30.44%). Likewise, PL decreased significantly in the patient group following application of c-tDCS. The small number of studies precluded subgroup analysis. Nevertheless, meta-analysis showed that in all groups (except c-tDCS of S1) active c-tDCS and sham stimulation produced significant differences in STh/PTh in healthy and PL in patient group. This review provides evidence for the site-specific effectiveness of c-tDCS in increasing STh/PTh in healthy individuals and decreasing PL in patients with chronic pain. However, due to small sample sizes in the included studies, our results should be interpreted with caution. Given that the level of blinding was not considered in the inclusion criteria, the results of the current study should be interpreted with caution.

How does anodal transcranial direct current stimulation of the pain neuromatrix affect brain excitability and pain perception? A randomised, double-blind, sham-control study.

Background Integration of information between multiple cortical regions of the pain neuromatrix is thought to underpin pain modulation. Although altered processing in the primary motor (M1) and sensory (S1) cortices is implicated in separate studies, the simultaneous changes in and the relationship between these regions are unknown yet. The primary aim was to assess the effects of anodal transcranial direct current stimulation (a-tDCS) over superficial regions of the pain neuromatrix on M1 and S1 excitability. The secondary aim was to investigate how M1 and S1 excitability changes affect sensory (STh) and pain thresholds (PTh). Methods Twelve healthy participants received 20 min a-tDCS under five different conditions including a-tDCS of M1, a-tDCS of S1, a-tDCS of DLPFC, sham a-tDCS, and no-tDCS. Excitability of dominant M1 and S1 were measured before, immediately, and 30 minutes after intervention respectively. Moreover, STh and PTh to peripheral electrical and mechanical stimulation were evaluated. All outcome measures were assessed at three time-points of measurement by a blind rater. Results A-tDCS of M1 and dorsolateral prefrontal cortex (DLPFC) significantly increased brain excitability in M1 (p < 0.05) for at least 30 min. Following application of a-tDCS over the S1, the amplitude of the N20-P25 component of SEPs increased immediately after the stimulation (p < 0.05), whilst M1 stimulation decreased it. Compared to baseline values, significant STh and PTh increase was observed after a-tDCS of all three stimulated areas. Except in M1 stimulation, there was significant PTh difference between a-tDCS and sham tDCS. Conclusion a-tDCS of M1 is the best spots to enhance brain excitability than a-tDCS of S1 and DLPFC. Surprisingly, a-tDCS of M1 and S1 has diverse effects on S1 and M1 excitability. A-tDCS of M1, S1, and DLPFC increased STh and PTh levels. Given the placebo effects of a-tDCS of M1 in pain perception, our results should be interpreted with caution, particularly with respect to the behavioural aspects of pain modulation. Trial Registration Australian New Zealand Clinical Trials, ACTRN12614000817640, http://www.anzctr.org.au/.

Effects of training on upper limb function after cervical spinal cord injury: a systematic review

Objective: To summarize the evidence for the effectiveness of exercise training in promoting recovery of upper extremity function after cervical spinal cord injury. Data sources: Medline, Cochrane, CINAHL, EMBASE and PEDro were used to search the literature. Review methods: Two reviewers independently selected and summarized the included studies. Methodological quality of the selected articles was scored using the Downs and Black checklist. Results: A total of 16 studies were included, representing a total of 426 participants. Overall, the internal validity and reporting of the studies was fair to good, while power and external validity were poor. Interventions included exercise therapy, electrical stimulation, functional electrical stimulation, robotic training and repetitive transcranial magnetic stimulation. Most of the studies reported improvements in muscle strength, arm and hand function, activity of daily living or quality of life after intervention. Conclusions: Training including exercise therapy, electrical stimulation, functional electrical stimulation of the upper limb following cervical spinal cord injury leads to improvements in muscle strength, upper limb function and activity of daily living or quality of life. Further research is needed into the effects of repetitive transcranial magnetic stimulation and robotic training on upper limb function.

The Effects of Sex Hormonal Fluctuations during Menstrual Cycle on Cortical Excitability and Manual Dexterity (a Pilot Study)

Aim To investigate whether hormonal fluctuations during the menstrual cycle affect corticospinal excitability, intracortical inhibition (ICI) or facilitation (ICF) in primary motor cortex, and also whether the hormonal fluctuations have any effect on manual dexterity in neurologically intact women. Materials and Methods Twenty volunteers (10 Female, 10 Male) were included in this study. The levels of progesterone and estradiol were measured from saliva during the women’s menstrual follicular, ovulation and mid-luteal phases. Motor evoked potentials were recorded from the right first dorsal interosseous muscle. Single and paired-pulse Transcranial Magnetic Stimulation (TMS) were delivered in a block of 20 stimuli. With paired-pulse technique, 3ms and 10ms inter-stimulus intervals were used to assess ICI and ICF, respectively. The Grooved Pegboard Test (GPT) was completed in each session before the TMS assessments. Male participants were tested at similar time intervals as female participants. Results Mixed design ANOVA revealed that GPT score in female participants was significantly lower at the mid-luteal phase compared to the ovulation phase (p = 0.017). However, it was not correlated with progesterone or estrogen fluctuations during the menstrual cycle. The results also showed that the effect of phase, sex and the interaction of phase by sex for resting motor threshold, ICI or ICF were not significant (p > 0.05). Conclusion Manual dexterity performance fluctuates during the menstrual cycle in neurologically intact women, which might be due to the balance of the neuromodulatory effects of P4 and E2 in the motor cortex during different phases.