Changes In Intracortical Inhibition Research Articles

Enhanced inhibitory input to triceps brachii in humans with spinal cord injury.

Most individuals with cervical spinal cord injury (SCI) show increased muscle weakness in the elbow extensor compared to elbow flexor muscles. Although this is a well-known functional deficit, the underlying neural mechanisms remain poorly understood. To address this question, we measured the suppression of voluntary electromyographic activity (svEMG; a measurement thought to reflect changes in intracortical inhibition) by applying low-intensity transcranial magnetic stimulation over the arm representation of the primary motor cortex during 10% of isometric maximal voluntary contraction (MVC) into elbow flexion or extension in individuals with and without chronic cervical SCI. We found that the svEMG latency and duration were not different between the biceps and triceps brachii in controls but prolonged in the triceps in individuals with SCI. The svEMG area was larger in the triceps compared to the biceps in both groups and further increased in SCI participants, suggesting a pronounced intracortical inhibitory input during elbow extension. A negative correlation was found between svEMG area and MVCs indicating that control and SCI participants with lower svEMG area had larger MVCs. The svEMG area was not different between 5% and 30% of MVC, making it less probable that differences in muscle strength between groups contributed to our results. These findings support the existence of strong inhibitory input to corticospinal projections controlling elbow extensor compared to flexor muscles, which is more pronounced after chronic cervical SCI. KEY POINTS: After cervical spinal cord injury (SCI), people often recover function in elbow flexor, but much less in elbow extensor muscles. The neural mechanisms contributing to this difference remain unknown. We measured the suppression of voluntary electromyographic activity (svEMG) elicited through low-intensity transcranial magnetic stimulation of the primary motor cortex (assumed to reflect changes in intracortical inhibition) in the biceps and triceps muscles in controls and individuals with cervical chronic incomplete SCI. We found increased svEMG area in the triceps compared to the biceps in controls and SCI participants, with this measurement being even more pronounced in the triceps after SCI. The svEMG area correlated with maximal voluntary contraction values in both groups, suggesting the people with lesser inhibition had larger motor output. Our results support the presence of strong cortical inhibitory input to corticospinal projections controlling elbow extensor compared to elbow flexors muscles after cervical SCI.

The effect of single and dual task training on the intracortical inhibition in healthy young adults

Introduction
 The evidence for changes in intracortical inhibition when executing two tasks simultaneously (i.e., dual tasking) is ambiguous as decreased (Corp et al., 2014) and increased (Corp et al., 2016) inhibition were reported. One way to bring more light into this question is to tests the effect of a single task training (STT) and a dual task training (DTT) on the short interval intracortical inhibition (SICI) during a single balancing task and two different dual tasks in healthy young adults.
 Methods
 Twenty-nine healthy young adults were randomly separated into two groups participating in STT (n = 15) or DTT (n = 14) consisting of 6 training sessions within 3 weeks. Before and after the training, a single task (balancing on a rocker board) was performed at two resistance levels (easy and hard). Additionally to the single task, either a cognitive (2-back number recall) or a motor (balancing a ball on a hand-held tray) dual task was executed simultaneously. During execution of these three tasks, SICI was measured with transcranial magnetic stimulation over the motor cortical area representing the right tibialis anterior.
 Results
 Training improvements in balance performance were group and task-specific over time (p = .018). While the STT group improved more in the single balance task (12.3% vs. 6.6% DTT), the DTT group had more sway reductions in the motor dual task condition (13.7% vs. 4.5% STT). Similar statistical outcome (p = .034) was observed for the dual task costs (DTC). There was a tendence for SICI (p = .075), mainly indicating higher increase in SICI for the DTT group in the motor dual task (16.0% vs. 5.8% STT). During the execution of the single balance task, the group-specific adaptations in SICI were less pronounced (13.7% DTT vs. 16.2% STT). When analyzing the SICI dual task difference (Δ) from single to dual task, SICI is altered group and task specific (p = .011). The DTT group could increase the dual task difference in SICI in the dual motor condition (Δ 3.2%), whereas the STT group had a decrease (Δ -9.6%).
 Discussion/Conclusion
 The results of this study show that DTT causes gains in balance performance and increases in SICI when the secondary task is also a motor task, but not when the second task is a cognitive one. STT is particularly beneficial in the single task. It is therefore assumed that intracortical inhibition is important during the simultaneous performance of two motor tasks, while intracortical inhibition was not modulated in a group-specific manner by the additional cognitive task.
 References
 Corp, D. T., Lum, J. A. G., Tooley, G. A., & Pearce, A. J. (2014). Corticospinal activity during dual tasking: A systematic review and meta-analysis of TMS literature from 1995 to 2013. Neuroscience & Biobehavioral Reviews, 43, 74-87. https://doi.org/10.1016/j.neubiorev.2014.03.017
 Corp, D. T., Rogers, M. A., Youssef, G. J., & Pearce, A. J. (2016). The effect of dual-task difficulty on the inhibition of the motor cortex. Experimental Brain Research, 234, 443-452. https://doi.org/10.1007/s00221-015-4479-2

Short-term arm immobilization modulates excitability of inhibitory circuits within, and between, primary motor cortices.

Previous research has suggested that short‐term immobilization of the arm may be a low‐cost, non‐invasive strategy to enhance the capacity for long‐term potentiation (LTP)‐like plasticity in primary motor cortex (M1). Short‐term immobilization reduces corticospinal excitability (CSE) in the contralateral M1, and interhemispheric inhibition (IHI) from ipsi‐ onto contralateral M1 is increased. However, it is unclear whether reduced CSE and increased IHI are associated with changes in intracortical inhibition, which has been shown to be important for regulating neuroplasticity in M1. The current study used transcranial magnetic stimulation to evaluate the effects of short‐term (6 h) arm immobilization on CSE, IHI, and intracortical inhibition measured bilaterally in 43 neurotypical young adults (23 immobilized). We replicated previous findings demonstrating that immobilization decreased CSE in, and increased IHI onto, the immobilized hemisphere, but a significant change in intracortical inhibition was not observed at the group level. Across individuals, decreased CSE was associated with a decreased short‐interval intracortical inhibition, an index of GABAA‐ergic inhibition, within the immobilized hemisphere only in the immobilization group. Previous research has demonstrated that decreases in GABAA‐ergic inhibition are necessary for the induction of LTP‐like plasticity in M1; therefore, decreased intracortical inhibition after short‐term arm immobilization may provide a novel mechanism to enhance the capacity for LTP‐like plasticity within M1 and may be a potential target for strategies to augment plasticity capacity to enhance motor learning in health and disease.

Intracortical Inhibition in the Affected Hemisphere in Limb Amputation.

Phantom limb pain (PLP) affects up to 80% of amputees. Despite the lack of consensus about the etiology and pathophysiology of phantom experiences, previous evidence pointed out the role of changes in motor cortex excitability as an important factor associated with amputation and PLP. In this systematic review, we investigated changes in intracortical inhibition as indexed by transcranial magnetic stimulation (TMS) in amputees and its relationship to pain. Four electronic databases were screened to identify studies using TMS to measure cortical inhibition, such as short intracortical inhibition (SICI), long intracortical inhibition (LICI) and cortical silent period (CSP). Seven articles were included and evaluated cortical excitability comparing the affected hemisphere with the non-affected hemisphere or with healthy controls. None of them correlated cortical disinhibition and clinical parameters, such as the presence or intensity of PLP. However, most studies showed decreased SICI in amputees affected hemisphere. These results highlight that although SICI seems to be changed in the affected hemisphere in amputees, most of the studies did not investigate its clinical correlation. Thus, the question of whether they are a valid diagnostic marker remains unanswered. Also, the results were highly variable for both measurements due to the heterogeneity of study designs and group comparisons in each study. Although these results underscore the role of inhibitory networks after amputation, more studies are needed to investigate the role of a decreased inhibitory drive in the motor cortex to the cause and maintenance of PLP.

Modulation of Corticospinal Excitability by Two Different Somatosensory Stimulation Patterns; A Pilot Study.

Following amputation, almost two-thirds of amputees experience unpleasant to painful sensations in the area of the missing limb. Whereas the mechanism of phantom limb pain (PLP) remains unknown, it has been shown that maladaptive cortical plasticity plays a major role in PLP. Transcutaneous electrical nerve stimulation (TENS) generating sensory input is believed to be beneficial for PLP relief. TENS effect may be caused by possible reversing reorganization at the cortical level that can be evaluated by changes in the excitability of the corticospinal (CS) pathway. Excitability changes are dependent on the chosen stimulation patterns and parameters. The aim of this study was to investigate the effect of two TENS patterns on the excitability of the CS tract among healthy subjects. We compared a non-modulated TENS as a conventional pattern with pulse width modulated TENS pattern. Motor evoked potentials (MEPs) from APB muscles of stimulated arm (TENS-APB) and contralateral arm (Control-APB) were recorded. We applied single TMS pulses on two subjects for each TENS pattern. The results showed that both patterns increase the CS excitability, while the effects of the conventional TENS is stronger. However, the amplitude of MEPs from control-APB after TENS delivery remained almost the same.Clinical Relevance- The primary results revealed changes in the activity of CS pathway for both patterns. A future study on a larger population is needed to provide strong evidence on the changes in CS excitability. The evaluation part with more factors such as changes in intracortical inhibition (ICI) may be beneficial to find an optimal modulated TENS pattern to enhance pain alleviation process in PLP.

High-intensity, low-frequency repetitive transcranial magnetic stimulation enhances excitability of the human corticospinal pathway.

Paired corticospinal-motoneuronal stimulation (PCMS) is the repeated pairing of transcranial magnetic stimulation (TMS) with peripheral nerve stimulation to modify corticospinal synapses; however, it has yet to be determined whether PCMS modulates cortical excitability in a manner similar to paired-associative stimulation protocols. In this study, we first examined the effects of PCMS on adductor pollicis motor evoked potentials (MEPs). In experiment 1, on 2 separate days PCMS (repetitive, high-intensity TMS and ulnar nerve stimulation pairs; 1.5-ms interstimulus interval; 0.1 Hz) was compared with control conditioning of repetitive high-intensity TMS-only stimuli (0.1 Hz). Before and after conditioning, adductor pollicis MEPs were elicited using low-intensity TMS in three different coil orientations to preferentially activate corticospinal axons directly (thus bypassing cortical effects) or indirectly (cortical effects present). Unexpectedly, similar MEP increases were seen for all orientations on both PCMS (129 to 136% of baseline) and control days (108 to 129% of baseline). Given the common factor between conditioning protocols was repeated, high-intensity TMS, further experiments were performed to characterize this repetitive TMS (rTMS) protocol. In experiment 2, an intensity dependence of the rTMS protocol was revealed by a lack of change in MEPs elicited after repetitive low-intensity TMS (0.1 Hz; P = 0.37). In experiment 3, MEP recruitment curve and paired pulse analyses showed that the high-intensity rTMS protocol increased MEPs over a range of stimulus intensities but that effects were not accompanied by changes in intracortical inhibition or facilitation (P > 0.12). These experiments reveal a novel high-intensity, low-frequency rTMS protocol for enhancing corticospinal excitability.NEW & NOTEWORTHY In this study, we present a novel, intensity-dependent repetitive transcranial magnetic stimulation (rTMS) protocol that induces lasting, plastic changes within the corticospinal tract. High-intensity rTMS at a frequency of 0.1 Hz induces facilitation of motor evoked potentials (MEPs) lasting at least 35 min. Additionally, these changes are not limited only to small MEPs but occur throughout the recruitment curve. Finally, facilitation of MEPs following high-intensity rTMS does not appear to be due to changes in intracortical inhibition or facilitation.

Skillful Cycling Training Induces Cortical Plasticity in the Lower Extremity Motor Cortex Area in Healthy Persons.

Cycling exercise is commonly used in rehabilitation to improve lower extremity (LE) motor function and gait performance after stroke. Motor learning is important for regaining motor skills, suggesting that training of motor skills influences cortical plasticity. However, the effects of motor skill learning in dynamic alternating movements of both legs on cortical plasticity remain unclear. Here, we examined the effects of skillful cycling training on cortical plasticity of the LE motor area in healthy adults. Eleven healthy volunteers participated in the following three sessions on different days: skillful cycling training, constant-speed cycling training, and rest condition. Skillful cycling training required the navigation of a marker up and down curves by controlling the rotation speed of the pedals. Participants were instructed to fit the marker to the target curves as accurately as possible. Amplitudes of motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) evoked using transcranial magnetic stimulation (TMS) were assessed at baseline, after every 10 min of the task (a total of 30 min), and 30 min after the third and final trial. A decrease in tracking errors was representative of the formation of motor learning following skillful cycling training. Compared to baseline, SICI was significantly decreased after skillful cycling training in the tibialis anterior (TA) muscle. The task-induced alterations of SICI were more prominent and lasted longer with skillful cycling training than with the other conditions. The changes in SICI were negatively correlated with a change in tracking error ratio at 20 min the task. MEP amplitudes were not significantly altered with any condition. In conclusion, skillful cycling training induced long-lasting plastic changes of intracortical inhibition, which corresponded to the learning process in the LE motor cortex. These findings suggest that skillful cycling training would be an effective LE rehabilitation method after stroke.

Multisession anodal transcranial direct current stimulation induces motor cortex plasticity enhancement and motor learning generalization in an aging population

ObjectivesThe present aging study investigated the impact of a multisession anodal-tDCS protocol applied over the primary motor cortex (M1) during motor sequence learning on generalization of motor learning and plasticity-dependent measures of cortical excitability. MethodsA total of 32 cognitively-intact aging participants performed five consecutive daily 20-min sessions of the serial-reaction time task (SRTT) concomitant with either anodal (n = 16) or sham (n = 16) tDCS over M1. Before and after the intervention, all participants performed the Purdue Pegboard Test (PPT) and Transcranial Magnetic Stimulation (TMS) measures of cortical excitability were collected. ResultsRelative to sham, participants assigned to the anodal-tDCS intervention revealed significantly greater performance gains on both the trained SRTT and the untrained PPT as well as a greater disinhibition of long-interval cortical inhibition (LICI). Generalization effects of anodal-tDCS significantly correlated with LICI disinhibition. ConclusionAnodal-tDCS facilitates motor learning generalisation in an aging population through intracortical disinhibition effects. SignificanceThe current findings demonstrate the potential clinical utility of a multisession anodal-tDCS over M1 protocol as an adjuvant to motor training in alleviating age-associated motor function decline. This study also reveals the pertinence of implementing brain stimulation techniques to modulate age-associated intracortical inhibition changes in order to facilitate motor function gains.

Cortical and reticular contributions to human precision and power grip.

The corticospinal tract contributes to the control of finger muscles during precision and power grip. We explored the neural mechanisms contributing to changes in corticospinal excitability during these gripping configurations. Motor evoked potentials (MEPs) elicited by cortical, but not by subcortical, stimulation were more suppressed during power grip compared with precision grip and index finger abduction. Intracortical inhibition was more reduced during power grip compared with the other tasks. An acoustic startle cue, a stimulus that engages the reticular system, suppressed MEP size during power grip to a lesser extent than during the other tasks at a cortical level and this positively correlated with changes in intracortical inhibition. Our findings suggest that changes in corticospinal excitability during gross more than fine finger manipulations are largely cortical in origin and that the reticular system contributed, at least in part, to these effects. It is well accepted that the corticospinal tract contributes to the control of finger muscles during precision and power grip in humans but the neural mechanisms involved remain poorly understood. Here, we examined motor evoked potentials elicited by cortical and subcortical stimulation of corticospinal axons (MEPs and CMEPs, respectively) and the activity in intracortical circuits (suppression of voluntary electromyography) and spinal motoneurons (F-waves) in an intrinsic hand muscle during index finger abduction, precision grip and power grip. We found that the size of MEPs, but not CMEPs, was more suppressed during power grip compared with precision grip and index finger abduction, suggesting a cortical origin for these effects. Notably, intracortical inhibition was more reduced during power grip compared with the other tasks. To further examine the origin of changes in intracortical inhibition we assessed the contribution of the reticular system, which projects to cortical neurons, and projects to spinal motoneurons controlling hand muscles. An acoustic startle cue, which engages the reticular system, suppressed MEP size during power grip to a lesser extent than during the other tasks and this positively correlated with changes in intracortical inhibition. A startle cue decreased intracortical inhibition, but not CMEPs, during power grip. F-waves remained unchanged across conditions. Our novel findings show that changes in corticospinal excitability present during power grip compared with fine finger manipulations are largely cortical in origin and suggest that the reticular system contributed, at least in part, to these effects.

Changes in intracortical inhibition and clinical symptoms after STN-DBS in Parkinson’s disease

To examine effects of subthalamic nucleus deep brain stimulation (STN-DBS) on intracortical inhibition in Parkinson's disease (PD) and the correlation between intracortical inhibition and clinical symptoms after alteration of STN-DBS status. Nine PD patients treated by STN-DBS were compared with eight age-matched controls. Antiparkinsonian medication was withdrawn 12h before the study. Short-interval intracortical inhibition (SICI) with a 3-ms interval and silent period (SP) were examined using transcranial magnetic stimulation. SP duration, SICI and motor symptoms (rigidity and tremor) were evaluated with STN-DBS ON, and over 120 min during STN-DBS OFF. Even during STN-DBS, PD patients showed a shortened SP and reduced SICI relative to normal controls. SICI decreased further throughout STN-DBS OFF, resulting in facilitation rather than inhibition; SP shortened only after 120 min STN-DBS OFF. Both rigidity and tremor worsened throughout STN-DBS OFF, with a time course similar to SICI. Even during STN-DBS, both SICI and SP in PD patients remain impaired without medication. Changes in SICI, but not SP, show a time course similar to those of motor symptoms. The dissimilarity of SICI and SP changes suggests differences in mediation of inhibitory mechanisms and/or superimposition of exaggerated intracortical facilitation on SICI.

Virtual Reality-Guided Motor Imagery Increases Corticomotor Excitability in Healthy Volunteers and Stroke Patients.

ObjectiveTo investigate the effects of using motor imagery (MI) in combination with a virtual reality (VR) program on healthy volunteers and stroke patients. In addition, this study investigated whether task variability within the VR-guided MI programs would influence corticomotor excitability.MethodsThe present study included 15 stroke patients and 15 healthy right-handed volunteers who were presented with four different conditions in a random order: rest, MI alone, VR-guided MI, and VR-guided MI with task variability. The corticomotor excitability of each participant was assessed before, during, and after each condition by measuring changes in the various parameters of motor-evoked potentials (MEPs) of the extensor carpi radials (ECR). Changes in intracortical inhibition (ICI) and intracortical facilitation (ICF) were calculated after each condition as percentages of inhibition (%INH) and facilitation (%FAC) at rest.ResultsIn both groups, the increases in MEP amplitudes were greater during the two VR-guided MI conditions than during MI alone. Additionally, the reductions in ECR %INH in both groups were greater under the condition involving VR-guided MI with task variability than under that involving VR-guided MI with regular interval.ConclusionThe corticomotor excitability elicited by MI using a VR avatar representation was greater than that elicited by MI with real body observations. Furthermore, the use of task variability in a VR program may enhance neural regeneration after stroke by reducing ICI. The present findings support the use of various VR programs as well as the concept of combining MI with VR programs for neurorehabilitation.

Motor Cortex Plasticity during Unilateral Finger Movement with Mirror Visual Feedback.

Plasticity is one of the most important physiological mechanisms underlying motor recovery from brain lesions. Rehabilitation methods, such as mirror visual feedback therapy, which are based on multisensory integration of motor, cognitive, and perceptual processes, are considered effective methods to induce cortical reorganization. The present study investigated 3 different types of visual feedback (direct, mirrored, and blocked visual feedback: DVF, MVF, and BVF, resp.) on M1 cortex excitability and intracortical inhibition/facilitation at rest and during phasic unimanual motor task in 11 healthy individuals. The excitability of the ipsilateral M1 cortex and the intracortical facilitation increased during motor task performance in the DVF and MVF but not in the BVF condition. In addition, MVF induced cortical disinhibition of the ipsilateral hemisphere to the index finger performing the motor task, which was greater when compared to the BVF and restricted to the homologue first dorsal interosseous muscle. The visual feedback is relevant to M1 cortex excitability modulation but the MVF plays a crucial role in promoting changes in intracortical inhibition in comparison to BVF. Altogether, it can be concluded that a combination of motor training with MVF therapy may induce more robust neuroplastic changes through multisensory integration that is relevant to motor rehabilitation.

Disinhibition of the primary somatosensory cortex in patients with fibromyalgia.

Fibromyalgia (FM) is a chronic widespread pain condition linked to central sensitization. Altered excitability of sensorimotor cortex has been proposed as an underlying pathology of FM. This study aimed to investigate intracortical excitability of the primary somatosensory cortex (S1) and its potential role in clinical pain in patients with FM. Somatosensory evoked magnetic fields were recorded in 17 right-handed females with FM and 21 age-, sex-, and handedness-matched healthy control subjects. Paired-pulse median nerve stimulation was delivered to the left and right wrist. We assessed the peak-to-peak amplitudes of the N20m-P35m and peak amplitude of each N20m and P35m component. Paired-pulse suppression (PPS) of the second response was quantified as the ratio of the amplitudes of the second to the first response. Patients with FM displayed significantly higher PPS ratio for the N20m-P35m in both hemispheres, indicating reduced intracortical inhibition in the S1. Notably, PPS ratio for the P35m was higher in patients with FM than in healthy controls, whereas no differences were apparent in PPS ratio for the N20m in both hemispheres. For both the N20m-P35m and the P35m in the left hemisphere, PPS ratios were positively associated with the sensory pain on the short-form McGill Pain Questionnaire. This study demonstrated that intracortical inhibition in the S1 is compromised bilaterally in patients with FM, and the extent of disinhibition can be closely associated with increased clinical pain. Our results suggest that changes of intracortical inhibition of the S1 may contribute to the pathophysiology of FM pain.

Using transcranial magnetic stimulation to quantify electrophysiological changes following concussive brain injury: a systematic review.

Mild traumatic brain injury (mTBI) and sports concussion are a growing public health concern, with increasing demands for more rigorous methods to quantify changes in the brain post-injury. Electrophysiology, and in particular, transcranial magnetic stimulation (TMS), have been demonstrated to provide prognostic value in a range of neurological conditions; however, no review has quantified the efficacy of TMS in mTBI/concussion. In the present study, we present a systematic review and critical evaluation of the scientific literature from 1990 to 2014 that has used TMS to investigate corticomotor excitability responses at short-term (< 12 months), medium-term (1-5 years), and long-term (> 5 years) post-mTBI/concussion. Thirteen studies met the selection criteria, with six studies presenting short-term changes, five studies presenting medium-term changes, and two studies presenting long-term changes. Irrespective of time post-concussion, change in intracortical inhibition was the most reported observation. Other findings included increased stimulation threshold, and slowed neurological conduction time. Although currently limited, the data suggest that TMS has prognostic value in detecting neurophysiological changes post-mTBI/concussion.

Task-related changes in intracortical inhibition assessed with paired- and triple-pulse transcranial magnetic stimulation.

Recent research has demonstrated a task-related modulation of postsynaptic intracortical inhibition within primary motor cortex for tasks requiring isolated (abduction) or synergistic (precision grip) muscle activation. The current study sought to investigate task-related changes in pre- and postsynaptic intracortical inhibition in motor cortex. In 13 young adults (22.5 ± 3.5 yr), paired-pulse transcranial magnetic stimulation (TMS) was used to measure short (SICI)- and long-interval intracortical inhibition (LICI) (i.e., postsynaptic motor cortex inhibition) in first dorsal interosseous muscle, and triple-pulse TMS was used to investigate changes in SICI-LICI interactions (i.e., presynaptic motor cortex inhibition). These measurements were obtained at rest and during muscle activation involving isolated abduction of the index finger and during a precision grip using the index finger and thumb. SICI was reduced during abduction and precision grip compared with rest, with greater reductions during precision grip. The modulation of LICI during muscle activation depended on the interstimulus interval (ISI; 100 and 150 ms) but was not different between abduction and precision grip. For triple-pulse TMS, SICI was reduced in the presence of LICI at both ISIs in resting muscle (reflecting presynaptic motor cortex inhibition) but was only modulated at the 150-ms ISI during index finger abduction. Results suggest that synergistic contractions are accompanied by greater reductions in postsynaptic motor cortex inhibition than isolated contractions, but the contribution of presynaptic mechanisms to this disinhibition is limited. Furthermore, timing-dependent variations in LICI provide additional evidence that measurements using different ISIs may not represent activation of the same cortical process.

Age-related changes in intracortical inhibition are mental-cognitive state-dependent

IntroductionThis study aimed to assess the impact of aging and ‘state-dependency’ on cortical excitability. Two studies investigated these factors using a motor task and found that the age-related differences observed at rest disappeared in the task condition. However, as both their tasks and excitability measurements involved the motor cortex, their results could be specific only to the motor system. To overcome this problem, the present study used a cognitive task to control mental state. MethodIntracortical inhibition/facilitation (ICI/ICF) were assessed in young and older adults at rest and during the cognitive task. The cortical silent period (CSP) was also evaluated. ResultsICI and CSP were reduced with aging. However, ICI differences between young and old people disappeared when they performed the cognitive task. ConclusionAge and mental state modify cortical excitability. Taking these factors into consideration is crucial to clinical research using cortical excitability as a possible biomarker of pathology.

Modulation of Training by Single-Session Transcranial Direct Current Stimulation to the Intact Motor Cortex Enhances Motor Skill Acquisition of the Paretic Hand

Mechanisms of skill learning are paramount components for stroke recovery. Recent noninvasive brain stimulation studies demonstrated that decreasing activity in the contralesional motor cortex might be beneficial, providing transient functional improvements after stroke. The more crucial question, however, is whether this intervention can also enhance the acquisition of complex motor tasks, yielding longer-lasting functional improvements. In the present study, we tested the capacity of cathodal transcranial direct current stimulation (tDCS) applied over the contralesional motor cortex during training to enhance the acquisition and retention of complex sequential finger movements of the paretic hand. Twelve well-recovered chronic patients with subcortical stroke attended 2 training sessions during which either cathodal tDCS or a sham intervention were applied to the contralesional motor cortex in a double-blind, crossover design. Two different motor sequences, matched for their degree of complexity, were tested in a counterbalanced order during as well as 90 minutes and 24 hours after the intervention. Potential underlying mechanisms were evaluated with transcranial magnetic stimulation. tDCS facilitated the acquisition of a new motor skill compared with sham stimulation (P=0.04) yielding better task retention results. A significant correlation was observed between the tDCS-induced improvement during training and the tDCS-induced changes of intracortical inhibition (R(2)=0.63). These results indicate that tDCS is a promising tool to improve not only motor behavior, but also procedural learning. They further underline the potential of noninvasive brain stimulation as an adjuvant treatment for long-term recovery, at least in patients with mild functional impairment after stroke.

Increased Excitability of Somatosensory Cortex in Aged Humans is Associated with Impaired Tactile Acuity

Aging affects all levels of neural processing, including changes of intracortical inhibition and cortical excitability. Paired-pulse stimulation, the application of two stimuli in close succession, is a useful tool to investigate cortical excitability in humans. The paired-pulse behavior is characterized by the second response being significantly suppressed at short stimulus onset asynchronies. While in rat somatosensory cortex, intracortical inhibition has been demonstrated to decline with increasing age, data from human motor cortex of elderly subjects are controversial and there are no data for the human somatosensory cortex (SI). Moreover, behavioral implications of age-related changes of cortical excitability remain elusive. We therefore assessed SI excitability by combining paired-pulse median nerve stimulation with recording somatosensory evoked potentials in 138 healthy subjects aged 17-86 years. We found that paired-pulse suppression was characterized by substantial interindividual variability, but declined significantly with age, confirming reduced intracortical inhibition in elderly subjects. To link the age-related increase of cortical excitability to perceptual changes, we measured tactile two-point discrimination in a subsample of 26 aged participants who showed either low or high paired-pulse suppression. We found that tactile performance was particularly impaired in subjects showing markedly enhanced cortical excitability. Our data demonstrate that paired-pulse suppression of human SI is significantly reduced in older adults, and that age-related enhancement of cortical excitability correlates with degradation of tactile perception. These findings indicate that cortical excitability constitutes an important mechanism that links age-related neurophysiological changes to behavioral alterations in humans.

Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia

We assessed for the first time the long-term maintenance of repetitive transcranial magnetic stimulation (rTMS)-induced analgesia in patients with chronic widespread pain due to fibromyalgia. Forty consecutive patients were randomly assigned, in a double-blind fashion, to 2 groups: one receiving active rTMS (n=20) and the other, sham stimulation (n=20), applied to the left primary motor cortex. The stimulation protocol consisted of 14 sessions: an “induction phase” of 5 daily sessions followed by a “maintenance phase” of 3 sessions a week apart, 3 sessions a fortnight apart, and 3 sessions a month apart. The primary outcome was average pain intensity over the last 24 hours, measured before each stimulation from day 1 to week 21 and at week 25 (1month after the last stimulation). Other outcomes measured included quality of life, mood and anxiety, and several parameters of motor cortical excitability. Thirty patients completed the study (14 in the sham stimulation group and 16 in the active stimulation group). Active rTMS significantly reduced pain intensity from day 5 to week 25. These analgesic effects were associated with a long-term improvement in items related to quality of life (including fatigue, morning tiredness, general activity, walking, and sleep) and were directly correlated with changes in intracortical inhibition. In conclusion, these results suggest that TMS may be a valuable and safe new therapeutic option in patients with fibromyalgia.The analgesic effects induced by repetitive transcranial magnetic stimulation of the motor cortex can be maintained over 6months in patients with fibromyalgia, using monthly stimulation.

Effects of Aging on Paired-Pulse Behavior of Rat Somatosensory Cortical Neurons

Aging affects all levels of neural processing including changes of intracortical inhibition and cortical excitability. The paired-pulse stimulation protocol, the application of 2 stimuli in close succession, is used to investigate cortical excitability. The paired-pulse behavior is characterized by the fact that the second response is significantly suppressed at short interstimulus intervals (ISIs) but approaches the first response with increasing ISIs. However, there are controversial reports about the influence of age on paired-pulse behavior. We therefore used pairs of tactile stimuli (ISIs from tens to hundreds of milliseconds) to record extracellular responses of somatosensory cortical neurons of young and aged rats. Paired-pulse behavior was quantified as the ratio of the amplitude of the second response divided by the first. For all ISIs, we found significantly higher ratios in the old animals indicating reduced paired-pulse suppression (PPS). Evaluation of the single response components revealed a significant reduction of the response to the first stimulus for old animals but no age-dependent decrement to the second. Changes in PPS are usually mediated by modulating the second response characteristics. Thus, our data demonstrate reduced PPS due to an overall reduction of the first response as a form of modified PPS developing at old age.