Short-latency Afferent Inhibition Research Articles

Reduced Short-Latency Afferent Inhibition Indicates Impaired Sensorimotor Integrity During Migraine Attacks.

Migraine attacks disrupt sensory information processing and may also disturb sensorimotor integration. This prospective pilot study aimed to assess the sensorimotor integration and inhibitory circuitry in the sensorimotor cortex using short-latency afferent inhibition (SAI) paradigm in migraine. Twenty-five migraine without aura patients (10 interictal, 5 preictal, 10 ictal) and 16 healthy controls were enrolled. SAI was elicited by combining the right median nerve electrical stimulation and left motor cortical magnetic stimulation at the 21-millisecond interval. Mean motor evoked potential (MEP) amplitude ratio, recorded from right abductor pollicis muscle after single and conditioned stimulations, was calculated as SAI. Average MEP inhibition ratio after single and conditioned stimuli in healthy controls was not significantly different from interictal patients (45.1%±20.3% vs 44.5%±14.75% [P = .93]). However, SAI was significantly reduced during preictal/prodromal (-14.6%±42.8% [P = .002]) and ictal/headache (-7.4%±31.1% [P = .0001]) periods of migraine compared to healthy controls. Pronounced decrease in SAI during preictal and ictal periods in migraine was shown for the first time. Instead of inhibition to a conditioned stimulus, facilitation in the sensorimotor cortex was detected both ictally and preictally. Preictal SAI results suggest the presence of increased excitability state several hours prior to the headache phase. This phenomenon could be related to the cortical hyperresponsivity to sensory stimuli and cognitive disturbances accompanying migraine attacks as SAI is modulated by cholinergic activity.

Selective sensorimotor modulation operates during cognitive representation of movement

Before movement onset, during the reaction time, excitability of M1 is selectively modulated by somatosensory inputs, only in the movement-related muscle. If a similar mechanism operates before the onset of mental movements, then somatosensory afferent inputs are exploited during cognitive representation of movement. We assessed sensorimotor modulation through short latency afferent inhibition (SAI) paradigm before the onset of executed and imagined movements.Participants performed or imagined an abduction of index or little finger, in response to an acoustic signal. SAI was evaluated between a Warning and a Go signal and 100 ms after the Go signal, before the real or expected EMG activity. Results showed a reduction of SAI after the Go signal, in the movement-related muscle, during motor imagery as well as movement execution. There was a positive correlation between the individual degree of sensorimotor modulation during executed and mental movements and between the sensorimotor modulation during mental movements and motor imagery ability. Sensorimotor modulation operates during the cognitive representation of movement with selective disinhibition of the cortical representation of the muscle involved in the task. Sensorimotor modulation mechanisms prior to mental and executed movements likely share overlapping circuits.

Fast Intracortical Sensory-Motor Integration: A Window Into the Pathophysiology of Parkinson's Disease.

Parkinson’s Disease (PD) is a prototypical basal ganglia disorder. Nigrostriatal dopaminergic denervation leads to progressive dysfunction of the cortico-basal ganglia-thalamo-cortical sensorimotor loops, causing the classical motor symptoms. Although the basal ganglia do not receive direct sensory input, they are important for sensorimotor integration. Therefore, the basal ganglia dysfunction in PD may profoundly affect sensory-motor interaction in the cortex. Cortical sensorimotor integration can be probed with transcranial magnetic stimulation (TMS) using a well-established conditioning-test paradigm, called short-latency afferent inhibition (SAI). SAI probes the fast-inhibitory effect of a conditioning peripheral electrical stimulus on the motor response evoked by a TMS test pulse given to the contralateral primary motor cortex (M1). Since SAI occurs at latencies that match the peaks of early cortical somatosensory potentials, the cortical circuitry generating SAI may play an important role in rapid online adjustments of cortical motor output to changes in somatosensory inputs. Here we review the existing studies that have used SAI to examine how PD affects fast cortical sensory-motor integration. Studies of SAI in PD have yielded variable results, showing reduced, normal or even enhanced levels of SAI. This variability may be attributed to the fact that the strength of SAI is influenced by several factors, such as differences in dopaminergic treatment or the clinical phenotype of PD. Inter-individual differences in the expression of SAI has been shown to scale with individual motor impairment as revealed by UPDRS motor score and thus, may reflect the magnitude of dopaminergic neurodegeneration. The magnitude of SAI has also been linked to cognitive dysfunction, and it has been suggested that SAI also reflects cholinergic denervation at the cortical level. Together, the results indicate that SAI is a useful marker of disease-related alterations in fast cortical sensory-motor integration driven by subcortical changes in the dopaminergic and cholinergic system. Since a multitude of neurobiological factors contribute to the magnitude of inhibition, any mechanistic interpretation of SAI changes in PD needs to consider the group characteristics in terms of phenotypical spectrum, disease stage, and medication.

Short-latency afferent-induced facilitation and inhibition as predictors of thermally induced variations in corticomotor excitability.

Recently (Ansari et al., PeerJ 6:e6163, 2018a; Somatosens Mot Res 35:69-79, 2018b), we showed using transcranial magnetic stimulation (TMS) that focal application of innocuous thermal stimuli to the distal hand produced variable responses in terms of motor-evoked potential (MEP) suppression or enhancement. Here, we sought to investigate possible causes of this variability by examining circuits mediating sensorimotor integration and intra-cortical inhibition. Participants (n = 21) first underwent TMS to assess baseline corticomotor excitability by measuring MEPs at rest with the index finger wrapped in a gel pack at room temperature (24°C). Then, conditioned protocols were applied to assess short-latency afferent inhibition (SAI), short-latency afferent facilitation (SAF) and short-interval intra-cortical inhibition (SICI). Following baseline measures, MEP modulation in response to distal cooling was recorded with the index finger wrapped ina gel pack at ~ 10°C. At baseline, participants exhibited variable levels of SAI, SAF and SICI. Participant also exhibited variable responses to cooling with about half of them (11/21) showing suppressed excitability and one-third showing enhanced excitability (7/21). A linear regression analysis revealed that SAI and SAF proved to be good predictors of cooling-induced variations in corticomotor excitability but not SICI. These results provide novel evidence linking variations in SAI and SAF with those in corticomotor excitability elicited in response to focal thermal stimulation, suggesting that these markers could be used to predict responses to sensory stimulation protocols.

A Multimodal Training Modulates Short Afferent Inhibition and Improves Complex Walking in a Cohort of Faller Older Adults With an Increased Prevalence of Parkinson's Disease.

Falls are frequent in Parkinson's disease and aging. Impairments in the cholinergic-mediated attentional supervision of gait may contribute to increased fall risk, especially when obstacles challenge gait. Interventions combining motor-cognitive approaches have been shown to improve motor performance, cognitive skills, and falls number. Here, we hypothesized that an intervention simulating an attention-demanding walking condition could affect not only complex gait performance and fall risk but also short-latency afferent inhibition (SAI), as a marker of cholinergic activity. Thirty-nine participants at falls risk (24 Parkinson's disease participants and 15 older adults) were recruited in a randomized controlled trial. Participants were assigned to treadmill training or treadmill training with non-immersive virtual reality intervention and trained three times a week for 6 weeks. SAI, a transcranial magnetic stimulation paradigm, was used to assess cholinergic activity. Gait kinematics was measured during usual walking and while negotiating physical obstacles. Transcranial magnetic stimulation and gait assessments were performed pre, post, and 6 months post-intervention. Treadmill training combined with non-immersive virtual reality induced an increase in inhibition of the SAI protocol on cortical excitability, improved obstacle negotiation performance, and induced a reduction of the number of falls compared with treadmill training. Furthermore, the more SAI increased after training, the more the obstacle negotiation performance improved and fall rate decreased. We provide evidence that an innovative rehabilitation approach targeting cognitive components of complex motor actions can induce changes in cortical cholinergic activity, as indexed by SAI, thereby enabling functional gait improvements.

Does hand robotic rehabilitation improve motor function by rebalancing interhemispheric connectivity after chronic stroke? Encouraging data from a randomised-clinical-trial

ObjectiveThe objective of this study was the evaluation of the clinical and neurophysiological effects of intensive robot-assisted hand therapy compared to intensive occupational therapy in the chronic recovery phase after stroke. Methods50 patients with a first-ever stroke occurred at least six months before, were enrolled and randomised into two groups. The experimental group was provided with the Amadeo™ hand training (AHT), whereas the control group underwent occupational therapist-guided conventional hand training (CHT). Both of the groups received 40 hand training sessions (robotic and conventional, respectively) of 45 min each, 5 times a week, for 8 consecutive weeks. All of the participants underwent a clinical and electrophysiological assessment (task-related coherence, TRCoh, and short-latency afferent inhibition, SAI) at baseline and after the completion of the training. ResultsThe AHT group presented improvements in both of the primary outcomes (Fugl-Meyer Assessment for of Upper Extremity and the Nine-Hole Peg Test) greater than CHT (both p < 0.001). These results were paralleled by a larger increase in the frontoparietal TRCoh in the AHT than in the CHT group (p < 0.001) and a greater rebalance between the SAI of both the hemispheres (p < 0.001). ConclusionsThese data suggest a wider remodelling of sensorimotor plasticity and interhemispheric inhibition between sensorimotor cortices in the AHT compared to the CHT group. SignificanceThese results provide neurophysiological support for the therapeutic impact of intensive robot-assisted treatment on hand function recovery in individuals with chronic stroke.

Somatosensory and transcranial direct current stimulation effects on manual dexterity and motor cortex function: A metaplasticity study

BackgroundNon-invasive neuromodulation may provide treatment strategies for neurological deficits affecting movement, such as stroke. For example, weak electrical stimulation applied to the hand by wearing a “mesh glove” (MGS) can transiently increase primary motor cortex (M1) excitability. Conversely, transcranial direct current stimulation with the cathode over M1 (c-tDCS) can decrease corticomotor excitability.Objective/Hypothesis: We applied M1 c-tDCS as a priming adjuvant to MGS and hypothesised metaplastic effects would be apparent in improved motor performance and modulation of M1 inhibitory and facilitatory circuits. MethodsSixteen right-handed neurologically healthy individuals participated in a repeated measures cross-over study; nine minutes of sham- or c-tDCS followed by 30 min of suprasensory threshold MGS. Dexterity of the non-dominant (left) hand was assessed using the grooved pegboard task, and measures of corticomotor excitability, intracortical facilitation, short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI), and SAI in the presence of SICI (SAIxSICI), were obtained at baseline, post-tDCS, and 0, 30 and 60 min post-MGS. ResultsThere was a greater improvement in grooved pegboard completion times with c-tDCS primed MGS than sham + MGS. There was also more pronounced disinhibition of SAI. However, disinhibition of SAI in the presence of SICI was less and rest motor threshold higher compared to sham + MGS. ConclusionsThe results indicate a metaplastic modulation of corticomotor excitability with c-tDCS primed MGS. Further studies are warranted to determine how various stimulation approaches can induce metaplastic effects on M1 neuronal circuits to boost functional gains obtained with motor practice.

Rubber hand illusion modulates the influences of somatosensory and parietal inputs to the motor cortex

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.

Mitochondrial cholesterol enrichment affects PINK1-PRKN-mediated mitophagy in Alzheimer's disease

Niemann Pick disease type C (NPC) is a lysosomal lipid storage disorder presenting visceral and neurological impairment with cognitive decline. Neurodegeneration in NPC is associated to deposition of amyloid-β and abnormal tau aggregations likewise Alzheimer disease (AD). Dementia is also related to intracortical circuiting abnormalities that can be detected by neurophysiological procedures both in NPC and in AD. Aim of this study is to find the in vivo evidence of amyloid deposition in NPC patients with cognitive impairment and to investigate the pathophysiology of dementia according to similarities with AD.Two sisters affected by NPC and cognitive decline underwent neuropsychological tests, PET scans with 18F- Florbetaben and neurophysiological protocols to assess cortex excitability by means of transcranial magnetic stimulation (TMS), such as short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF).Both patients presented a multidomain cognitive impairment. 18F- Florbetaben uptake was detected in brain frontal areas, while SAI and SICI were abnormal in both patients.Cognitive impairment in NPC is associated to cortical amyloid deposition as revealed by 18F- Florbetaben PET scan. Amyloid imaging data, together with specific abnormalities found at TMS studies, suggest similar mechanisms underlying NPC and AD dementia.

Looking toward predicting functional recovery in disorders of consciousness: can sensorimotor integration help us?

ABSTRACTPrimary Objective: Only a few objective prognostic markers are available for patients with disorders of consciousness (DoC). We assessed whether the magnitude of short-latency afferent inhibition (SAI) might be a useful predictor of responsiveness recovery and functional outcome in patients with DoC.Research Design: We enrolled 40 patients with prolonged Minimally Conscious State (MCS) and Unresponsive Wakefulness Syndrome (UWS) in a longitudinal, observational study.Methods and Procedures: Clinical features (including Coma Recovery Scale-Revised, CRS-R, and Glasgow Outcome Scale, GOS) and SAI were collected at the study entry and after 18 months from study inclusion, to assess a correlation between SAI and the clinical outcome.Main Outcomes and Results: At the follow-up, 19 patients remained in their baseline condition, whereas 7 UWS evolved into MCS or emerged-from-MCS (EMCS), eight MCS evolved into EMCS, and two MCS− evolved into MCS+. Two UWS and one MCS+ died for cardiopulmonary complications. The patients who showed the highest GOS, the highest CRS-R and the lowest SAI strength at study entry, improved at the follow-up.Conclusions: Our findings suggest that an objective and simple neurophysiologic measure as SAI strength could provide useful information to predict the outcome and the behavioral responsiveness of patients with DoC.

Verbal working memory modulates afferent circuits in motor cortex.

Verbal instruction and strategies informed by declarative memory are key to performance and acquisition of skilled actions. We previously demonstrated that anatomically distinct sensory-motor inputs converging on the corticospinal neurons of motor cortex are differentially sensitive to visual attention load. However, how loading of working memory shapes afferent input to motor cortex is unknown. This study used short-latency afferent inhibition (SAI) to probe the effect of verbal working memory upon anatomically distinct afferent circuits converging on corticospinal neurons in the motor cortex. SAI was elicited by preceding a suprathreshold transcranial magnetic stimulus (TMS) with electrical stimulation of the median nerve at the wrist while participants mentally rehearsed a two- or six-digit numeric memory set. To isolate different afferent intracortical circuits in motor cortex SAI was elicited, using TMS involving posterior-anterior (PA) or anterior-posterior (AP) monophasic current. Both PA and AP SAI were significantly reduced during maintenance of the six-digit compared to two-digit memory set. The generalized effect of working memory across anatomically distinct circuits converging upon corticospinal neurons in motor cortex is in contrast to the specific sensitivity of AP SAI to increased attention load. The common response across the PA and AP SAI circuits to increased working memory load may reflect an indiscriminate perisomatic mechanism involved in the voluntary facilitation of desired and/or suppression of unwanted actions during action selection or response conflict.

Effects of lorazepam and baclofen on short- and long-latency afferent inhibition.

Short-latency afferent inhibition (SAI) is modulated by GABAA receptor activity, whereas the pharmacological origin of long-latency afferent inhibition remains unknown. This is the first study to report that long-latency afferent inhibition (LAI) is reduced by the GABAA positive allosteric modulator lorazepam, and that both SAI and LAI are not modulated by the GABAB agonist baclofen. These findings advance our understanding of the neural mechanisms underlying afferent inhibition. The afferent volley evoked by peripheral nerve stimulation has an inhibitory influence on transcranial magnetic stimulation induced motor evoked potentials. This phenomenon, known as afferent inhibition, occurs in two phases: short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI). SAI exerts its inhibitory influence via cholinergic and GABAergic activity. The neurotransmitter receptors that mediate LAI remain unclear. The present study aimed to determine whether LAI is contributed by GABAA and/or GABAB receptor activity. In a double-blinded, placebo-controlled study, 2.5mg of lorazepam (GABAA agonist), 20mg of baclofen (GABAB agonist) and placebo were administered to 14 males (mean age 22.7±1.9 years) in three separate sessions. SAI and LAI, evoked by stimulation of the median nerve and recorded from the first dorsal interosseous muscle, were quantified before and at the peak plasma concentration following drug ingestion. Results indicate that lorazepam reduced LAI by ∼40% and, in support of previous work, reduced SAI by ∼19%. However, neither SAI, nor LAI were altered by baclofen. In a follow-up double-blinded, placebo-controlled study, 10 returning participants received placebo or 40mg of baclofen (double the dosage used in Experiment 1). The results obtained indicate that SAI and LAI were unchanged by baclofen. This is the first study to show that LAI is modulated by GABAA receptor activity, similar to SAI, and that afferent inhibition does not appear to be a GABAB mediated process.

Effect of acute exposure to toluene on cortical excitability, neuroplasticity, and motor learning in healthy humans.

Toluene is a well-known neurotoxic organic solvent and a major component of many industrial and commercial products such as adhesives, paint thinners and gasoline. Many workers are regularly exposed to toluene in their working environment and occupational exposure limits (OELs) have been set to avoid adverse health effects. These OELs or short-term exposure limits vary from 14 to 300ppm across countries partly due to heterogeneity of the findings from animal and human studies about its neurotoxic effects and the evaluation of the adversity of the underlying mechanisms. Furthermore, its acute neurophysiological effects remain poorly understood in humans. The purpose of this study was to investigate the effects of acute exposure to toluene on cortical excitability, plasticity, and implicit motor learning in healthy volunteers. Seventeen subjects were assessed with different transcranial magnetic stimulation measurements: motor thresholds, short-latency intracortical inhibition and intracortical facilitation, and short-interval afferent inhibition before and after clean air or toluene (single peak of 200ppm) administration. Furthermore, we evaluated long-term potentiation-like neuroplasticity induced by anodal transcranial direct current stimulation (tDCS) over the motor cortex, and the participants conducted a motor sequence learning task, the serial reaction time task. Our findings revealed that toluene abolished the plasticity induced by anodal tDCS, attenuated intracortical facilitation, and increased inhibition in the short-latency afferent inhibition measure, while cortico-spinal excitability and intracortical inhibition were not affected. On the behavioural level, toluene did not alter performance of the motor learning task. These results suggest that toluene might act by modulating NMDA receptor activity, as well as cortical glutamatergic and cholinergic neurotransmission in the human brain. This study encourages further research to obtain more knowledge about mechanisms of action and effects of toluene on both naïve and chronically exposed populations.

Diagnosis of Mild Cognitive Impairment Due to Alzheimer's Disease with Transcranial Magnetic Stimulation.

Considering the increasing evidence that disease-modifying treatments for Alzheimer's disease (AD) must be administered early in the disease course, the development of diagnostic tools capable of accurately identifying AD at early disease stages has become a crucial target. In this view, transcranial magnetic stimulation (TMS) has become an effective tool to discriminate between different forms of neurodegenerative dementia. To determine whether a TMS multi-paradigm approach can be used to correctly identify mild cognitive impairment (MCI) due to AD (AD MCI). A sample of 69 subjects with MCI were included and classified as AD MCI or MCI unlikely due to AD (non-AD MCI) based on 1) extensive neurological and neuropsychological evaluation, 2) MRI imaging, and 3) cerebrospinal fluid analysis or/and amyloid PET imaging. A paired-pulse TMS multi-paradigm approach assessing short interval intracortical inhibition-facilitation (SICI-ICF), dependent on GABAergic and glutamatergic intracortical circuits, respectively, and short latency afferent inhibition (SAI), dependent on cholinergic circuits, was performed. We observed a significant impairment of SAI and unimpaired SICI and ICF in AD MCI as compared to non-AD MCI. According to ROC curve analysis, the SICI-ICF / SAI index differentiated AD MCI from non-AD MCI with a specificity of 87.9% and a sensitivity of 94.4%. The assessment of intracortical connectivity with TMS could aid in the characterization of MCI subtypes, correctly identifying AD pathophysiology. TMS can be proposed as an adjunctive, non-invasive, inexpensive, and time-saving screening tool in MCI differential diagnosis.

Emergence of neurophysiological biomarkers of Alzheimer disease

Motta and coworkers ( in their JNNP paper1) used a non-invasive repetitive transcranial magnetic stimulation (TMS) protocol to evaluate brain plasticity in patients with Alzheimer disease (AD). More than 15...

Modulation of Cerebellar-Cortical Connections in Multiple System Atrophy Type C by Cerebellar Repetitive Transcranial Magnetic Stimulation

This study aims at modulating the altered cerebellar-cortical interactions in patients with multiple system atrophy-cerebellar subtype (MSA-C) by using cerebellar repetitive transcranial magnetic stimulation (rTMS). We hypothesized that cerebellar modulation by low-frequency rTMS can resolve the abnormal cortical excitability in multiple system atrophy cerebellar subtype. We studied detailed effects of rTMS of the cerebellum on reaction time (RT) and short-latency afferent inhibition (SAI) response in MSA-C group, Alzheimer Disease (AD) group, and a control group of healthy individuals. The RT and SAI responses were measured before and after 1 Hz cerebellar rTMS in all groups. The study was conducted in the neurophysiology laboratory in Hacettepe University Hospital. Our results indicated that motor cortex disinhibition was predominant in patients with AD and MSA-C. In AD and control groups, there were no changes in SAI after rTMS. However, after application of rTMS over the cerebellum in MSA-C patients, the pathological disinhibition and RT results showed an improvement compared to their previous results. Our study highlights that cerebellar rTMS impairs abnormal cerebellar-cortical inhibitory connections in case of MSA-C.

T49. Motor cortical circuit interactions in Parkinson’s disease

Introduction Using transcranial magnetic stimulation (TMS), previous work has established that motor cortical inhibitory and facilitatory circuits are aberrant in patients with Parkinson’s disease (PD). Three such circuits are short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF) and short latency afferent inhibition (SAI). They assess GABAAergic, glutamatergic and cholinergic function, respectively. Importantly, these circuits interact with each other and their interactions can be tested using a triple-pulse TMS paradigm, which elicits one circuit in the presence of another. However, these interactions have not been studied in PD. Methods 14 right-handed PD patients (10 males; 65.1 ± 8.0 years) were studied ON and OFF dopaminergic medication. Unified Parkinson’s Disease Rating Scale Part III was used to assess disease severity. 14 right-handed, age-matched healthy participants (8 males; 64.4 ± 7.3 years) served as controls. Surface electromyography measured target muscle (first dorsal interosseous) motor evoked potentials generated by TMS of left M1 in controls and of M1 in the more affected hemisphere in PD patients. SICI was tested at an interstimulus interval (ISI) of 2 ms and SICF at an ISI of 1.5 ms. The interactions between SICI and SICF were evaluated by comparing SICF alone to SICF in the presence of SICI. The latency of the median nerve N20 somatosensory evoked potential plus 2 ms was used as the ISI for SAI. The interactions between SAI and SICI were evaluated by comparing SAI alone to SAI in the presence of SICI and by comparing SICI alone to SICI in the presence of SAI. Repeated measures analyses of variance were applied to test the within-subject effect of condition (circuit A alone; circuit A in the presence of circuit B) and the between-subject factor of group (PD ON; PD OFF; control). Results For the comparison between SAI alone and SAI in the presence of SICI, there was a significant effect of condition, but no effect of group. SAI was disinhibited in the presence of SICI. For the comparison between SICI alone and SICI in the presence of SAI, there was a significant effect of condition, but no effect of group. SICI was disinhibited in the presence of SAI. For the comparison between SICF alone and SICF in the presence of SICI, there was no significant effect of condition or group, or interaction between the two. When groups were tested separately, SICF was facilitated in the presence of SICI in controls, but not in PD ON or OFF. Conclusion While previous studies showed that individual cortical circuits of SICI and SAI are abnormal in PD, our findings suggest the interactions between these circuits are preserved in PD. Thus, abnormal SICI and SAI cannot be attributed to abnormal interaction among these circuits. Our results suggest that the facilitatory effect of SICI on SICF is diminished in PD and is not affected by dopaminergic medications. Altered interaction between cortical circuits may contribute to the pathophysiology of PD.

F63. Short latency afferent inhibition predicts cholinergic deficit in Parkinson’s disease patients with mild cognitive impairment

Introduction In vivo evaluation of cholinergic circuits of the human brain had been introduced by using short latency afferent inhibition (SAI). This protocol is coupled motor cortex transcranial stimulation (TMS) with prior contralateral peripheral nerve stimulation. SAI is reduced in deficient cholinergic brain condition and restored with drugs enhancing cholinergic transmission. Cholinergic deficits have been considered involved in Parkinson’s disease (PD) with cognitive decline. In the study, we investigated whether SAI can be a useful tool for evaluating PD with cognitive decline. Methods Twenty-three advanced PD patients admitted for deep brain stimulation pre-surgical evaluation in Hualien Tzu-Chi hospital were enrolled to the study. The SAI test was performed in OFF state. CASI and MMSE were measured for cognitive evaluation. Results Motor evoked potential (MEP) in eight PD patients with severe tremor were discarded because of poor quality. Ten patients with normal cognition (MMSE 27–30), the SAI-22 (inter-stimulation interval: 22 ms) was 34.73% and SAI-25 (inter-stimulation interval: 25 ms) was 38.9%. Five patients with mild cognitive impairment (MMSE 24–26), the SAI-22 was 54.47% and SAI-25 was 81.32%. Compared the two groups, SAI-25 was significantly different (with unpaired T-test), reduced SAI-25 was found in PD with mild cognitive impairment. Conclusion The short latency inhibition (SAI-25) effectively detect the cholinergic deficits in PD with mild cognitive impairment.

F137. Effects of repetitive transcranial magnetic stimulation on short-latency afferent inhibition: A study in treatment-resistant depression

Short-latency afferent inhibition (SAI) is a phenomenon in which transcranial magnetic stimulation (TMS) induced motor evoked potentials (MEPs) are decreased in amplitude due to preceding electrical stimulation of the peripheral nerve, such as the median nerve at the wrist. If the nerve is stimulated around 21 ms before giving the TMS pulse to the cortical representation area of a muscle innervated by the same nerve, the resulting MEP amplitude is smaller than without electrical stimulation. On the contrary, if the nerve is stimulated 30 ms before giving the TMS pulse, there is no effect in MEP amplitude in healthy humans. In some movement disorders, such as in writer’s cramp, the 30 ms stimulation may, however, result in facilitation of the MEP amplitude. SAI is thought to reflect the sensorimotor interaction and cholinergic activity of the cerebral cortex and is likely mediated by the GABAA receptor subtype bearing the α1-subunit. In this study, we evaluated the effects of repetitive TMS (rTMS) therapy on SAI in treatment-resistant depression (TRD). Two patient groups received either active (12 patients) or sham (12 patients) rTMS daily for 27 days. During treatment, excitatory 10 Hz stimulation was applied on the left and inhibitory 1 Hz on the right dorsolateral prefrontal cortex. Before and after the treatment, SAI was measured from right abductor pollicis brevis muscle by using time-intervals of 21 ms and 30 ms between the electric stimulation of the right median nerve at the wrist and TMS of the left motor cortex. Furthermore, baseline MEPs were recorded before and after the treatment. Before the treatment, the 21 ms SAI was inhibitory (p = 0.001) whereas the 30 ms SAI was facilitatory (p = 0.023) in TRD patients. After treatment in the active group, the baseline MEPs decreased in amplitude (p = 0.030), the 21 ms SAI MEPs stayed the same (p = 0.299) and the 30 ms SAI MEPs decreased (p = 0.047) compared to pre-treatment amplitudes. In the sham group, treatment did not induce any changes (p ⩾ 0.188). rTMS treatment modulates the sensorimotor interaction of TRD patients.

Exploring Behavioral Correlates of Afferent Inhibition.

(1) Background: Afferent inhibition is the attenuation of the muscle response evoked from transcranial magnetic stimulation (TMS) by a prior conditioning electrical stimulus to a peripheral nerve. It is unclear whether the magnitude of afferent inhibition relates to sensation and movement; (2) Methods: 24 healthy, young adults were tested. Short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) were obtained following median and digital nerve stimulation. Temporal tactile acuity was assessed with a temporal order judgement (TOJ) task, spatial tactile acuity was assessed using a grating orientation task (GOT), and fine manual dexterity was assessed with the Pegboard task; (3) Results: Correlation analyses revealed no association between the magnitude of SAI or LAI with performance on the TOJ, GOT, or Pegboard tasks; (4) Conclusion: The magnitude of SAI and LAI does not relate to performance on the sensory and motor tasks tested. Future studies are needed to better understand whether the afferent inhibition phenomenon relates to human behavior.