Transcranial alternating current stimulation can modulate the blink reflex excitability. Effects of a 10- and 20-Hz tACS session on the blink reflex recovery cycle in healthy subjects.

BACKGROUND: The blink reflex excitability, assessed through paired electrical stimuli responses, has been modulated using traditional non-invasive neurostimulation techniques. Recently, transcranial Alternating Current Stimulation (tACS) emerged as a tool to modulate brain oscillations implicated in various motor, perceptual, and cognitive functions. This study aims to investigate the influence of 20-Hz and 10-Hz tACS sessions on the primary motor cortex and their impact on blink reflex excitability. MATERIALS AND METHODS: Fifteen healthy volunteers underwent 10-min tACS sessions (intensity 1 mA) with active/reference electrodes placed over C4/Pz, delivering 20-Hz, 10-Hz, and sham stimulation. The blink reflex recovery cycle (BRrc) was assessed using the R2 amplitude ratio at various interstimulus intervals (ISIs) before (T0), immediately after (T1), and 30 min post-tACS (T2). RESULTS: Both 10-Hz and 20-Hz tACS sessions significantly increased R2 ratio at T1 (10-Hz: p = 0.02; 20-Hz: p < 0.001) and T2 (10-Hz: p = 0.01; 20-Hz: p < 0.001) compared to baseline (T0). Notably, 20-Hz tACS induced a significantly greater increase in blink reflex excitability compared to sham at both T1 (p = 0.04) and T2 (p < 0.001). CONCLUSION: This study demonstrates the modulatory effect of tACS on trigemino-facial reflex circuits, with a lasting impact on BRrc. Beta-band frequency tACS exhibited a more pronounced effect than alpha-band frequency, highlighting the influential role of beta-band oscillations in the motor cortex on blink reflex excitability modulation.

Blink reflex recovery cycle to differentiate progressive supranuclear palsy from corticobasal syndrome.

BACKGROUND AND PURPOSE: Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) may share similar clinical findings and tests to distinguish between the two disorders could be useful. We evaluated the blink reflex and R2 blink reflex recovery cycle (R2BRRC), determining diagnostic sensitivity, specificity and positive and negative predictive value of R2BRRC in differentiating patients with PSP from those with CBS. METHODS: This was a prospective data collection study investigating blink reflex and R2BRRC at interstimulus intervals (ISIs) of 100, 150, 200, 300, 400, 500 and 750 ms in 12 patients with PSP, eight patients with CBS and 10 controls. RESULTS: Patients with PSP have earlier recruitment of R2BRRC as compared with patients with CBS (ISI: 100 ms, P = 0.002; 150 ms, P < 0.001; 200 ms, P < 0.001; 300 ms, P = 0.02) and controls (ISI: 100 ms, P < 0.001; 150 ms, P < 0.001; 200 ms, P < 0.001; 300 ms, P = 0.004). The presence of an early recovery of the R2 differentiated PSP from CBS with a specificity and sensitivity of 87.5% and 91.7%, respectively. CONCLUSIONS: The R2BRRC curve might be considered to be a useful tool in differentiating patients with PSP from those with CBS.

Reorganization of sensory input at brainstem in hemifacial spasm and postparalytic facial syndrome.

We hypothesized the filtering of sensory input from face and hand at brainstem may reorganize in hemifacial spasm (HFS) and postparalytic facial syndrome (PFS). Thus, we examined the prepulse inhibition of blink reflex (BR-PPI) in HFS and PFS. We included 12 healthy subjects, 13 patients with HFS, and 11 patients with PFS. Baseline BR, BR recovery at interstimulus interval (ISI) of 300 ms and BR-PPI at ISI of 100 ms were performed on the right sides of healthy subjects and on both sides of patients. Within-subject analysis showed baseline BR and BR-PPI were similar between asymptomatic and symptomatic sides of patients with HFS whereas BR recovery was higher on the symptomatic side. In the PFS group, latency of R2 during baseline BR recording was longer (p = 0.022) and R2 amplitude (p = 0.046) was reduced on the symptomatic side compared to asymptomatic side. Reduction of R2 area in BR-PPI recordings was also the lowest in HFS compared to other two groups (p = 0.000); however, it was also lower in patients with PFS compared to healthy subjects (p = 0.018). BR-PPI was decreased on both sides of patients. The mean R2 recovery was higher on both sides of patients with HFS and PFS (p = 0.007). Filtering of facial sensory input is decreased probably to monitor and to correct the sequence of facial movements in these disorders.

Brainstem reflex excitability changes in patients with amyotrophic lateral sclerosis.

INTRODUCTION: In this study we explored brainstem reflex excitability changes, blink reflex recovery cycles (BRRCs), and masseter inhibitory reflexes (MIRs) in patients with amyotrophic lateral sclerosis (ALS). METHODS: Fourteen ALS patients and 14 healthy control subjects were recruited. The BRRC was examined at interstimulus intervals (ISIs) of 100, 200, 300, 400, 500, and 600 ms. The latencies and durations of silent period 1 (SP1) and silent period 2 (SP2) of the MIR were measured. RESULTS: Decreased R2 area suppression was prominent in the ALS group at ISIs of 200, 300, and 400 ms (P < 0.02), whereas no significant differences between groups at 100, 500, and 600 ms ISIs (P > 0.05) were observed. SP2 duration was significantly prolonged in the ALS group compared with controls (P = 0.01). CONCLUSIONS: Brainstem inhibitory and excitatory interneuronal activity is altered in ALS, possibly brought about by physiological and morphological changes at the cortical or bulbar levels. Muscle Nerve 56: 925-929, 2017.

Cerebellar voxel-based morphometry in essential tremor.

BACKGROUND: Imaging studies investigating cerebellar gray matter (GM) in essential tremor (ET) showed conflicting results. Moreover, no large study explored the cerebellum in ET patients with resting tremor (rET), a syndrome showing enhanced blink reflex recovery cycle (BRrc). OBJECTIVE: To investigate cerebellar GM in ET and rET patients using voxel-based morphometry (VBM) analysis. METHODS: Seventy ET patients with or without resting tremor and 39 healthy controls were enrolled. All subjects underwent brain 3 T-MRI and BRrc recording. We compared the cerebellar GM volumes between ET (n = 40) and rET (n = 30) patients and controls through a VBM analysis. Moreover, we investigated possible correlations between cerebellar GM volume and R2 component of BRrc. RESULTS: rET and ET patients had similar disease duration. All rET patients and none of ET patients had enhanced BRrc. No differences in the cerebellar volume were found when ET and rET patients were compared to each other or with controls. By considering together the two tremor syndromes in a large patient group, the VBM analysis showed bilateral clusters of reduced GM volumes in Crus II in comparison with controls. The linear regression analysis in rET patients revealed a cluster in the left Crus II where the decrease in GM volume correlated with the R2BRrc increase. CONCLUSION: Our study suggests that ET and rET are different tremor syndromes with similar mild cerebellar gray matter involvement. In rET patients, the left Crus II may play a role in modulating the brainstem excitability, encouraging further studies on the role of cerebellum in these patients.

Blink reflex recovery cycle distinguishes patients with idiopathic normal pressure hydrocephalus from elderly subjects.

BACKGROUND: The R2 component of blink reflex recovery cycle (R2BRrc) is a simple neurophysiological tool to detect the brainstem hyperexcitability commonly occurring in several neurological diseases such as Parkinson's disease and atypical parkinsonisms. In our study, we investigated for the first time the usefulness of R2BRrc to assess brainstem excitability in patients with idiopathic Normal Pressure Hydrocephalus (iNPH) in comparison with healthy subjects. METHODS: Eighteen iNPH patients and 25 age-matched control subjects were enrolled. R2BRrc was bilaterally evaluated at interstimulus intervals (ISIs) of 100, 150, 200, 300, 400, 500 and 750 ms in all participants. We investigated the diagnostic performance of R2BRrc in differentiating iNPH patients from control subjects using ROC analysis. Midbrain area and Magnetic Resonance Hydrocephalic Index (MRHI), an MRI biomarker for the diagnosis of iNPH, were measured on T1-weighted MR images, and correlations between R2BRrc values and MRI measurements were investigated. RESULTS: Fourteen (78%) of 18 iNPH patients showed an enhanced R2BRrc at ISIs 100-150-200 ms, while no control subjects had abnormal R2BRrc. The mean amplitude of bilateral R2BRrc at the shortest ISIs (100-150-200 ms) showed high accuracy in differentiating iNPH patients from controls (AUC = 0.89). R2BRrc values significantly correlated with midbrain area and MRHI values. CONCLUSIONS: This study represents the first evidence of brainstem hyperexcitability in iNPH patients. Given its low cost and wide availability, R2BRrc could be a useful tool for selecting elderly subjects with mild gait and urinary dysfunction who should undergo an extensive diagnostic workup for the diagnosis of NPH.

Contribution of brainstem circuits in pathophysiology of NREM-sleep parasomnias.

OBJECTIVE: We aimed to investigate the brainstem circuits to reveal if there was any abnormality in these circuits in clinically diagnosed patients with NREM parasomnias during wakefulness. METHODS: Twelve patients with NREM-sleep parasomnia diagnosed according to ICSD-3 criteria and a control group of 16 healthy subjects were enrolled into our study. We analyzed the auditory startle reflex (ASR), blink reflex (BR), prepulse inhibition (PPI) of BR and recovery excitability of BR. RESULTS: There was a trend for longer responses from orbicularis oculi and sternocleidomastoid muscles after auditory stimulation in the patients compared to those in the healthy subjects. The recovery percentages at 200 ms and 300 ms showed a borderline significance in the patients. No significant difference was found in the R2-PPI between the patients and healthy subjects. CONCLUSIONS: Our results suggest a mildly enhanced ASR and relatively early facilitation of BR excitability in patients with NREM-sleep parasomnia during daytime. Although our findings suggest involvement of brainstem networks in NREM-sleep parasomnia during wakefulness, it would be better to study these networks at night and during daytime to see if there is any contribution.

Asymmetry index of Blink Reflex Recovery Cycle differentiates Parkinson's disease from atypical Parkinsonian syndromes.

BACKGROUND: Differential diagnosis between Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), is often difficult because of overlap of common clinical features. We evaluated R2 Blink Reflex Recovery Cycle (R2BRRC) in drug-naive PD patients and in MSA and PSP patients to differentiate early PD from APS. METHODS: We investigated 43 patients: 15 drug-naive PD patients, 16 MSA patients, and 12 PSP patients. R2BRRC was evaluated bilaterally at interstimulus intervals (ISIs) of 100, 150, 200, 300, 400, 500, and 750 ms. An asymmetry index (AI) of R2BRRC for each ISI was computed. RESULTS: R2BRRC of PD patients showed an increased brainstem excitability for less affected side (LAS) stimulation at ISIs of 100, 150, 200 (p < 0.001), and 300 ms (p = 0.03) compared to more affected side (MAS) stimulation, whereas no differences between LAS and MAS stimulation were found in APS. AI of 0.87 at ISI of 100 ms differentiated PD from MSA with a sensitivity of 86.7% and a specificity of 100%, whereas AI of 0.78 at ISI of 100 ms permitted to discriminate PD from PSP with a sensitivity of 86.7% and a specificity of 91.7%. CONCLUSION: AI of R2BRRC may represent a reliable tool in differentiating PD from APS, especially at the early stage of the disease.

Temporal discrimination threshold and blink reflex recovery cycle in cervical dystonia - two sides of the same coin?

INTRODUCTION: Elevated temporal discrimination thresholds (TDT) have been found in cervical dystonia (CD) and unaffected first-degree relatives, indicating autosomal dominant inheritance with reduced penetrance, serving as an endophenotype and being indicative of abnormal inhibitory processing within the brainstem-basal ganglia circuits. The blink reflex R2 recovery cycle (BRRC) is also a measure of excitability of brainstem-basal ganglia circuits, and inconsistent findings are reported in CD. The aim was to investigate TDT and BRRC in CD and evaluate its reliability as an endophenotype. METHODS: 29 patients with isolated cervical dystonia (mean age: 56.1 ±â€¯14.3, female n = 18) and 29 age- and gender-matched healthy controls (mean age: 56.0 ±â€¯14.2, female n = 18) were evaluated using a TDT-paradigm, performed as previously described by testing visual, tactile and visual-tactile temporal discrimination thresholds, and the BRRC, investigated with electrical and air puff stimulation. RESULTS: Mean visual-tactile (p = 0.001) and visual TDTs (p = 0.015) differed between CD and controls; tactile TDTs revealed no group differences (p = 0.232). No between group differences were found for BRRC using either electrical or air puff stimulation (p = 0.117). There was no correlation between the elevation of TDTs and the degree of BRRC-inhibition in CD. CONCLUSION: Our findings support the hypothesis that the TDT is an endophenotype in CD. BRRC testing did not demonstrate disinhibition of brainstem-basal ganglia circuits in CD. In contrast to TDT, the BRRC seems not to represent an endophenotype in cervical dystonia.

Blink Reflex in Episodic and Chronic Migraine.

INTRODUCTION: Activation of the trigeminovascular system and sensitization of brainstem trigeminal nuclei play a significant role in the physiopathology of migraine. Our aim was to investigate blink reflex (BR) and its recovery in episodic and chronic migraine patients. METHODS: Twenty-eight chronic migraine patients, thirty-two episodic migraine without aura patients and thirty healthy controls were included in the study. The study was performed using a portable electromyography device with a software specifically prepared for BR. Blink reflex assessments were performed in patients during the pain-free period and in healthy controls using the 'standard method - double stimulation' technique in 200 ms, 500 ms, 1000 ms, 2000 ms, and 5000 ms intervals. RESULTS: Blink reflex recovery was significantly increased in both patient groups as compared to the control group in 200 ms interstimulus interval (ISI) on both sides (p<0.005). Moreover, when it was compared to the control group, recovery was also significantly increased in the chronic migraine group in 2000 ms ISI on the right side and in 5000 ms ISI on the left side as well as in 500 and 1000 ms ISIs on the left side in the migraine without aura group (p<0.002, p<0.003). R2 recovery curve was noted to be higher in both patient groups as compared to the control group, although could not be demonstrated statistically in all intervals. A statistically significant increase was observed in the migraine group without auras compared with the controls (p <0,037, p <0,011) in the left side at 500 and 1000 ms ISIs. For all intervals in our study, although the increase in recovery was not statistically significant, it was noted that the R2 recovery curve was higher in the patient groups, with respect to the normals. The increase in R2 recovery noted in both patient groups suggested increased sensitization of the trigeminal structures. Significantly increased recovery in low ISI (200 ms) in the two patient groups as compared to the control group raised the thought that the migraine brain goes through two different excitability periods (ictal and interictal). CONCLUSION: In conclusion, similar to the previous studies, the findings of this study suggested that there was a reduction in central inhibitory mechanisms during interictal period in migraine patients.

Circadian Change in Blink Reflex Recovery in Restless Legs Syndrome.

INTRODUCTION: Restless legs syndrome (RLS) is associated with dysfunction of the dopaminergic systems in the pathways that specifically link the sensory input and motor output. Keeping in mind that clinical symptomatology in RLS and cerebrospinal fluid dopamine concentrations in healthy individuals show changes throughout the day, we hypothesized that excitability of the related pathways increases during the night in RLS, and in the present study, we aimed to analyze our hypothesis by the assessment of blink reflex (BR) recovery. METHODS: Eleven patients with primary RLS and eight age- and gender-matched healthy subjects were included in the study. All participants underwent detailed interviews and neurological examinations. BR responses were recorded after single and paired supraorbital stimulation during the early afternoon and late at night. For double stimulation, interstimulus intervals (ISI) of 100, 300, and 500 ms were used. Daytime and nighttime investigations were separately compared between the patient and control groups (between-group analyses). In-group analyses were conducted between daytime and nighttime investigations of the patient and control groups. RESULTS: BR responses to single stimuli were normal in all participants at all sessions. R2 recovery was the highest in the patient group during nighttime investigations. In-group analysis showed a reduction of R2 recovery during the night in healthy subjects. R2 recoveries at ISIs of 300 and 500 ms at nighttime were higher in RLS patients but did not reach statistical significance. CONCLUSION: The BR circuit is less excitable during the night in healthy individuals, whereas the reduction of excitability is lost in RLS. Despite the limited number of included subjects, we suggest that the normal circadian modulation of the BR circuit is lost in RLS.

Enhanced blink reflex recovery in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME), which has been attributed to the dysfunction of cortico-thalamic pathway, has been considered to be one of the system epilepsies. However, electrophysiological and functional neuroimaging techniques have revealed the functional involvement of various parts of the central nervous system, also. Here, we aimed to analyze the role of brainstem circuits in JME by using the blink reflex recovery cycle (BRrc). Electrophysiological recordings of 18 JME patients together with age and gender matched 18 healthy subjects were made during single and paired supraorbital stimulation. Constant current paired stimuli were delivered at interstimulus intervals (ISI) of 200 and 400ms. Amplitudes of R2 responses were measured on the non-dominant side, and percentages of the recovery cycles were calculated. All participants had normal and similar R1 and R2 components of blink reflex (BR). At ISI of 400ms, R2 recoveries were significantly higher in the JME group compared to healthy subjects (p=0.040). There was no correlation between R2-BRrc and ages of JME patients, disease duration and daily dosage of valproic acid. We suggest that in JME, the integrity of BR circuit is preserved while the excitability of the brainstem BR circuitry is enhanced.

Abnormalities of Masseteric Inhibitory Reflex in Hereditary Geniospasm: Evidence for a Brainstem Myoclonus.

We studied two unrelated families with several members suffering from geniospasm. Here, we aim to clarify the pathophysiology underlying the hereditary geniospasm through testing of brainstem excitability by the recovery cycles of the blink reflex (BR) and the masseteric inhibitory reflex (MIR). The R2 component of the BR and the SP2 component of the MIR and their recovery cycle were analyzed in 3 patients and 8 healthy, age-matched subjects as the control group. Patients with geniospasm exhibited a different excitability of the BR, compared to the control, group, as shown by the larger R2 component area of BR in controls than patients. Notably, the mean recovery index was 0.61 ± 0.19 in geniospasm patients and 0.40 ± 0.15 in controls (P ≤ 0.05). Interestingly, the recovery cycle of the MIR showed a loss of inhibition in both patients studied, as indicated by the behavior of the SP2 component. Our cases showed a partial impairment of the activity of brainstem inhibitory interneurons, indicated by the abnormal recovery cycle of MIR. These results would implicate a mechanism akin to brainstem myoclonus for the generation of geniospasm.

Blink reflex recovery cycle distinguishes essential tremor with resting tremor from de novo Parkinson's disease: an exploratory study.

An increased R2 recovery component of the blink reflex (R2-BRrc) has been observed in Parkinson's disease (PD), cranio-cervical dystonia, dystonic tremor and essential tremor with associated resting tremor (rET), while the BRrc was reported normal in patients with essential tremor (ET). Distinguishing rET from tremor dominant PD (tPD) may be challenging especially in the first stages of the diseases, in the absence of DAT-SPECT investigation. We evaluated the possible usefulness of BRrc for differentiating subjects with de novo tPD from those with rET. We investigated R2-BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 ms in 11 participants with tPD, 10 with rET and 20 healthy controls. All participants underwent DAT-SPECT and cardiac MIBG scintigraphy. R2 recovery was significantly enhanced in tPD compared to controls at all investigated ISIs (p < 0.001), while in subjects with rET patients BRrc was significantly increased compared to controls at ISI 150, 200, 300, 400, 500 and 750 ms (p < 0.001). At ISI 100 R2-BRrc distinguished patients participants with de novo tPD from those with rET with a sensitivity, specificity and accuracy of 100%. Our findings demonstrate the usefulness of BRrc for differentiating de novo tPD from rET.