Intermovement Interval Research Articles

Comparison of auditory cueing in toe tapping and gait in persons with Parkinson's disease.

Much research has examined the relationship between bradykinesia and gait impairment in persons with Parkinson's disease (PD). Specifically, impairments in repetitive movements of the upper extremity have been associated with freezing of gait. Studies examining lower extremity repetitive movements are limited. Moreover, the use of external cueing has been a treatment strategy for both bradykinesia and gait, but information on how cues should be used is lacking. The purpose of this study was to compare the effects of auditory cueing on one side versus both sides for bilateral repetitive toe tapping and gait, and to determine if there was a relationship between toe tapping and gait. We hypothesize that there will be no difference between the cueing conditions, but that there will be a significant association between repetitive toe tapping performance and gait performance. Twenty-seven persons with PD completed a toe tapping task in which the more affected side was cued at 70 beats per minute (BPM), the less affected side was cued at 70 BPM, and both sides were cued at 140 BPM. The same cueing conditions were completed for the gait task. Inter movement interval and amplitude data was collected and analyzed for the toe tapping task. Stance time, swing time, step length, and step width were collected and analyzed for the gait task. Results revealed a significant difference in movement performance between the single side cueing conditions and both sides cued condition for inter movement interval (toe tapping), stance time (gait), step length (gait), and step width (gait). Moreover, results revealed a significant association between inter movement interval and stance time and step length. These results would suggest that cueing both sides is better than only one side and that there is a relationship between toe tapping and gait performance when both sides are cued in persons with PD. This study adds to the literature exploring possible shared mechanisms between bradykinesia and gait in persons with PD.

Leg movements during sleep in children treated with serotonergic antidepressants.

To evaluate leg movements during sleep (LMS) in children taking serotonergic antidepressants, compared to those of children with restless legs syndrome (RLS) and controls, and to assess the time structure of intermovement intervals (IMI). Twenty-three children (12 girls, mean age 14.1 years) on antidepressants and with a total LMS index ≥ 15/h, 21 drug-naïve RLS children (11 girls, mean age 13.6 years) also with total LMS index ≥ 15/h, and 35 control children (17 girls, mean age 14.3 years) were recruited. LMS were scored and a series of parameters was calculated, along with the analysis of their time structure. Children taking antidepressants showed higher total and periodic LMS (PLMS) indexes than both controls and RLS children, as well as higher short-interval and isolated LMS indexes than controls. LMS periodicity was highest in children on antidepressants. In children taking antidepressants, a well-defined PLMS IMI peak corresponding to approximately 10-60 s, with a maximum at approximately 20 s was present, which was much less evident in RLS patients and absent in controls. A progressive decrease of PLMS during the night and more frequent arousals were found in children on antidepressants and with RLS. Children taking serotonergic antidepressants show higher periodicity LMS than children with RLS or controls and have a higher number of PLMS through the night. Antidepressant-associated PLMS in children seem to have features similar to PLMS of adults with RLS. Whether this is a marker of an increased risk to develop RLS later in life needs to be determined.

Substantia nigra pars reticulata-mediated sleep and motor activity regulation.

The substantia nigra pars reticulata (SNR) is a major output nucleus of the basal ganglia. Animal studies have shown that lesions of the SNR cause hyposomnia and motor hyperactivity, indicating that the SNR may play a role in the control of sleep and motor activity. Eight 8- to 10-week-old adult male Sprague-Dawley rats were used. After 3 days of baseline polysomnographic recording, dialysates were collected from the lateral SNR across natural sleep-wake states. Muscimol and bicuculline were microinfused into the lateral SNR. We found that GABA release in the lateral SNR is negatively correlated with slow wave sleep (SWS; R = -0.266, p < 0.01, n = 240) and positively correlated with waking (R = 0.265, p < 0.01, n = 240) in rats. Microinfusion of muscimol into the lateral SNR decreased sleep time and sleep quality, as well as eliciting motor hyperactivity in wake and increased periodic leg movement in SWS, while bicuculline infused into the lateral SNR increased sleep and decreased motor activity in SWS in rats. Muscimol infusion skewed the distribution of inter-movement intervals, with most between 10 and 20 s, while a flat distribution of intervals between 10 and 90 s was seen in baseline conditions. Activation of the lateral SNR is important for inducing sleep and inhibiting motor activity prior to and during sleep, and thus to the maintenance of sleep. Abnormal function of the lateral SNR may cause hyposomnia and motor hyperactivity in quiet wake and in sleep.

Effects of new PLM scoring rules on PLM rate in relation to sleep and resting wake for RLS and healthy controls.

This study evaluates the differences in periodic leg movement (PLM) rates for Restless Legs Syndrome (RLS) and healthy controls when using the updated PLM scoring criteria developed by IRLSSG in 2016 versus the prior PLM scoring criteria developed by IRLSSG in 2006. Four major problems with the prior standards had been objectively identified, i.e. minimum inter-movement interval should be 10 not 5s, non-PLM leg movements should end any preceding PLM sequence, a leg movement (LM) can be any length > 0.5s, and a PLM should be a persisting movement not a couple or a series of closely spaced, very brief events. Each of these led to including, erroneously, various random leg movements as PLM. Correcting these problems was expected to increase specificity, reducing the number of PLM detected, particularly in situations producing relatively more random leg movements, e.g. wake vs. sleep and controls without PLMD vs. RLS patients. This study evaluated the putative benefits of the updated, 2016-scoring criteria. The LMs from 42 RLS patients and 30 age- and gender-matched controls were scored for PLMS and PLMW from standard all-night PSG recordings using both 2006 and 2016 WASM criteria. The results confirmed that that the 2016 compared to the 2006 criteria generally decreased the PLM rates with particularly large decreases for the conditions with more random non-PLM events, e.g. wake times and normal healthy controls. This supported the view that the new criteria succeeded in increasing the specificity of PLM detection. Moreover, the changes in PLM rates were generally small for the conditions with relatively few random LM, e.g. RLS and sleep. Thus the bulk of existing PLMS research does not require reconsideration of results, with possible exception of special situations with relatively more random leg movements than periodic leg movements, e.g. wake, healthy normals and children.

1122 Sleep Architecture and Leg Movement Activity During Sleep in Patients with Multiple Sclerosis

Abstract Introduction Although sleep in patients with Multiple Sclerosis (MS) has been investigated in several studies using subjective measures, objective sleep data collected using polysomnography (PSG) are still scanty and often divergent. We herein present the largest study to date evaluating sleep architecture and total leg movement activity during sleep (LMS) in patients with MS. Methods We collected PSG recordings from 80 patients affected by multiple sclerosis (MS, 48.1±10.61yo 67.5% females), and 60 age and gender matched healthy control subjects (HC, 48.5±17.20 yo, 56% females). Group differences were computed using non-parametric statistics for all traditional sleep architecture parameters, LMS, short-interval (SILMS), periodic (PLMS), isolated LMS (ISOLMS) indices and duration, inter-movement interval (IMI) graphs and time-of-night distribution of LMS. Results Patients with MS showed a significantly decreased total sleep period, an increased number of awakenings and stages shifts per hour of sleep, and an increased representation of stage 1 (min and %) compared to the HC group; 26 (32.5%) MS patients had PLMS ≥15/hour versus 8 (13.3%) HC subjects. On average, the comparison between MS and HC groups yielded significant results in terms of an increase in LMS, PLMS, SILMS and ISOLMS indices but not durations. Moreover, MS patients displayed a higher periodicity index, an increased PLMS activity at all inter-movement intervals considered and their PLMS time-of-night distribution revealed that the PLMS increase was stable over the course of the night. Conclusion Sleep continuity is significantly impaired in patients with MS. Moreover, MS patients also an increased total LMS activity, including PLMS, which may contribute to disrupt sleep continuity. A disinhibition of lower spinal network due to cervical or supraspinal MS lesions might be implicated in the mechanisms underlying this latter finding. Support The Employer Department of Neurology, Regional Hospital Lugano (EOC), Lugano, Switzerland receives financial support from Teva, Merck Serono, Biogen Idec, Bayer Schering, Genzyme, Roche and Novartis. The submitted work is not related to these agreements.

Leg Movement Activity During Sleep in Adults With Attention-Deficit/Hyperactivity Disorder.

Objectives: To conduct a first detailed analysis of the pattern of leg movement (LM) activity during sleep in adult subjects with Attention-Deficit/Hyperactivity Disorder (ADHD) compared to healthy controls.Methods: Fifteen ADHD patients and 18 control subjects underwent an in-lab polysomnographic sleep study. The periodic character of LMs was evaluated with established markers of “periodicity,” i.e., the periodicity index, intermovement intervals, and time distribution of LM during sleep, in addition to standard parameters such as the periodic leg movement during sleep index (PLMSI) and the periodic leg movement during sleep arousal index (PLMSAI). Subjective sleep and psychiatric symptoms were assessed using several, self-administered, screening questionnaires.Results: Objective sleep parameters from the baseline night did not significantly differ between ADHD and control subjects, except for a longer sleep latency (SL), a longer duration of the periodic leg movements during sleep (PLMS) in REM sleep and a higher PLMSI also in REM sleep. Data from the sleep questionnaires showed perception of poor sleep quality in ADHD patients.Conclusions: Leg movements during sleep in ADHD adults are not significantly more frequent than in healthy controls and the nocturnal motor events do not show an increased periodicity in these patients. The non-periodic character of LMs in ADHD has already been shown in children and seems to differentiate ADHD from other pathophysiological related conditions like restless legs syndrome (RLS) or periodic limb movement disorder (PLMD). The reduced subjective sleep quality reported by ADHD adults contrasted with the normal objective polysomnographic parameters, which could suggest a sleep-state misperception in these individuals or more subtle sleep abnormalities not picked up by the traditional sleep staging.

Influence of Music Style and Rate on Repetitive Finger Tapping

Auditory cues, including music, are commonly used in the treatment of persons with Parkinson's disease. Yet, how music style and movement rate modulate movement performance in persons with Parkinson's disease have been neglected and remain limited in healthy young populations. The purpose of this study was to determine how music style and movement rate influence movement performance in healthy young adults. Healthy participants were asked to perform repetitive finger movements at two pacing rates (70 and 140beats per minute) for the following conditions: (a)a tone only, (b)activating music, and (c)relaxing music. Electromyography, movement kinematics, and variability were collected. Results revealed that the provision of music, regardless of style, reduced amplitude variability at both pacing rates. Intermovement interval was longer, and acceleration variability was reduced during both music conditions at the lower pacing rate only. These results may prove beneficial for designing therapeutic interventions for persons with Parkinson's disease.

Leg movement activity during sleep in school-age children and adolescents: a detailed study in normal controls and participants with restless legs syndrome and narcolepsy type 1.

To evaluate leg movement activity during sleep (LMS) in normal school-age children and adolescents, to eventually establish age-specific periodic LMS (PLMS) index thresholds that support the diagnosis of restless legs syndrome (RLS), and to evaluate the utility of other LMS indices. Polysomnographic recordings from 61 controls, 46 children with RLS, and 44 children with narcolepsy type 1 (NT1) were analyzed for total leg movements (LMS), PLMS, and isolated leg movements (ISOLMS) duration and indices, separately for school-age children and adolescents. Moreover, intermovement interval (IMI) graphs and time-of-night distribution of LMS were analyzed, and cut-off thresholds for PLMS index and total LMS index were assessed for the separation of RLS from controls. All indices tended to decrease from school-age children to adolescents in normal controls and in NT1, whereas in RLS, only PLMS index increased. All school-age children had a similar IMI distribution with a single peak at IMI 2-4 s followed by gradual decline. In adolescents with RLS, a second peak at IMI 10-50 s was seen. Time-of-night distribution of most indices decreased in RLS, whereas most tended to increase in NT1. A PLMS index cutoff of 2 per hour best differentiated RLS from controls in school-age children (accuracy 70.0%) and in adolescents (accuracy 70.8%); however, most participants with NT1 also showed PLMS indices higher than this threshold. PLMS index alone does not reliably predict the diagnosis of RLS in children and adolescents. However, analyses of IMI distribution and time-of-night distribution provide additional elements to support a diagnosis of RLS.

Data-driven approaches to define the upper limit of the intermovement interval of periodic leg movements during sleep.

To define statistically the upper limit of the intermovement interval (IMI, the time interval between the onset of consecutive movements) of periodic leg movements during sleep (PLMS). We computed the IMI distribution of a large sample (n = 141) of patients with restless legs syndrome (RLS) and analyzed it with two independent approaches, based on fitting either empirical functions or normal and exponential functions to the data. The two fitting approaches consistently pointed to an upper limit of the PLMS IMI in the range between 50 and 60 s. Decreasing the upper limit of PLMS IMI from 90 to 60 s evidently decreased the PLMS index in patients with RLS and control participants; nevertheless, the PLMS index remained significantly higher in RLS vs. control participants. Shifting the upper limit of PLMS IMI to 60 s did not significantly modify the effectiveness of discrimination of PLMS between controls and patients with RLS. These results seem to indicate that a conservative, yet data-driven upper limit for IMI contributing to the PLMS in patients with RLS might be 60 s instead of 90 s, as recommended by the present guidelines.

1127 LEG MOVEMENT ACTIVITY DURING SLEEP IN ADULTS WITH ATTENTION DEFICIT HYPERACTIVITY DISORDER

Sleep disturbances are prevalent in Attention Deficit Hyperactivity Disorder (ADHD). The hypothesis that the typical daytime hyperactivity observed in these patients may correspond to an increased motor activity during the night, thus causing sleep disruption, has been studied in children, but rarely in adults. Here we present a first detailed analysis of the nocturnal motor activity in ADHD adults compared to healthy controls, including the time structure of leg movements (LM) during sleep. Fifteen ADHD patients and eighteen control subjects underwent four in-lab polysomnographic sleep recordings. The periodic character of LM was evaluated using validated markers of “periodicity”, i.e. the periodicity index, inter-movement intervals and time distribution of LM during sleep, in addition to standard parameters, such as the periodic leg movement during sleep index (PLMSI) and periodic leg movement during sleep arousal index (PLMSAI). Sleep quality and the prevalence of insomnia symptoms were assessed with the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). None of the participants had restless legs syndrome. Objective sleep parameters from the baseline night did not differ between ADHD and control subjects, with the exception of a longer sleep latency (p=0.007) in the patient group, as well as a slightly higher PLMSI (p=0.044) and PLMS duration (p=0.023), only in REM sleep. The PSQI questionnaire indicated a poor sleep quality and the ISI the prevalence of subclinical insomnia symptoms in ADHD patients. Leg movement activity during sleep in ADHD adult subjects was neither more frequent than in healthy controls nor did the nocturnal motor events show an increased periodicity. The reduced subjective sleep quality reported by ADHD adults was in contrast to the normal objective polysomnographic parameters, suggesting a sleep-state misperception in these individuals or more subtle sleep abnormalities not picked up by the traditional sleep staging. none

Short-interval leg movements during sleep entail greater cardiac activation than periodic leg movements during sleep in restless legs syndrome patients.

Periodic leg movements during sleep (PLMS) are sequences of ≥4 motor events with intermovement intervals (IMI) of 10-90s. PLMS are a supportive diagnostic criterion for restless legs syndrome (RLS) and entail cardiac activation, particularly when associated with arousal. RLS patients also over-express short-interval leg movements during sleep (SILMS), which have IMI <10s and are organized mainly in sequences of two movements (doublets). We tested whether the cardiac activation associated with SILMS doublets differs from that associated with PLMS in a sample of 25 RLS patients. We analysed time-series of R-R intervals synchronized to the onset of SILMS doublets or PLMS that entailed an arousal during non-rapid eye movement (NREM) sleep. We assessed cardiac activation based on the R-R interval decrease with respect to baseline during NREM sleep without leg movements. We found that the duration of the R-R interval decrease with SILMS doublets was significantly longer than that with PLMS, whereas the maximal decrease in R-R interval was similar. Scoring SILMS in RLS patients may therefore be relevant from a cardiac autonomic perspective.

Validation of a leg movements count and periodic leg movements analysis in a custom polysomnography system

BackgroundPeriodic leg movements (PLM) during sleep (PLMS) are considered strongly related to restless legs syndrome (RLS), and are associated with polymorphisms in RLS risk genes. Various software for automatic analysis of PLMS are available, but only few of them have been validated. Aim of this study was to validate a leg movements count and analysis integrated in a commercially available polysomnography (PSG) system against manual scoring.MethodsTwenty RLS patients with a PLMS index > 20/h and 20 controls with a PLMS index < 5/h were included. Manual and computerized scoring of leg movements (LM) and PLM was performed according to the standard American Academy of Sleep Medicine (AASM) criteria. LM and PLM indices during sleep and wakefulness, the rate of PLMS associated with respiratory events, intermovement interval and periodicity indices were manually and automatically scored.ResultsThe correlation between manual and computerized scoring was high for all investigated parameters (Spearman correlation coefficients 0.751–0.996, p < 0.001; intraclass correlation coefficients 0.775–0.999, p < 0.001). Bland-Altman plots showed high agreement between manual and automatic analysis.ConclusionsThis study validated an automatic LM count and PLM analysis against the gold standard manual scoring according to AASM criteria. The data demonstrate that the software used in this study has an outstanding performance for computerized LM and PLM scoring, and LM and PLM indices generated with this software can be reliably integrated in the routine PSG report. This automatic analysis is also an excellent tool for research purposes.

Sequence analysis of leg movements during sleep with different intervals (90s) in restless legs syndrome.

The aim of this study was to define the time structure of leg movements during sleep occurring with an intermovement interval (onset-to-onset) shorter than 10s in patients with restless legs syndrome and controls, and to compare it to the structure of movements with intervals of 10-90s or >90s. Polysomnographic recordings of 141 untreated patients and 68 age-matched normal controls were analysed. All movements were detected and classified into three categories, separated by intervals of <10, 10-90 or >90s. The number of movements included in each category was significantly higher in patients than in controls. The movements with an interval of >90s occurred steadily during the night, whereas the hourly distribution of movements with intervals of <10 or 10-90s was decreasing or bell-shaped in patients or controls, respectively. Movements with an interval of <10s tended to have a shorter duration and constituted shorter sequences than movements with intervals of 10-90 or >90s. The time structure features of the three categories of movements considered in this study were found to be clearly different. This, together with previous observations on the differential effects of dopamine agonists on movements with different intervals, suggests that movements with intervals of <10 and >90s are regulated by neurotransmitter mechanisms different from those modulating movements with an interval of 10-90s.

Intervening Leg Movements Disrupt PLMS Sequences.

Periodic leg movements during sleep (PLMS) occur within a subject as a series with a remarkably stable period defined by the intermovement interval (IMI). Sometimes a non-PLMS movement occurs intervening between two PLMS. PLMS scoring rules totally ignore these intervening leg movements (iLM). This implicitly assumes an iLM results from a process sufficiently independent from the periodic process producing PLMS that it does not affect the periodicity of the surrounding PLMS. This study for the first time tests this basic assumption and explores characteristics of iLM as a potentially significant class of leg movements during sleep. Leg movements were analyzed from two nights of polysomnography recordings from 27 RLS patients and 22 controls using the validated MATPLM1.1 program. All periods (IMI) between PLMS containing an iLM were compared to the local PLMS period defined as the immediately preceding PLMS IMI using pairwise two-sided Wilcoxon sign-rank tests. Similarly, iLM were tested to see if they started a new PLMS series by having the same period as the subsequent PLMS. The periods (IMIs) containing iLM were longer than the previous periods in RLS subjects, but not controls (p < .05). The periods beginning with the iLM were shorter than the subsequent periods in both RLS and controls (p < .05). iLM as a separate type of LM distort PLMS periodicity and do not restart PLMS series. iLM end PLMS series.

Offline Optimization of the Relative Timing of Movements in a Sequence Is Blocked by Retroactive Behavioral Interference.

Acquisition of motor skills often involves the concatenation of single movements into sequences. Along the course of learning, sequential performance becomes progressively faster and smoother, presumably by optimization of both motor planning and motor execution. Following its encoding during training, “how-to” memory undergoes consolidation, reflecting transformations in performance and its neurobiological underpinnings over time. This offline post-training memory process is characterized by two phenomena: reduced sensitivity to interference and the emergence of delayed, typically overnight, gains in performance. Here, using a training protocol that effectively induces motor sequence memory consolidation, we tested temporal and kinematic parameters of performance within (online) and between (offline) sessions, and their sensitivity to retroactive interference. One group learned a given finger-to-thumb opposition sequence (FOS), and showed robust delayed (consolidation) gains in the number of correct sequences performed at 24 h. A second group learned an additional (interference) FOS shortly after the first and did not show delayed gains. Reduction of touch times and inter-movement intervals significantly contributed to the overall offline improvement of performance overnight. However, only the offline inter-movement interval shortening was selectively blocked by the interference experience. Velocity and amplitude, comprising movement time, also significantly changed across the consolidation period but were interference –insensitive. Moreover, they paradoxically canceled out each other. Current results suggest that shifts in the representation of the trained sequence are subserved by multiple processes: from distinct changes in kinematic characteristics of individual finger movements to high-level, temporal reorganization of the movements as a unit. Each of these processes has a distinct time course and a specific susceptibility to retroactive interference. This multiple-component view may bridge the gap in understanding the link between the behavioral changes, which define online and offline learning, and the biological mechanisms that support those changes.

World Association of Sleep Medicine (WASM) 2016 standards for recording and scoring leg movements in polysomnograms developed by a joint task force from the International and the European Restless Legs Syndrome Study Groups (IRLSSG and EURLSSG)

This report presents the results of the work by a joint task force of the International and European Restless Legs Syndrome Study Groups and World Association of Sleep Medicine that revised and updated the current standards for recording and scoring leg movements (LM) in polysomnographic recordings (PSG). First, the background of the decisions made and the explanations of the new rules are reported and then specific standard rules are presented for recording, detecting, scoring and reporting LM activity in PSG. Each standard rule has been classified with a level of evidence. At the end of the paper, Appendix 1 provides algorithms to aid implementation of these new standards in software tools. There are two main changes introduced by these new rules: 1) Candidate LM (CLM), are any monolateral LM 0.5–10 s long or bilateral LM 0.5–15 s long; 2) periodic LM (PLM) are now defined by runs of at least four consecutive CLM with an intermovement interval ≥10 and ≤ 90 s without any CLM preceded by an interval <10 s interrupting the PLM series. There are also new options defining CLM associated with respiratory events. The PLM rate may now first be determined for all CLM not excluding any related to respiration (providing a consistent number across studies regardless of the rules used to define association with respiration) and, subsequently, the PLM rate should also be calculated without considering the respiratory related events. Finally, special considerations for pediatric studies are provided. The expert visual scoringof LM has only been altered by the new standards to require accepting all LM > 0.5 s regardless of duration, otherwise the technician scores the LM as for the old standards. There is a new criterion for the morphology of LM that applies only to computerized LM detection to better match expert visual detection. Available automatic scoring programs will incorporate all the new rules so that the new standards should reduce technician burden for scoring PLMS.

Isolated rapid eye movement sleep without atonia in amyotrophic lateral sclerosis

ObjectiveThe aim of this study was to quantitatively analyze, with the most recent and advanced tools, the presence of periodic leg movements during sleep (PLMS) and/or rapid eye movement (REM) sleep without atonia (RSWA), in a group of patients with amyotrophic lateral sclerosis (ALS), and to assess their eventual correlation with the clinical severity of the disease. MethodsTwenty-nine ALS patients were enrolled (mean age 63.6 years) along with 28 age-matched “normal” controls (mean age 63.8 years). Functional impairment due to ALS was evaluated using the ALS-Functional Rating Scale-Revised (ALS-FRS) and the ALS severity scale (ALSSS). Full video polysomnographic night recordings were obtained, and PLMS were analyzed by considering their number/hour of sleep and periodicity index, the distribution of intermovement intervals, and the distribution during the night. The characteristics of the chin electromyogram (EMG) amplitude during REM sleep were analyzed by means of the automatic atonia index and the number of chin EMG activations (movements). ResultsThe ALS patients showed longer sleep latency than the controls, together with an increase in number of stage shifts, increased sleep stage 1, and decreased sleep stage 2. None of the leg PLMS parameters were different between the ALS patients and controls. The REM atonia index was significantly decreased in the ALS patients, and the number of chin movements/hour tended to increase. Both REM atonia index and number of chin movements/hour correlated significantly with the ALS-FRS; REM atonia was higher and chin movements were less in ALS patients with more preserved function (higher scores on the ALS-FRS). ConclusionAbnormal REM sleep atonia seemed to be a genuine effect of ALS pathology per se and correlated with the clinical severity of the disease. It is unclear if this might constitute the basis of a possible risk for the development of REM sleep behavior disorder or represent a form of isolated RSWA in ALS.

Autonomous control for mechanically stable navigation of microscale implants in brain tissue to record neural activity.

Emerging neural prosthetics require precise positional tuning and stable interfaces with single neurons for optimal function over a lifetime. In this study, we report an autonomous control to precisely navigate microscale electrodes in soft, viscoelastic brain tissue without visual feedback. The autonomous control optimizes signal-to-noise ratio (SNR) of single neuronal recordings in viscoelastic brain tissue while maintaining quasi-static mechanical stress conditions to improve stability of the implant-tissue interface. Force-displacement curves from microelectrodes in in vivo rodent experiments are used to estimate viscoelastic parameters of the brain. Using a combination of computational models and experiments, we determined an optimal movement for the microelectrodes with bidirectional displacements of 3:2 ratio between forward and backward displacements and a inter-movement interval of 40s for minimizing mechanical stress in the surrounding brain tissue. A regulator with the above optimal bidirectional motion for the microelectrodes in in vivo experiments resulted in significant reduction in the number of microelectrode movements (0.23 movements/min) and longer periods of stable SNR (53% of the time) compared to a regulator using a conventional linear, unidirectional microelectrode movement (with 1.48 movements/min and stable SNR 23% of the time).

Inter-movement interval as a primary stable measure of periodic limb movements of sleep

AimPeriodic leg movements in sleep (PLMS) are generally evaluated by the number of events per hour during sleep, but this is an unstable measure with marked nightly variability and also fails to assess the basic periodicity that essentially characterizes these movements. The inter-movement interval (IMI) evaluates a putative biological process producing the period of PLMS. By contrast, the actual number of PLMS reflects the expression of this biological process that would likely be affected by multiple factors, particularly those disrupting sleep. Thus, this study tests the hypothesis that measurement of IMI duration should be more stable over nights in comparison to any measure based on counting the number of movements. IMI approximates a log-normal distribution. This study, therefore, tests the hypothesis that the means of the log IMI are more stable from night 1 (N1) to night 2 (N2) sleep recordings compared with measures of the number of PLMS. MethodsPLMS/h and IMI were measured for two consecutive nights of full sleep recordings for 29 restless legs syndrome (RLS) patients not being treated and 22 healthy controls without RLS. N1–N2 difference between nights was measured as percent of average for the nights. ResultsMean log IMI showed little nightly variability (mean ± SD for RLS: 3.6% ± 3.7, controls: 7.1% ± 7.0) significantly less p < 0.001) in comparison to PLMS/h (mean ± SD for RLS: 43.2 ± 37.1, controls: 63.7 ± 40.8). The IMI nightly variability was also significantly better than that for the periodicity index. IMI also varied considerably between individuals. ConclusionMean log IMI is a remarkably stable measure across nights within a subject and shows differences between subjects that may have clinical and biological significance. Because of this consistency, the mean log IMI should be considered as one standard measure of PLMS alongside the PLMS index.

Putting the periodicity back into the periodic leg movement index: an alternative data-driven algorithm for the computation of this index during sleep and wakefulness

ObjectiveTo evaluate an alternative index for periodic leg movements during sleep (PLMS) and wakefulness (PLMW) expected to be similar to the standard index when leg movement activity is genuinely periodic, but significantly lower when periodicity is low. Subjects and methodsOne-hundred-and-seven subjects with restless legs syndrome (RLS) were retrospectively identified and included (47 males, 60 females, mean age 56.9 years), along with 63 controls (33 males, 30 females, 42.2 years). Night-to-night variability was analysed in a subgroup of 17 subjects with RLS. PLMW were evaluated in a subgroup of 66 RLS subjects. Two ‘alternative’ PLMS/PLMW indices were calculated: one increased the lower limit of the inter-movement intervals from 5 to 10 s (‘Alt1’) and another additionally considered only series not interrupted by LMs with a short inter-movement interval (‘Alt2’). ResultsDespite a high correlation between methods, only the Alt2 algorithm provided significantly different results, with PLMS/PLMW indices being consistently lower than those provided by the other two methods. The difference was more evident in the controls and during wakefulness, when periodicity was lower. The difference between the Alt2 and the standard PLMS index showed a significantly negative correlation with the Periodicity Index. Night-to-night variability was similar for all PLMS indices and significantly higher than the variability seen in the Periodicity Index. ConclusionThis methodological study introduces an alternative to the standard PLMS/PLMW indices, initiating the validation process for a new way of computing the PLMS/PLMW index, more adherent to the parameters that allows a reliable evaluation of their periodicity.