Selectivity of upper limb posterior root muscle reflexes via cervicothoracic spinal cord stimulation.

Recent studies have reported that transcutaneous spinal stimulation (tSCS) may facilitate improved upper limb motor function in those with incomplete tetraplesia. However, little is known about how tSCS engages upper limb motor pools. This study aimed to explore the extent to which discrete upper limb motor pools can be selectively engaged via altering stimulus location and intensity. 14 participants with intact nervous systems completed two test visits, during which posterior root-muscle reflexes (PRMR) were evoked via a 3x3 cathode matrix applied over the cervicothoracic spine. An incremental recruitment curve at C7 vertebral level was initially performed to attain minimal threshold intensity (MTI) in each muscle. Paired pulses (1ms square monophasic with inter-pulse interval of 50ms) were subsequently delivered at a frequency of 0.25Hz at two intensities (MTI and [Formula: see text]) across all nine locations. in a random order. Evoked response to the 1st (PRMR1) and 2nd (PRMR2) stimuli were recorded from four upper limb muscles. A significant effect of spinal level was observed in all muscles for PRMR1 with greater responses recorded more caudally. Unexpectedly, contralateral cathode placement significantly increased PRMR1 in Biceps Brachii (P=0.012), Flexor Carpi Radialis (P=0.035) and Abductor Pollicis Brevis (P=0.001). Post-activation depression (PAD) was also significantly increased with contralateral cathode placement in Biceps Brachii (P=0.001), Triceps Brachii (P=0.012) and Flexor Carpi Radialis (P=0.001). These results suggest that some level of unilateral motor pool selectivity may be attained via altering stimulus intensity and location during cervicothoracic tSCS.

Effect of Initial Knee angle and Arm Facilitation on biomechanics of the Sit-to-Stand movement.

Spinal cord injuries cause loss of muscle function and subsequently reduce independence. Therapeutic interventions such as transcutaneous spinal cord stimulation are increasingly being used to help improve motor functioning however, a comprehensive understanding of the biomechanical elements of movement may help optimize stimulation protocols. Twenty healthy participants completed five sit-to-stand (STS) transitions while initial knee angle and arm facilitation were altered. Electromyography (EMG) activation of four lower limb muscles and centre of pressure dynamics were recorded. Acute initial knee angles resulted in a change in duration of phases within the STS, and restrictive arm positioning caused the time to completion to increase (p=0.04). Muscle activation patterns across phases were compared and showed significant differences between phases in both the Tibialis Anterior and Rectus Femoris (p<0.006). Acute initial knee angles were also found to significantly increase Biceps Femoris activation across multiple phases (p=0.034). Altering the starting position and limb movement result in vastly different temporal and muscular strategies to complete the STS. Thus, joint angle and upper limb facilitation should be considered when designing rehabilitative interventions for clinical cohorts.

Clinical utility of portable electrophysiology to measure fatigue in treatment-naïve non-small cell lung cancer.

PURPOSE: Cancer-related fatigue (CRF) biology remains poorly understood. Responsible mechanisms may be central or peripheral and originate anywhere from the brain to muscle fiber. Objective measurement is complex and previously limited to specialized laboratories. Portable electroencephalography (EEG) and electromyography (EMG) may enhance objective measurement. This study evaluated the feasibility and acceptability of portable EMG-EEG in CRF assessment. METHODS: A prospective observational feasibility study compared ten outpatients with inoperable, treatment-naïve non-small cell lung cancer and CRF to ten healthy volunteers. All completed a sustained isometric hand-grip contraction at 30% maximal level until self-perceived exhaustion. 128-channel EEG and 2-channel EMG signals of forearm muscles were recorded. Device acceptability was evaluated by questionnaire. RESULTS: The task was evaluated in two stages; first and last 20 s. CRF cohort perceived exhaustion earlier than volunteers (mean 137 ± 76 s vs 208 ± 51 s). As fatigue progressed, EMG amplitude increased significantly (CRF p = 0.02; volunteers: p = 0.04) in both groups as did EMG beta band power (CRF p = 0.008; volunteers: p = 0.006). The increase was significantly less in CRF (amplitude p = 0.032; beta power: p = 0.014). EEG beta band power in the contralateral motor cortex increased significantly (CRF p = 0.03; volunteers: p = 0.019) in both cohorts but to greater extent (p = 0.024) in CRF. One hundred percent device acceptability was reported. CONCLUSIONS: A laboratory-based evaluation was successfully adapted to the outpatient setting during routine visits. High acceptability supports clinical utility. In CRF, a higher degree of cortical activation was required to drive a much lower level of muscle performance. This suggests impairment of both central and peripheral mechanisms in CRF.

Automatic Disability Categorisation based on ADLs among Older Adults in a Nationally Representative Population using Data Mining Methods.

The world's ageing population is rapidly increasing but people's healthspan is not being sustained. Activities of daily living and Montreal Cognitive Assessment scores from the first wave of a large nationally representative longitudinal study in ageing (TILDA) were analysed using multiple correspondence analysis, k-means clustering, network analysis and association rules mining, to find latent patterns in the data and categorise disability among older adults. It was observed that 6.2% of the population had a greater degree of frailty, specifically cognitive impairment. Additionally, the overall population showed difficulty in performing physically demanding activities. Thus, self-reported ADLs have a diagnostic importance as they indicate the level of cognitive and physical functional decline in the older population.

The pathophysiology of cancer-related fatigue: current controversies.

Fatigue is one of the most common and debilitating cancer symptoms, and is associated with impaired quality of life. The exact pathophysiology of cancer-related fatigue (CRF) is poorly understood, but in any individual, it is likely multifactorial and involves inter-related cytokine, muscular, neurotransmitter, and neuroendocrine changes. Underlying CRF mechanisms proposed include central and peripheral hypotheses. Central mechanisms include hypotheses about cytokine dysregulation, hypothalamic-pituitary-adrenal-axis disruption, circadian rhythm disruption, serotonin, and vagal afferent nerve function while peripheral mechanisms include hypotheses about adenosine triphosphate and muscle contractile properties. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is characteristic. The purpose of this article is to provide a narrative review of the literature and present the current controversies in the pathophysiology of CRF, particularly in relation to central and peripheral hypotheses for CRF. An understanding of pathophysiology may facilitate direct and simple therapeutic interventions for those with cancer.

The vegetative and minimally conscious states: a review of the literature and preliminary survey of prevalence in Ireland.

BACKGROUND: In the absence of reliable, objective and direct measures of awareness, the diagnosis and prognosis of the vegetative and minimally conscious states are greatly complicated. This has led to an unacceptably high level of misdiagnosis. Although diagnosis and prognosis have typically relied on bedside behavioural measures, a number of recent studies on neuroimaging and neurophysiological methods offer the possibility of improvement in these areas. OBJECTIVES: We examined current clinical practice and possible future directions in the diagnosis, prognosis and treatment of disorders of consciousness, as well as the ethical and legal dilemmas associated with these disorders. We also summarise epidemiological data from three specialist rehabilitation hospitals in Ireland. CONCLUSIONS: We recommend an international agreement on standard behavioural assessment. This would enable greater consistency in diagnosis and prognostication, as well as improved accuracy of epidemiological data. Based on the current evidence, we advocate the introduction of neuroimaging and neurophysiological techniques into the standardised investigation profile. A more detailed epidemiological study is also required in Ireland.

Quantification of anaesthetic effects on atrial fibrillation rate by partial least-squares.

The mechanism underlying atrial fibrillation (AF) remains poorly understood. Multiple wandering propagation wavelets drifting through both atria under hierarchical models are not understood. Some pharmacological drugs, known as antiarrhythmics, modify the cardiac ionic currents supporting the fibrillation process within the atria and may modify the AF propagation dynamics terminating the fibrillation process. Other medications, theoretically non-antiarrhythmic, may slightly affect the fibrillation process in non-defined mechanisms. We evaluated whether the most commonly used anaesthetic agent, propofol, affects AF patterns. Partial least-squares (PLS) analysis was performed to reduce significant noise into the main latent variables to find the differences between groups. The final results showed an excellent discrimination between groups with slow atrial activity during the propofol infusion.

Neural correlates of oddball detection in self-motion heading: a high-density event-related potential study of vestibular integration.

The perception of self-motion is a product of the integration of information from both visual and non-visual cues, to which the vestibular system is a central contributor. It is well documented that vestibular dysfunction leads to impaired movement and balance, dizziness and falls, and yet our knowledge of the neuronal processing of vestibular signals remains relatively sparse. In this study, high-density electroencephalographic recordings were deployed to investigate the neural processes associated with vestibular detection of changes in heading. To this end, a self-motion oddball paradigm was designed. Participants were translated linearly 7.8 cm on a motion platform using a one second motion profile, at a 45° angle leftward or rightward of straight ahead. These headings were presented with a stimulus probability of 80-20 %. Participants responded when they detected the infrequent direction change via button-press. Event-related potentials (ERPs) were calculated in response to the standard (80 %) and target (20 %) movement directions. Statistical parametric mapping showed that ERPs to standard and target movements differed significantly from 490 to 950 ms post-stimulus. Topographic analysis showed that this difference had a typical P3 topography. Individual participant bootstrap analysis revealed that 93.3 % of participants exhibited a clear P3 component. These results indicate that a perceived change in vestibular heading can readily elicit a P3 response, wholly similar to that evoked by oddball stimuli presented in other sensory modalities. This vestibular-evoked P3 response may provide a readily and robustly detectable objective measure for the evaluation of vestibular integrity in various disease models.

Temporal discrimination thresholds in adult-onset primary torsion dystonia: an analysis by task type and by dystonia phenotype.

Adult-onset primary torsion dystonia (AOPTD) is an autosomal dominant disorder with markedly reduced penetrance. Sensory abnormalities are present in AOPTD and also in unaffected relatives, possibly indicating non-manifesting gene carriage (acting as an endophenotype). The temporal discrimination threshold (TDT) is the shortest time interval at which two stimuli are detected to be asynchronous. We aimed to compare the sensitivity and specificity of three different TDT tasks (visual, tactile and mixed/visual-tactile). We also aimed to examine the sensitivity of TDTs in different AOPTD phenotypes. To examine tasks, we tested TDT in 41 patients and 51 controls using visual (2 lights), tactile (non-painful electrical stimulation) and mixed (1 light, 1 electrical) stimuli. To investigate phenotypes, we examined 71 AOPTD patients (37 cervical dystonia, 14 writer's cramp, 9 blepharospasm, 11 spasmodic dysphonia) and 8 musician's dystonia patients. The upper limit of normal was defined as control mean +2.5 SD. In dystonia patients, the visual task detected abnormalities in 35/41 (85%), the tactile task in 35/41 (85%) and the mixed task in 26/41 (63%); the mixed task was less sensitive than the other two (p = 0.04). Specificity was 100% for the visual and tactile tasks. Abnormal TDTs were found in 36 of 37 (97.3%) cervical dystonia, 12 of 14 (85.7%) writer's cramp, 8 of 9 (88.8%) blepharospasm, 10 of 11 (90.1%) spasmodic dysphonia patients and 5 of 8 (62.5%) musicians. The visual and tactile tasks were found to be more sensitive than the mixed task. Temporal discrimination threshold results were comparable across common adult-onset primary torsion dystonia phenotypes, with lower sensitivity in the musicians.

Change in PASAT performance correlates with change in P3 ERP amplitude over a 12-month period in multiple sclerosis patients.

OBJECTIVE: To examine the correlation between the change in PASAT and the change in P3 event-related potentials (ERPs) over a 12-month period in multiple sclerosis (MS) patients, and to compare the 12-month change in the P3 ERP between MS patients and controls. METHODS: Forty-four subjects (27 MS patients, 17 controls) completed visual and auditory two-stimulus oddball and three-stimulus oddball tasks at Month 0 and Month 12. Data were recorded from a 128-scalp channel electroencephalography array. Data from scalp channels were converted into continuous interpolated images (incorporating the entire scalp and time). Amplitude, topographical differences and correlations were then tested using statistical parametric mapping. RESULTS: The change in visual and auditory P3a correlated significantly with the change in PASAT score (r=0.56, p<0.001 and r=0.48, p=0.003, respectively). Visual P3b and P3a showed greater decrease in 12 months in MS patients relative to controls. Visual P3b, auditory P3b and auditory P3a amplitudes had significantly decreased in MS patients after 12-month period. CONCLUSIONS: Change in visual and auditory P3a ERP amplitudes correlate with change in PASAT scores in MS patients. Visual modality is more sensitive to changes in P3 ERP amplitudes over 12-month period. SIGNIFICANCE: P3 ERPs may have utility in monitoring the change in cognitive functioning in MS.

Automated spike sorting algorithm based on Laplacian eigenmaps and k-means clustering.

This study presents a new automatic spike sorting method based on feature extraction by Laplacian eigenmaps combined with k-means clustering. The performance of the proposed method was compared against previously reported algorithms such as principal component analysis (PCA) and amplitude-based feature extraction. Two types of classifier (namely k-means and classification expectation-maximization) were incorporated within the spike sorting algorithms, in order to find a suitable classifier for the feature sets. Simulated data sets and in-vivo tetrode multichannel recordings were employed to assess the performance of the spike sorting algorithms. The results show that the proposed algorithm yields significantly improved performance with mean sorting accuracy of 73% and sorting error of 10% compared to PCA which combined with k-means had a sorting accuracy of 58% and sorting error of 10%.A correction was made to this article on 22 February 2011. The spacing of the title was amended on the abstract page. No changes were made to the article PDF and the print version was unaffected.

Preliminary evidence for correlation between PASAT performance and P3a and P3b amplitudes in progressive multiple sclerosis.

BACKGROUND: The no-go P3a event-related potential (ERP) is a measure of attentional engagement and the P3b is a measure of context updating. The aim of this study was to compare ERP topographies: (i) to Paced Auditory Serial Addition Test (PASAT) results, (ii) of visual and auditory P3a and P3b of patients with primary progressive multiple sclerosis (PPMS) versus patients with secondary-progressive multiple sclerosis (SPMS) and (iii) of both progressive subtypes to healthy controls. METHODS: Thirty subjects (10 PPMS, 10 SPMS and 10 age-matched controls) completed visual and auditory no-go P3a and P3b tasks whilst data were recorded from a 128-scalp channel electroencephalography (EEG) array. Data from scalp channels were converted into continuous interpolated images (incorporating the entire scalp and time). Topographical differences and correlations were then tested using statistical parametric mapping. RESULTS: For the patients with multiple sclerosis (MS), PASAT score correlated significantly with parietal regions in the auditory P3b, auditory P3a and visual P3b conditions, and with central regions in the visual P3a condition. Patients with PPMS had significantly lower amplitude than patients with SPMS in the auditory P3b condition over the parietal area. The control group had greater amplitude than the patients with MS in all the P3 tasks, with the exception of the auditory P3b. CONCLUSIONS: These data suggest that PASAT performance and P3 ERPs correlate for MS progressive subtypes and that PPMS and SPMS differ in electrophysiological responses during auditory P3b tasks.

FASTER: Fully Automated Statistical Thresholding for EEG artifact Rejection.

Electroencephalogram (EEG) data are typically contaminated with artifacts (e.g., by eye movements). The effect of artifacts can be attenuated by deleting data with amplitudes over a certain value, for example. Independent component analysis (ICA) separates EEG data into neural activity and artifact; once identified, artifactual components can be deleted from the data. Often, artifact rejection algorithms require supervision (e.g., training using canonical artifacts). Many artifact rejection methods are time consuming when applied to high-density EEG data. We describe FASTER (Fully Automated Statistical Thresholding for EEG artifact Rejection). Parameters were estimated for various aspects of data (e.g., channel variance) in both the EEG time series and in the independent components of the EEG: outliers were detected and removed. FASTER was tested on both simulated EEG (n=47) and real EEG (n=47) data on 128-, 64-, and 32-scalp electrode arrays. FASTER was compared to supervised artifact detection by experts and to a variant of the Statistical Control for Dense Arrays of Sensors (SCADS) method. FASTER had >90% sensitivity and specificity for detection of contaminated channels, eye movement and EMG artifacts, linear trends and white noise. FASTER generally had >60% sensitivity and specificity for detection of contaminated epochs, vs. 0.15% for SCADS. FASTER also aggregates the ERP across subject datasets, and detects outlier datasets. The variance in the ERP baseline, a measure of noise, was significantly lower for FASTER than either the supervised or SCADS methods. ERP amplitude did not differ significantly between FASTER and the supervised approach.

Entropy measurements in paroxysmal and persistent atrial fibrillation.

Recent studies on atrial fibrillation (AF) have identified different activation patterns in paroxysmal and persistent AF. In this study, bipolar intra-atrial registers from 28 patients (14 paroxysmal AF and 14 persistent AF) were analyzed in order to find out regional differences in the organization in both types of arrhythmias. The organization of atrial electrical activity was assessed in terms of nonlinear parameters, such as entropy measurements. Results showed differences between the atrial chambers with a higher disorganization in the left atrium in paroxysmal AF patients and a more homogenous behavior along the atria in persistent AF patients.

A high-density ERP study reveals latency, amplitude, and topographical differences in multiple sclerosis patients versus controls.

OBJECTIVE: To quantify latency, amplitude and topographical differences in event-related potential (ERP) components between multiple sclerosis (MS) patients and controls and to compare ERP findings with results from the paced auditory serial addition test (PASAT). METHODS: Fifty-four subjects (17 relapsing remitting (RRMS) patients, 16 secondary progressive (SPMS) patients, and 21 controls) completed visual and auditory oddball tasks while data were recorded from 134 EEG channels. Latency and amplitude differences, calculated using composite mean amplitude measures, were tested using an ANOVA. Topographical differences were tested using statistical parametric mapping (SPM). RESULTS: In the visual modality, P2, P3 amplitudes and N2 latency were significantly different across groups. In the auditory modality, P2, N2, and P3 latencies and N1 amplitude were significantly different across groups. There were no significant differences between RRMS and SPMS patients on any ERP component. There were topographical differences between MS patients and controls for both early and late components for the visual modality, but only in the early components for the auditory modality. PASAT score correlated significantly with auditory P3 latency for MS patients. CONCLUSIONS: There were significant ERP differences between MS patients and controls. SIGNIFICANCE: The present study indicated that both early sensory and later cognitive ERP components are impaired in MS patients relative to controls.

Impaired information processing speed and attention allocation in multiple sclerosis patients versus controls: a high-density EEG study.

BACKGROUND: The no-go P3a is a variant of the P300 event-related potential (ERP) that indexes speed of information processing and attention allocation. The aim of this study was to compare ERP findings with results from the paced auditory serial addition test (PASAT) and to quantify latency, amplitude and topographical differences in P3a ERP components between multiple sclerosis (MS) patients and controls. PATIENTS AND METHODS: Seventy-four subjects (20 relapsing remitting (RRMS) patients, 20 secondary progressive (SPMS) patients and 34 controls) completed a three-stimulus oddball paradigm (target, standard, and non-target). Subjects participated in separate visual and auditory tasks while data were recorded from 134 EEG channels. Latency differences were tested using an ANCOVA. Topographical differences were tested using statistical parametric mapping. RESULTS: Visual P3a amplitude correlated with PASAT score in all MS patients over frontal and parietal areas. There were significant differences in latency, amplitude, and topography between MS patients and controls in the visual condition. RRMS and SPMS patients differed in visual P3a latency and amplitude at frontal and parietal scalp regions. In the auditory condition, there were latency differences between MS patients and controls only over the parietal region. CONCLUSION: The present results demonstrate that information processing speed and attention allocation are impaired in MS.

Ventricular rhythm in atrial fibrillation under anaesthetic infusion with propofol.

Changes in patients' autonomic tone and specific pharmacologic interventions may modify the ventricular response (actual heart rate) during atrial fibrillation (AF). Hypnotic agents such as propofol may modify autonomic balance as they promote a sedative state. It has been shown that propofol slightly slows atrial fibrillatory activity, but the net global effect on the ventricular response remains unknown. We aimed to evaluate in patients in AF the effect of a propofol bolus on the ventricular rate and regularity at ECG. We analysed the possible relation with local atrial fibrillatory activities, as ratios between atrial and ventricular rates (AVRs), analysing atrial activity from intracardiac electrograms at the free wall of the right and left atria and at the interatrial septum. We compared data at the baseline and after complete hypnosis. Propofol was associated with a more homogeneous ventricular response and lower AVR values at the interatrial septum.

Temporal discrimination threshold: VBM evidence for an endophenotype in adult onset primary torsion dystonia.

Familial adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance. Most adult-onset primary torsion dystonia patients are sporadic cases. Disordered sensory processing is found in adult-onset primary torsion dystonia patients; if also present in their unaffected relatives this abnormality may indicate non-manifesting gene carriage. Temporal discrimination thresholds (TDTs) are abnormal in adult-onset primary torsion dystonia, but their utility as a possible endophenotype has not been examined. We examined 35 adult-onset primary torsion dystonia patients (17 familial, 18 sporadic), 42 unaffected first-degree relatives of both familial and sporadic adult-onset primary torsion dystonia patients, 32 unaffected second-degree relatives of familial adult-onset primary torsion dystonia (AOPTD) patients and 43 control subjects. TDT was measured using visual and tactile stimuli. In 33 unaffected relatives, voxel-based morphometry was used to compare putaminal volumes between relatives with abnormal and normal TDTs. The mean TDT in 26 control subjects under 50 years of age was 22.85 ms (SD 8.00; 95% CI: 19.62-26.09 ms). The mean TDT in 17 control subjects over 50 years was 30.87 ms (SD 5.48; 95% CI: 28.05-33.69 ms). The upper limit of normal, defined as control mean + 2.5 SD, was 42.86 ms in the under 50 years group and 44.58 ms in the over 50 years group. Thirty out of thirty-five (86%) AOPTD patients had abnormal TDTs with similar frequencies of abnormalities in sporadic and familial patients. Twenty-two out of forty-two (52%) unaffected first-degree relatives had abnormal TDTs with similar frequencies in relatives of sporadic and familial AOPTD patients. Abnormal TDTs were found in 16/32 (50%) of second-degree relatives. Voxel-based morphometry analysis comparing 13 unaffected relatives with abnormal TDTs and 20 with normal TDTs demonstrated a bilateral increase in putaminal grey matter in unaffected relatives with abnormal TDTs. The prevalence of abnormal TDTs in sporadic and familial AOPTD patients and their first-degree relatives follows the rules for a useful endophenotype. A structural correlate of abnormal TDTs in unaffected first-degree relatives was demonstrated using voxel-based morphometry. Voxel-based morphometry findings indicate that putaminal enlargement in AOPTD is a primary phenomenon. TDTs may be an effective tool in AOPTD research with particular relevance to genetic studies of the disorder.

Classifier models and architectures for EEG-based neonatal seizure detection.

Neonatal seizures are the most common neurological emergency in the neonatal period and are associated with a poor long-term outcome. Early detection and treatment may improve prognosis. This paper aims to develop an optimal set of parameters and a comprehensive scheme for patient-independent multi-channel EEG-based neonatal seizure detection. We employed a dataset containing 411 neonatal seizures. The dataset consists of multi-channel EEG recordings with a mean duration of 14.8 h from 17 neonatal patients. Early-integration and late-integration classifier architectures were considered for the combination of information across EEG channels. Three classifier models based on linear discriminants, quadratic discriminants and regularized discriminants were employed. Furthermore, the effect of electrode montage was considered. The best performing seizure detection system was found to be an early integration configuration employing a regularized discriminant classifier model. A referential EEG montage was found to outperform the more standard bipolar electrode montage for automated neonatal seizure detection. A cross-fold validation estimate of the classifier performance for the best performing system yielded 81.03% of seizures correctly detected with a false detection rate of 3.82%. With post-processing, the false detection rate was reduced to 1.30% with 59.49% of seizures correctly detected. These results represent a comprehensive illustration that robust reliable patient-independent neonatal seizure detection is possible using multi-channel EEG.