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.

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.

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.

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.

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.

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.

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.

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.

Bayesian estimation of synaptic physiology from the spectral responses of neural masses.

We describe a Bayesian inference scheme for quantifying the active physiology of neuronal ensembles using local field recordings of synaptic potentials. This entails the inversion of a generative neural mass model of steady-state spectral activity. The inversion uses Expectation Maximization (EM) to furnish the posterior probability of key synaptic parameters and the marginal likelihood of the model itself. The neural mass model embeds prior knowledge pertaining to both the anatomical [synaptic] circuitry and plausible trajectories of neuronal dynamics. This model comprises a population of excitatory pyramidal cells, under local interneuron inhibition and driving excitation from layer IV stellate cells. Under quasi-stationary assumptions, the model can predict the spectral profile of local field potentials (LFP). This means model parameters can be optimised given real electrophysiological observations. The validity of inferences about synaptic parameters is demonstrated using simulated data and experimental recordings from the medial prefrontal cortex of control and isolation-reared Wistar rats. Specifically, we examined the maximum a posteriori estimates of parameters describing synaptic function in the two groups and tested predictions derived from concomitant microdialysis measures. The modelling of the LFP recordings revealed (i) a sensitization of post-synaptic excitatory responses, particularly marked in pyramidal cells, in the medial prefrontal cortex of socially isolated rats and (ii) increased neuronal adaptation. These inferences were consistent with predictions derived from experimental microdialysis measures of extracellular glutamate levels.

Changes in effective connectivity of human superior parietal lobule under multisensory and unisensory stimulation.

Previous event-related potential (ERP) studies have identified the superior parietal lobule (SPL) as actively multisensory. This study compares effective, or contextually active, connections to this region under unisensory and multisensory conditions. Effective connectivity, the influence of one brain region over another, during unisensory visual, unisensory auditory and multisensory audiovisual stimulation was investigated. ERPs were recorded from subdural electrodes placed over the parietal lobe of three patients while they conducted a rapid reaction-time task. A generative model of interacting neuronal ensembles for ERPs was inverted in a scheme allowing investigation of the connections from and to the SPL, a multisensory processing area. Important features of the ensemble model include inhibitory and excitatory feedback connections to pyramidal cells and extrinsic input to the stellate cell pool, with extrinsic forward and backward connections delineated by laminar connection differences between ensembles. The framework embeds the SPL in a plausible connection of distinct neuronal ensembles mirroring the integrated brain regions involved in the response task. Bayesian model comparison was used to test competing feed-forward and feed-backward models of how the electrophysiological data were generated. Comparisons were performed between multisensory and unisensory data. Findings from three patients show differences in summed unisensory and multisensory ERPs that can be accounted for by a mediation of both forward and backward connections to the SPL. In particular, a negative gain in all forward and backward connections to the SPL from other regions was observed during the period of multisensory integration, while a positive gain was observed for forward projections that arise from the SPL.

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.

Survey of 1276 shoeprint impressions and development of an automatic shoeprint pattern matching facility.

1276 shoeprints were collected at a scientific exhibition. Details regarding the age groups of the participants, style, size and manufacturer/brand of their shoes were recorded. The impressions were assigned to pattern groups showing that the most common pattern was present in only 1% of the population studied and most patterns were much less common. The impressions were digitized and a system developed for automatically sorting a database of images of outsole patterns in response to a reference image. The database images are ranked so that those from the same pattern group as the reference shoeprint are likely to be at the start of the list. A database of 486 complete shoeprint images belonging to 142 pattern groups was established with each group containing two or more examples. Tests of the system have shown that the first-ranked database image belongs to the same pattern group as the reference image 60% of the time and that a correct match appears within the first 5% of the ranked images 88% of the time. The system has translational and rotational invariance so that the spatial positioning of the reference shoeprint images does not have to correspond with the spatial positioning of the shoeprint images of the database. The performance of the system for matching partial shoeprints was also determined.

Automated processing of shoeprint images based on the Fourier transform for use in forensic science.

The development of a system for automatically sorting a database of shoeprint images based on the outsole pattern in response to a reference shoeprint image is presented. The database images are sorted so that those from the same pattern group as the reference shoeprint are likely to be at the start of the list. A database of 476 complete shoeprint images belonging to 140 pattern groups was established with each group containing two or more examples. A panel of human observers performed the grouping of the images into pattern categories. Tests of the system using the database showed that the first-ranked database image belongs to the same pattern category as the reference image 65 percent of the time and that a correct match appears within the first 5 percent of the sorted images 87 percent of the time. The system has translational and rotational invariance so that the spatial positioning of the reference shoeprint images does not have to correspond with the spatial positioning of the shoeprint images of the database. The performance of the system for matching partial-prints was also determined.

Localized pleural mesothelioma. The clinical spectrum.

Localized pleural mesotheliomas are rare tumors that have a variety of clinical presentations, from an asymptomatic solitary nodule to a massive, highly symptomatic neoplasm filling most of the pleural cavity. Two cases are reported which show the clinical spectrum of the more common benign variant. The clinical differentiation between the benign tumor as well as the less frequent malignant neoplasms of localized mesotheliomas has been disappointing. Complete surgical resection is the preferred treatment for both types and is usually curative with the benign mesothelioma.

Projecting patients' preferences from living wills: an invalid strategy for management of dementia with life-threatening illness.

OBJECTIVE: To examine variation in elders' choices of therapies in different clinical scenarios and to assess the validity of extending preferences expressed in scenarios of usual health, terminal illness, and coma to preferences in a scenario of moderately advanced Alzheimer disease. DESIGN: Questionnaire study of community-dwelling elders. SETTING: Houston metropolitan area. PARTICIPANTS: 218 community-dwellers age 60 years and older. MEASUREMENTS: Responses regarding choices of 10 interventions in 4 scenarios. Interventions were: cardiopulmonary resuscitation (CPR), ventilator, total parenteral nutrition (TPN), i.v. medication and hydration, any medication, enteral feeding, dialysis, ICU admission, hospitalization, and antibiotics. Interventions were selected "never", "always," or a "trial of intervention to assess efficacy." Independent variables were responses in scenarios of usual state of health with a life-threatening illness, irreversible coma, and terminal illness causing pain. Dependent variables were responses in a scenario of moderately advanced Alzheimer disease with a life-threatening illness. Frequencies of responses were calculated using "never," "trial," and "always." Subsequently "trial" and "always" were collapsed into a category of "accepting intervention" for dichotomous analysis with "refusing intervention" (the "never" category). Logistic regression was used to assess validity of predicting responses in one scenario from the others. MAIN RESULTS: Preferences regarding medical therapies varied across scenarios (P < 0.01). In the Usual Health scenario, all interventions were accepted more frequently than refused. In Terminal Illness and Coma scenarios, CPR, ventilator, TPN, enteral feedings and dialysis were refused more frequently than accepted. In the Alzheimer scenario, medications, ICU admission, hospitalization, and antibiotics were accepted more often than rejected. Trial was preferred to always in 90% of all choices across all scenarios. Preferences expressed in Terminal Illness, Coma, and Usual Health scenarios predicted choices in the Alzheimer disease scenario poorly. CONCLUSIONS: (1) Use of a scenario-based advance directive may be limited to the precise scenario described. (2) The common acceptance of interventions in the Alzheimer disease scenario differs from findings in earlier studies, possibly because of differences in populations surveyed or the stage of the disease described, highlighting the variability of preferences in this scenario. (3) Trial of intervention is attractive to many respondents, perhaps because it allows the advantage of potentially beneficial therapies without commitment to a course of therapy not leading to cure. (4) Results of this study should be interpreted in light of the study population, consisting largely of well educated, healthy Caucasians. Findings are likely not to be generalizable to other populations.

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.

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.