Lower cognitive reserve is related to worse working memory performance in older adults after mTBI. An ERP study.

OBJECTIVE: Older adults (OA) after mild traumatic brain injury (mTBI) have a high risk of developing persistent post-injury cognitive impairments. Lower pre-morbid cognitive reserve (CR) is increasingly investigated as a risk factor for cognitive dysfunction in OA. However, how CR protects against effects of mTBI at the brain level remains largely understudied. METHODS: We examined 22 OA who sustained mTBI (mean 67.69 years, SD 5.11) in the sub-acute phase and 15 age- and CR-matched healthy OA (mean 68 years, SD 5.55) performing a three-level visual N-back task using electroencephalography. We calculated inverse efficiency scores of performance from accuracy and reaction times. Event-related potentials served as neurocognitive correlates of attentional (P2) and working memory (P3) processing. RESULTS: Overall, mTBI OA performed worse than healthy OA (p = 0.031). Lower CR generally decreased performance (p < 0.001). Furthermore, with increasing task difficulty, task performance was more affected by CR (p = 0.004). At the brain level, P2 amplitude was lower in mTBI OA than in healthy OA (p = 0.05). There was no clear effect of CR on P2 or P3 measures. CONCLUSION: As mTBI OA with lower CR performed worse on a working-memory task, lower CR may be a risk factor for worse recovery after mTBI in this group.

Age-dependent modulation of motor network connectivity for skill acquisition, consolidation and interlimb transfer after motor practice.

OBJECTIVE: Age-related differences in neural strategies for motor learning are not fully understood. We determined the effects of age on the relationship between motor network connectivity and motor skill acquisition, consolidation, and interlimb transfer using dynamic imaging of coherent sources. METHODS: Healthy younger (n = 24, 18-24 y) and older (n = 24, 65-87 y) adults unilaterally practiced a visuomotor task and resting-state electroencephalographic data was acquired before and after practice as well as at retention. RESULTS: The results showed that right-hand skill acquisition and consolidation did not differ between age groups. However, age affected the ability to transfer the newly acquired motor skill to the non-practiced limb. Moreover, strengthened left- and right-primary motor cortex-related beta connectivity was negatively and positively associated with right-hand skill acquisition and left-hand skill consolidation in older adults, respectively. CONCLUSION: Age-dependent modulations of bilateral resting-state motor network connectivity indicate age-specific strategies for the acquisition, consolidation, and interlimb transfer of novel motor tasks. SIGNIFICANCE: The present results provide insights into the mechanisms underlying motor learning that are important for the development of interventions for patients with unilateral injuries.

Disentangling the effects of age and mild traumatic brain injury on brain network connectivity: A resting state fMRI study.

INTRODUCTION: Cognitive complaints are common shortly after mild traumatic brain injury (mTBI) but may persist up to years. Age-related cognitive decline can worsen these symptoms. However, effects of age on mTBI sequelae have scarcely been investigated. METHODS: Fifty-four mTBI patients (median age: 35 years, range 19-64 years, 67% male) and twenty age- and sex-matched healthy controls were studied using resting state functional magnetic resonance imaging in the sub-acute phase. Independent component analysis was used to identify intrinsic connectivity networks (ICNs). A multivariate approach was adopted to evaluate the effects of age and group on the ICNs in terms of (static) functional network connectivity (FNC), intensities of spatial maps (SMs) and time-course spectral power (TC). RESULTS: We observed significant age-related changes for a) FNC: changes between 10 pairs of ICNs, mostly involving the default mode (DM) and/or the cognitive-control (CC) domains; b) SMs: intensity decrease in clusters across three domains and intensity increase in clusters across two domains, including the CC but not the DM and c) TC: spectral power decrease within the 0-0.15 Hz range and increase within the 0.20-0.25 Hz range for increasing age within networks located in frontal areas, including the anterior DM. Groups only differed for TC within the 0.065-0.10 Hz range in the cerebellar ICN and no age × group interaction effect was found. CONCLUSIONS: We showed robust effects of age on connectivity between and within ICNs that are associated with cognitive functioning. Differences between mTBI patients and controls were only found for activity in the cerebellar network, increasingly recognized to participate in cognition. Our results suggest that to allow for capturing the true effects related to mTBI and its effects on cognitive functioning, age should be included as a covariate in mTBI studies, in addition to age-matching groups.

Quadriceps muscle characteristics and subcutaneous fat assessed by ultrasound and relationship with function in patients with knee osteoarthritis awaiting knee arthroplasty.

BACKGROUND: Patients with severe knee osteoarthritis are evaluated for total knee replacement (TKR), whose main indications are persistent pain and severe functional limitations substantially affecting mobility. However, evaluation of pain intensity and functional disability is difficult to standardize. OBJECTIVE: To evaluate the relationship between quadriceps muscle thickness (QMT) and quality; the QMT and subcutaneous fat thickness (SFT) and QMT and function in patients with knee OA on a waiting list for TKR. METHODS: Cross-sectional study in consecutively-enrolled patients. Variables: SFT, QMT and rectus femoris muscle quality, assessed by echointensity (EI). Function by the Timed Up & Go Test (TUG); sociodemographic and clinical variables and physical activity were determined. Karl Pearson correlations and multiple linear regression were used. RESULTS: 61 patients (45 female, mean age 69.7 years [SD 7.2], mean BMI 33.0 [SD 5.7], mean comorbidities 3.3 [SD 2.0], 52.5% regular physical activity) were studied. Mean TUG was 15.1 (SD 6.1). Variables retained in the regression model explained 36% of variability in the TUG. Greater muscle content (percentage) (r = -0,291) was associated with better TUG scores (p = 0.001). Greater muscle EI was negatively (r = -0,364) associated with function (p = 0.006). Older age was associated with worse TUG scores while regular physical activity was associated with better TUG scores (p = 0.001 and p = 0.008, respectively). CONCLUSIONS: A higher percentage of quadriceps muscle and better muscle quality (lower EI) was associated with better function. Age and exercise levels influenced function. Ultrasound may provide.

Age-related changes in brain deactivation but not in activation after motor learning.

It is poorly understood how healthy aging affects neural mechanisms underlying motor learning. We used blood-oxygen-level dependent (BOLD) contrasts to examine age-related changes in brain activation after acquisition and consolidation (24 h) of a visuomotor tracking skill. Additionally, structural magnetic resonance imaging and diffusion tensor imaging were used to examine age-related structural changes in the brain. Older adults had reduced gray matter volume (628 ±â€¯57 ml) and mean white matter anisotropy (0.18 ±â€¯0.03) compared with young adults (741 ±â€¯59 ml and 0.22 ±â€¯0.02, respectively). Although motor performance was 53% lower in older (n = 15, mean age 63.1 years) compared with young adults (n = 15, mean age 25.5 years), motor practice improved motor performance similarly in both age groups. While executing the task, older adults showed in general greater brain activation compared with young adults. BOLD activation decreased in parietal and occipital areas after skill acquisition but activation increased in these areas after consolidation in both age groups, indicating more efficient visuospatial processing immediately after skill acquisition. Changes in deactivation in specific areas were age-dependent after consolidating the motor skill into motor memory. Young adults showed greater deactivations from post-test to retention in parietal, occipital and temporal cortices, whereas older adults showed smaller deactivation in the frontal cortex. Since learning rate was similar between age groups, age-related changes in activation patterns may be interpreted as a compensatory mechanism for age-related structural decline.

Instrumented finger-to-nose test classification in children with ataxia or developmental coordination disorder and controls.

BACKGROUND: During childhood, many conditions may impact coordination. Examples are physiological age-related development and pathological conditions, such as early onset ataxia and developmental coordination disorder. These conditions are generally diagnosed by clinical specialists. However, in absence of a gold phenotypic standard, objective reproducibility among specialists appears limited. METHODS: We investigated whether quantitative analysis of an upper limb coordination task (the finger-to-nose test) could discriminate between physiological and pathological conditions impacting coordination. We used inertial measurement units to estimate movement trajectories of the participants while they executed the finger-to-nose test. We employed random forests to classify each participant in one category. FINDINGS: On average, 87.4% of controls, 74.4% of early onset ataxia and 24.8% of developmental coordination disorder patients were correctly classified. The relatively good classification of early onset ataxia patients and controls contrasts with the poor classification of developmental coordination disorder patients. INTERPRETATION: In absence of a gold phenotypic standard for developmental coordination disorder recognition, it remains elusive whether the finger-to-nose test in these patients represents a sufficiently accurate entity to reflect symptoms distinctive of this disorder. Based on the relatively good results in early onset ataxia patients and controls, we conclude that quantitative analysis of the finger-to-nose test can provide a reliable support tool during the assessment of phenotypic early onset ataxia.

Spectral and temporal electroencephalography measures reveal distinct neural networks for the acquisition, consolidation, and interlimb transfer of motor skills in healthy young adults.

OBJECTIVE: Plasticity of the central nervous system likely underlies motor learning. It is however unclear, whether plasticity in cortical motor networks is motor learning stage-, activity-, or connectivity-dependent. METHODS: From electroencephalography (EEG) data, we quantified effective connectivity by the phase slope index (PSI), neuronal activity by event-related desynchronization, and sensorimotor integration by N30 during the stages of visuomotor skill acquisition, consolidation, and interlimb transfer. RESULTS: Although N30 amplitudes and event-related desynchronization in parietal electrodes increased with skill acquisition, changes in PSI correlated most with motor performance in all stages of motor learning. Specifically, changes in PSI between the premotor, supplementary motor, and primary motor cortex (M1) electrodes correlated with skill acquisition, whereas changes in PSI between electrodes representing M1 and the parietal and primary sensory cortex (S1) correlated with skill consolidation. The magnitude of consolidated interlimb transfer correlated with PSI between bilateral M1s and between S1 and M1 in the non-practiced hemisphere. CONCLUSIONS: Spectral and temporal EEG measures but especially PSI correlated with improvements in complex motor behavior and revealed distinct neural networks in the acquisition, consolidation, and interlimb transfer of motor skills. SIGNIFICANCE: A complete understanding of the neuronal mechanisms underlying motor learning can contribute to optimizing rehabilitation protocols.

Assessing dynamic postural control during exergaming in older adults: A probabilistic approach.

Digital games controlled by body movements (exergames) have been proposed as a way to improve postural control among older adults. Exergames are meant to be played at home in an unsupervised way. However, only few studies have investigated the effect of unsupervised home-exergaming on postural control. Moreover, suitable methods to dynamically assess postural control during exergaming are still scarce. Dynamic postural control (DPC) assessment could be used to provide both meaningful feedback and automatic adjustment of exergame difficulty. These features could potentially foster unsupervised exergaming at home and improve the effectiveness of exergames as tools to improve balance control. The main aim of this study is to investigate the effect of six weeks of unsupervised home-exergaming on DPC as assessed by a recently developed probabilistic model. High probability values suggest 'deteriorated' postural control, whereas low probability values suggest 'good' postural control. In a pilot study, ten healthy older adults (average 77.9, SD 7.2 years) played an ice-skating exergame at home half an hour per day, three times a week during six weeks. The intervention effect on DPC was assessed using exergaming trials recorded by Kinect at baseline and every other week. Visualization of the results suggests that the probabilistic model is suitable for real-time DPC assessment. Moreover, linear mixed model analysis and parametric bootstrapping suggest a significant intervention effect on DPC. In conclusion, these results suggest that unsupervised exergaming for improving DPC among older adults is indeed feasible and that probabilistic models could be a new approach to assess DPC.

Wavelet coherence analysis: A new approach to distinguish organic and functional tremor types.

OBJECTIVE: To distinguish tremor subtypes using wavelet coherence analysis (WCA). WCA enables to detect variations in coherence and phase difference between two signals over time and might be especially useful in distinguishing functional from organic tremor. METHODS: In this pilot study, polymyography recordings were studied retrospectively of 26 Parkinsonian (PT), 26 functional (FT), 26 essential (ET), and 20 enhanced physiological (EPT) tremor patients. Per patient one segment of 20 s in duration, in which tremor was present continuously in the same posture, was selected. We studied several coherence and phase related parameters, and analysed all possible muscle combinations of the flexor and extensor muscles of the upper and fore arm. The area under the receiver operating characteristic curve (AUC-ROC) was applied to compare WCA and standard coherence analysis to distinguish tremor subtypes. RESULTS: The percentage of time with significant coherence (PTSC) and the number of periods without significant coherence (NOV) proved the most discriminative parameters. FT could be discriminated from organic (PT, ET, EPT) tremor by high NOV (31.88 vs 21.58, 23.12 and 10.20 respectively) with an AUC-ROC of 0.809, while standard coherence analysis resulted in an AUC-ROC of 0.552. CONCLUSIONS: EMG-EMG WCA analysis might provide additional variables to distinguish functional from organic tremor. SIGNIFICANCE: WCA might prove to be of additional value to discriminate between tremor types.

How typical are 'typical' tremor characteristics? Sensitivity and specificity of five tremor phenomena.

INTRODUCTION: Distinguishing between different tremor disorders can be challenging. Some tremor disorders are thought to have typical tremor characteristics: the current study aims to provide sensitivity and specificity for five 'typical' tremor phenomena. METHODS: Retrospectively, we examined 210 tremor patients referred for electrophysiological recordings between January 2008 and January 2014. The final clinical diagnosis was used as the gold standard. The first step was to determine whether patients met neurophysiological criteria for their type of tremor. Once established, we focused on 'typical' characteristics: tremor frequency decrease upon loading (enhanced physiological tremor (EPT)), amplitude increase upon loading, distractibility and entrainment (functional tremor (FT)), and intention tremor (essential tremor (ET)). The prevalence of these phenomena in the 'typical' group was compared to the whole group. RESULTS: Most patients (87%) concurred with all core clinical neurophysiological criteria for their tremor type. We found a frequency decrease upon loading to be a specific (95%), but not a sensitive (42%) test for EPT. Distractibility and entrainment both scored high on sensitivity (92%, 91%) and specificity (94%, 91%) in FT, whereas a tremor amplitude increase was specific (92%), but not sensitive (22%). Intention tremor was a specific finding in ET (85%), but not a sensitive test (45%). Combination of characteristics improved sensitivity. CONCLUSION: In this study, we retrospectively determined sensitivity and specificity for five 'typical' tremor characteristics. Characteristics proved specific, but few were sensitive. These data on tremor phenomenology will help practicing neurologists to improve distinction between different tremor disorders.

A Method for Automatic and Objective Scoring of Bradykinesia Using Orientation Sensors and Classification Algorithms.

Correct assessment of bradykinesia is a key element in the diagnosis and monitoring of Parkinson's disease. Its evaluation is based on a careful assessment of symptoms and it is quantified using rating scales, where the Movement Disorders Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the gold standard. Regardless of their importance, the bradykinesia-related items show low agreement between different evaluators. In this study, we design an applicable tool that provides an objective quantification of bradykinesia and that evaluates all characteristics described in the MDS-UPDRS. Twenty-five patients with Parkinson's disease performed three of the five bradykinesia-related items of the MDS-UPDRS. Their movements were assessed by four evaluators and were recorded with a nine degrees-of-freedom sensor. Sensor fusion was employed to obtain a 3-D representation of movements. Based on the resulting signals, a set of features related to the characteristics described in the MDS-UPDRS was defined. Feature selection methods were employed to determine the most important features to quantify bradykinesia. The features selected were used to train support vector machine classifiers to obtain an automatic score of the movements of each patient. The best results were obtained when seven features were included in the classifiers. The classification errors for finger tapping, diadochokinesis and toe tapping were 15-16.5%, 9.3-9.8%, and 18.2-20.2% smaller than the average interrater scoring error, respectively. The introduction of objective scoring in the assessment of bradykinesia might eliminate inconsistencies within evaluators and interrater assessment disagreements and might improve the monitoring of movement disorders.

Cerebellar Atrophy in Cortical Myoclonic Tremor and Not in Hereditary Essential Tremor-a Voxel-Based Morphometry Study.

Essential tremor (ET) presumably has a cerebellar origin. Imaging studies showed various cerebellar and also cortical structural changes. A number of pathology studies indicated cerebellar Purkinje cell pathology. ET is a heterogeneous disorder, possibly indicating different underlying disease mechanisms. Familial cortical myoclonic tremor with epilepsy (FCMTE), with evident Purkinje cell degeneration, can be an ET mimic. Here, we investigate whole brain and, more specifically, cerebellar morphological changes in hereditary ET, FCMTE, and healthy controls. Anatomical magnetic resonance images were preprocessed using voxel-based morphometry. Study 1 included voxel-wise comparisons of 36 familial, propranolol-sensitive ET patients, with subgroup analysis on age at onset and head tremor, and 30 healthy controls. Study 2 included voxel-wise comparisons in another nine ET patients, eight FCMTE patients, and nine healthy controls. Study 3 compared total cerebellar volume between 45 ET patients, 8 FCTME patients, and 39 controls. In our large sample of selected hereditary ET patients and ET subgroups, no local atrophy was observed compared to healthy controls or FCMTE. In ET patients with head tremor, a volume increase in cortical motor regions was observed. In FCMTE, a decrease in total cerebellar volume and in local cerebellar gray matter was observed compared to healthy controls and ET patients. The current study did not find local atrophy, specifically not in the cerebellum in hereditary ET, contrary to FCMTE. Volume increase of cortical motor areas in ET patients with head tremor might suggest cortical plasticity changes due to continuous involuntary head movements.

Muscle co-activity tuning in Parkinsonian hand movement: disease-specific changes at behavioral and cerebral level.

We investigated simple directional hand movements based on different degrees of muscle co-activity, at behavioral and cerebral level in healthy subjects and Parkinson's disease (PD) patients. We compared "singular" movements, dominated by the activity of one agonist muscle, to "composite" movements, requiring conjoint activity of multiple muscles, in a center-out (right hand) step-tracking task. Behavioral parameters were obtained by EMG and kinematic recordings. fMRI was used to investigate differences in underlying brain activations between PD patients (N = 12) and healthy (age-matched) subjects (N = 18). In healthy subjects, composite movements recruited the striatum and cortical areas comprising bilaterally the supplementary motor area and premotor cortex, contralateral medial prefrontal cortex, primary motor cortex, primary visual cortex, and ipsilateral superior parietal cortex. Contrarily, the ipsilateral cerebellum was more involved in singular movements. This striking dichotomy between striatal and cortical recruitment vs. cerebellar involvement was considered to reflect the complementary roles of these areas in motor control, in which the basal ganglia are involved in movement selection and the cerebellum in movement optimization. Compared to healthy subjects, PD patients showed decreased activation of the striatum and cortical areas in composite movement, while performing worse at behavioral level. This implies that PD patients are especially impaired on tasks requiring highly tuned muscle co-activity. Singular movement, on the other hand, was characterized by a combination of increased activation of the ipsilateral parietal cortex and left cerebellum. As singular movement performance was only slightly compromised, we interpret this as a reflection of increased visuospatial processing, possibly as a compensational mechanism.

Parkinson bradykinesia correlates with EEG background frequency and perceptual forward projection.

BACKGROUND: To deal with processing-time in the nervous system, visuomotor control requires anticipation. An index for such anticipation is provided by the 'flash-lag illusion' in which moving objects are perceived ahead of static objects while actually being in the same place. We investigated the neurophysiological relation between visuomotor anticipation and motor velocity in Parkinson's disease (PD) and controls. METHODS: Motor velocity was assessed by the number of keystrokes in 30s ('kinesia score') and visuomotor anticipation in a behavioural flash-lag paradigm while electroencephalography data was obtained. PD patients (n = 24) were divided in a 'PDslow' and a 'PDfast' group based on kinesia score. RESULTS: The PDslow group had a lower kinesia score than controls (resp. 40.3 ± 1.7 and 64.9 ± 4.6, p < 0.001). The flash-lag illusion was weaker in the PDslow group than in controls (resp. fractions 0.32 ± 0.04 and 0.50 ± 0.09 of the responses indicating perceived lagging, p = 0.03). Furthermore, the magnitude of the flash-lag illusion correlated with the kinesia score (cc = 0.45, p = 0.02). Finally, electroencephalography background frequency was lower in the PDslow group than in controls (resp 8.24 ± 0.24 and 9.1 ± 0.32 Hz, p = 0.01) and background frequency correlated with the kinesia score (cc = 0.58, p = 0.001). CONCLUSIONS: The decreased flash-lag illusion and lower electroencephalography background frequency in more bradykinetic PD patients provides support for disturbed visuomotor anticipations, putatively caused by reduced, sub-cortically mediated, network efficiency. This suggests a link between anticipation in early-stage visual motion processing and motor preparation.

Limited correlations between clinician-based and patient-based measures of essential tremor severity.

INTRODUCTION: We investigated the relation between changes in clinician-based and patient-based measures of tremor severity, within the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) and Visual Analogue Scale (VAS) in essential tremor patients. METHODS: Thirty-seven patients were assessed twice: on- and off-medication. Clinician-based, objective TRS assessments, consisting of part A (postures/movements) and part B (tremor-inducing tasks) were conducted by a blinded assessor using video-tapes. Patients completed TRS part C (limitations in activities of daily life) and indicated subjective tremor severity using VAS. RESULTS: Patients' total TRS and VAS scores improved on-medication (both p < 0.001). Mean improvement was 6.3 (sd 5.4) points on the total TRS and 2.3 (sd 2.3) points on the VAS score. Within the TRS, we found moderate correlations between changes in clinician-based TRS-B and patient-based TRS-C scores (ρ = 0.387, p = 0.011), but not between changes in clinician-based TRS-A and TRS-C scores (ρ = 0.128, p = 0.232). Moreover, changes in subjective VAS scores correlated with changes in total TRS (ρ = 0.422, p = 0.007), changes in TRS-C scores (ρ = 0.367, p = 0.015) and, more weakly, with changes in TRS-B scores (ρ = 0.281, p = 0.049), but again: not with changes in TRS-A scores (ρ = -0.008, p = 0.482). DISCUSSION: We found no correlation between changes in clinician-based TRS-A, and patient-based measures TRS-C or VAS scores, and a weak correlation between clinician-based TRS-B and VAS scores. The limited correlations between changes in clinician-based and patient-based measures of tremor severity suggest that the different scales measure different aspects of tremor severity and support the additional use of subjective patient-based assessments in clinical practice and clinical trials.

Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor.

INTRODUCTION: Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar output in essential tremor during rhythmic finger tapping employing functional MRI. METHODS: Thirty-one propranolol-sensitive essential tremor patients with upper limb tremor and 29 healthy controls were measured. T2*-weighted EPI sequences were acquired. The task consisted of alternating rest and finger tapping blocks. A whole-brain and region-of-interest analysis was performed, the latter focusing on the cerebellar cortex, dentate nucleus and inferior olive nucleus. Activations were also related to tremor severity. RESULTS: In patients, dentate activation correlated positively with tremor severity as measured by the tremor rating scale part A. Patients had reduced activation in widespread cerebellar cortical regions, and additionally in the inferior olive nucleus, and parietal and frontal cortex, compared to controls. CONCLUSION: The increase in dentate activation with tremor severity supports involvement of the dentate nucleus in essential tremor. Cortical and cerebellar changes during a motor timing task in essential tremor might point to widespread changes in cerebellar output in essential tremor.

Can repetitive transcranial magnetic stimulation increase muscle strength in functional neurological paresis? A proof-of-principle study.

BACKGROUND AND PURPOSE: Therapeutic options are limited in functional neurological paresis disorder. Earlier intervention studies did not control for a placebo effect, hampering assessment of effectivity. A proof-of-principle investigation was conducted into the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS), using a single-blind two-period placebo-controlled cross-over design. METHODS: Eleven patients received active 15 Hz rTMS over the contralateral motor cortex (hand area), in two periods of 5 days, for 30 min once a day at 80% of resting motor threshold, with a train length of 2 s and an intertrain interval of 4 s. Eight of these eleven patients were also included in the placebo treatment condition. Primary outcome measure was change in muscle strength as measured by dynamometry after treatment. Secondary outcome measure was the subjective change in muscle strength after treatment. RESULTS: In patients who received both treatments, active rTMS induced a significantly larger median increase in objectively measured muscle strength (24%) compared to placebo rTMS (6%; P < 0.04). Subjective ratings showed no difference due to treatment, i.e. patients did not perceive these objectively measured motor improvements (P = 0.40). CONCLUSIONS: Our findings suggest that rTMS by itself can potentially improve muscle weakness in functional neurological paresis disorder. Whereas patients' muscle strength increased as measured with dynamometry, patients did not report increased functioning of the affected hand, subjectively. The results may indicate that decreased muscle strength is not the core symptom and that rTMS should be added to behavioral approaches in functional neurological paresis.

Usefulness of intermuscular coherence and cumulant analysis in the diagnosis of postural tremor.

OBJECTIVE: To investigate the potential value of two advanced EMG measures as additional diagnostic measures in the polymyographic assessment of postural upper-limb tremor. METHODS: We investigated coherence as a measure of dependency between two EMG signals, and cumulant analysis to reveal patterns of synchronicity in EMG activity in muscle pairs. Eighty datasets were analyzed retrospectively, obtained from four groups: essential tremor (ET), Parkinson's disease (PD), enhanced physiological tremor (EPT), and functional tremor (FT). RESULTS: Intermuscular coherence was highest in the PD group (0.58), intermediate in FT (0.43) and ET (0.40), and weakest in EPT (0.16) (p=0.002). EPT patients could be distinguished by low coherence: coherence <0.18 in the wrist+elbow extensors differentiates EPT in this sample with a sensitivity of 86% and specificity of 84%. Cumulant analysis showed predominantly alternating activity between wrist and elbow extensor in ET patients, while a more synchronous pattern was predominant in PD, EPT and FT (p=0.008). EMG activity in wrist and elbow flexors tended to be more synchronous in PD (p=0.059). CONCLUSION: Our results suggest that coherence and cumulant analysis may be of additional value in the diagnostic work-up of postural tremor. SIGNIFICANCE: These additional measures may be helpful in diagnosing difficult tremor cases.

Variability of the autoregulation index decreases after removing the effect of the very low frequency band.

Dynamic cerebral autoregulation (dCA) estimates show large between and within subject variability. Sources of variability include low coherence and influence of CO2 in the very low frequency (VLF) band, where dCA is active. This may lead to unreliable transfer function and autoregulation index (ARI) estimates. We tested whether variability of the ARI could be decreased by suppressing the effect of the VLF band through filtering. We also evaluated whether filtering had any effect on mean group differences between healthy subjects and acute stroke patients. Data from a recent mobilization stroke study were re-analyzed. Middle cerebral artery cerebral blood flow velocity (MCA-CBFV), mean arterial blood pressure (MABP) and end tidal PCO2 (PetCO2) were obtained in 16 healthy subjects and 27 acute ischemic stroke patients in the supine position. The ARI index was calculated from the transfer function (TF) by using spontaneous BP fluctuations. Three different filtering strategies were compared; no filtering (NF), a high pass filter at 0.04 Hz (Time Domain Filtering: TDF) and a high pass Transfer Function Filter (TFF) at 0.04 Hz. In addition, a simulation study was done to obtain further insight into the effects of the applied filters. The variability of the ARI index decreased significantly only with TFF in healthy subjects (standard deviation (left vs. right) after NF 2.28 vs. 2.36, after TDF 2.13 vs. 2.31 after TFF 1.09 vs. 1.19, p<0.001). Variability was not significantly reduced in stroke patients. The mean ARI was significantly lower in stroke patients compared to healthy subjects after TFF (affected hemisphere 5.85±1.96 vs. 7.13±1.09, non-affected hemisphere 5.96±1.64 vs. 7.31±1.19, p<0.01 for both hemispheres), but not after NF or TDF. The simulation study showed that TFF results in an overestimation of the ARI index at low ARI levels (0-3), but in correct estimates at higher ARI levels. Removing the effect of the VLF band with TFF results in less ARI variability in healthy subjects, and in more pronounced group differences between stroke patients and healthy subjects. This will improve diagnostic properties when using TFA for ARI calculation.

Reproducibility and variability of dynamic cerebral autoregulation during passive cyclic leg raising.

Dynamic cerebral autoregulation (dCA) estimates require mean arterial blood pressure (MABP) fluctuations of sufficient amplitude. Current methods to induce fluctuations are not easily implemented or require patient cooperation. In search of an alternative method, we evaluated if MABP fluctuations could be increased by passive cyclic leg raising (LR) and tested if reproducibility and variability of dCA parameters could be improved. Middle cerebral artery cerebral blood flow velocity (CBFV), MABP and end tidal CO2 (PetCO2) were obtained at rest and during LR at 0.1 Hz in 16 healthy subjects. The MABP-CBFV phase difference and gain were determined at 0.1 Hz and in the low frequency (LF) range (0.06-0.14 Hz). In addition the autoregulation index (ARI) was calculated. The LR maneuver increased the power of MABP fluctuations at 0.1 Hz and across the LF range. Despite a clear correlation between both phase and gain reproducibility and MABP variability in the rest condition, only the reproducibility of gain increased significantly with the maneuver. During the maneuver patients were breathing faster and more irregularly, accompanied by increased PetCO2 fluctuations and increased coherence between PetCO2 and CBFV. Multiple regression analysis showed that these concomitant changes were negatively correlated with the MABP-CBFV phase difference at 0.1 Hz Variability was not reduced by LR for any of the dCA parameters. The clinical utility of cyclic passive leg raising is limited because of the concomitant changes in PetCO2. This limits reproducibility of the most important dCA parameters. Future research on reproducibility and variability of dCA parameters should incorporate PetCO2 variability or find methods to keep PetCO2 levels constant.