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-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.

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.

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.

In spina bifida aperta, muscle ultrasound can quantify the "second hit of damage".

PURPOSE: In spina bifida aperta (SBA), the "second-hit hypothesis" addresses consequences by delayed neurological damage superimposed upon the congenital myelomeningocele (MMC). This secondary damage is postulated to underlie the disappearance of leg movements shortly after birth. Innovative fetal surgery might prevent this, but results are methodologically hard to prove in small and heterogeneous treatment groups. We reasoned that delayed postnatal alterations in muscle ultrasound density (MUD = muscle echogenicity) could quantitatively reflect consequences by "the second hit" of damage. In the present study, we investigated whether delayed postnatal leg-MUD alterations are associated with postnatal muscle function loss. METHODS: We cross-sectionally assessed leg-MUD in 16 postnatally operated SBA children (MMC-L5; at 0, 6, and 12 months; in n = 11/16; 11/16, and 15/16 children, respectively) and compared outcomes with 13 healthy control children. Additionally, we assessed SBA MUD caudal and cranial to the MMC and calculated MMC-L5 impact by: dMUD((MMC-L5)) = [MUD(calf muscle/S1-2)] - [MUD(quadriceps muscle/L2-4)] and associated outcomes with leg muscle function caudal to the MMC. RESULTS: At 0 month, clinically discernible dMUD was more often increased in SBA than in control newborns (p < .05), but a relationship between absolute quantitative differences and leg muscle dysfunction was still lacking. At 6-12 months, additionally increased dMUD outcomes coincided with SBA leg muscle dysfunction (p < .05). CONCLUSIONS: In post-neonatal SBA, secondarily increased dMUD (i.e., MMC impact) coincides with leg muscle dysfunction. This may implicate that muscle ultrasound could provide a quantitative tool to assess the neuromuscular impact by the second hit of damage.

Mechanisms underlying muscle fatigue differ between multiple sclerosis patients and controls: a combined electrophysiological and neuroimaging study.

Increased sense of fatigue is an important and conspicuous symptom in multiple sclerosis (MS). Muscle fatigue is associated with increased sense of fatigue in MS (Steens et al., 2011). The aim of this study was to investigate mechanisms that can explain muscle fatigue in MS patients and controls. We assessed changes in cortical activation (BOLD), voluntary activation (twitch interpolation) and muscle force during a sustained maximal voluntary contraction (MVC) in twenty MS patients and twenty healthy controls. In control participants, individual differences in force decline (mean 65% MVC, 8 SD) during the sustained maximal contraction could be accounted for by differences in maximal voluntary force (R(2): 0.49, p = 0.001); stronger participants presented a larger force decline. The small decline in voluntary activation (mean 7.8%, 11.8 SD) did not contribute significantly to the force decline. During the sustained contraction, the force decline was accompanied by an increase in cortical activation in the main motor areas. In MS patients, the differences in the decline in force (mean 67% MVC, 9 SD) were significantly associated (R(2): 0.51, p = 0.001) with a decline in voluntary activation (mean 20.1%, 20.6 SD) and not with maximal force or decline in rest twitch. The corresponding cortical activation in motor areas showed an increase in the first two intervals of the sustained contraction but declined during the last interval. Our data indicate that muscle fatigue during a sustained contraction in MS patients is associated with changes in the voluntary activation that are not sufficiently compensated by increased cortical activation. Control participants, however, show increased cortical activation to compensate for these fatigue-related changes in voluntary activation and the major cause of force decline is therefore to be found in the periphery (muscles).

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.

Multichannel recording of tibial-nerve somatosensory evoked potentials.

STUDY AIMS: The topography of the peaks of tibial-nerve somatosensory evoked potential (SEP) varies among healthy subjects, most likely because of differences in position and orientation of their cortical generator(s). Therefore, amplitude estimation with a standard one- or two-channel derivation is likely to be inaccurate and might partly cause the low sensitivity of SEP amplitude to pathological changes. In this study, we investigate whether 128-channel tibial-nerve SEP recordings can improve amplitude estimation and reduce the coefficient of variation. METHODS: We recorded tibial-nerve SEPs using a 128-channel EEG system in 48 healthy subjects aged 20 to 70 years (47 provided analyzable data). We compared P39, N50, and P60 amplitudes obtained with a 128-channel analysis method (based on butterfly plots and spatial topographies) with those obtained using a one-channel conventional configuration and analysis. Scalp and earlobe references were compared. RESULTS: Tibial-nerve SEP amplitudes obtained with the 128-channel method were significantly higher as compared to the one-channel conventional method. Consequently, the coefficient of variation was lower for the 128-channel method. In addition, in both methods, the N50-peak amplitude was sometimes hard to identify, because of its low amplitude. Besides, in some subjects, the N50 peak, as obtained with the conventional method, rather seemed to be a period between two positivities rather than an activation peak on itself. CONCLUSIONS: The 128-channel method can measure tibial-nerve SEP amplitude more accurately and might therefore be more sensitive to pathological changes. Our results indicate that the N50 component is less useful for clinical practice.

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.

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.

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.

Abnormal surface EMG during clinically normal wrist movement in cervical dystonia.

We investigated whether patients with cervical dystonia (CD) have abnormal muscle activation in non-dystonic body parts. Eight healthy controls and eight CD patients performed a flexion-extension movement of the right wrist. Movement execution was recorded by surface electromyography (EMG) from forearm muscles. Although patients had no complaints concerning wrist movement and had no apparent difficulty in executing the task, they demonstrated lower mean EMG amplitude (flexor: 0.32 mV and extensor: 0.61 mV) than controls (flexor: 0.67 mV; P = 0.021 and extensor: 1.18 mV; P = 0.068; borderline significant). Mean extensor muscle contraction was prolonged in patients (1860 ms) compared with controls (1334 ms; P = 0.026). Variation in mean EMG amplitude over movements tended to be higher in patients (flexor: 43% and extensor: 35%) than controls (flexor: 34%; P = 0.072 and extensor: 26%; P = 0.073). These results suggest that CD patients also have abnormal muscle activation in non-dystonic body parts at a subclinical level. This would support the concept that in dystonia, non-dystonic limbs are in a 'pre-dystonic state'.

The influence of vessel wall elasticity and peripheral resistance on the carotid artery flow wave form: a CFD model compared to in vivo ultrasound measurements.

The Doppler flow wave form and its derived measures such as the pulsatility index provide clinically important tools for the investigation of arterial disease. The typical shape of Doppler flow wave forms is physiologically known to be largely determined by both peripheral resistance and elastic properties of the arterial wall. In the present study we systematically investigate the influence of both vessel wall elasticity and peripheral resistance on the flow wave form obtained from a CFD-simulation of blood flow in the carotid bifurcation. Numerical results are compared to in vivo ultrasound measurements. The in vivo measurement provides a realistic geometry, local elasticities and an input flow wave form for the numerical experiment. Numerical and experimental results are compared at three different sites in the carotid branches. Peripheral resistance has a profoundly decreasing effect on velocities in the external carotid artery. If elasticity is taken into account, the computed peak systolic velocities are considerably lower and a more realistic smoothing of the flow wave form is found. Together, the results indicate that only if both vessel wall elasticity and positive peripheral resistance are taken into account, experimentally obtained Doppler flow wave forms can be reproduced numerically.

Pyridoxine induces non-specific EEG alterations in infants with therapy resistant seizures.

PURPOSE: In infants with frequent therapy resistant seizures (TRS-infants), clinical detection of pyridoxine-dependency (PD) or -responsiveness (PR) occurs by empirical intravenous (IV) pyridoxine administration during recording of the EEG. However, in undiagnosed TRS-infants it is still unclear to what extent EEG alterations by pyridoxine-IV are attributable to PD/PR or to non-specific responses. Before EEG alterations by pyridoxine-IV can be ascribed to PD/PR, these non-specific responses should be excluded first. METHODS: In 10 TRS-infants under 1 year of age, we determined the EEG effect by pyridoxine-IV on the EEG-recording. RESULTS: After pyridoxine-IV administration, our data indicate declined (10-15%; p<0.05) EEG-amplitudes and total power (magnitude/frequency-band) at frontal, central and centro-temporal electrodes. CONCLUSION: In TRS-infants, pyridoxine-IV affects EEG-amplitude and -total power in a non-specific way, which does not identify PD/PR.

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.

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.

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.