Tremor Fluctuations Research Articles

Feasibility of Magnetic Resonance-Compatible Accelerometers to Monitor Tremor Fluctuations During Magnetic Resonance-Guided Focused Ultrasound Thalamotomy: Technical Note.

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is used to treat essential tremor and tremor-dominant Parkinson disease. Feedback is collected throughout the procedure to verify the location of the target and completeness of response; however, variability in clinical judgments may underestimate or overestimate treatment response. To objectively quantify joint motion after each sonication using accelerometers secured to the contralateral upper extremity in an effort to optimize MRgFUS treatment. Before the procedure, 3 accelerometers were secured to the patient's arm, forearm, and index finger. Throughout the procedure, tremor motion was regularly recorded during postural and kinetic tremor testing and individual joint angle measures were modeled. The joint angle from each accelerometer was compared with baseline measurements to assess changes in angles. Subsequent adjustments to the target location and sonication energy were made at the discretion of the neurosurgeon and neuroradiologist. Intraoperative accelerometer measurements of hand tremor from 18 patients provided quantified data regarding joint angle reduction: 87.3%, 94.2%, and 86.7% for signature writing, spiral drawing, and line drawing tests, respectively. Target adjustment based on accelerometer monitoring of the angle at each joint added substantial value toward achieving optimal tremor reduction. Real-time accelerometer recordings collected during MRgFUS thalamotomy offered objective quantification of changes in joint angle after each sonication, and these findings were consistent with clinical judgments of tremor response. These results suggest that this technique could be used for fine adjustment of the location of sonication energy and number of sonications to consistently achieve optimal tremor reduction.

Closing the loop: Novel quantitative fMRI approach for manipulation of the sensorimotor loop in tremor

Tremor is thought to be an effect of oscillatory activity within the sensorimotor network. To date, the underlying pathological brain networks are not fully understood. Disentangling tremor activity from voluntary motor output and sensorimotor feedback systems is challenging. To better understand the intrinsic sensorimotor fingerprint underlying tremor, we aimed to disentangle the sensorimotor system into driving (motor) and feedback/compensatory (sensory) neuronal involvement, and aimed to pinpoint tremor activity in essential tremor (ET) and tremor-dominant Parkinson's disease (PD) with a novel closed-loop approach.Eighteen ET patients, 14 tremor-dominant PD patients, and 18 healthy controls were included. An MR-compatible wrist manipulator was employed during functional MRI (fMRI) while muscle activity during (in)voluntary movements was concurrently recorded using electromyography (EMG). Tremor was quantified based on EMG and correlated to brain activity. Participants performed three tasks: an active wrist motor task, a passive wrist movement task, and rest (no wrist movement).The results in healthy controls proved that our experimental paradigm activated the expected motor and sensory networks separately using the active (motor) and passive (sensory) task. ET patients showed similar patterns of activation within the motor and sensory networks. PD patients had less activity during the active motor task in the cerebellum and basal ganglia compared to ET and healthy controls. EMG showed that in ET, tremor fluctuations correlated positively with activity in the inferior olive region, and that in PD tremor fluctuations correlated positively with cerebellar activity.Our novel approach with an MR-compatible wrist manipulator, allowed to investigate the involvement of the motor and sensory networks separately, and as such to better understand tremor pathophysiology. In ET sensorimotor network function did not differ from healthy controls. PD showed less motor-related activity. Focusing on tremor, our results indicate involvement of the inferior olive in ET tremor modulation, and cerebellar involvement in PD tremor modulation.

Immediate and Early Postoperative Tremor Fluctuation and 6 to 12-month Tremor Outcomes after Magnetic Resonance-guided Focused Ultrasound for Essential Tremor

Immediate and Early Postoperative Tremor Fluctuation and 6 to 12-month Tremor Outcomes after Magnetic Resonance-guided Focused Ultrasound for Essential Tremor

Cerebello-thalamic activity drives an abnormal motor network into dystonic tremor

Dystonic tremor syndromes are highly burdensome and treatment is often inadequate. This is partly due to poor understanding of the underlying pathophysiology. Several lines of research suggest involvement of the cerebello-thalamo-cortical circuit and the basal ganglia in dystonic tremor syndromes, but their role is unclear. Here we aimed to investigate the contribution of the cerebello-thalamo-cortical circuit and the basal ganglia to the pathophysiology of dystonic tremor syndrome, by directly linking tremor fluctuations to cerebral activity during scanning.In 27 patients with dystonic tremor syndrome (dystonic tremor: n = 23; tremor associated with dystonia: n = 4), we used concurrent accelerometery and functional MRI during a posture holding task that evoked tremor, alternated with rest. Using multiple regression analyses, we separated tremor-related activity from brain activity related to (voluntary) posture holding. Using dynamic causal modelling, we tested for altered effective connectivity between tremor-related brain regions as a function of tremor amplitude fluctuations. Finally, we compared grey matter volume between patients (n = 27) and matched controls (n = 27).We found tremor-related activity in sensorimotor regions of the bilateral cerebellum, contralateral posterior and anterior ventral lateral nuclei of the thalamus (VLp and VLa), contralateral primary motor cortex (hand area), contralateral pallidum, and the bilateral frontal cortex (laterality with respect to the tremor). Grey matter volume was increased in patients compared to controls in the portion of contralateral thalamus also showing tremor-related activity, as well as in bilateral medial and left lateral primary motor cortex, where no tremor-related activity was present. Effective connectivity analyses showed that inter-regional coupling in the cerebello-thalamic pathway, as well as the thalamic self-connection, were strengthened as a function of increasing tremor power.These findings indicate that the pathophysiology of dystonic tremor syndromes involves functional and structural changes in the cerebello-thalamo-cortical circuit and pallidum. Deficient input from the cerebellum towards the thalamo-cortical circuit, together with hypertrophy of the thalamus, may play a key role in the generation of dystonic tremor syndrome.

Support vector machine classification of Parkinson's disease and essential tremor subjects based on temporal fluctuation.

Tremor is a common symptom shared in both Parkinson's disease (PD) and Essential tremor (ET) subjects. The differential diagnosis of PD and ET tremor is important since the realization of treatment depends on specific medication. A novel feature is developed based on a hypothesis that tremor of PD subject has a larger fluctuation during resting than action task. Tremor signal is collected using a triaxial gyroscope sensor attached to subject's finger during kinetic and resting task. The angular velocity signal is analyzed by transforming a one-dimensional to two-dimensional signal using a relation of signal and its delay versions. Tremor fluctuation is defined as the area of 95% confidence ellipse covering the two-dimensional signal. The tremor fluctuation during kinetic and resting task is used as classification features. The support vector machine is used as a classifier and tested with 10-fold cross-validation. This novel feature provides a perfect PD/ET classification with 100% accuracy, sensitivity and specificity.

Temporal fluctuation analysis of tremor signal in Parkinson's disease and Essential tremor subjects.

Tremor is a common symptom shared in both Parkinson's disease (PD) and Essential tremor (ET) subjects. The differential diagnosis of PD and ET tremor is important since the treatment depends on specific medication. A novel feature was developed based on a hypothesis stating that the tremor of PD subject has a larger fluctuation while performing resting task than action task. Tremor signal was collected using a gyroscope sensor attached to subject's finger. The angular velocity signal was analyzed by transforming a one-dimensional to two-dimensional signal based on relation of different units of time-delay. The tremor fluctuation was defined as the area of 95% confidence ellipse covering the two-dimensional signal. Experimenting with 32 PD and 20 ET subjects, a ratio of fluctuation of resting to kinetic task can be a sensitive feature to discriminate PD from ET with 100% accuracy.

Testing for alcohol sensitivity of tremor amplitude in a large cohort with essential tremor.

Improvement of essential tremor (ET) amplitude after alcohol ingestion is usually based on patient reports but a quantitative test for large numbers of patients is lacking and the percentage of ET patients with a detectable alcohol effect is therefore unknown. A validated and published alcohol home test was used in 104 ET patients. The Archimedes spiral was drawn before alcohol ingestion and at 4 time points after alcohol consumption and rated on a 10-point rating scale according to Bain and Findley. A second identical test without alcohol ingestion was performed by the same patients and evaluated by the same two raters to analyze the total variability of the spiral ratings. Alcohol reduces tremor in ET patients as a group and a rebound effect with an increase in tremor intensity was found the next morning. Sex, family history of ET, diagnosis (definite vs. probable) and medical history of alcohol responsiveness do not predict the alcohol response. The minimal detectable difference in the spiral score was 2 due to spontaneous tremor fluctuations and inter-rater differences. The test demonstrated alcohol sensitivity of the tremor in 46% of the patients. Responsivity to alcohol could only be seen in patients with spiral scores above 3. Alcohol sensitivity is a feature of ET in at least 46% of the patients. We could not find predictors for alcohol sensitivity. The minimal detectable change is 2 scores and alcohol responsivity was only detected in patients with baseline Archimedes spiral rating of ≥3.

A direct relationship between oscillatory subthalamic nucleus–cortex coupling and rest tremor in Parkinson’s disease

Electrophysiological studies suggest that rest tremor in Parkinson's disease is associated with an alteration of oscillatory activity. Although it is well known that tremor depends on cortico-muscular coupling, it is unclear whether synchronization within and between brain areas is specifically related to the presence and severity of tremor. To tackle this longstanding issue, we took advantage of naturally occurring spontaneous tremor fluctuations and investigated cerebral synchronization in the presence and absence of rest tremor. We simultaneously recorded local field potentials from the subthalamic nucleus, the magnetoencephalogram and the electromyogram of forearm muscles in 11 patients with Parkinson's disease (all male, age: 52-74 years). Recordings took place the day after surgery for deep brain stimulation, after withdrawal of anti-parkinsonian medication. We selected epochs containing spontaneous rest tremor and tremor-free epochs, respectively, and compared power and coherence between subthalamic nucleus, cortex and muscle across conditions. Tremor-associated changes in cerebro-muscular coherence were localized by Dynamic Imaging of Coherent Sources. Subsequently, cortico-cortical coupling was analysed by computation of the imaginary part of coherency, a coupling measure insensitive to volume conduction. After tremor onset, local field potential power increased at individual tremor frequency and cortical power decreased in the beta band (13-30 Hz). Sensor level subthalamic nucleus-cortex, cortico-muscular and subthalamic nucleus-muscle coherence increased during tremor specifically at tremor frequency. The increase in subthalamic nucleus-cortex coherence correlated with the increase in electromyogram power. On the source level, we observed tremor-associated increases in cortico-muscular coherence in primary motor cortex, premotor cortex and posterior parietal cortex contralateral to the tremulous limb. Analysis of the imaginary part of coherency revealed tremor-dependent coupling between these cortical areas at tremor frequency and double tremor frequency. Our findings demonstrate a direct relationship between the synchronization of cerebral oscillations and tremor manifestation. Furthermore, they suggest the feasibility of tremor detection based on local field potentials and might thus become relevant for the design of closed-loop stimulation systems.

Essential tremor quantification during activities of daily living

BackgroundEssential tremor (ET), characterized primarily by postural and kinetic tremor, is typically measured in the clinic with subjective tremor rating scales. These ratings are often used to adjust medications and assess efficacy in clinical trials. However, tremor ratings require the presence of a clinician and do not necessarily capture tremor fluctuations throughout the day during activities of daily living (ADL). ObjectiveTo evaluate the ability of motion sensors to discriminate tremor from voluntary posture and motion, classify tremor as postural or kinetic, and rate tremor severity during standardized tasks and non-standardized activities of daily living. MethodsTen subjects with ET wore motion sensors on the index finger and performed standardized motor tasks from the Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) tremor rating scale (wTRS) and non-standardized ADL tasks. Four movement disorder specialists independently rated video segments of the standardized tasks but not the ADL tasks. Quantitative features were extracted from the motion sensors and used to develop mathematical models for predicting rating scores from kinematic data. ResultsThe quantitative motion features were highly correlated with wTRS ratings for postural (r = 0.90) and kinetic (r = 0.80) tremors. Mathematical models produced tremor ratings that correlated strongly with clinician ratings of the wTRS tasks (mean r = 0.80) and also produced ADL task ratings that correlated well with the most recent clinician wTRS ratings (mean r = 0.72). ConclusionsRecordings from motion sensors can be used to classify tremor as postural or kinetic and quantify tremor severity during both standardized and non-standardized activities.

New actigraph for long-term tremor recording

A new method of movement analysis is validated, allowing an actigraph to discriminate tremor from other movements and store duration and intensity measures of both movement types. For algorithm optimization, wrist acceleration was recorded in nine controls and nine Parkinson's disease patients, while simultaneously rating their observed tremor minute by minute on item 20 of the Unified Parkinson's Disease Rating Scale. An optimization procedure to minimize false positives in controls while maximizing tremor detection in patients resulted in false positive tremor classification in 2.4% +/- 2.5% of the movement time of control subjects (range, 0%-7%), while providing tremor classification in 82.1% +/- 15.4% of the movement time in patients (range, 55%-100%), correlating r = 0.93 with their averaged observed tremor score. A second, generalizability study showed that application of the optimized algorithm resulted in accurate classification of 71% +/- 14% of the observed tremor time (range, 46%-90%) in another 9 patients and in a false positive classification in only 0.5% +/- 0.8% of the time in another 10 controls (range, 0%-2.4%). The commercial availability of this actigraph now for the first time makes it possible to investigate tremor fluctuations over several weeks. An example is given of how long-term monitoring can be of use in evaluation of symptom management.

A model of degassing and seismicity at Arenal Volcano, Costa Rica

Arenal volcano is the most active volcano in Costa Rica and has emitted at least 1.3Mt of SO2 since its reactivation in July 1968. Gas emissions from the volcano have been both by passive degassing and explosive eruptions, with passive degassing being dominant. Based on correlation spectrometry (COSPEC) measurements made during 1982, 1995 and 1996, the minimum average daily output is 130±60td−1 SO2 emitted from Arenal. Arenal is extremely active, with tremor fluctuations showing a distinct correlation with Earth tides; decreased explosive activity and increased tremor appear to coincide with the maximum rate of change in Earth tides. This suggests that a system such as Arenal may be extremely sensitive to small changes in the confining pressure or stress regime of the conduit. The cyclic nature of explosive activity also may be caused by corresponding fluctuations in the extrusion rate of lava. At high extrusion rates, lava from the non-explosive conduit may overflow into the explosive conduit, temporarily blocking it with a resulting pressurisation of the system. Arenal is likely tapping a deep to mid crustal magma chamber and, unlike many volcanoes, there is a comparatively small difference between petrological and COSPEC SO2 estimates (0.41 vs. 1.3Mt, respectively, since 1968), suggesting that Arenal is being continuously supplied by fresh magma.

Fluctuations in tremor at rest and eye movements during ocular fixation in subjects with Parkinson's disease

This exploratory study investigates possible relationships between fluctuations in tremor at rest (TR) and fluctuations in eye movement amplitude during ocular fixation. TR of the hand and eye movements were analyzed in five subjects with Parkinson's disease (PD) and five age-matched controls. TR was recorded using a position laser system and eye movements were recorded using an infrared reflectometry technique (Ober2). TR amplitudes were significantly larger in the group of subjects with PD than in the control group (p</=0.01). In addition, subjects with PD showed more fluctuations in their TR (p</=0.01). Eye movements did not present more fluctuations in amplitude during ocular fixation (p>/=0.05). Changes in TR amplitude were not systematically correlated with modifications of eye movement amplitude in either group. However, occasional but distinct monocular oscillations were found in subjects with PD. Coherence values between frequencies of TR from the tested hand (3.5-7Hz) and frequencies of oscillatory eye movements (within the same frequency band) were clearly higher for the eye ipsilateral to the side of the body most affected by the disease in three subjects with PD. It is believed that these monocular oscillations may be a consequence of PD. Results from two previously published exploratory studies are integrated with the present results and new avenues of research are proposed.

Fluctuations in tremor at rest and saccadic eye movements in subjects with Parkinsons disease

This study investigates the possible relationships between fluctuations in finger tremor amplitude and the performance of visual saccades. Saccadic eye movements were analyzed in five subjects with Parkinson's disease (PD) and five age-matched controls. Tremor was recorded by using a position laser system, and eye movements were recorded with an infrared reflectometry technique (Ober2). Tremor amplitude (root mean square) was significantly larger in the group of subjects with PD (2.87 +/- 4.37 mm) than in the control group (0.017 +/- 0.005 mm, U = 0, p < 0.01). In addition, subjects with PD showed more fluctuations in their tremor at rest (0.52 +/- 0.98 mm versus 0.003 +/- 0.006 mm, U = 1, p < 0.05). Latency, saccade error and percentage of predictive saccades were not significantly different between subjects with PD and control subjects. Average saccade amplitude was smaller in the group of subjects with PD (16.1 +/- 2.31 degrees ) than in the control group (18.49 +/- 3.62 degrees , U = 1, p < 0.05). Spearman's rank correlation coefficient showed no direct relationship between saccade amplitude and changes in tremor amplitude at the time of each saccade but, in general, subjects with PD who had more fluctuations in their tremor at rest had also more fluctuations in their saccade error (Rho = 0.9). These results suggest that the mechanisms causing short-term fluctuations in tremor at rest do not directly influence the visual saccadic system.

Fluctuations in tremor and respiration in patients with Parkinson's disease

Fluctuations in tremor were investigated in patients with Parkinson's disease. Two patients with fluctuations of tremor (H and V) and one patient with no fluctuations in tremor (C) were tested. Blood pressure, ECG, respiration and tremor were recorded continuously for 5 min while the patients were relaxing with eyes closed, performing subtractions mentally or listening to a story. Results indicate the presence of abrupt transitions in both tremor and respiration for patients H and V. In patient V the fluctuations appear to be simultaneous, in patient H a delay exists between the onset of fluctuations in respiration and the fluctuations in tremor. In Patient C, no fluctuation was recorded in either respiration or tremor. Although the mechanisms underlying these fluctuations are not yet understood, this preliminary study has begun to characterize the qualitative changes occurring in tremor and respiratory patterns associated with Parkinson's disease. Such an approach combined with the knowledge that some temporal rhythms respond best to certain treatment strategies, may provide a new basis for therapy.

Tremor: Is Parkinson's disease a dynamical disease?

Experimental evidence has shown a plethora of short-term fluctuations in patients with Parkinson's disease. We investigate these transitory events using the concept of dynamical disease. Several examples of short-term fluctuations in tremor are analyzed, and in two cases, other systemic variables (i.e., respiration and blood pressure) are examined as well. A model for tremor, based on negative feedback with delays is proposed, and the transient events are simulated. The theoretical implications of the model suggest that interactions between the central and peripheral loops, as well as interactions between the control loops and other systemic signals, can give rise to transitory events in tremor, both in the pathological and in the normal case. (c) 1995 American Institute of Physics.