Entrainment Characteristics of Functional Tremor

Movement clinical neurophysiology studies of functional tremor are helpful in cases where clinical diagnosis is challenging.1 Tapping at a frequency with the contralateral hand may induce tremor suppression, tremor irregularity, a change in frequency, or entrainment (synchronization with the tapping frequency).2, 3 During entrainment analysis, the original tremor may disappear, showing a new peak at the tapping frequency, or there could be two distinct peaks observed at both the tapping and the original tremor frequencies. We labeled the first condition as “pure entrainment” and the second condition as “mixed entrainment.” The pure entrainment is also described as true entrainment, but the significance and prevalence of mixed entrainment in functional tremor is unclear. Persistence of the original tremor with a new peak at the tapping frequency can also be because of mirror movements.4 This retrospective study analyzed kinematic data collected from 10 patients with clinically established functional tremor disorder.5 Data was collected using two motion transducers (Mbientlab 9-axis-IMU). Tremor was recorded from the more affected hand, and tapping from the opposite hand, with transducers placed on each hand's dorsal surface. Rest tremor was recorded with the forearm pronated, supported on the armrest, and the hand freely suspended in the air. Postural tremor was recorded with the arm outstretched and the wrist extended. Subjects tapped at 2 Hz, 3 Hz, and 4 Hz to a metronome, making small wrist flexion-extension movements with the arm rested. Gyroscopic signals were analyzed using custom MATLAB (The MathWorks, Natick, MA) scripts. Neurophysiology data and MATLAB scripts are available on request. The power spectrum was generated using fast Fourier transformation with a 100 Hz sampling rate, a 5-second window and 15- to 20-second epochs. A spectral peak at tapping frequency was labeled “pure” or “mixed” based on the absence or presence of the original tremor peak (Fig 1B–D). Half-power-bandwidth (HPB), the width of the spectral peak at 50% peak power, was calculated to measure frequency stability. An increase of 100% or more in HPB from baseline indicated a loss of tremor rhythmicity (Fig. 1B). Pathological frequency shift, defined as a tremor frequency change greater than 20% from baseline, and the ability of the subject to tap at metronome frequencies were measured.3 Postural tremor was recorded in nine patients, whereas rest tremor was recorded in one patient. Seven of 10 patients showed entrainment at one or more tapping frequencies. One patient showed pure entrainment only, four showed mixed entrainment only, and two showed both at different frequencies. Four patients had a 100% or greater increase in HPB from baseline, and three had a pathological frequency shift. All patients with increased HPB and pathological frequency shifts also had mixed entrainment. Three patients who did not show an entrainment peak failed to tap accurately at the metronome frequencies. The combination of positive entrainment at one or more frequencies and the inability to accurately tap at metronome frequencies successfully identified all patients with functional tremor. In conclusion, functional tremor entrainment reveals two distinct types of entrainment patterns, characterized by either the presence or absence of the original tremor frequency peak. Mixed entrainment is a promising finding in movement clinical neurophysiology studies that warrants further investigation. HPB may be a useful quantitative measure of tremor stability and distractibility. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique; A.M.: 1A, 1B, 1C, 3A. S.I.: 3B. Ethical Compliance Statement: The study was approved by the institutional review board: WesternREM. Declaration of patient consent: Informed patient consent was not necessary for this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflict of Interest: A.M. received no specific funding for this work. The authors declare that there are no conflicts of interest relevant to this work. The author declares that there are no additional disclosures to report. S.I. received no specific funding for this work. The author declares that there are no conflicts of interest relevant to this work. The author declares that there are no additional disclosures to report. Financial Disclosures for the previous 12 months: A.M. has received honorarium form Merz Pharmaceutical. S.I. has no financial disclosures for the previous 12 months. The data that support the findings of this study are available from the corresponding author upon reasonable request.

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