Is there a role for combined EMG-fMRI in exploring the pathophysiology of essential tremor and improving functional neurosurgery?

Abstract

Background: Functional MRI combined with electromyography (EMG-fMRI) is a new technique to investigate the functional association of movement to brain activations. Thalamic stereotactic surgery is effective in reducing tremor. However, while some patients have satisfying benefit, others have only partial or temporary relief. This could be due to suboptimal targeting in some cases. By identifying tremor-related areas, EMG-fMRI could provide more insight into the pathophysiology of tremor and be potentially useful in refining surgical targeting.

Objective: Aim of the study was to evaluate whether EMG-fMRI could detect blood oxygen level dependent brain activations associated with tremor in patients with Essential Tremor. Second, we explored whether EMG-fMRI could improve the delineation of targets for stereotactic surgery.

Methods: Simultaneous EMG-fMRI was performed in six Essential Tremor patients with unilateral thalamotomy. EMG was recorded from the trembling arm (non-operated side) and from the contralateral arm (operated side). Protocols were designed to study brain activations related to voluntary muscle contractions and postural tremor.

Results: Analysis with the EMG regressor was able to show the association of voluntary movements with activity in the contralateral motor cortex and supplementary motor area, and ipsilateral cerebellum. The EMG tremor frequency regressor showed an association between tremor and activity in the ipsilateral cerebellum and contralateral thalamus. The activation spot in the thalamus varied across patients and did not correspond to the thalamic nucleus ventralis intermedius.

Conclusion: EMG-fMRI is potentially useful in detecting brain activations associated with tremor in patients with Essential Tremor. The technique must be further developed before being useful in supporting targeting for stereotactic surgery.

Figure 1. Spectrograms of EMG recorded during “Tremor” protocol.

Spectrograms of the continuous simultaneous EMG recording from the Extensor of the fingers (EF) of the left (top panel) and right arm (bottom panel), during the conditions rest, left arm stretching (L stretch), right arm stretching (R stretch), and both arms stretching (B stretch) in patient No.1. The color bar on the right of the figure indicates power intensity going from low (deep blue) to high (red). A clear increase in the tremor frequency range is visible as an orange band between 4 and 6 Hz on the left EF spectrogram, during extension of the arms and fingers inducing postural tremor (conditions L stretch and B stretch). No increase in power in the tremor frequency is visible on the right EF spectrogram.

Figure 2. Single-subject analysis for protocol “Tremor” with the “Circuit mask”.

The right hemisphere is represented on the right (“neurological view”). SPM t-contrasts, superimposed on the subjects’ own T1, are shown at a threshold of p<.001 uncorrected. For patient No. 2 and 4, Left EMG, no activity was seen at this threshold: for explorative purpose, these scans are shown at a threshold of p<.005 (p value indicated in the figure above the corresponding images). The crosshair points to the global maxima. Panels on the left show activity related to left EMG during left arm stretching (non-operated side). Ipsilateral cerebellar activation is present in all the patients except for patient 5. In four patients (No. 1, 3, 4, and 6) this represented the maximal activity, while in patient No. 2 the maximal activity was in the right caudate. In patient No. 5 the maximal activity was located in the right cerebellum and there was no clear activation of the left cerebellum. Panels on the right show activity related to right EMG during right arm stretching (operated side). Ipsilateral cerebellar activation is present in all patients. In patient No. 4 activity was maximal in the right caudate and in patient No. 2 in the left putamen.

Figure 3. Single-subjects analysis for protocol “Tremor” with masking on the thalamus area.

The right hemisphere is represented on the right (“neurological view”). SPM t-contrasts, superimposed on the subjects’ own T1, are shown at a threshold of p<.001 uncorrected. For patient No. 1 and No. 4, Left EMG, no activity was seen at this threshold: for explorative purpose these scans are shown at a threshold of p<.005 and p<.05 respectively (p value indicated in the figure above the corresponding images). The crosshair points to the global maxima. Panels on the left show activity related to left EMG during left arm stretching. Contralateral thalamic activation was present in the thalamic dorsal complex (No.1 and 6) or in the posterior thalamic region (No. 2 and 4). In patients No.3 and No. 5 there was no activation. Panels on the right show activity related to right EMG during right arm stretching. There was no thalamic activation in patients No. 1, 3, 5, and 6. In patient No. 2 and 4, bilateral thalamic activation was present, with global maxima in the left posterior thalamus (No.2) and in the right thalamic dorsal complex (No.4).