Table 1
Details of DBS setting in ET DBS subjects. Anode and cathode contacts, voltage, pulse width, and frequency for both left and right lateralized DBS for each participant.
| SUBJECT | LEFT VIM OF THALAMUS | RIGHT VIM OF THALAMUS | ||||||
|---|---|---|---|---|---|---|---|---|
| LEAD CONTACTS | VOLTAGE (V) | PULSE WIDTH (μS) | FREQUENCY (HZ) | LEAD CONTACTS | VOLTAGE (V) | PULSE WIDTH (μS) | FREQUENCY (HZ) | |
| 1 | 1-2+ | 2.7 | 90 | 185 | 1-2+ | 2.7 | 90 | 185 |
| 2 | 2-3+ | 2.6 | 120 | 200 | 2-3+ | 3.5 | 120 | 200 |
| 3 | 1-C+ | 2.1 | 90 | 135 | 2-C+ | 2.2 | 90 | 135 |
| 4 | 1-C+ | 2.6 | 90 | 145 | – | - | – | – |
| 5 | 2-C+ | 2 | 90 | 135 | 2-C+ | 2 | 90 | 135 |
| 6 | 1-C+ | 2 | 90 | 135 | 1-C+ | 1.8 | 90 | 135 |
| 7 | 1+2 | 3.3 | 90 | 135 | – | – | – | – |
| 8 | 0-1-2+ | 2.2 | 180 | 130 | – | – | – | – |
| 9 | 2-C+ | 2.3 | 90 | 180 | – | – | – | – |
| 10 | 0-1+ | 2.7 | 90 | 135 | – | – | – | – |
| 11 | 1-3+ | 2.2 | 90 | 130 | – | – | – | – |
| 12 | – | – | – | – | 2-C+ | 2.7 | 104 | 150 |
| 13 | 2-3+ | 3.3 | 117 | 150 | – | – | – | – |
| 14 | 1-C+ | 2.2 | 90 | 145 | – | – | – | – |
| 15 | 2-C+ | 2.5 | 60 | 180 | 2-C+ | 2.6 | 90 | 130 |
| 16 | 2-1+ | 2.7 | 90 | 185 | 2-3+ | 3 | 90 | 180 |
| 17 | 2-3+ | 5 | 60 | 180 | – | – | – | – |
Figure 1
Quantification of tremor during the balance and gait tasks. A) Participants performed a postural balance task while standing quietly on both legs for 30 seconds and quantified their sway path length. We recorded fluctuations in acceleration from sensors placed on the sternum (upper trunk), L5 (lower trunk), left and right wrists (upper limb), and left and right ankles (lower limb). B) The top panel shows a representative acceleration from the sternum sensor during the middle 20 s of the postural balance task (gray) for an ET DBS subject and a HC. The red area in the acceleration signal shown in the left indicates the power from 4–8 Hz (upper trunk tremor) for an ET DBS subject when the DBS was OFF, whereas the yellow area in the right acceleration signal indicates the power from 4–8 Hz for the HC. The bottom panel shows the power spectrum of the acceleration signal for the ET DBS and HC participants. C) Participants walked overground for 14 m with their preferred speed. We recorded fluctuations in acceleration from the same sensors as in the postural balance task. D) The top panel shows the sternum acceleration during the initial 5 s of the gait task for an ET DBS subject with the DBS off (red) and a HC (yellow). The bottom panel shows the wavelet of the corresponding acceleration signal during the gait task. Tremor at each sensor location during balance and gait tasks was quantified as the power from 4–8 Hz relative to the total power from 0–12 Hz.
Table 2
Disease severity, gait and balance performance, and tremors quantified during the gait and balance tasks comparing between unilateral and bilateral DBS treatment. There were no differences between the two DBS types. Values are shown as mean ± SD. * p < 0.05.
| UNILATERAL DBS (N = 10) | BILATERAL DBS (N = 7) | |||
|---|---|---|---|---|
| OFF | ON | OFF | ON | |
| Stride length variability (CV, %) | 2.6 ± 0.5 | 2.1 ± 0.4 | 2.4 ± 0.6 | 2.4 ± 0.6 |
| Sway path length (m/s2) | 9.8 ± 6.2 | 7.0 ± 3.8 | 9.9 ± 5.9 | 6.6 ± 2.1 |
| FTM-TRS | ||||
| Total | 47.8 ± 14.3 | 28.4 ± 14.9 | 43.4 ± 9.3 | 16.0 ± 7.1 |
| Tremor | 13.4 ± 5.0 | 9.1 ± 5.0 | 11.2 ± 2.9 | 7.8 ± 2.4 |
| Manual | 19.6 ± 7.4 | 12.2 ± 8.0 | 17.4 ± 6.8 | 5.5 ± 4.1 |
| Self | 14.8 ± 4.3 | 7.1 ± 4.6 | 14.7 ± 2.9 | 2.5 ± 2.2 |
| TETRAS | ||||
| Total | 49.1 ± 12.0 | 27.2 ± 12.4 | 50.0 ± 5.4 | 18.1 ± 7.6 |
| Tremor | 8.6 ± 3.2 | 6.4 ± 3.1 | 9.0 ± 2.8 | 6.1 ± 2.8 |
| Manual | 11.3 ± 3.1 | 7.4 ± 3.0 | 9.9 ± 2.7 | 4.4 ± 1.6 |
| Self | 29.2 ± 8.8 | 13.4 ± 8.5 | 31.0 ± 5.2 | 7.5 ± 4.9 |
| Balance tremor (%) | ||||
| Upper limb | 9.3 ± 5.8 | 9.1 ± 6.7 | 6.7 ± 5.2 | 7.3 ± 4.3 |
| Lower limb | 4.8 ± 3.4 | 4.5 ± 4.0 | 7.5 ± 7.8 | 5.8 ± 3.5 |
| Upper trunk | 7.0 ± 6.6 | 5.5 ± 4.9 | 7.0 ± 6.3 | 4.8 ± 1.2 |
| Lower trunk | 8.6 ± 7.6 | 6.3 ± 5.2 | 9.6 ± 7.9 | 6.1 ± 3.2 |
| Gait tremor (%) | ||||
| Upper limb | 6.5 ± 2.4 | 6.3 ± 3.4 | 7.0 ± 1.9 | 6.9 ± 2.1 |
| Lower limb | 8.4 ± 2.1 | 9.1 ± 2.5 | 9.1 ± 2.1 | 8.5 ± 2.1 |
| Upper trunk | 5.3 ± 1.3 | 5.0 ± 1.6 | 5.6 ± 1.2 | 5.4 ± 1.2 |
| Lower trunk | 9.0 ± 1.9 | 9.1 ± 2.1 | 9.2 ± 1.9 | 9.5 ± 2.6 |
Table 3
Demographic characteristics, disease severity, gait and balance performance, and tremors quantified during the gait and balance tasks. Values are shown as mean ± SD. * p < 0.05. All p-values are FDR corrected.
| ET DBS OFF (N = 17) | HC (N = 17) | ET DBS ON (N = 17) | P-VALUE | |||
|---|---|---|---|---|---|---|
| DBS OFF VS. HC | DBS OFF VS. DBS ON | DBS ON VS. HC | ||||
| Age (yrs) | 69.5 ± 8.7 | 68.6 ± 7.9 | – | 0.4 | ||
| Sex | M = 12, F = 5 | M = 12, F = 5 | – | – | ||
| MoCA | 26.1 ± 1.5 | 27.6 ± 1.7 | – | 0.003* | ||
| BDI | 5.9 ± 6.0 | 2.8 ± 4.3 | – | 0.04* | ||
| Stride length variability (CV, %) | 2.6 ± 0.6 | 2.0 ± 0.5 | 2.3 ± 0.5 | 0.003* | 0.04* | 0.09 |
| Sway path length (m/s2) | 9.9 ± 6.0 | 4.4 ± 0.9 | 6.9 ± 3.2 | <0.001* | 0.005* | 0.008* |
| FTM-TRS | 46.0 ± 12.4 | 2.5 ± 2.4 | 23.3 ± 13.6 | <0.001* | <0.001* | <0.001* |
| Part A | 12.5 ± 4.3 | 1.8 ± 1.9 | 8.6 ± 4.1 | <0.001* | 0.001* | <0.001* |
| Part B | 18.7 ± 7.1 | 0.6 ± 1.4 | 9.5 ± 7.4 | <0.001* | <0.001* | <0.001* |
| Part C | 14.8 ± 3.8 | 0.1 ± 0.3 | 5.2 ± 4.4 | <0.001* | <0.001* | <0.001* |
| TETRAS | 49.5 ± 9.6 | 2.4 ± 2.2 | 23.5 ± 11.4 | <0.001* | <0.001* | <0.001* |
| Part A | 8.8 ± 3.0 | 1.5 ± 1.4 | 6.3 ± 3.0 | <0.001* | 0.002* | <0.001* |
| Part B | 10.7 ± 3.0 | 0.5 ± 0.9 | 6.2 ± 2.9 | <0.001* | <0.001* | <0.001* |
| Part C | 29.9 ± 7.4 | 0.4 ± 0.8 | 11.0 ± 7.7 | <0.001* | <0.001* | <0.001* |
| Balance tremor (%) | ||||||
| Upper limb | 8.3 ± 5.6 | 7.5 ± 3.8 | 8.4 ± 5.8 | 0.5 | 0.43 | 0.49 |
| Lower limb | 6.0 ± 5.6 | 3.1 ± 2.1 | 5.1 ± 3.8 | 0.04* | 0.38 | 0.09 |
| Upper trunk | 7.1 ± 6.3 | 4.5 ± 2.4 | 5.3 ± 3.8 | 0.3 | 0.31 | 0.49 |
| Lower trunk | 9.0 ± 7.6 | 4.6 ± 2.8 | 6.2 ± 4.4 | 0.05* | 0.05* | 0.18 |
| Gait tremor (%) | ||||||
| Upper limb | 6.8 ± 2.2 | 5.0 ± 1.9 | 6.6 ± 2.9 | 0.02* | 0.31 | 0.06 |
| Lower limb | 8.7 ± 2.1 | 8.2 ± 1.1 | 8.9 ± 2.3 | 0.2 | 0.31 | 0.19 |
| Upper trunk | 5.5 ± 1.3 | 5.2 ± 1.5 | 5.2 ± 1.4 | 0.3 | 0.17 | 0.42 |
| Lower trunk | 9.2 ± 1.9 | 7.9 ± 1.3 | 9.3 ± 2.3 | 0.025* | 0.38 | 0.03* |
Figure 2
Tremor during balance and gait tasks in ET DBS subjects and HC. Relative to matched HC (yellow), ET DBS subjects with DBS OFF (red) had greater tremor in the upper limb and lower trunk during the gait task (A), and had greater tremor in the lower limb and lower trunk during the postural balance task (B). Relative to DBS OFF (red), DBS ON (green) did not significantly reduced tremors during the gait task (C), but significantly reduced tremor in the lower trunk during postural balance task (D). * p < 0.05.
Figure 3
DBS-induced changes in disease severity and in gait and balance performance. A) DBS reduced disease severity in all 17 ET DBS subjects, as quantified with FTM-TRS and TETRAS. B) DBS reduced stride length variability in 11/17 ET DBS subjects and reduced sway path length in 14/17 ET DBS subjects. The relation between tremor and balance and gait performance with neurostimulation. C) The reduction in stride length variability with neurostimulation associated with tremor reduction in upper limb and upper trunk during the gait task. D) The reduction in sway path length with neurostimulation associated with tremor reduction in the upper trunk during the postural balance task. Percent change (% Δ) = ((DBS ON-OFF)/DBS OFF) × 100.