Table 1
Demographic information: participants analyzed with essential tremor.
| PARTICIPANTa | AGE(YEARS) | SEX | FAMILY HISTORY | DURATION (YEARS) | TRSb | ΔTRS(OFF-ON)b | DOMINANT HAND | TREMOR MEDICATIONS(TOTAL DAILY DOSE IN MG) | INITIAL STIMULATION PARAMETERS | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SITE | CONTACTS | V | PW | FREQ | |||||||||
| ET1 | 66 | F | sporadic | 41 | 22 | 0 | Right | propranolol 120, primidone 500, gabapentin 1800 | L VIM | C+2- | 1.0 V | 60 µs | 185 Hz |
| ET2 | 80 | F | familial | 12 | 44 | 2.5 | Right | propranolol 140, primidone 750, gabapentin 300 | L VIM | 0–3+ | 2.3 V | 60 µs | 185 Hz |
| ET3 | 69 | M | familial | 41 | 41 | 8 | Right | primidone 500, clonazepam 1.5 | L VIM | C+0- | 2.6 V | 60 µs | 185 Hz |
| ET4 | 77 | M | familial | 47 | 21 | 6 | Right | primidone 350, metoprolol 25 | L VIM | 0–3+ | 2.5 V | 60 µs | 185 Hz |
| ET5 | 65 | M | sporadic | 55 | 36 | 2.5 | Right | primidone 750 | L VIM | C+1- | 1.5 V | 60 µs | 185 Hz |
| ET6 | 58 | F | sporadic | 12 | 59 | 5.5 | Right | propranolol 40, gabapentin 300 | L VIM | C+2- | 3.0 V | 60 µs | 185 Hz |
| ET7 | 62 | M | familial | 47 | 21 | 1 | Right | propranolol 80 | L VIM | C+2- | 1.5 V | 60 µs | 185 Hz |
| ET8 | 55 | M | familial | 30 | 20 | 1 | Right | clonazepam 3, carbidopa-levodopa 100/400 | L VIM | 1–3+ | 2.8 V | 60 µs | 185 Hz |
| ET9 | 48 | M | sporadic | 18 | 29 | 2 | Left | propranolol 320, primidone 600 | R VIM | 1–3+ | 2.5 V | 60 µs | 185 Hz |
| ET10 | 81 | M | familial | 41 | 31 | 3 | Right | propranolol 80 | L VIM | 1–3+ | 2.5 V | 60 µs | 185 Hz |
| ET11 | 62 | M | sporadic | 12 | 14 | 1 | Right | none | L VIM | C+2- | 2.0 V | 60 µs | 185 Hz |
| ET12 | 55 | M | sporadic | 10 | 27 | 5 | Right | diazepam 30, zolpidem 10 | R VIM | 0+3- | 2.0 V | 60 µs | 185 Hz |
| ET13 | 56 | M | familial | 2c | 23 | 5 | Right | propranolol 200, primidone 750 | L VIM | 1–3+ | 2.0 V | 60 µs | 185 Hz |
| ET14 | 52 | F | sporadic | 38 | 38 | 3 | Right | carbidopa/levodopa 75/300 | L VIM | 0–3+ | 2.0 V | 60 µs | 185 Hz |
| ET15 | 49 | F | sporadic | 11 | 20 | 3.5 | Right | clonazepam 1, carbidopa-levodopa 150/600 | R VIM | 1–3+ | 1.6 V | 60 µs | 185 Hz |
| ET16 | 66 | M | familial | 6 | 15 | 2.5 | Right | none | L VIM | 0–3+ | 1.3 V | 60 µs | 185 Hz |
| ET17 | 75 | F | sporadic | 35 | 18 | 2 | Right | topiramate 200, primidone 500 | L VIM | 0+3- | 2.0 V | 60 µs | 185 Hz |
| ET18 | 62 | F | familial | 10 | 30 | 2 | Right | topiramate 100, propranolol 160 | L VIM | 1–3+ | 2.0 V | 60 µs | 185 Hz |
| ET19 | 76 | M | familial | 36 | 26 | 2 | Right | propranolol 180, primidone 400 | L VIM | C+1–3+ | 1.5 V | 60 µs | 185 Hz |
| ET20 | 55 | F | familial | 52 | 30 | 2.5 | Left | pramipexole 1 | R VIM | C+0+2- | 2.0 V | 60 µs | 185 Hz |
| ET21 | 57 | M | familial | 38 | 21 | 2 | Right | topiramate 200, primidone 1000 | L VIM | C+1- | 1.8 V | 60 µs | 130 Hz |
[i] a19 additional participants were excluded from final analyses (N = 5: observed movement throughout scanning, N = 2: comorbid neuropsychiatric diagnoses, N = 2: anatomic abnormalities on structural MRI, N = 8: did not meet motion quality assurance criteria, N = 2: to correct group imbalance of the MRI scanners used for data collection).
bTRS represents the total score while TRSOff-On reflects only tremor scores for limbs contralateral to VIM surgery.
cClinical follow-up confirmed diagnosis of ET (symptoms >3 years).
Abbreviations: V = Voltage, PW = Pulse Width; Freq = Frequency.
Table 2
Group matching data: essential tremor and control.
| ET (N = 21)MEAN (SD) | CONTROL (N = 34)MEAN (SD) | STATISTIC | P VALUE | |
|---|---|---|---|---|
| Age in years [range] | 63.1 (10.1) [48–81] | 61.9 (8.0) [49–82] | T = 0.5 | 0.62 |
| Sex | 38% F, 62% M | 38% F, 62% M | χ2 = 0.00 | 1.00 |
| Scanner | 43% S1, 57% S2 | 41% S1, 59% S2 | χ2 = 0.02 | 0.90 |
| Handedness | 90% right-handed | 88% right-handed | χ2 = 0.07 | 0.80 |
| Root mean square framewise displacement (mm) | 0.056 (0.008) | 0.053 (0.008) | T = 3.34 | 0.17 |
| Number of frames kept | 408.0 (107.8) | 446.0 (118.2) | T = –1.19 | 0.24 |
| TRS [range] | 27.9 (10.9) [14–59] |
Figure 1
Group-level connectomes in ET and Controls. Large-scale functional connectomes in (A) Control and (B) ET participants reveal grossly similar resting state network organization, consistent with resting state network architecture found in other cohorts of healthy adults. Warm and cool colors indicate positive and negative correlations, respectively. C: A subtraction matrix (Control minus ET) shows selective network-to-network blocks of altered FC in ET, particularly involving thalamus and visual internetwork FC.
Figure 2
Disruption of large-scale network structure in ET. Central weighted connectome object (g*) for (A) Control and (B) ET groups and (C) subtraction (Control g* – ET g*). Upper triangles show composite block FC scores (average cross-correlation between seeds) while the lower triangles show the matrix objects with all edges preserved. Connectome objects differ significantly between ET and controls. Black outlines in the upper triangle indicate blocks chosen a priori for hypothesis testing of ET versus controls. Stars indicate blocks with significantly different network FC between ET and controls. Note the color scale difference in (C). D: Multidimensional scaling plot demonstrates separation of ET and control connectomes represented in 2-dimensional space. Diamonds indicate the central object for each group.
Table 3
ET versus Health Control (HC) a priori network- (top) and regional- (bottom) functional connectivity (FC).
| A PRIORI NETWORK | CONTROLS | ET | t-SCORE | p |
|---|---|---|---|---|
| Thalamus – Lateral Somatomotor | –0.07 | 0.00 | 2.89 | < 0.01a |
| Thalamus – Dorsal Somatomotor | –0.08 | –0.03 | 2.50 | 0.02a |
| Thalamus – Visual | –0.13 | –0.08 | 2.17 | < 0.04a |
| Thalamus – Cerebellum | 0.11 | 0.08 | –1.70 | 0.09 |
| Visual – Lateral Somatomotor | 0.12 | 0.07 | –1.66 | 0.10 |
| Visual-Auditory | 0.06 | 0.00 | –2.54 | 0.02a |
| Significant Clusters | ET compared to HC FC | t-score | cluster contiguous voxels | |
| B. Motor Thalamus-Rt. sensorimotor cortex | (+) | ≥ 2.9* | 113 | |
| B. Motor Thalamus – B. occipitoparietal lobes | (–) | ≥ 4.0a | 8 | |
| B. Motor Thalamus – Cerebellum | (–) | ≥ 2.0a | 1161 |
[i] a Significant results.
Figure 3
Medication effects on network FC. Composite FC scores for (clockwise from top left) thalamus-lateral somatomotor, visual-auditory, thalamus-dorsal somatomotor, and visual-thalamus networks in ET participants taking (red) and not taking (blue) propranolol (N: taking = 9, not taking = 12) or primidone (N: taking = 10, not taking = 11) at the time of MRI. The central line within each box indicates median FC. The bottom and top edges of the box represent the 25th and 75th percentiles, respectively. The whiskers indicate the minimum and maximum FC values within each group. *P < 0.05, uncorrected.
Figure 4
Bilateral motor thalamus FC in ET and controls. A-B: ET and control group average correlation maps for a bilateral motor thalamus seed are depicted in the (A) sagittal and (B) axial planes. In both groups, motor thalamus has positive FC with sensorimotor areas, cerebellum, and the whole thalamus and negative FC with occipitoparietal and superior temporal lobes. Color maps are thresholded at |z| ≥ 0.1. Warm colors represent positive and cool colors represent negative correlations. C: Clusters of significant group difference are shown for the group effect z-score subtraction map (control minus ET) in the axial, coronal, and sagittal planes. The ET group has significantly increased FC with right sensorimotor cortex and decreased FC with occipitoparietal lobes, depicted in the first two columns. Note, ET has an increased magnitude of positive FC with sensorimotor cortex and decreased magnitude of negative FC with occipitoparietal cortex, both of which appear as net negative values in the difference map. The cerebellum has decreased FC in ET, shown in the rightmost column.