Neurofunction > Volume 17(1); 2021 > Article |
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Study | Animal | Sample size | Disease | Devices (1. Electrode/2. Generator/3. Output monitor) | Target+coordinates (mm) | Parameter | Outcome measurement | Conclusion | Comments |
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Doucette et al. [18] (2015) | Sprague-Dawley rats | 12 (DBS) vs. 6 (control) | BE | 1. Plastics, Roanoke | NA core, | Monophasic, continuous | 1. Binge size change (%) | 1. Reduction of binge size in DBS group | Relapse model; No significant improvement in binge size |
2. S11, Grass instruments | Bilateral; | 60 µsec, 50 Hz, 150 µA | |||||||
3. PSIU6, Grass Technologies | 1.2 (A), 2.8 (L), 7.6 (V) 4° from bregma | ||||||||
Halpern et al. [11] (2013) | Mice (male, C57BL/6J) | NA shell (n=12) vs. dorsal striatum (n=11) vs. control (n=7) | BE | 1. Custom bipolar tungsten electrode | NA shell | Monophasic, continuous | 1. High-fat diet (kcal) | 1. Decrease in high-fat diet intake | NA DBS can produce behavioral change (reducing high-fat diet intake) via the D2R pathway |
2. SD9 Square Pulse Stimulator, Grass Technologies | Unilateral; | 60 µsec, 160 Hz, 150 µA | 2. Activity | 2. No activity change | |||||
3. CT3684, Cal Test/TPS2000B, Tektronix | 1.34 (A), 0.6 (L), 4.25 (V) | 3. c-Fos-IR in the NAS and ILC | 3. Increased c-Fos-IR in the bilateral NA | ||||||
Dorsal striatum | 4. Pharmacological effect (D1R, D2R) | 4. Only D2R antagonist attenuated the effects of DBS | |||||||
1.34 (A), 1.5 (L), 2.2 (V) from bregma | |||||||||
Sani et al. [22] (2007) | Sprague-Dawley rats | 8 vs. 8 (DBS vs. sham) | BE | 1. 0.25 mm bipolar product (Plastic) | LH | Continuous | 1. Body weight | 1. Significant weight reduction in stimulated rats | Stimulation of LH might reduce metabolic rate, rather than modulating appetite control |
2. Medtronic products | Bilateral; | 100 msec, 180-200 Hz, 2.0 V | 2. Food intake | 2. No change in food or water intake | |||||
2.3 (P; bregma), 2 (L; sagittal), 8.6 (below dura) | 3. Water intake | ||||||||
Prinz et al. [21] (2017) | Sprague-Dawley rats (female) | 6 vs. 6 (DBS vs. sham) | Normal | 1. platinum/iridium wire with 70 µm diameter | Medial NA shell; | Biphasic | 1. Food/water intake | 1. High trend of an increase in weight gain in DBS group | Day time food intake >night food intake (DBS group) |
2. Implantable stimulator | Unilateral; | 130 Hz, 100 µA for 7 days | 2. Weight gain | 2. No changes in food intake and behavior | Reduction of satiation | ||||
3. None | 1.44 (A), 3.0 (L), 7.3 (V) 18° | 3. Behavior | |||||||
Zhang et al. [24] (2015) | Sprague-Dawley rats | 1. DIO (DBS, n=8) vs. control (sham, n=8) | 2 groups; | 1. CBCRJ30 (FHC) | Left NA shell; | 90 µsec, 130 Hz, 500 µA | 1. Body weight/food intake | 1. Significant weight loss and food intake reduction in DIO-DBS rats | DBS has effect only in DIO rats |
2. Normal (DBS, n=8) vs. control (sham, n=8) | 1. DIO rats | 2. Master 8 (AMPI) | Unilateral; | 2. D1/2 receptor mRNA | 2. Increased D2R mRNA expression in DIO-DBS rats | No significant change in weight loss (or food intake) and dopamine-related activity was noted in normal rats | |||
2. Normal rats | 3. NA | 1.2 (A), 0.7 (L), 7.4 (V) from bregma | 3. DA/DOPAC | 3. Increased dopamine levels in DIO-DBS rats but no significant change in DOPAC level was noted | |||||
Torres et al. [23] (2012) | Monkeys (Macaca fascicularis) | 4 (DBS) vs. 1 (sham) | Normal | 1. 1.5 mm/four contact or 3.0 mm/one contact (specific information about products is not shown) | VMH, | 30-130 Hz | 1. Body weight and body fat | 1. Significant reduction in body weight and body fat in DBS monkeys | Only 80 Hz stimulation showed anti-obesity effect |
Anterior to 3rd ventricle; | 2. Fat intake | 2. No significant change in fat intake during stimulation | |||||||
Unilateral | 3. Glucose and leptin | 3. No change in glucose or leptin level during stimulation | No hormonal change during stimulation and no change in serum leptin levels during weight loss | ||||||
4. Locomotion | 4. Increased velocity during stimulation | ||||||||
Oterdoom et al. [20] (2020) | Wister rats | 7 (NA core) vs. 7 (NA lateral shell) vs. 7 (NA medial shell) | BE | Not specified | NA core vs. NA shell; | 60 µsec, 140, 50, 10 Hz, 250 µA (or 150 µA in cases with side effects) | High-fat food intake | NA core-stimulation before binge eating produced significant decrease in high-fat food intake | Different mechanism on binge eating between NA core and NA shell; wanting vs. liking |
Coordinates were not specified; | NA lateral shell-stimulation during binge eating led to suppression of high-fat food intake | Stimulation of medial NA shell led to major side effect (e.g., fear and escape behavior) | |||||||
Unilateral | |||||||||
Casquero-Veiga et al. [17] (2018) | Zucker rats | 6 (NA core) vs. 9 (sham) | Obesity model (leptin-resistant model) | 1. Platinum-iridium electrodes (MS303/8-AIU/Spc, Bilaney Consultants GmbH, Germany) | NA core; | Biphasic, continuous, | 1. Glucose metabolism using FDG-PET | 1. Alteration in glucose metabolism in DBS rats; decreased metabolism in the NA, thalamic and pretectal nuclei, and increased metabolism in the cingulate-retrosplenial-parietal association cortices | Over-activated striatum and thalamus in obese rats can be counteracted by NA DBS since it reduced glucose metabolism in the striatum and thalamus |
2. CS 120 8i (CIBERTEC S.A., Spain) | 1.2 (P), 1.5 (L) from bregma, -8.2 from dura; | 100 µsec, 130 Hz, 150 µA | 2. Weight | 2. No significant change in weight and food intake | No significant weight loss in DBS rats can indicate that NA-DBS cannot resolve imbalance caused by the lack of leptin signaling in the hypothalamus | ||||
Unilateral | 3. Food and water intake | ||||||||
Melega et al. [19] (2012) | Göttingen | 4 (DBS) vs. 4 (non-DBS) | Obesity | 1. A miniature DBS (custom-made, NuMED Inc., Hopkin-ton, NY) | Bilateral VMH; | Monopolar | 1. Weight gain | 1. Significantly lower in stimulated-VMH | |
2. Genesis, 8-Channel #3608 (ANS, Plano, TX) | Navigation-assisted | 507 µsec, 50 Hz, 0.5 mA | 2. Blood glucose level | 2. No difference | |||||
3. Behavioral change |
DBS: deep brain stimulation, NA: nucleus accumbens, DIO: diet-induced obese, BE: binge eating, A: anterior, L: lateral, V: ventral, LH: lateral hypothalamus, P: posterior, VMH, ventromedial hypothalamus, c-Fos-IR: c-Fos immunoreactivity, NAS: nucleus accumbens shell, ILC: infralimbic cortex, D1R: dopamine receptor 1, D2R: dopamine receptor 2, DA/DOPAC: dopamine/dihydroxyphenylacetic acid.
Study | Sample size | Devices(1. Electrode/2. Generator | Target+coordinates (mm) | Parameter | Outcome measurement | Conclusion | Significance or comments |
---|---|---|---|---|---|---|---|
Whiting (2013) et al. [44] | n=3 | 1. Model 3389 (Medtronic) | LH; | Monopolar or bipolar; 90 µsec; 185 Hz | 1. Psychological tests | 1. Improvement in Binge Eating score (1/3), cognitive restraint subscale (1/3), hunger scale (2/3), body shape questionnaire (2/3) | Parameters that appeared to augment RMR induce significant weight loss in 2/3 patients |
2. Soletra (Medtronic) | Bilateral; | 2. Biochemical analysis | 2. No changes in biochemical analysis | Contact 1 (most closely located to mid-LH) increased RMR in 2/3 | |||
6.5 (L), 3 (I) to intercommissural line, 4.5 (P) to AC ±adjustment in relation to fornix | 3. Energy metabolism | 3. Significant increase in RMR | Contact 3 produced increased activity and increased arousal in all patients. | ||||
4. Body weight | 4. Significant weight loss in 2/3 and stable weight in 1/3 | No significant adverse effects | |||||
Whiting et al. [45] (2019, follow-up study) | n=2 (one patient was excluded due to lead breakage) | 1. Model 3389 (Medtronic) | LH; | Various settings were tested to identify optimal setting | 1. Optimal setting for increasing RMR | Patient 1: contact 2 with pulse width of 60 msec and a frequency of 185 Hz | This different optimal setting might indicate the activation of different nuclei and regions |
2. Soletra (Medtronic) | Bilateral | Patient 2: contact 0 with pulse width of 90 msec and a frequency of 60 Hz | Long-term investigations of weight loss and metabolic rate at optimized settings are mandatory | ||||
Mantione et al. [46] (2010) | n=1 (OCD patient with obesity; BMI 37 kg/m2 (107 kg) | 1. Model 3389 (Medtronic) | NA; | Monopolar; 90 msec; 185 Hz; | 1. Various psychiatric batteries | 1. Significant improvement in various tests for OCD, depression, and anxiety | Compulsions, smoking, and excessive food intake have a shared pathophysiology that can be improved by NA modulation |
2. Soletra (Medtronic) | Bilateral | 3.5 V | 2. Weight loss | 2. Significant reduction in weight | |||
3. Smoking cessation | 3. Success in smoking cessation | ||||||
Harat et al. [47] (2016) | n=1 (hypothalamic obesity due to earlier craniopharyngioma surgery) | Not shown | NA; | 208 µsec; 130 Hz; 2 mA (increases to 3.5 mA) | 1. Various psychiatric tests | 1. Significant improvement in various psychiatric tests | Modulation of the immediate brain reward system can treat hypothalamic obesity |
Bilateral | 2. Weight control | 2. Significant weight reduction |
Study | RCT numbers | Inclusion & estimated sample size | Target | Parameters | Outcome measurements | Current status |
---|---|---|---|---|---|---|
De Salles et al. [43] (BLESS study, 2018) | NCT 02232919 | BMI>40 kg/m2 or >35 kg/m2 with therapeutic failure | VMH; | Low frequency (50 Hz) | 1. Various psychiatric batteries | Recruited |
Sample size: 6 patients | Bilateral | 2. Weight changes | ||||
3. Indirect calorimetry and dual-energy X-ray absorptiometry (DEXA 62) | ||||||
4. Food intake | ||||||
Wu et al. [48] (DBSLOC, 2020) | NCT 03868670 | BMI 40-60 kg/m2 | NA; | RNS® system (closed-loop DBS); Stimulation setting is not specified. | 1. Adverse events | Recruiting |
Sample size: 6 patients | Bilateral | 2. Decrease in loss of control episodes |
Jong Hyun Kim
https://orcid.org/0000-0002-8300-9486
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