Deep Transcranial Magnetic Stimulation promotes weight loss and thermoregulation in obesity through Neuro-Endocrine Modulation

Deep Transcranial Magnetic Stimulation (dTMS) induces long lasting changes in neural excitability and dopamine release. Consistently with its modulatory effect on dopaminergic reward system, we hypothesized a potential role of dTMS in inducing satiety and weight loss via modulation of neuronal circuits. Neuro-endocrine abnormalities could lead to an altered body Temperature (T) regulation in obesity: to maintain normothermia, extremities heat dissipation increases, whereas central sites heat reduces. Primary outcome of this study was to evaluate dTMS effects on satiety and body weight in obesity; secondly, the acute and chronic effects of dTMS on the neurophysiological mechanisms underlying obesity and the concomitant body T dysregulation were investigated. Thirty-five obese subjects (OB) (10 M, 25 F; 46.6±9.3 years; BMI 36.3±4.7) were randomized into 3 groups receiving 15 sessions (3 per week for 5 weeks) of high-frequency (18 Hz), low-frequency (1 Hz) or sham stimulation. Pre-frontal Cortex and Insula were bilaterally stimulated. Weight, metabolic, neuro-endocrine parameters and food craving were evaluated at baseline and after 15 dTMS sessions. Under thermo-neutral conditions, 22 of the 35 OB underwent a T measurement of the fingernail-bed of both hands, abdominal skin and interscapular region (only 4 OB), using infrared thermography (AVIO TVS700, 320x240 pixel, spatial resolution 1.4 mrad, T resolution 0.08°C). After 5 weeks, 18 Hz group OB experienced a significant decrease in food craving (-42.7±16.1% vs basal, p<0.0001) and body weight (-4.1±2.3% vs basal, p<0.0001; p<0.05 vs Sham). In the same group, a significant improvement of insulin (-10.0±11.9% vs basal, p<0.05), HOMA-IR index (-10.3±12.6% vs basal, p<0.05), glycated hemoglobin (-8.8±2.5% vs basal, p=0.001) was found. After a single 18 Hz dTMS session, the average T of fingernail-bed of both hands significantly decreased (right hand: 34.4±1 vs 32.8±2.5 °C, -4.6±0.3%; p<0.05; left hand: 34.3±1.2 vs 33.4±1.3 °C, -2.7±0.3%; p<0.05). In 2 OB receiving 18 Hz dTMS, an increase of interscapular T was observed (32±0.4 vs 33.9±0.1 °C, +6.0±1.0%). Concurrently, a significant increase of norepinephrine (+18.8±7.7%, p<0.05 vs baseline), β-endorphins (+14.3±5.4%, p<0.05 vs Sham), and glucose (+7.0±7.6%, p<0.005 vs baseline) was found after a single 18 Hz dTMS session. Chronically, a trend to decrease of the abdominal skin T was observed in 18 Hz group (33.9±1.1 vs 33.2±1.4 °C, -1.7±2.8%; p=0.085). Deep TMS revealed to be effective in controlling food craving and body weight and in modulating body T, reversing obesity-induced T alterations. Preliminary evidence of T increase in interscapular region after a single 18 Hz dTMS session could suggest a possible brown fat activation, which needs to be more widely confirmed. Modulation of neuro-endocrine circuitries is hypothesized as the potential mechanism through which dTMS acts.