Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex reduces cocaine craving in patients with cocaine use disorder

Rapinesi, Chiara; Casale, Antonio Del; Pietro, Simone Di; Ferri, Vittoria Rachele; Piacentino, Daria; Sani, Gabriele; Raccah, Ruggero; Zangen, Abraham; Ferracuti, Stefano; Vento, Alessandro; Angeletti, Gloria; Brugnoli, Roberto; Kotzalidis, Georgios D.; Girardi, Paolo

doi:10.1016/j.neulet.2016.06.049

Cited by 66 publications

(58 citation statements)

References 38 publications

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“…Patients fulfilling all inclusion/exclusion criteria were randomized to one of three experimental groups: 18 Hz dTMS (HF group); 1 Hz dTMS (LF group) or sham treatment (sham group). The range of stimulatory (18 Hz) and inhibitory (1 Hz) frequencies were based on previous evidence in the literature on addiction disorders . Participants were randomized in a 1:1:1 allocation ratio.…”

Section: Methodsmentioning

confidence: 99%

“…The range of stimulatory (18 Hz) and inhibitory (1 Hz) frequencies were based on previous evidence in the literature on addiction disorders. 19,22 Participants were randomized in a 1:1:1 allocation ratio. The study design is shown in the Figure 1.…”

Section: Randomization and Maskingmentioning

confidence: 99%

“…Compared to conventional coils, the H‐coil contains an array of elements which are contoured to the shape of the skull, allowing deeper (up to 4.5–5.5 cm from the skull vs. 1.5 cm of the standard coils) and larger volumes of brain stimulation, affecting both cortical and subcortical regions. Promising results have been obtained by the application of deep TMS (dTMS) in reducing nicotine dependence, alcohol craving and cocaine abuse . dTMS (H‐coil) can generate an electric field which can penetrate the cortex up to 4 cm, noticeably increasing the penetration depth of the traditional TMS systems …”

Section: Introductionmentioning

confidence: 99%

“…Promising results have been obtained by the application of deep TMS (dTMS) in reducing nicotine dependence, 19 alcohol craving 20,21 and cocaine abuse. 22 dTMS (H-coil) can generate an electric field which can penetrate the cortex up to 4 cm, noticeably increasing the penetration depth of the traditional TMS systems. 23 Consistent with the dysregulation of the PFC inhibitory control and brain reward system in obese people and with the dTMS modulatory effect on the reward system, we hypothesized a potential role of repetitive dTMS in reducing food craving.…”

mentioning

confidence: 99%

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Weight loss induced by deep transcranial magnetic stimulation in obesity: A randomized, double‐blind, sham‐controlled study

Ferrulli

Macrì

Terruzzi

et al. 2019

Diabetes Obesity Metabolism

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Aim: To test the hypothesis that deep transcranial magnetic stimulation (dTMS) reduces food craving and causes weight loss via neuromodulation. Materials and methods:This pilot study was designed as a randomized, double-blind, sham-controlled study. A total of 33 obese people (nine men, 24 women, mean age 48.1 ± 10.6 years, body mass index [BMI] 36.9 ± 4.7 kg/m 2 ) were randomized and completed the study: 13 participants underwent a 5-week treatment with highfrequency (HF) dTMS (18 Hz; HF group), 10 were treated with low-frequency (LF) dTMS (1 Hz; LF group), and 10 were sham-treated (sham group). Food craving, and metabolic and neuro-endocrine variables were evaluated at baseline, after the 5-week treatment, and at follow-up visits (1 month, 6 months, 1 year after the end of treatment).Results: The mixed-model analysis for repeated measures showed a significant interaction of time and groups for body weight (P = 0.001) and BMI (P = 0.001), with a significant body weight (−7.83 ± 2.28 kg; P = 0.0009) and BMI (−2.83 ± 0.83, P = 0.0009) decrease in the HF versus the sham group. A decreasing trend in food craving in the HF versus the LF and sham groups (P = 0.073) was observed. A significant improvement of metabolic and physical activity variables was found (P < 0.05) in the HF group.Conclusions: We demonstrated the safety and efficacy of dTMS, in addition to physical exercise and a hypocaloric diet, in reducing body weight for up to 1 year in obese people. We hypothesize that a possible mechanism of HF dTMS treatment is modulation of the dopaminergic pathway and stimulation of physical activity. K E Y W O R D Sappetite control, obesity therapy, randomised trial, weight control

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Section: Methodsmentioning

confidence: 99%

Section: Randomization and Maskingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Weight loss induced by deep transcranial magnetic stimulation in obesity: A randomized, double‐blind, sham‐controlled study

Ferrulli

Macrì

Terruzzi

et al. 2019

Diabetes Obesity Metabolism

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“…In support of this idea preexisting hyperexcitability of prefrontal and ventral striatum neurons in Tmod2 mutants could actively resist the cocaine-induced depression of these regions, thereby masking the maladaptive behavioral effects of cocaine 104,105 . Interestingly, high frequency (5-20 hz) transcranial magnetic stimulation that increases cortical excitability has been shown to be an effective treatment for cocaine craving [106][107][108] , indicating that cortical excitability in naive Tmod2 KO could interfere and prevent cocaine-induced addiction behavior. Basal and cocaine-induced changes in synaptic properties of accumbens neurons are also distinct from their WT counterparts and support behavioral results.…”

Section: Discussionmentioning

confidence: 99%

Tmod2 is a regulator of cocaine responses through control of striatal and cortical excitability, and drug-induced plasticity

Mitra

Deats

Dickson

et al. 2019

Preprint

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Drugs of abuse induce neuroadaptations, including synaptic plasticity, that are critical for transition to addiction, and genes and pathways that regulate these neuroadaptations are potential therapeutic targets.Tropomodulin 2 (Tmod2) is an actin-regulating gene that plays an important role in synapse maturation and dendritic arborization and has been implicated in substance-abuse and intellectual disability in humans. Here we mine the KOMP2 data and find that Tmod2 knockout mice show emotionality phenotypes that are predictive of addiction. Detailed addiction phenotyping showed that Tmod2 deletion does not affect the acute locomotor response to cocaine administration. However, sensitized locomotor responses are highly attenuated in these knockouts, indicating a potential lack of necessary drug-induced plasticity. In addition, Tmod2 mutant animals do not self-administer cocaine indicating lack of hedonic responses to cocaine. Whole brain MR imaging shows differences in brain volume across multiple regions although transcriptomic experiments did not reveal perturbations in gene co-expression networks.Detailed electrophysiological characterization of Tmod2 KO neurons, showed increased spontaneous firing rate of early postnatal and adult cortical and striatal neurons. Cocaine-induced synaptic plasticity that is critical for sensitization is either missing or reciprocal in Tmod2 KO nucleus accumbens shell medium spiny neurons, providing a mechanistic explanation of the cocaine response phenotypes.Combined, these data provide compelling evidence that Tmod2 is a major regulator of plasticity in the mesolimbic system and regulates the reinforcing and addictive properties of cocaine.

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Repetitive Transcranial Magnetic Stimulation in Addiction

Martinotti

Pettorruso

Montemitro

et al. 2020

Non Invasive Brain Stimulation in Psychiatry and Clinical Neurosciences

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Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex reduces cocaine craving in patients with cocaine use disorder

Cited by 66 publications

References 38 publications

Weight loss induced by deep transcranial magnetic stimulation in obesity: A randomized, double‐blind, sham‐controlled study

Weight loss induced by deep transcranial magnetic stimulation in obesity: A randomized, double‐blind, sham‐controlled study

Tmod2 is a regulator of cocaine responses through control of striatal and cortical excitability, and drug-induced plasticity

Repetitive Transcranial Magnetic Stimulation in Addiction

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