Neuromodulation in eating disorders and obesity: a promising way of treatment?

Figures & data

Table 1 Summary of important studies on neuromodulation in eating disorders and obesity

Age (years)	Population	Sample size	Number of participants in each group	Gender	Comorbidity	Type of intervention	Length of intervention period	Measures	Outcomes	Year	Authors
35–36	Refractory AN	16	8 AN; 8 age- and sex-matched HC	Females	MDD, anxiety, PTSD, OCD, others	DBS of the SCC	Changes in psychometric assessments between 0 and 12 months	dMRI and DMTT; several psychometric assessments: HAMD, BDI, BAI, YBOCS, YBC-EDS, QOL Symptoms of anxiety and depression, QOL, obsessive-compulsive symptoms and ED symptoms	Higher (eg, left parieto-occipital cortices) and lower (eg, thalamus) connectivity in those with AN compared to controls. Correlations between dMRI metrics and clinical assessments. Decreases in fractional anisotropy and alterations in axial and radial diffusivities, in the left fornix crus, ALIC, right anterior cingulum, and left inferior fronto-occipital fasciculus. Correlations between dMRI metrics and clinical assessments, such as low presurgical left fornixand right ALIC fractional anisotropy being related to post-DBS improvementsin QOL and depressive symptoms, respectively.	2015	Hayes et al^Citation15
18–35	BN	14	7 real group (rTMS); 7 sham group	Females	No (HDRS >18 were excluded)	rTMS to the left DLPFC	15 sessions (10 second trains/ 60 second intertrain intervals)	Change in binges and purges, HDRS, BDI, YBOCS	The average number of binges per day declined significantly between baseline and the end of treatment in the two groups. There was no significant difference between sham and active stimulation in terms of purge behavior, BDI, HDRS, and YBOCS over time.	2008	Walpoth et al^Citation16
19–55	Frequent food craving	17	All participants received 1 real or sham tDCS	Females	No	tDCS to the left/right DLPFC	One 20-minute real/sham tDCS session to the right (anode) and left (cathode) DLPFC	FCT, FCQ-S, salivary cortisol, TD task, free-eating task	Craving for sweet but not savory foods was reduced following real tDCS. No differences were seen in TD or food consumption after real vs sham tDCS. Efficacy of tDCS in temporarily lowering food cravings and identification of the moderating role of TD behavior.	2014	Kekic et al^Citation17
20–60	Refractory AN	6	6 AN; no HC/ CG	Females	PTSD, anxiety, depression, OCD, SUD	DBS of the SCC	Patients were followed up for 9 months after DBS activation	BMI, psychometric (HAMD, BD I, BAI, YBOCS, YBC-EDS, QOL), and neuroimaging (MR I, PET)	Three patients achieved and maintained a BMI greater than their historical baselines. Improvements in mood, anxiety, affective regulation, and AN-related obsessions and compulsions in four patients. Improvements in QOL in three patients after6 months of stimulation.	2013	Lipsman et al^Citation22
45–60	Intractable obesity	3	3 obese patients; no HC/ CG	2 females, 1 male	No psychiatric disorders	DBS of bilateral LHA	Patients were followed up for 30–39 months after DBS	MBMD, GBES, CRS, BSQ, IWQL-LQ	Across a wide spectrum of psychological and eating/ weight-related measures, LHA DBS did not appear to create negative effects in this small patient population.	2013	Whiting et al^Citation23
18–60	Obesity	9	5 real group (tDCS); 4 sham group	6 females, 3 males	No psychiatric disorders	tDCS to the left DLPFC	Study 1: cathodal/ sham DCS (3 sessions); Study 2: anodal/ sham DCS (3 sessions)	Kcal/d, Kcal from soda and fat, % weight loss	Participants tended to consume fewer kcal/d, significantly fewer kcal from soda and fat and had a greater % weight loss during anodal vs cathodal tDCS.	2015	Gluck et al^Citation24
18–43	Obesity	25	All participants received three sessions of tDCS: 1) anodal; 2) cathodal; 3) sham	Females	No	tDCS to the left DLPFC/ contralateral frontal operculum	1 session anodal, 1 session cathodal, 1 session sham tDCS	BDI, EDE-Q, TEF-Q, BIS-15, IWQl-LQ, ATQ, several VAS	No effects of anodal or cathodal tDCS, neither on the ability to modulate the desire for visually presented foods nor on calorie consumption were confirmed.	2017	Grundeis et al^Citation25
18 or over	BN	39	All participants received three sessions of tDCS: 1) AR/ CL; 2) AL/CR; and 3) sham	37 females, 2 males	No data about specific diagnostics	tDCS to the left/right DLPFC	3 sessions AR/ CL-AL/CR or sham DCS	DASS-21, TD task, POMS, PANAS, FCT, VAS (urge to binge-eat), MEDCQ-R, blood pressure, pulse	AR/CL tDCS reduced ED cognitions when compared to AL/CR and sham tDCS. Both active conditions suppressed the self-reported urge to binge-eat and increased self-regulatory control during a TD task. Mood improved after AR/CL but not after AL/CR tDCS.	2017	Kekic et al^Citation26
Mean 23.7	Frequent food craving	21	1 real or sham tDCS	Females and males	No	tDCS to the left/right DLPFC	1 session AR/ CL, AL-CR, or sham DCS (48-hour intersession interval)	VAS, eye tracking, craving after craving-cues exposure (movies and food exposure)	Craving for viewed foods was reduced by AR/ CL tDCS. After sham stimulation, exposure to real food or food-related movie increased craving, whereas after AL/CR tDCS, the food-related stimuli did not increase craving levels.	2008	Fregni et al^Citation27
18 or over	Normal/ overweight, food craving	27	13 active tDCS, 14 sham tDCS	8 females, 19 males	No	tDCS to the left/right DLPFC	5 real tDCS sessions; 1 real+4 sham sessions. Anode-right, cathode-left DLPFC	CESD-R, FCQ (T/S), FCI	Single session of tDCS has immediate effects in reducing food craving. They also show that repeated tDCS over the right DLPFC may increase the duration of its effects, which may be present 30 days after the stimulation.	2016	Ljubisavljevic et al^Citation28
18–44	AN	10	10 AN; no HC/ CG	Females	No data about specific diagnostics	rTMS to the left DLPFC	20 rTMS trains (5 second trains/ 55 second intertrain intervals)	VAS, FCT, salivary cortisol, blood pressure, heart rate	Compared to pre-rTMS, post-rTMS sensations of “feeling fat” and “feeling full” were decreased. There was also a significant decrease in “anxiety”. There were no changes in mood, tension, or hunger. FCT resulted in an increase in the “urge to restrict” and the sensation of “feeling full”.	2013	van den Eynde et al^Citation29
18 or over	AN	44	22 real group (rTMS); 22 sham group	Females and males	No data about specific diagnostics	rTMS to the left DLPFC	20 rTMS trains (5 second trains/ 55 second intertrain intervals)	BMI, psychometric, neuropsychological, neuroimaging (structural MRI, fMRI, arterial spin labeling)	Study protocol for a randomized controlled feasibility trial; This study provides a foundation for the development of future large-scale RCTs.	2015	Bartholdy et al^Citation30
25–27	AN	49	21 real group (rTMS); 28 sham group	Females	No data about specific diagnostics	rTMS to the left DLPFC	20 rTMS trains (5 second trains/ 55 second intertrain intervals)	FCT, TD task, VAS, salivary cortisol, EDE-Q, blood pressure, heart rate	No interaction effects of rTMS on core AN symptoms; individuals who received real rTMS had reduced symptoms post-rTMS and after 24-hour follow-up, relative to those who received sham stimulation. Other psychopathology was not altered differentially following real/sham rTMS. Real vs sham rTMS resulted in reduced rates of TD (more reflective choice behavior). Salivary cortisol concentrations were unchanged by stimulation.	2016	McClelland et al^Citation31
19–40	BN	47	23 real group (rTMS); 24 sham group	Females	Depression, anxiety, SUD	rTMS targeting the DLPFC	10 rTMS sessions	EDI dimensions, number of binge episodes	No significant improvement in binging and purging symptoms was noted after the program. 10 sessions of high-frequency rTMSto the left DLPFC provide no greater benefit than placebo.	2016	Gay et al^Citation32
18–60	BN, EDNOS	38	17 real group (rTMS); 20 sham group (1 dropped out)	Females and males	9 were taking antidepressants	TMS to the left DLPFC	1 single session (5 second trains/ 55 second intertrain intervals)	HADS, FCQ-T, VAS (urge to eat, hunger, tension, mood, urge to binge eat)	Compared with sham control, real rTMS was associated with decreased self-reported urge to eat and fewer binge-eating episodes over the 24 hours following stimulation.	2010	van den Eynde et al^Citation33
N/A	BN, EDNOS	38	18 real group (rTMS); 20 sham group	Females and males	No data about specific diagnostics	rTMS to the left DLPFC	1 single session (5 second trains/ 55 second intertrain intervals)	Blood pressure, heart rate	There were no significant differences between groups in systolic or diastolic blood pressure or heart rate. There was no significant effect of time on any of these measures. Cardiac vital signs are not affected by the administration of rTMS in people with bulimic disorders.	2011	van den Eynde et al^Citation34
Mean 29	BN, EDNOS	33	A single session of real or sham rTMS	28 females, 5 males	9 were taking antidepressants	TMS to the left DLPFC	1 session of TMS (real/ sham), 5 second trains/55 second intertrain intervals	EDE-Q, HADS, FCQ (T/S), Stroop color word task	Selective attention is unaffected by a single session of rTMS.	2011	van den Eynde et al^Citation35
28–29	BN, EDNOS	22	11 real group (rTMS); 11 sham group	Females	6 were taking antidepressants	rTMS to the left DLPFC	20 rTMS trains (5 second trains/ 55 second intertrain intervals)	HADS, FCQ (T/S), salivary cortisol, VAS (urge to eat)	Salivary cortisol concentrations following real rTMS were significantly lower compared with those following sham rTMS. There was also a trend for real rTMS to reduce food craving more than sham rTMS.	2011	Claudino et al^Citation36
40	ED	14	6 AN, 5 BN, 3 EDNOS; no HC/CG	Females	PTSD (all), anxiety, depression, others	rTMS targeting the DMPFC	20 sessions extended to 30 sessions in treatment responders	PTSD checklist-Civilian, DERS	PCL-C scores were reduced by 51.99%– 627.24% overall; DERS scores improved by 36.02%–624.24% overall.	2017	Woodside et al^Citation37
18–55	Obesity with BED	90	60 obese (real/ sham) with BED, 30 CG (15 obese, 15 normal weight)	Females	No data about specific diagnostics	rTMS to the left DLPFC	20 sessions of neuronavigated rTMS	FCQ-T, BES, TEF-Q, LOCES, UPPS Impulsive Behavior Scale, BSQ, food diary, 12-item Short Form Health Survey (SF-12), BMI, blood test, MRI, fMRI, FCT	This study is a protocol for a double-blinded, randomized, sham-controlled trial.	2015	Maranhão et al^Citation38

Abbreviations: AN, anorexia nervosa; AL/CR, anode left/cathode right; ALIC, anterior limb of the internal capsule; AR/CL, anode right/cathode left; ATQ, adult temperament questionnaire; BAI, Beck anxiety inventory; BDI, Beck depression inventory; BES, binge eating scale; BIS-15, 15-item Barrat impulsiveness scale; BMI, body mass index; BN, bulimia nervosa; BSQ, body shape questionnaire; CESD-R, center for epidemiologic studies depression scale-revised; CG, control group; CRS, cognitive restraint subscale; DASS-21, 21-item depression anxiety stress scale; DBS, deep brain stimulation; DCS, direct current stimulation; DERS, difficulties in emotional regulation scale; DMTT, deterministic multitensor tractography; DLPFC, dorsolateral prefrontal cortex; dMRI, diffusion magnetic resonance imaging; DMPFC, dorsomedial prefrontal cortex; ED, eating disorder; EDE-Q, eating disorder examination questionnaire; FCI, food craving inventory; FCQ-S, food craving questionnaire-state; FCQ-T, food craving questionnaire-trait; FCQ (T/S), food craving questionnaire (trait/state); FCT, food challenge task; GBES, Gormally binge eating scale; HADS, hospital anxiety and depression scale; HAMD, Hamilton depression inventory; HC, healthy control; HDRS, Hamilton depression rating scale; IWQL-LQ, impact of weight on quality of life-Lite questionnaire; LHA, lateral hypothalamic area; LOCES, loss of control over eating scale; MBMD, millon behavioral medicine diagnostic; MRI, magnetic resonance imaging; PANAS, positive and negative affect schedule; PCL-C, PTSD Checklist-Civilian; PET, positron emission tomography; POMS, profile of mood states; PTSD, posttraumatic stress disorder; QOL, quality of life; RCTs, randomized control trials; rTMS, repetitive transcranial magnetic stimulation; SCC, subcallosal cingulate cortex; SUD, substance use disorder; tDCS, transcranial direct current stimulation; TD, temporal discounting; TFE-Q, three factor eating questionnaire; TMS, transcranial magnetic stimulation; YBC-EDS, Yale-Brown-Cornell eating disorder scale; YBOCS, Yale-Brown obsessive-compulsive scale; MDD, major depressive disorder; OCD, obssesive-compulsive disorder; EDI, eating disorder inventory; UPPS, urgency, premeditation, perseverance, sensation seeking; EDNOS, eating disorders not otherwise specified; VAS, visual analogue scale; BED, binge eating disorder; N/A, not available.

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