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 al15 |
| 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 al16 |
| 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 al17 |
| 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 al22 |
| 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 al23 |
| 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 al24 |
| 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 al25 |
| 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 al26 |
| 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 al27 |
| 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 al28 |
| 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 al29 |
| 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 al30 |
| 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 al31 |
| 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 al32 |
| 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 al33 |
| 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 al34 |
| 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 al35 |
| 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 al36 |
| 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 al37 |
| 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 al38 |
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.