Table 3.
Research studies assessing the effects of neurostimulation in people with anorexia nervosa.
| Author | N | Sample | Treatment Type | Design | Area | Protocol | Findings | Comments | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Deep brain stimulation | |||||||||||||||||||||||||||||||||||
| Blomstedt et al. [60] | 1 | Adult female with chronic AN and severe MDD | DBS | Single case | Bed nucleus of the stria terminalis (BNST) | Bilateral stimulation of 130 Hz, 120 μs pulse width, and 4.3V (at 12 months post-surgery) to the BNST | Food and eating-related anxiety and obsessive thoughts vanished. Virtually stopped vomiting. Food intake more stable and less prone to large variations. No effect on BMI. Profound improvement in depression nine months post-surgery. | Electrodes were initially implanted in the medial forebrain bundle. Due to side effects, stimulation was turned off. Re-operated on for DBS of the BNST two years after first operation. | |||||||||||||||||||||||||||
| Lipsman et al. [44] |
16 | Adults with enduring AN | DBS | Open-label trial | Subcallosal cingulate | Bilateral stimulation of 130 Hz, 90 μs pulse width and 5-6.5 V (at 12 months post-surgery) to the subcallosal cingulate | Mean BMI increased significantly and, anxiety, depression and affective regulation improved over the 12 months post-surgery. | This study is an extension of Lipsman et al. [42] and Hayes et al. [43]. PET imaging identified significant changes in glucose metabolism in several brain structures implicated in AN at 6 and 12 months follow-ups, compared with baseline. |
|||||||||||||||||||||||||||
| Hayes et al. [43] | 8 | Female adults with treatment-refractory DSM-IV AN | DBS | Open-label trial | Subcallosal cingulate | As in Lipsman et al. [44] | Compared to healthy controls widely distributed differences in SCC connectivity were found in AN patients. | These cases are included in the Lipsman et al. [44] series. The study used diffusion magnetic resonance imaging and deterministic multi-tensor tractography to compare anatomical connectivity and microstructure in SCC-associated white matter tracts. |
|||||||||||||||||||||||||||
| Lipsman et al. [42] |
6 | Female adults with chronic or treatment resistant DSM-IV AN | DBS | Open-label trial | Subcallosal cingulate | As in Lipsman et al. [44] | Included in Lipsman et al. [44] | These cases are included in the Lipsman et al. [44] series. | |||||||||||||||||||||||||||
| Wang et al. [57] | 2 | Female adults with AN | DBS | Case series | Nucleus accumbens | Bilateral stimulation of 135-185 Hz, 120-210 μs pulse width, and 2.5-3.8 V to the nucleus accumbens | Pre-operative BMI: Case 1 –13.3 Case 2 – 12.9 BMI at 1 year post-op: Case 1 – 18 Case 2 – 20.8 |
Patient’s illness duration was 2 and 3 years respectively. Depression, anxiety and obsessive compulsive symptoms reduced significantly from pre-op to 1 year post-op. |
|||||||||||||||||||||||||||
| Author | N | Sample | Treatment Type | Design | Area | Protocol | Findings | Comments | |||||||||||||||||||||||||||
| Deep brain stimulation | |||||||||||||||||||||||||||||||||||
| Wu et al. [47] | 4 | Female adolescents with AN with failure to respond to standard psychiatric treatment programme of at least 12 month | DBS | Open-label trial | Nucleus accumbens | Bilateral stimulation of 180 Hz, 90 μs pulse width and >6 V to the nucleus accumbens | Average increase of 65% body weight from baseline to post-surgery follow-up (mean 38 months). Menstruation restored in all participants following surgery. | Patients had short illness duration (13 to 28 months) and BMIs between 10 to 13.3 kgs/m2 at pre-treatment. Improvements in anxiety and obsessive-compulsive symptoms. No definition is given of the standard psychiatric treatment that patients had previously failed to respond to. |
|||||||||||||||||||||||||||
| Zhang et al. [58] | 6 | Adolescent Patients with restricting type AN (age 13 to 17) | DBS | Case series | Nucleus accumbens | DBS protocol not described | Follow-up data at 1 month post-DBS is available for 4 out of 6 patients. All 4 showed improvements in BMI. No longer term follow-up provided. | Patients had a short illness duration (13-42 months) and BMIs between 11.2 and 13.5 at pre-treatment. All had previous unsuccessful behavioural and medication treatments. The main focus of the study was on PET imaging. Compared to healthy controls AN patients showed baseline hypermetabolism in the frontal lobe, hippocampus, and lentiform nucleus. This decreased after DBS. | |||||||||||||||||||||||||||
| McLaughlin et al. [45] | 1 | AN and Obsessive compulsive disorder | DBS | Single case report | VC/VS Bilateral |
Bilateral stimulation of 120 Hz, 120 μs pulse width and 7.5 V to the VC/VS | Food intake, food variety and body weight were increased. BMI maintained between 18.9 and 19.6 postoperatively. | Symptoms worsened when cathode electrode was added. | |||||||||||||||||||||||||||
| Israel et al. [59] | 1 | Adult female with AN and depression | DBS | Single case report | Subgenual cingulate cortex Bilateral |
Right-sided intermittent stimulation (2 minutes on/1 minute off) at 130 Hz, 5 mA and 91 μs pulse width to the subgenual cingulate cortex |
Remission of ED, no relapse and maintained average BMI of 19.1. Remission from ED persisted despite depressive breakthrough. | - | |||||||||||||||||||||||||||
| Author | N | Sample | Treatment Type | Design | Area | Protocol | Findings | Comments | |||||||||||||||||||||||||||
| Repetitive transcranial magnetic stimulation | |||||||||||||||||||||||||||||||||||
| Schmidt [personal communication; for protocol 63] | 34 | Females with chronic treatment-refractory DSM-5 AN Right handed |
rTMS | Feasibility RCT | Left DLPFC Neuronavigation |
20 × 5 s trains/55 s inter-train interval at 10 Hz = 1000 pulses per session; 110% MT ~20 sessions |
At 3-month follow-up between-group differences of medium effect size were noted in measures of depression, anxiety, and obsessional symptoms, favouring active rTMS. Changes in eating disorder symptoms were less pronounced. | Neurocognitive (e.g. temporal discounting) and neural predictors and correlates of rTMS are also being assessed. | |||||||||||||||||||||||||||
| McClelland et al. [41] [40] | 5 | Females with chronic treatment-refractory DSM-5 AN Right handed |
rTMS | Case series | Left DLPFC Neuronavigation |
20 × 5 s trains/55 s inter-train interval at 10 Hz = 1000 pulses per session; 110% MT ~20 sessions |
Compared to baseline, at post-treatment, participants showed significant improvements in ED and affective symptoms. Further improvements were seen at 6 months post-treatment. | - | |||||||||||||||||||||||||||
| McClelland et al. [62] | 60 | Adults with DSM-5 AN Right handed |
rTMS | RCT Double-blind parallel group Conditions: (i) Real rTMS (ii) Sham rTMS |
Left DLPFC Neuronavigation |
20 × 5 s trains/55 s inter-train interval at 10 Hz = 1000 pulses per session; 110% MT 1 session |
In completers (n=49), core AN symptoms were significantly reduced post-rTMS and at 24-hour follow-up in the real, but not sham, rTMS group. | This study also assessed cognitive (temporal discounting; TD) and biomarkers (salivary cortisol) of rTMS. In relation to TD, there was an interaction trend (p = 0.060): real vs sham rTMS resulted in reduced rates of TD (more reflective choice behaviour). Salivary cortisol concentrations were unchanged by stimulation. |
|||||||||||||||||||||||||||
| Van den Eynde et al. [46] | 10 | Adults with DSM-IV-TR AN Right-handed |
rTMS | Pilot study | Left DLPFC Located using 5 cm anterior method |
20 × 5 s trains/55 s inter-train interval at 10 Hz = 1000 pulses per session; 110% MT 1 session |
In completers (n=9), based on VAS scales, sensations of “feeling fat” and “feeling full”, and “anxiety” decreased between pre- and post-rTMS. No change observed in “urge to restrict” or “urge to eat”. No changes in mood following rTMS. | - | |||||||||||||||||||||||||||
| Author | N | Sample | Treatment Type | Design | Area | Protocol | Findings | Comments | |||||||||||||||||||||||||||
| Repetitive transcranial magnetic stimulation | |||||||||||||||||||||||||||||||||||
| Kamolz et al. [61] |
1 | Adult with AN and depression | rTMS | Case report | Left DLPFC Located using 10-20 EEG system (F3) |
100 x 2 s trains/10 s inter-train interval at 10 Hz = 2000 pulses per session, 110% MT 41 sessions |
Improvements in depression and ED symptoms after 10 sessions, after deterioration further rTMS sessions were given including maintenance sessions (2 p/week). This resulted in continuing improvement of depression and ED symptoms. | - | |||||||||||||||||||||||||||
| Transcranial direct current stimulation | |||||||||||||||||||||||||||||||||||
| Khedr et al. [65] | 7 | Adults (n=1 male) with DSM-IV AN | tDCS | Open-label pilot study Active tDCS: anode left / cathode contralateral arm |
Left DLPFC Located using 6 cm anterior method |
2mA; 20 minutes 10 sessions |
Variable response in participants. Significant improvement compared with baseline in the BDI, EDI and EAT at post session and also at one month post-treatment (n=3). | - | |||||||||||||||||||||||||||
Abbreviations: AN - anorexia nervosa; MDD - major depressive disorder; DBS - deep brain stimulation; BNST - bed nucleus of the stria terminalis; Hz - Hertz; μs - micro seconds; V - volts; BMI - body mass index; PET - positron emission tomography; DSM - Diagnostic and Statistical Manual [74, 75]; SCC - subcallosal cingulate; VC/VS - ventral capsule/ventral striatum; ED - eating disorder; rTMS - repetitive transcranial magnetic stimulation; RCT - randomised controlled trial; DLPFC - dorsolateral prefrontal cortex; s - seconds; Hz - Hertz; MT - motor threshold; TD - temporal discounting; VAS - visual analogue scales; tDCS - transcranial direct current stimulation; mA - milliAmpere; EEG - electroencephalography; BDI - Beck Depression Inventory [76]; EDI - Eating Disorder Inventory [77]; EAT - Eating Attitudes Test [78].