Targeting Neural Endophenotypes of Eating Disorders with Non-invasive Brain Stimulation

Abstract

The term "eating disorders" (ED) encompasses a wide variety of disordered eating and compensatory behaviors, and so the term is associated with considerable clinical and phenotypic heterogeneity. This heterogeneity makes optimizing treatment techniques difficult. One class of treatments is non-invasive brain stimulation (NIBS). NIBS, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), are accessible forms of neuromodulation that alter the cortical excitability of a target brain region. It is crucial for NIBS to be successful that the target is well selected for the patient population in question. Targets may best be selected by stepping back from conventional DSM-5 diagnostic criteria to identify neural substrates of more basic phenotypes, including behavior related to rewards and punishment, cognitive control, and social processes. These phenotypic dimensions have been recently laid out by the Research Domain Criteria (RDoC) initiative. Consequently, this review is intended to identify potential dimensions as outlined by the RDoC and the underlying behavioral and neurobiological targets associated with ED. This review will also identify candidate targets for NIBS based on these dimensions and review the available literature on rTMS and tDCS in ED. This review systematically reviews abnormal neural circuitry in ED within the RDoC framework, and also systematically reviews the available literature investigating NIBS as a treatment for ED.

Keywords: Eating Disorders (ED); RDoC; fMRI; rTMS; tDCS.

Figure 1

Cognitive and behavioral phenotypes by RDoC dimension (Insel et al., 2010) for anorexia nervosa, bulimia nervosa, and binge eating disorder (Schebendach et al., , ; Fernández-Aranda et al., ; Zastrow et al., ; Harrison et al., ; Klein et al., ; Miyake et al., ; Manwaring et al., ; Bohon and Stice, ; Hoffman et al., ; Steinglass et al., ; Chan et al., ; Giel et al., ; Strigo et al., ; Wu et al., ; Glashouwer et al., ; Kullmann et al., ; Mole et al., ; Berg et al., ; Racine et al., ; Tapajóz P de Sampaio et al., 2015). NR, Natural Rewards.

Figure 2

Candidate NIBS targets that address abnormal phenotypes related to the RDoC negative valence dimension. (A) Candidate negative valence NIBS targets for anorexia nervosa (AN) (Ellison et al., ; Frank et al., , ; Seeger et al., ; Uher et al., ; Friederich et al., ; Vocks et al., ; Cowdrey et al., ; Bischoff-Grethe et al., ; Strigo et al., ; Bär et al., 2015). The dorsolateral prefrontal cortex (DL) is abnormally hyperactive for pain anticipation and the receipt of punishment. The anterior cingulate cortex (ACC) is hyperactive for aversive food stimuli, the receipt of punishment, and anxiety. Finally, the anterior insula (IN) is abnormally hyperactive during anxiety and the anticipation of pain. (B) Candidate negative valence NIBS targets for bulimia nervosa (BN) and binge eating disorder (BED). The ACC is abnormally activated for negative words about the body (Miyake et al., 2010), while the insula is hyperactive during negative affect (Bohon and Stice, 2012).

Figure 3

Candidate NIBS targets that address abnormal phenotypes related to the RDoC positive valence dimension. (A) Candidate positive valence NIBS targets for anorexia nervosa (AN) (Wagner et al., , ; Rothemund et al., ; Vocks et al., ; Holsen et al., ; Oberndorfer et al., ; Torresan et al., ; Decker et al., ; Suda et al., ; Ehrlich et al., ; Sanders et al., 2015). The dorsolateral prefrontal cortex (DL) is both hyperactive when the participant views images of food, but hypoactive during symptom, particularly OCD-related, provocation. The anterior cingulate cortex (ACC) is also differentially activated; it is hyperactive when the participant views images of food, but hypoactive when the participant delays a reward. Also, the insula (IN) is hypoactive when the participant views images of food. (B) Candidate positive valence NIBS targets for bulimia nervosa (BN) (Frank et al., , ; Bohon and Stice, ; Broft et al., ; Radeloff et al., ; Weygandt et al., ; Oberndorfer et al., ; Galusca et al., 2014). The ACC is hypoactive during reward anticipation, and this hypoactivity predicts later overeating. The orbitofrontal cortex (OFC) is hyperactive during the receipt of a reward. The IN is both hyperactive during the receipt of a reward, but hypoactive during reward anticipation. (C) Candidate positive valence NIBS targets for binge eating disorder (BED) (Schienle et al., ; Frank et al., ; Weygandt et al., ; Balodis et al., 2013a, 2014). Both the OFC and the IN are abnormally hyperactive during the receipt of a reward, while the inferior frontal gyrus (IFG) is hyperactive during reward anticipation.

Figure 4

Candidate NIBS targets that address abnormal phenotypes related to the RDoC cognitive control dimension. (A) Candidate cognitive control NIBS targets for anorexia nervosa (AN) (Oberndorfer et al., ; Sato et al., ; Garrett et al., ; Wierenga et al., ; Wildes et al., ; Biezonski et al., ; Lao-Kaim et al., 2015). The dorsolateral prefrontal cortex (DL) is both hyperactive during interference control tasks (such as the Stroop task), and for working memory, but hypoactive during cognitive flexibility and set-shifting tasks. The anterior cingulate cortex (ACC) is hypoactive during response inhibition tasks, while the ventrolateral prefrontal cortex (VL) is hypoactive during cognitive flexibility tasks. (B) Candidate cognitive control NIBS targets for bulimia nervosa (BN) (Marsh et al., ; Rossi and Hallett, ; Celone et al., ; Lock et al., 2011). Both the ACC and the DL are hyperactive during response inhibition tasks, but hypoactive during interference control tasks, while both the orbitofrontal cortex (OFC) and inferior frontal gyrus (IFG) are hypoactive during inference control tasks. (C) Candidate cognitive control NIBS targets for binge eating disorder (BED) (Balodis et al., ; Hege et al., 2014). The ventromedial prefrontal cortex (VM), insula (IN), and IFG are abnormally hypoactive during interference control, poor dietary restraint, impulsivity, and response inhibition.

Figure 5

Candidate NIBS targets that address abnormal phenotypes related to the RDoC social processing dimension in anorexia nervosa (AN) (Cowdrey et al., ; Miyake et al., ; Spangler and Allen, ; Castellini et al., ; Fladung et al., ; Suda et al., ; Boehm et al., ; Fonville et al., ; Kerr et al., ; McAdams et al., ; Via et al., 2015). The anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and temporoparietal junction (TPJ) are abnormally hypoactive during deficits in social decision-making and alexithymia, while low insula (IN) activity is related to deficits in interoceptive awareness. The dorsolateral prefrontal cortex (DL) is both abnormally hyperactive when the participant views oversized images of themselves, but hypoactive when viewing images depicting body-checking behavior. The fusiform face area (FFA) is both abnormally hyperactive when the participant views highly emotional facial expressions, but hypoactive when viewing distorted body shapes and images depicting body-checking behavior. The extrastriate body area (EBA) is both abnormally hyperactive when the participant views images of their own body, but hypoactive when those images are distorted.