Brain stimulation for treatment of obesity: will stimulating the prefrontal cortex reduce overeating?

See corresponding article on page 1347.

Altering the function of brain networks implicated in appetitive processes holds tremendous promise for obesity treatment. Transcranial direct stimulation (tDCS) delivers low-level electric currents to the brain to excite or inhibit neuronal populations in targeted regions. Several previous studies have shown reductions in food cravings by delivering excitatory impulses to the dorsolateral prefrontal cortex (DLPFC) in adults (1, 2). Despite this, the influence of stimulating the DLPFC on food consumption has been inconsistent. In this issue of the Journal, Heinitz et al. (3) publish an impressive, well-executed follow-up trial to compare the efficacy of excitatory tDCS of the left DLPFC against sham stimulation on food intake, appetite, and body weight. Although they report some promising results, overall the findings suggest the need to pause and reflect on whether we know enough about the brain’s role in eating behavior to recommend this treatment to patients struggling with compulsive overeating and obesity.

The primary findings reported in Heinitz et al. (3) are that stimulating the neurons in the left DLPFC reduced snack intake and self-reported hunger after an extended 4-wk stimulation period compared with sham treatment. However, no change was reported immediately after 3 sessions of tDCS on 3-d ad libitum intake assessed with a validated vending machine protocol. These results are surprising given that a previous report from this group showed that 3 d of tDCS significantly reduced energy intake from fat and soda, as well as body weight, relative to a group who received the sham treatment (4). Given the potential implications of altering neuronal excitability, there are some important questions to address before moving forward.

First, do we know enough about the relation between the brain and eating behavior to understand the implications of stimulating neurons in a single region? The DLPFC plays a critical role in executive function and self-control. Several studies have shown that obese individuals show lower activation in this region (5, 6), whereas successful dieters show increased activation in this region relative to nondieters (7). Despite these findings, we do not know if low neuronal firing in this region is a cause or consequence of obesity. The reasonable hypothesis made by Heinitz et al. (3) is that stimulating the left DLPFC will enhance dietary self-control and, as a result, reduce overconsumption. However, this assumes that low DLPFC activity is a cause of overeating. Bruce (8) showed that children with obesity have greater (not less) activation in a range of brain regions than do children who are lean, including the prefrontal cortex. In our own studies in children, we also found that greater DLPFC activation was positively correlated with laboratory measures of overconsumption (9). These findings suggest that, among children, activation in the DLPFC may reflect effort to exert self-control rather than successful self-control capabilities. In addition, we do not know whether subjects included in the study by Heinitz et al. (3) actually had reduced activation in the left DLPFC before tDCS. Incorporating measures of fMRI to assess baseline and follow-up brain activation may shed light on whether the treatment is actually altering neuronal activation in the intended region.

Second, do we understand the role of the DLPFC in driving overconsumption? Heinitz et al. (3) found no effect on 3-d ad libitum food intake assessed by a validated vending machine paradigm. The foods included in the vending machine were those that had “intermediate” preference ratings as indicated by a food preference questionnaire. Perhaps including highly palatable, favorite foods might have overwhelmed self-control processes and resulted in overconsumption among both the sham and experimental groups. However, it is possible that DLPFC function may be necessary in the face of highly palatable “treat” foods (i.e., hedonically stimulated consumption) but less critical for typical eating occasions driven by homeostatic needs. Average daily energy intakes among the tDCS and sham groups were 3018 and 3242 kcal, respectively, which suggests that patients were consuming just about their daily energy needs. Under homeostatic conditions, and without the availability of a large variety of favorite, highly palatable foods to stimulate overconsumption, the role of the DLPFC in moderating food intake may be less important. This is perhaps why the authors found that 4 wk of tDCS reduced snack food intake but had no effect on 3-d intake of moderately preferred foods from the vending machines.

Third, the DLPFC has multiple functions, beyond cognitive control and inhibition, and we do not know exactly which functions are influenced by tDCS: for example, the DLPFC serves as a secondary taste cortex (10). Heinitz et al. (3) observed reductions in participants’ perceived saltiness and sweetness of snack foods after 4 wk. Reductions in taste can affect appetite, and therefore it is possible that the changes in perceived hunger and energy intake from snacks were due to changes in taste sensitivity, as opposed to improvements in overall self-control. Including direct measures of inhibitory control in future studies will help to determine whether tDCS directed at the DLPFC improves dietary restraint, or affects eating behavior via other mechanisms. The long-term implications of reducing taste sensitivity on appetite and food intake are not known.

One final consideration with regard to stimulating a single brain region is that we do not understand the implications on the surrounding networks and anatomy. There are anatomic and functional connections between the DLPFC and the orbitofrontal cortex, ventromedial prefrontal cortex thalamus, basal ganglia, and others. Electrically stimulating one of these regions may have downstream effects on activation, and potentially function, of other regions. The implications of this on appetitive processes and related functions, including mood and motivated behavior, require additional investigation.

As we learn more about the role of the brain in eating behavior, there will be additional opportunities to develop treatments that target specific neuronal populations to improve central energy balance regulation and moderate overconsumption. The work by Heinitz et al. (3) is a critically important step toward developing novel and effective treatments for complex conditions such as obesity and compulsive overeating. Although there are still many questions left unanswered, the results suggest potential improvements in eating behavior that may come from this noninvasive treatment.