Steffen Nestler

The effects of prefrontal cortex transcranial direct current stimulation (tDCS) on food craving and temporal discounting in women with frequent food cravings.

Bulimia nervosa, binge-eating disorder, and some forms of obesity are characterised by compulsive overeating that is often precipitated by food craving. Transcranial direct current stimulation (tDCS) has been used to suppress food cravings, but there is insufficient evidence to support its application in clinical practice. Furthermore, the potential moderating role of impulsivity has not been considered. This study used a randomised within-subjects crossover design to examine whether a 20-minute session of sham-controlled bilateral tDCS to the dorsolateral prefrontal cortex (anode right/cathode left) would transiently modify food cravings and temporal discounting (TD; a measure of choice impulsivity) in 17 healthy women with frequent food cravings. Whether the effects of tDCS on food craving were moderated by individual differences in TD behaviour was also explored. Participants were exposed to food and a film of people eating, and food cravings and TD were assessed before and after active and sham stimulation. Craving for sweet but not savoury foods was reduced following real tDCS. Participants that exhibited more reflective choice behaviour were more susceptible to the anti-craving effects of tDCS than those that displayed more impulsive choice behaviour. No differences were seen in TD or food consumption after real versus sham tDCS. These findings support the efficacy of tDCS in temporarily lowering food cravings and identify the moderating role of TD behaviour.

A Randomised Controlled Trial of Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Anorexia Nervosa.

Background Anorexia nervosa (AN) is associated with morbid fear of fatness, extreme food restriction and altered self-regulation. Neuroimaging data implicate fronto-striatal circuitry, including the dorsolateral prefrontal cortex (DLPFC). Methods In this double-blind parallel group study, we investigated the effects of one session of sham-controlled high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC (l-DLPFC) in 60 individuals with AN. A food exposure task was administered before and after the procedure to elicit AN-related symptoms. Outcomes The primary outcome measure was ‘core AN symptoms’, a variable which combined several subjective AN-related experiences. The effects of rTMS on other measures of psychopathology (e.g. mood), temporal discounting (TD; intertemporal choice behaviour) and on salivary cortisol concentrations were also investigated. Safety, tolerability and acceptability were assessed. Results Fourty-nine participants completed the study. Whilst there were no interaction effects of rTMS on core AN symptoms, there was a trend for group differences (p = 0.056): after controlling for pre-rTMS scores, individuals who received real rTMS had reduced symptoms post-rTMS and at 24-hour follow-up, relative to those who received sham stimulation. Other psychopathology was not altered differentially following real/sham rTMS. In relation to TD, there was an interaction trend (p = 0.060): real versus sham rTMS resulted in reduced rates of TD (more reflective choice behaviour). Salivary cortisol concentrations were unchanged by stimulation. rTMS was safe, well–tolerated and was considered an acceptable intervention. Conclusions This study provides modest evidence that rTMS to the l-DLPFC transiently reduces core symptoms of AN and encourages prudent decision making. Importantly, individuals with AN considered rTMS to be a viable treatment option. These findings require replication in multiple-session studies to evaluate therapeutic efficacy. Trial Registration www.Controlled-Trials.com ISRCTN22851337

Improvements in Symptoms Following Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Severe and Enduring Anorexia Nervosa: Findings from two Case Studies

BACKGROUND Advances in the treatment of anorexia nervosa (AN) are most likely to arise from targeted, brain-directed treatments, such as repetitive transcranial magnetic stimulation (rTMS). We describe findings from two individuals with treatment-resistant AN who received 19-20 sessions of neuronavigated, high frequency rTMS, applied to the left dorsolateral prefrontal cortex. METHOD Within-session measures assessed changes pre-rTMS, post-rTMS in subjective eating disorder (ED) experiences. Weight, ED symptoms and mood were assessed pre-treatment, post-treatment and at 1 month follow-up. RESULTS In both cases, there was improvement in ED symptomatology and mood after 19-20 sessions of neuronavigated rTMS, and these changes persisted or continued to improve at follow-up. Within sessions, Patient A demonstrated a consistent reduction in subjective ED experiences, and Patient B a reduction in some ED related experiences. CONCLUSIONS These findings suggest that rTMS has potential as an adjunct to the treatment of AN and deserves further study.

A structural MRI study of cortical thickness in depersonalisation disorder

Depersonalisation disorder (DPD) is characterised by a sense of unreality about the self and the world. Research suggests altered autonomic responsivity and dysfunction in prefrontal and temporal lobe areas in this condition. We report the first structural magnetic resonance imaging study of 20 patients with DPD and 21 controls using the FreeSurfer analysis tool employing both region-of-interest and vertex-based methods. DPD patients showed significantly lower cortical thickness in the right middle temporal region according to both methods of analysis. The vertex-based method revealed additional differences in bilateral temporal lobes, inferior frontal regions, the right posterior cingulate, and increased thickness in the right gyrus rectus and left precuneus. Clinical severity scores were negatively correlated with cortical thickness in middle and right inferior frontal regions. In sum, grey matter changes in the frontal, temporal, and parietal lobes are associated with DPD. Further research is required to specify the functional significance of the findings and whether they are vulnerability or disease markers.

Symptom Profiles in Depersonalization and Anxiety Disorders: An Analysis of the Beck Anxiety Inventory

Background: Depersonalization disorder (DPD) entails distressing alterations in self-experiencing. However, it has long been recognized that depersonalisation symptoms occur in other disorders, particularly anxiety and panic. One strand of research proposes that depersonalization phenomenology arises through altered autonomic arousal in response to stress. Sampling and Methods: We sought to examine profiles of anxiety symptoms through a secondary data analysis of individual items and factor subscales on the Beck Anxiety Inventory (BAI), comparing two relatively large patient samples with DPD or with a variety of anxiety conditions, respectively. The DPD sample (n = 106) had a lower overall BAI score than the combined anxiety disorders group (n = 525). Results: After controlling for this as well as for potential confounders such as age and gender, the DPD group presented significantly lower scores on the panic subscale, marginally lower scores on the autonomic subscale and significantly higher scores on the neurophysiological subscale of the BAI. Conclusions: These differences imply similarities between the cognitive components of DPD and anxiety disorders while physiological experiences diverge. The findings encourage future research looking at direct physiological measures and longitudinal designs to confirm the mechanisms underlying different clinical manifestations of anxiety.

Improvements in Symptoms Following Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Severe and Enduring Anorexia Nervosa

BACKGROUND Advances in the treatment of anorexia nervosa (AN) are most likely to arise from targeted, brain-directed treatments, such as repetitive transcranial magnetic stimulation (rTMS). We describe findings from two individuals with treatment-resistant AN who received 19-20 sessions of neuronavigated, high frequency rTMS, applied to the left dorsolateral prefrontal cortex. METHOD Within-session measures assessed changes pre-rTMS, post-rTMS in subjective eating disorder (ED) experiences. Weight, ED symptoms and mood were assessed pre-treatment, post-treatment and at 1 month follow-up. RESULTS In both cases, there was improvement in ED symptomatology and mood after 19-20 sessions of neuronavigated rTMS, and these changes persisted or continued to improve at follow-up. Within sessions, Patient A demonstrated a consistent reduction in subjective ED experiences, and Patient B a reduction in some ED related experiences. CONCLUSIONS These findings suggest that rTMS has potential as an adjunct to the treatment of AN and deserves further study.

Ventrolateral prefrontal cortex repetitive transcranial magnetic stimulation in the treatment of depersonalization disorder: A consecutive case series

Case reports and an open trial have reported promising responses to repetitive transcranial magnetic stimulation (rTMS) to prefrontal and temporo-parietal sites in patients with depersonalization disorder (DPD). We recently showed that a single session of rTMS to the ventrolateral prefrontal cortex (VLPFC) was associated with a reduction in symptoms and increase in physiological arousal. Seven patients with medication-resistant DSM-IV DPD received up to 20 sessions of right-sided rTMS to the VLPFC for 10 weeks. Stimulation was guided using neuronavigation software based on participants’ individual structural MRIs, and delivered at 110% of resting motor threshold. A session consisted of 1 Hz repetitive TMS for 15 min. The primary outcome measure was reduction in depersonalization symptoms on the Cambridge Depersonalization Scale (CDS). Secondary outcomes included scores on the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). 20 sessions of rTMS treatment to right VLPFC significantly reduced scores on the CDS by on average 44% (range 2–83.5%). Two patients could be classified as “full responders”, four as “partial” and one a non-responder. Response usually occurred within the first 6 sessions. There were no significant adverse events. A randomized controlled clinical trial of VLPFC rTMS for DPD is warranted.

Improvements in Symptoms Following Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Severe and Enduring Anorexia Nervosa: Findings from two Case Studies: Improvements in symptoms of severe and enduring anorexia with rTMS

BACKGROUND Advances in the treatment of anorexia nervosa (AN) are most likely to arise from targeted, brain-directed treatments, such as repetitive transcranial magnetic stimulation (rTMS). We describe findings from two individuals with treatment-resistant AN who received 19-20 sessions of neuronavigated, high frequency rTMS, applied to the left dorsolateral prefrontal cortex. METHOD Within-session measures assessed changes pre-rTMS, post-rTMS in subjective eating disorder (ED) experiences. Weight, ED symptoms and mood were assessed pre-treatment, post-treatment and at 1 month follow-up. RESULTS In both cases, there was improvement in ED symptomatology and mood after 19-20 sessions of neuronavigated rTMS, and these changes persisted or continued to improve at follow-up. Within sessions, Patient A demonstrated a consistent reduction in subjective ED experiences, and Patient B a reduction in some ED related experiences. CONCLUSIONS These findings suggest that rTMS has potential as an adjunct to the treatment of AN and deserves further study.