Manifesto for an ECNP Neuromodulation Thematic Working Group (TWG): Non-invasive brain stimulation as a new Super-subspecialty.

Non-Invasive Brain Stimulation (NIBS) techniques and in particular, repetitive Transcranial Magnetic Stimulation (rTMS), are developing beyond mere clinical application. Although originally purposed for the treatment of resistant neuropsychiatric disorders, NIBS is also contributing to a deeper understanding of psychiatric disorders. rTMS is also changing the model of the disorder itself, from "mental" to one of neural connectivity. TMS allows the assessment of brain circuit excitability and eventually, of plastic changes affecting these circuits. While a clinical translational approach is, at the present time, the most adequate to meet the dimensional-circuit base model of the disorder, it refines the standard categorical classification of psychiatric disorders. The discovery of the fundamental importance of the balance between neuroplasticity and inflammation is also now explored through neuro-modulation findings consistently with the evidence of anti-inflammatory actions of the magnetic pulses. rTMS may activate, inhibit, or otherwise interfere with the activity of neuronal cortical networks, depending on stimulus frequency and intensity of brain-induced electric field. Of particular interest, yet still unclear, is how the relatively unspecific nature of TMS stimulation may lead to specific neuronal reorganization, as well as a definition of the TMS-triggered reorganization of functional brain modules, raising attention on the importance of the active participation of the patient to the treatment.. Configuration and state of consciousness of the subject have made subjective experience under treatment regain importance in the neuro-scientific Psychiatry based on the requirement of United States National Institute of Health (NIH) and the substantial importance of the consciousness state in the efficacy of the TMS treatment. By focusing on the subjective experience, a renaissance of the phenomenology offers Psychiatry an opportunity to become proficient and to distinguish itself from other disciplines. For all these reasons, TMS should be included in the cluster of the sub-specialties as a new "Super-Specialty" and an appropriate training course has to be inaugurated. Psychiatrists are nowadays multi-specialists, moving from a specialty to another, vs super-specialist. The cultivation of a properly trained cohort of TMS psychiatrists will better meet the challenges of treatment-resistant psychiatric conditions (disorders of connectivity), through appropriate and ethical practice, meanwhile facilitating an informed development and integration of additional emerging neuro-modulation techniques. The aim of this consensus paper is to underline the interdisciplinary nature of NIBS, that also encompasses the subjective experience and to point out the necessity of a neuroscience-applied approach to NIBS in the context of the European College of Neuro-psychopharmacology (ECNP).

Chemogenetic Activation of Midbrain Dopamine Neurons Affects Attention, but not Impulsivity, in the Five-Choice Serial Reaction Time Task in Rats.

Attentional impairments and exaggerated impulsivity are key features of psychiatric disorders, such as attention-deficit/hyperactivity disorder, schizophrenia, and addiction. These deficits in attentional performance and impulsive behaviors have been associated with aberrant dopamine (DA) signaling, but it remains unknown whether these deficits result from enhanced DA neuronal activity in the midbrain. Here, we took a novel approach by testing the impact of chemogenetically activating DA neurons in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNc) on attention and impulsivity in the five-choice serial reaction time task (5-CSRTT) in rats. We found that activation of DA neurons in both the VTA and SNc impaired attention by increasing trial omissions. In addition, SNc DA neuron activation decreased attentional accuracy. Surprisingly, enhanced DA neuron activity did not affect impulsive action in this task. These results show that enhanced midbrain DA neuronal activity induces deficits in attentional performance, but not impulsivity. Furthermore, DA neurons in the VTA and SNc have different roles in regulating attention. These findings contribute to our understanding of the neural substrates underlying attention deficits and impulsivity, and provide valuable insights to improve treatment of these symptoms.

Developmental differences in the brain response to unhealthy food cues: an fMRI study of children and adults.

BACKGROUND: Food cues are omnipresent and may trigger overconsumption. In the past 2 decades, the prevalence of childhood obesity has increased dramatically. Because children's brains are still developing, especially in areas important for inhibition, children may be more susceptible than adults to tempting food cues. OBJECTIVE: We examined potential developmental differences in children's and adults' responses to food cues to determine how these responses relate to weight status. DESIGN: We included 27 children aged 10-12 y and 32 adults aged 32-52 y. Functional magnetic resonance imaging data were acquired during a food-viewing task in which unhealthy and healthy food pictures were presented. RESULTS: Children had a stronger activation in the left precentral gyrus than did adults in response to unhealthy compared with healthy foods. In children, unhealthy foods elicited stronger activation in the right inferior temporal and middle occipital gyri, left precentral gyrus, bilateral opercular part of the inferior frontal gyrus, left hippocampus, and left middle frontal gyrus. Adults had stronger activation in the bilateral middle occipital gyrus and the right calcarine sulcus for unhealthy compared with healthy foods. Children with a higher body mass index (BMI) had lower activation in the bilateral dorsolateral prefrontal cortex while viewing unhealthy compared with healthy foods. In adults there was no correlation between BMI and neural response to unhealthy compared with healthy foods. CONCLUSIONS: Unhealthy foods might elicit more attention both in children and in adults. Children had stronger activation while viewing unhealthy compared with healthy foods in areas involved in reward, motivation, and memory. Furthermore, children activated a motivation and reward area located in the motor cortex more strongly than did adults in response to unhealthy foods. Finally, children with a higher BMI had less activation in inhibitory areas in response to unhealthy foods, which may mean they are more susceptible to tempting food cues. This trial was registered at www.trialregister.nl as NTR4255.

Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference.

BACKGROUND: New genetic loci, most of which are expressed in the brain, have recently been reported to contribute to the development of obesity. The brain, especially the hypothalamus, is strongly involved in regulating weight and food intake. OBJECTIVES: We investigated whether the recently reported obesity loci are associated with measures of abdominal adiposity and whether these variants affect dietary energy or macronutrient intake. DESIGN: We studied 1700 female Dutch participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Their anthropometric measurements and intake of macronutrients were available. Genotyping was performed by using KASPar chemistry. A linear regression model, with an assumption of an additive effect, was used to analyze the association between genotypes of 12 single nucleotide polymorphisms (SNPs) and adiposity measures and dietary intake. RESULTS: Seven SNPs were associated (P < 0.05) with weight, body mass index (BMI), and waist circumference (unadjusted for BMI). They were in or near to 6 loci: FTO, MC4R, KCTD15, MTCH2, NEGR1, and BDNF. Five SNPs were associated with dietary intake (P < 0.05) and were in or near 5 loci: SH2B1 (particularly with increased fat), KCTD15 (particularly with carbohydrate intake), MTCH2, NEGR1, and BDNF. CONCLUSIONS: We confirmed some of the findings for the newly identified obesity loci that are associated with general adiposity in a healthy Dutch female population. Our results suggest that these loci are not specifically associated with abdominal adiposity but more generally with obesity. We also found that some of the SNPs were associated with macronutrient-specific food intake.