Andre Aleman

Using noninvasive neurostimulation to target frontostriatal brain circuits: Implications for treatment of negative symptoms in schizophrenia 

Noninvasive brain stimulation (NIBS) using electromagnetic fields is increasingly used to treat depression, but is also tested experimentally for schizophrenia. Negative symptoms refer to a reduction in goal-directed behavior and are the most disabling aspect of schizophrenia pathology. Here we report neural effects of such rTMS and the results of a clinical trial of theta-burst repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (dLPFC) to reduce negative symptoms in patients with schizophrenia. The location of stimulation was based on theoretical models of the functional neuroanatomy of goal-directed behavior. We tested iTBS (intermittent theta-burst TMS) over the right DLPC for improving negative symptoms (especially apathy) in patients with schizophrenia. In addition, we investigated the neural effects of a single bout of this brain stimulation in healthy participants by measuring fMRI before and after stimulation. The randomized clinical trial using iTBS (as yet unpublished), did not reveal any significant improvement after real versus sham treatment (both groups improved somewhat). Notwithstanding, we did observe effects on brain activation as measured with fMRI in healthy subjects, in frontostriatal circuits and areas associated with the default-mode network. Methodological aspects of NIBS will be discussued, that may need adaptation to maximize effects. Results of optimized parameters may not only have clinical implications but will also inform neuroanatomical hypotheses. Quantification of neural effects is important to further aid the development of novel treatment strategies.