Studying and modifying brain function with non-invasive brain stimulation

Electromagnetic-based methods of stimulating brain activity require invasive procedures or have other limitations. Deep-brain stimulation requires surgically implanted electrodes. Transcranial magnetic stimulation does not require surgery, but suffers from low spatial resolution. Optogenetic-based approaches have unrivaled spatial precision, but require genetic manipulation. In search of a potential solution to these limitations, we began investigating the influence of transcranial pulsed ultrasound on neuronal activity in the intact mouse brain. In motor cortex, ultrasound-stimulated neuronal activity was sufficient to evoke motor behaviors. Deeper in subcortical circuits, we used targeted transcranial ultrasound to stimulate neuronal activity and synchronous oscillations in the intact hippocampus. We found that ultrasound triggers TTX-sensitive neuronal activity in the absence of a rise in brain temperature (<0.01 degrees C). Here, we also report that transcranial pulsed ultrasound for intact brain circuit stimulation has a lateral spatial resolution of approximately 2 mm and does not require exogenous factors or surgical invasion. Copyright 2010 Elsevier Inc. All rights reserved.

Brain rhythms regulate information processing in different states to enable learning and memory formation. The <1 Hz sleep slow oscillation hallmarks slow-wave sleep and is critical to memory consolidation. Here we show in sleeping humans that auditory stimulation in phase with the ongoing rhythmic occurrence of slow oscillation up states profoundly enhances the slow oscillation rhythm, phase-coupled spindle activity, and, consequently, the consolidation of declarative memory. Stimulation out of phase with the ongoing slow oscillation rhythm remained ineffective. Closed-loop in-phase stimulation provides a straight-forward tool to enhance sleep rhythms and their functional efficacy. Copyright © 2013 Elsevier Inc. All rights reserved.

Cortical excitability changes induced by tDCS and revealed by TMS, are increasingly being used as an index of neuronal plasticity in the human cortex. The aim of this paper is to summarize the partially adverse effects of 567 tDCS sessions over motor and non-motor cortical areas (occipital, temporal, parietal) from the last 2 years, on work performed in our laboratories. One-hundred and two of our subjects who participated in our tDCS studies completed a questionnaire. The questionnaire contained rating scales regarding the presence and severity of headache, difficulties in concentrating, acute mood changes, visual perceptual changes and any discomforting sensation like pain, tingling, itching or burning under the electrodes, during and after tDCS. Participants were healthy subjects (75.5%), migraine patients (8.8%), post-stroke patients (5.9%) and tinnitus patients (9.8%). During tDCS a mild tingling sensation was the most common reported adverse effect (70.6%), moderate fatigue was felt by 35.3% of the subjects, whereas a light itching sensation under the stimulation electrodes occurred in 30.4% of cases. After tDCS headache (11.8%), nausea (2.9%) and insomnia (0.98%) were reported, but fairly infrequently. In addition, the incidence of the itching sensation (p=0.02) and the intensity of tingling sensation (p=0.02) were significantly higher during tDCS in the group of the healthy subjects, in comparison to patients; whereas the occurrence of headache was significantly higher in the patient group (p=0.03) after the stimulation. Our results suggest that tDCS applied to motor and non-motor areas according to the present tDCS safety guidelines, is associated with relatively minor adverse effects in healthy humans and patients with varying neurological disorders.