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Yoo, Seung-Schik

Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer’s intention to stimulate a rat’s brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer’s intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications.

This study investigates the spatial profile and the temporal latency of the brain stimulation induced by the transcranial application of pulsed focused ultrasound (FUS). The site of neuromodulation was detected using 2-deoxy-2-[18F]fluoro-d-glucose PET immediately after FUS sonication on the unilateral thalamic area of Sprague–Dawley rats. The latency of the stimulation was estimated by measuring the time taken from the onset of the stimulation of the appropriate brain motor area to the corresponding tail motor response. The brain area showing elevated glucose uptake from the PET image was much smaller (56±10% in diameter, 24±6% in length) than the size of the acoustic focus, which is conventionally defined by the full-width at half-maximum of the acoustic intensity field. The spatial dimension of the FUS-mediated neuromodulatory area was more localized, approximated to be full-width at 90%-maximum of the acoustic intensity field. In addition, the time delay of motor responses elicited by the FUS sonication was 171±63 (SD) ms from the onset of sonication. When compared with latencies of other nonultrasonic neurostimulation techniques, the longer time delay associated with FUS-mediated motor responses is suggestive of the nonelectrical modes of neuromodulation, making it a distinctive brain stimulation method.

Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.

Objective: Previous research has noted functional and structural temporal lobe abnormalities in schizophrenia that relate to symptoms such as auditory hallucinations and thought disorder. The goal of the study was to determine whether the functional abnormalities are present in schizophrenia at early stages of auditory processing. Method: Functional magnetic resonance imaging activity was examined during the presentation of the mismatch stimuli, which are deviant tones embedded in a series of standard tones. The mismatch stimuli are used to elicit the mismatch negativity, an early auditory event-related potential. Ten patients with schizophrenia and 10 comparison subjects were presented the mismatch stimuli condition and a control condition in which only one tone was presented repeatedly. Results: The superior temporal gyrus showed the most prevalent and consistent activation. The superior temporal gyrus showed less activation in the schizophrenic subjects than in the comparison subjects only during the mismatch stimuli condition. Conclusions: This result is consistent with those of mismatch negativity event-related potential studies and suggests that early auditory processing is abnormal in chronic schizophrenia.

Background: One of the cardinal features of schizotypal personality disorder (SPD) is language abnormalities. The focus of this study was to determine whether or not there are also processing abnormalities of pure tones differing in pitch and duration in SPD. Methods: Thirteen neuroleptic-naïve male subjects met full criteria for SPD and were group-matched on age and parental socioeconomic status to 13 comparison subjects. Verbal learning was measured with the California Verbal Learning Test. Heschl’s gyrus volumes were measured using structural MRI. Whole-brain fMRI activation patterns in an auditory task of listening to tones including pitch and duration deviants were compared between SPD and control subjects. In a second and separate ROI analysis we found that peak activation in superior temporal gyrus (STG), Brodmann Areas 41 and 42, was correlated with verbal learning and clinical measures derived from the SCID-II interview. Results: In the region of the STG, SPD subjects demonstrated more activation to pitch deviants bilaterally (p<0.001); and to duration deviants in the left hemisphere (p=0.005) (two-sample t). SPD subjects also showed more bilateral parietal cortex activation to duration deviants. In no region did comparison subjects activate more than SPD subjects in either experiment. Exploratory correlations for SPD subjects suggest a relationship between peak activation on the right for deviant tones in the pitch experiment with odd speech and impaired verbal learning. There was no difference between groups on Heschl’s gyrus volume. Conclusions: These data suggest that SPD subjects have inefficient or hyper-responsive processing of pure tones both in terms of pitch and duration deviance that is not attributable to smaller Heschl’s gyrus volumes. Finally, these auditory processing abnormalities may have significance for the odd speech heard in some SPD subjects and downstream language and verbal learning deficits.

We present non-invasive means that detect unilateral hand motor brain activity from one individual and subsequently stimulate the somatosensory area of another individual, thus, enabling the remote hemispheric link between each brain hemisphere in humans. Healthy participants were paired as a sender and a receiver. A sender performed a motor imagery task of either right or left hand, and associated changes in the electroencephalogram (EEG) mu rhythm (8–10 Hz) originating from either hemisphere were programmed to move a computer cursor to a target that appeared in either left or right of the computer screen. When the cursor reaches its target, the outcome was transmitted to another computer over the internet, and actuated the focused ultrasound (FUS) devices that selectively and non-invasively stimulated either the right or left hand somatosensory area of the receiver. Small FUS transducers effectively allowed for the independent administration of stimulatory ultrasonic waves to somatosensory areas. The stimulation elicited unilateral tactile sensation of the hand from the receiver, thus establishing the hemispheric brain-to-brain interface (BBI). Although there was a degree of variability in task accuracy, six pairs of volunteers performed the BBI task in high accuracy, transferring approximately eight commands per minute. Linkage between the hemispheric brain activities among individuals suggests the possibility for expansion of the information bandwidth in the context of BBI.

Background: An ovine model can cast great insight in translational neuroscientific research due to its large brain volume and distinct regional neuroanatomical structures. The present study examined the applicability of brain functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to sheep using a clinical MR scanner (3 tesla) with a head coil. The blood-oxygenation-level-dependent (BOLD) fMRI was performed on anesthetized sheep during the block-based presentation of external tactile and visual stimuli using gradient echo-planar-imaging (EPI) sequence. Results: The individual as well as group-based data processing subsequently showed activation in the eloquent sensorimotor and visual areas. DTI was acquired using 26 differential magnetic gradient directions to derive directional fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values from the brain. White matter tractography was also applied to reveal the macrostructure of the corticospinal tracts and optic radiations. Conclusions: Utilization of fMRI and DTI along with anatomical MRI in the sheep brain could shed light on a broader use of an ovine model in the field of translational neuroscientific research targeting the brain.

Background: Transcranial focused ultrasound (FUS) is gaining momentum as a novel non-invasive brain stimulation method, with promising potential for superior spatial resolution and depth penetration compared to transcranial magnetic stimulation or transcranial direct current stimulation. We examined the presence of tactile sensations elicited by FUS stimulation of two separate brain regions in humans—the primary (SI) and secondary (SII) somatosensory areas of the hand, as guided by individual-specific functional magnetic resonance imaging data. Results: Under image-guidance, acoustic stimulations were delivered to the SI and SII areas either separately or simultaneously. The SII areas were divided into sub-regions that are activated by four types of external tactile sensations to the palmar side of the right hand—vibrotactile, pressure, warmth, and coolness. Across the stimulation conditions (SI only, SII only, SI and SII simultaneously), participants reported various types of tactile sensations that arose from the hand contralateral to the stimulation, such as the palm/back of the hand or as single/neighboring fingers. The type of tactile sensations did not match the sensations that are associated with specific sub-regions in the SII. The neuro-stimulatory effects of FUS were transient and reversible, and the procedure did not cause any adverse changes or discomforts in the subject’s mental/physical status. Conclusions: The use of multiple FUS transducers allowed for simultaneous stimulation of the SI/SII in the same hemisphere and elicited various tactile sensations in the absence of any external sensory stimuli. Stimulation of the SII area alone could also induce perception of tactile sensations. The ability to stimulate multiple brain areas in a spatially restricted fashion can be used to study causal relationships between regional brain activities and their cognitive/behavioral outcomes. Electronic supplementary material The online version of this article (doi:10.1186/s12868-016-0303-6) contains supplementary material, which is available to authorized users.

Background: Using mobile communication technology as new personalized approach to treat mental disorders or to more generally improve quality of life is highly promising. Knowledge about intervention components that target key psychopathological processes in terms of transdiagnostic psychotherapy approaches is urgently needed. We explored the use of smartphone-based micro-interventions based on psychotherapeutic techniques, guided by short video-clips, to elicit mood changes. Method: As part of a larger neurofeedback study, all subjects—after being randomly assigned to an experimental or control neurofeedback condition—underwent daily smartphone-based micro-interventions for 13 consecutive days. They were free to choose out of provided techniques, including viscerosensory attention, emotional imagery, facial expression, and contemplative repetition. Changes in mood were assessed in real world using the Multidimensional Mood State Questionnaire (scales: good–bad, GB; awake–tired, AT; and calm–nervous, CN). Results: Twenty-seven men participated on at least 11 days and were thus included in the analyses. Altogether, they underwent 335, generally well-tolerated, micro-intervention sessions, with viscerosensory attention (178 sessions, 53.13%) and contemplative repetition (68 sessions, 20.30%) being the most frequently applied techniques. Mixed models indicated that subjects showed better mood [GB: b = 0.464, 95%confidence interval (CI) [0.068, 0.860], t(613.3) = 2.298, p = 0.022] and became more awake [AT: b = 0.514, 95%CI [0.103, 0.925], t(612.4) = 2.456, p = 0.014] and calmer [CN: b = 0.685, 95%CI [0.360, 1.010], t(612.3) = 4.137, p < 0.001] from pre- to post-micro-intervention. These mood improvements from pre- to post-micro-intervention were associated with changes in mood from the 1st day until the last day with regard to GB mood (r = 0.614, 95%CI [0.297, 0.809], p < 0.001), but not AT mood (r = 0.279, 95%CI [−0.122, 0.602], p = 0.167) and CN mood (r = 0.277, 95%CI [0.124, 0.601], p = 0.170). Discussion: Our findings provide evidence for the applicability of smartphone-based micro-interventions eliciting short-term mood changes, based on techniques used in psychotherapeutic approaches, such as mindfulness-based psychotherapy, transcendental meditation, and other contemplative therapies. The results encourage exploring these techniques' capability to improve mood in randomized controlled studies and patients. Smartphone-based micro-interventions are promising to modify mood in real-world settings, complementing other psychotherapeutic interventions, in line with the precision medicine approach. The here presented data were collected within a randomized trial, registered at ClinicalTrials.gov (Identifier: NCT01921088) https://clinicaltrials.gov/ct2/show/NCT01921088.