Byoung Kyong Min

Focused ultrasound modulates region-specific brain activity

We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animals somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using image-guided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders.

A review of low-intensity focused ultrasound pulsation

With the recent approval by the Food and Drug Administration (FDA) of Deep Brain Stimulation (DBS) for Parkinsons Disease, dystonia and obsessive compulsive disorder (OCD), vagus nerve stimulation (VNS) for epilepsy and depression, and repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression, neuromodulation has become increasingly relevant to clinical research. However, these techniques have significant drawbacks (eg, lack of special specificity and depth for the rTMS, and invasiveness and cumbersome maintenance for DBS). This article reviews the background, rationale, and pilot studies to date, using a new brain stimulation method-low-intensity focused ultrasound pulsation (LIFUP). The ability of ultrasound to be focused noninvasively through the skull anywhere within the brain, together with concurrent imaging (ie, functional magnetic resonance imaging [fMRI]) techniques, may create a role for research and clinical use of LIFUP. This technique is still in preclinical testing and needs to be assessed thoroughly before being advanced to clinical trials. In this study, we review over 50 years of research data on the use of focused ultrasound (FUS) in neuronal tissue and live brain, and propose novel applications of this noninvasive neuromodulation method.

Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity

BackgroundEpilepsy is a common neurological disorder, which is attributed to uncontrollable abnormal hyper-excitability of neurons. We investigated the feasibility of using low-intensity, pulsed radiation of focused ultrasound (FUS) to non-invasively suppress epileptic activity in an animal model (rat), which was induced by the intraperitonial injection of pentylenetetrazol (PTZ).ResultsAfter the onset of induced seizures, FUS was transcranially administered to the brain twice for three minutes each while undergoing electroencephalographic (EEG) monitoring. An air-backed, spherical segment ultrasound transducer (diameter: 6 cm; radius-of-curvature: 7 cm) operating at a fundamental frequency of 690 KHz was used to deliver a train of 0.5 msec-long pulses of sonication at a repetitive rate of 100 Hz to the thalamic areas of the brain. The acoustic intensity (130 mW/cm2) used in the experiment was sufficiently within the range of safety guidelines for the clinical ultrasound imaging. The occurrence of epileptic EEG bursts from epilepsy-induced rats significantly decreased after sonication when it was compared to the pre-sonication epileptic state. The PTZ-induced control group that did not receive any sonication showed a sustained number of epileptic EEG signal bursts. The animals that underwent sonication also showed less severe epileptic behavior, as assessed by the Racine score. Histological analysis confirmed that the sonication did not cause any damage to the brain tissue.ConclusionsThese results revealed that low-intensity, pulsed FUS sonication suppressed the number of epileptic signal bursts using acute epilepsy model in animal. Due to its non-invasiveness and spatial selectivity, FUS may offer new perspectives for a possible non-invasive treatment of epilepsy.

Neuroimaging-based approaches in the brain–computer interface

Techniques to enable direct communication between the brain and computers/machines, such as the brain-computer interface (BCI) or the brain-machine interface (BMI), are gaining momentum in the neuroscientific realm, with potential applications ranging from medicine to general consumer electronics. Noninvasive BCI techniques based on neuroimaging modalities are reviewed in terms of their methodological approaches as well as their similarities and differences. Trends in automated data interpretation through machine learning algorithms are also introduced. Applications of functional neuromodulation techniques to BCI systems would allow for bidirectional communication between the brain and the computer. Such bidirectional interfaces can relay information directly from one brain to another using a computer as a medium, ultimately leading to the concept of a brain-to-brain interface (BBI).

A Thalamic Reticular Networking Model of Consciousness

Abstract[Background]It is reasonable to consider the thalamus a primary candidate for the location of consciousness, given that the thalamus has been referred to as the gateway of nearly all sensory inputs to the corresponding cortical areas. Interestingly, in an early stage of brain development, communicative innervations between the dorsal thalamus and telencephalon must pass through the ventral thalamus, the major derivative of which is the thalamic reticular nucleus (TRN). The TRN occupies a striking control position in the brain, sending inhibitory axons back to the thalamus, roughly to the same region where they receive afferents.[Hypotheses]The present study hypothesizes that the TRN plays a pivotal role in dynamic attention by controlling thalamocortical synchronization. The TRN is thus viewed as a functional networking filter to regulate conscious perception, which is possibly embedded in thalamocortical networks. Based on the anatomical structures and connections, modality-specific sectors of the TRN and the thalamus appear to be responsible for modality-specific perceptual representation. Furthermore, the coarsely overlapped topographic maps of the TRN appear to be associated with cross-modal or unitary conscious awareness. Throughout the latticework structure of the TRN, conscious perception could be accomplished and elaborated through accumulating intercommunicative processing across the first-order input signal and the higher-order signals from its functionally associated cortices. As the higher-order relay signals run cumulatively through the relevant thalamocortical loops, conscious awareness becomes more refined and sophisticated.[Conclusions]I propose that the thalamocortical integrative communication across first- and higher-order information circuits and repeated feedback looping may account for our conscious awareness. This TRN-modulation hypothesis for conscious awareness provides a comprehensive rationale regarding previously reported psychological phenomena and neurological symptoms such as blindsight, neglect, the priming effect, the threshold/duration problem, and TRN-impairment resembling coma. This hypothesis can be tested by neurosurgical investigations of thalamocortical loops via the TRN, while simultaneously evaluating the degree to which conscious perception depends on the severity of impairment in a TRN-modulated network.

Task-Related Modulation of Anterior Theta and Posterior Alpha EEG Reflects Top-Down Preparation

BackgroundPrestimulus EEG alpha activity in humans has been considered to reflect ongoing top-down preparation for the performance of subsequent tasks. Since theta oscillations may be related to poststimulus top-down processing, we investigated whether prestimulus EEG theta activity also reflects top-down cognitive preparation for a stimulus.ResultsWe recorded EEG data from 15 healthy controls performing a color and shape discrimination task, and used the wavelet transformation to investigate the time course and power of oscillatory activity in the signals. We observed a relationship between both anterior theta and posterior alpha power in the prestimulus period and the type of subsequent task.ConclusionsSince task-differences were reflected in both theta and alpha activities prior to stimulus onset, both prestimulus theta (particularly around the anterior region) and prestimulus alpha (particularly around the posterior region) activities may reflect prestimulus top-down preparation for the performance of subsequent tasks.

Focused ultrasound modulates the level of cortical neurotransmitters: Potential as a new functional brain mapping technique

Regional modulation of the level of cortical neurotransmitters in the brain would serve as a new functional brain mapping technique to interrogate the neurochemical actions of the brain. We investigated the utility of the application of low‐intensity, pulsed sonication of focused ultrasound (FUS) to the brain to modulate the extracellular level of dopamine (DA) and serotonin (5‐HT). FUS was delivered to the thalamic areas of rats, and extracellular DA and 5‐HT were sampled from the frontal lobe using the microdialysis technique. The concentration changes of the sampled DA and 5‐HT were measured through high‐performance liquid chromatography. We observed a significant increase of the extracellular concentrations of DA and 5‐HT in the FUS‐treated group as compared with those in the unsonicated group. Our results provide the first direct evidence that FUS sonication alters the level of extracellular concentration of these monoamine neurotransmitters and has a potential modulatory effect on their local release, uptake, or degradation. Our findings suggest that the pulsed application of FUS offers new perspectives for a possible noninvasive modulation of neurotransmitters and may have diagnostic as well as therapeutic implications for DA/5‐HT‐mediated neurological and psychiatric disorders.

Transcranial focused ultrasound to the thalamus alters anesthesia time in rats.

A pulsed application of focused ultrasound (FUS) to the regional brain tissue alters the state of tissue excitability and thus provides the means for noninvasive functional neuromodulation. We report that the application of transcranial FUS to the thalamus of anesthetized rats reduced the time to emergence of voluntary movement from intraperitoneal ketamine/xylazine anesthesia. Low-intensity FUS was applied to the thalamus of anesthetized animals. The times required for the animals to show distinct physiological/behavioral changes were measured and compared with those times required in a control session without sonication. The sonication significantly reduced the time to show pinch response and voluntary movement. The modulatory effects of FUS on anesthesia suggest potential therapeutic applications for disorders of consciousness such as minimally consciousness states.

Prestimulus EEG alpha activity reflects temporal expectancy

Since prestimulus EEG alpha activity has recently been considered to convey prestimulus top-down processing, we investigated whether prestimulus alpha activity reflects temporal expectancy of upcoming stimulation even under the non-classical contingent negative variation (CNV) paradigm. EEG was recorded from 16 subjects performing a color and a shape discrimination task manipulated with constant and variable inter-stimulus interval (ISI) conditions. The power of oscillatory activity was investigated by convolving the EEG signals with Morlet wavelets. The constant ISI condition yielded significantly shorter reaction times than the variable ISI condition, indicating more efficient preparation for upcoming stimuli during the constant ISI. We found significantly higher prestimulus alpha activity in the constant ISI condition than in the variable ISI condition, but no significant CNV even in the constant ISI condition. Such a reflection of temporal expectancy in the prestimulus alpha activity corroborates that the prestimulus top-down mental state for preparing upcoming task-performance is considerably reflected in the prestimulus ongoing alpha activity.

Neurophysiologic Correlates of Sonication Treatment in Patients with Essential Tremor

Transcranial magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) is gaining attention as a potent substitute for surgical intervention in the treatment of neurologic disorders. To discern the neurophysiologic correlates of its therapeutic effects, we applied MRgHIFU to an intractable neurologic disorder, essential tremor, while measuring magnetoencephalogram mu rhythms from the motor cortex. Focused ultrasound sonication destroyed tissues by focusing a high-energy beam on the ventralis intermedius nucleus of the thalamus. The post-treatment effectiveness was also evaluated using the clinical rating scale for tremors. Thalamic MRgHIFU had substantial therapeutic effects on patients, based on MRgHIFU-mediated improvements in movement control and significant changes in brain mu rhythms. Ultrasonic thalamotomy may reduce hyper-excitable activity in the motor cortex, resulting in normalized behavioral activity after sonication treatment. Thus, non-invasive and spatially accurate MRgHIFU technology can serve as a potent therapeutic tool with broad clinical applications.