MRI Free Targeting of Deep Brain Structures in the Anterior Cingulate Cortex Using Facial Landmarks.

Emerging neurostimulation methods aim to selectively modulate deep brain structures. Guiding these therapies has presented a substantial chal- lenge, since imaging modalities such as MRI limit the spectrum of benefi- ciaries. In this study, we assess the guidance accuracy of a neuronavigation method that does not require taking MRI scans.

A Physiological Marker for Deep Brain Ultrasonic Neuromodulation.

Objectives: Transcranial ultrasound neuromodulation (TUSN) is a noninvasive and spatially specific therapy that promises to deliver treatments tailored to the specific needs of individuals. To fulfill this promise, each treatment must be modified to adequately correct for variation across individual skulls and neural anatomy. This study examines the use of ultrasound-induced voltage potentials (measured with electroencephalography [EEG]) to guide TUSN therapies.

Noninvasive targeted modulation of pain circuits with focused ultrasonic waves.

Direct interventions into deep brain circuits constitute promising treatment modalities for chronic pain. Cingulotomy and deep brain stimulation targeting the anterior cingulate cortex have shown notable improvements in the unpleasantness of pain, but these interventions require brain surgeries. In this study, we have developed an approach that can modulate this deep brain affective hub entirely noninvasively, using low-intensity transcranial-focused ultrasound.

Controlled ultrasonic interventions through the human skull.

Transcranial focused ultrasound enables precise and non-invasive manipulations of deep brain circuits in humans, promising to provide safe and effective treatments of various neurological and mental health conditions. Ultrasound focused to deep brain targets can be used to modulate neural activity directly or localize the release of psychoactive drugs. However, these applications have been impeded by a key barrier-the human skull, which attenuates ultrasound strongly and unpredictably.

Targeted drug release from stable and safe ultrasound-sensitive nanocarriers.

Targeted delivery of medication has the promise of increasing the effectiveness and safety of current systemic drug treatments. Focused ultrasound is emerging as noninvasive and practical energy for targeted drug release. However, it has yet to be determined which nanocarriers and ultrasound parameters can provide both effective and safe release.

Sensorimotor faculties bias perceptual decision-making.

Decision-making is a deliberate process that seemingly evolves under our own volition. Yet, research on embodied cognition has demonstrated that higher-order cognitive processes may be influenced, in unexpected ways, by properties of motor and sensory systems. Here we tested whether and how simple decisions are influenced by handedness and by asymmetries in the auditory system.

Graded decisions in the human brain.

Decision-makers objectively commit to a definitive choice, yet at the subjective level, human decisions appear to be associated with a degree of uncertainty. Whether decisions are definitive (i.e.

Remotely controlled drug release in deep brain regions of non-human primates.

Many areas of science and medicine would benefit from selective release of drugs in specific regions. Nanoparticle drug carriers activated by focused ultrasound-remotely applied, depth-penetrating energy-may provide such selective interventions. Here, we developed stable, ultrasound-responsive nanoparticles that can be used to release drugs effectively and safely in non-human primates.

Matching provides efficient decisions.

How humans and animals distribute their behavior across choice options has been of key interest to economics, psychology, ecology, and related fields. Neoclassical and behavioral economics have provided prescriptions for how decision-makers can maximize their reward or utility, but these formalisms are used by decision-makers rarely. Instead, individuals allocate their behavior in proportion to the worth of their options, a phenomenon captured by the generalized matching law.

Matching provides efficient decisions.

How humans and animals distribute their behavior across choice options has been of key interest to economics, psychology, ecology, and related fields. Neoclassical and behavioral economics have provided prescriptions for how decision-makers can maximize their reward or utility, but these formalisms are used by decision-makers rarely. Instead, individuals allocate their behavior in proportion to the worth of their options, a phenomenon captured by the generalized matching law.

Noninvasive modulation of essential tremor with focused ultrasonic waves.

: Transcranial focused low-intensity ultrasound has the potential to noninvasively modulate confined regions deep inside the human brain, which could provide a new tool for causal interrogation of circuit function in humans. However, it has been unclear whether the approach is potent enough to modulate behavior.: To test this, we applied low-intensity ultrasound to a deep brain thalamic target, the ventral intermediate nucleus, in three patients with essential tremor.

Durable effects of deep brain ultrasonic neuromodulation on major depression: a case report.

Background: Severe forms of depression have been linked to hyperactivity of the subcallosal cingulate cortex. The ability to stimulate the subcallosal cingulate cortex or associated circuits noninvasively and directly would maximize the number of patients who could receive treatment. To this end, we have developed an ultrasound-based device for effective noninvasive modulation of deep brain circuits.

Remotely controlled drug release in deep brain regions of non-human primates.

Many areas of science and medicine would benefit from selective release of drugs in specific regions of interest. Nanoparticle drug carriers activated by focused ultrasound-remotely applied, depth-penetrating energy-may provide such selective interventions. Here, we developed stable, ultrasound-responsive nanoparticles that can be used to release drugs effectively and safely in non-human primates.

Device for Multifocal Delivery of Ultrasound Into Deep Brain Regions in Humans.

Low-intensity focused ultrasound provides the means to noninvasively stimulate or release drugs in specified deep brain targets. However, successful clinical translations require hardware that maximizes acoustic transmission through the skull, enables flexible electronic steering, and provides accurate and reproducible targeting while minimizing the use of MRI. We have developed a device that addresses these practical requirements.

Stem cell-derived brain organoids for controlled studies of transcranial neuromodulation.

Transcranial neuromodulation methods have the potential to diagnose and treat brain disorders at their neural source in a personalized manner. However, it has been difficult to investigate the direct effects of transcranial neuromodulation on neurons in human brain tissue. Here, we show that human brain organoids provide a detailed and artifact-free window into neuromodulation-evoked electrophysiological effects.

Remote targeted electrical stimulation.

The ability to generate electric fields in specific targets remotely would transform manipulations of processes that rest on electrical signaling.This article shows that focal electric fields are generated from distance by combining two orthogonal, remotely applied energies-magnetic and focused ultrasonic fields. The effect derives from the Lorentz force equation applied to magnetic and ultrasonic fields.

Sustained modulation of primate deep brain circuits with focused ultrasonic waves.

Background: Transcranial focused ultrasound has the potential to noninvasively modulate deep brain circuits and impart sustained, neuroplastic effects.

Objective: Bring the approach closer to translations by demonstrating sustained modulation of deep brain circuits and choice behavior in task-performing non-human primates.

Methods: Low-intensity transcranial ultrasound of 30 s in duration was delivered in a controlled manner into deep brain targets (left or right lateral geniculate nucleus; LGN) of non-human primates while the subjects decided whether a left or a right visual target appeared first.

Multifrequency-based sharpening of focal volume.

Systems that emit electromagnetic or sonic waves for diagnostic or interventional applications often have constraints on the size of their aperture, and thus produce an elongated focus in the axial dimension. This extended depth of focus limits imaging resolution and spatial specificity of the delivered energy. Here, we have developed a method that substantially minimizes the depth of focus.

Transcranial ultrasound neuromodulation of the thalamic visual pathway in a large animal model and the dose-response relationship with MR-ARFI.

Neuromodulation of deep brain structures via transcranial ultrasound stimulation (TUS) is a promising, but still elusive approach to non-invasive treatment of brain disorders. The purpose of this study was to confirm that MR-guided TUS of the lateral geniculate nucleus (LGN) can modulate visual evoked potentials (VEPs) in the intact large animal; and to study the impact on cortical brain oscillations. The LGN on one side was identified with T2-weighted MRI in sheep (all male, n = 9).

Remus: System for remote deep brain interventions.

Transcranial-focused ultrasound brings personalized medicine to the human brain. Ultrasound can modulate neural activity or release drugs in specific neural circuits but this personalized approach requires a system that delivers ultrasound into specified targets flexibly and on command. We developed a remote ultrasound system (Remus) that programmatically targets deep brain regions with high spatiotemporal precision and in a multi-focal manner.

Acoustic properties across the human skull.

Transcranial ultrasound is emerging as a noninvasive tool for targeted treatments of brain disorders. Transcranial ultrasound has been used for remotely mediated surgeries, transient opening of the blood-brain barrier, local drug delivery, and neuromodulation. However, all applications have been limited by the severe attenuation and phase distortion of ultrasound by the skull.

Effective Ultrasonic Stimulation in Human Peripheral Nervous System.

Objective: Low-intensity ultrasound can stimulate excitable cells in a noninvasive and targeted manner, but which parameters are effective has remained elusive. This question has been difficult to answer because differences in transducers and parameters-frequency in particular-lead to profound differences in the stimulated tissue volumes. The objective of this study is to control for these differences and evaluate which ultrasound parameters are effective in stimulating excitable cells.