Functional ultrasound imaging of human brain activity through an acoustically transparent cranial window.

Visualization of human brain activity is crucial for understanding normal and aberrant brain function. Currently available neural activity recording methods are highly invasive, have low sensitivity, and cannot be conducted outside of an operating room. Functional ultrasound imaging (fUSI) is an emerging technique that offers sensitive, large-scale, high-resolution neural imaging; however, fUSI cannot be performed through the adult human skull. Here, we used a polymeric skull replacement material to create an acoustic window compatible with fUSI to monitor adult human brain activity in a single individual. Using an in vitro cerebrovascular phantom to mimic brain vasculature and an in vivo rodent cranial defect model, first, we evaluated the fUSI signal intensity and signal-to-noise ratio through polymethyl methacrylate (PMMA) cranial implants of different thicknesses or a titanium mesh implant. We found that rat brain neural activity could be recorded with high sensitivity through a PMMA implant using a dedicated fUSI pulse sequence. We then designed a custom ultrasound-transparent cranial window implant for an adult patient undergoing reconstructive skull surgery after traumatic brain injury. We showed that fUSI could record brain activity in an awake human outside of the operating room. In a video game "connect the dots" task, we demonstrated mapping and decoding of task-modulated cortical activity in this individual. In a guitar-strumming task, we mapped additional task-specific cortical responses. Our proof-of-principle study shows that fUSI can be used as a high-resolution (200 µm) functional imaging modality for measuring adult human brain activity through an acoustically transparent cranial window.

Decoding motor plans using a closed-loop ultrasonic brain-machine interface.

Brain-machine interfaces (BMIs) enable people living with chronic paralysis to control computers, robots and more with nothing but thought. Existing BMIs have trade-offs across invasiveness, performance, spatial coverage and spatiotemporal resolution. Functional ultrasound (fUS) neuroimaging is an emerging technology that balances these attributes and may complement existing BMI recording technologies. In this study, we use fUS to demonstrate a successful implementation of a closed-loop ultrasonic BMI. We streamed fUS data from the posterior parietal cortex of two rhesus macaque monkeys while they performed eye and hand movements. After training, the monkeys controlled up to eight movement directions using the BMI. We also developed a method for pretraining the BMI using data from previous sessions. This enabled immediate control on subsequent days, even those that occurred months apart, without requiring extensive recalibration. These findings establish the feasibility of ultrasonic BMIs, paving the way for a new class of less-invasive (epidural) interfaces that generalize across extended time periods and promise to restore function to people with neurological impairments.

A window to the brain: ultrasound imaging of human neural activity through a permanent acoustic window.

Recording human brain activity is crucial for understanding normal and aberrant brain function. However, available recording methods are either highly invasive or have relatively low sensitivity. Functional ultrasound imaging (fUSI) is an emerging technique that offers sensitive, large-scale, high-resolution neural imaging. However, fUSI cannot be performed through adult human skull. Here, we use a polymeric skull replacement material to create an acoustic window allowing ultrasound to monitor brain activity in fully intact adult humans. We design the window through experiments in phantoms and rodents, then implement it in a participant undergoing reconstructive skull surgery. Subsequently, we demonstrate fully non-invasive mapping and decoding of cortical responses to finger movement, marking the first instance of high-resolution (200 µm) and large-scale (50 mmx38 mm) brain imaging through a permanent acoustic window.

Targeting neuroplasticity to improve motor recovery after stroke: an artificial neural network model.

After a neurological injury, people develop abnormal patterns of neural activity that limit motor recovery. Traditional rehabilitation, which concentrates on practicing impaired skills, is seldom fully effective. New targeted neuroplasticity protocols interact with the central nervous system to induce beneficial plasticity in key sites and thereby enable wider beneficial plasticity. They can complement traditional therapy and enhance recovery. However, their development and validation is difficult because many different targeted neuroplasticity protocols are conceivable, and evaluating even one of them is lengthy, laborious, and expensive. Computational models can address this problem by triaging numerous candidate protocols rapidly and effectively. Animal and human empirical testing can then concentrate on the most promising ones. Here, we simulate a neural network of corticospinal neurons that control motoneurons eliciting unilateral finger extension. We use this network to (i) study the mechanisms and patterns of cortical reorganization after a stroke; and (ii) identify and parameterize a targeted neuroplasticity protocol that improves recovery of extension torque. After a simulated stroke, standard training produced abnormal bilateral cortical activation and suboptimal torque recovery. To enhance recovery, we interdigitated standard training with trials in which the network was given feedback only from a targeted population of sub-optimized neurons. Targeting neurons in secondary motor areas on ∼20% of the total trials restored lateralized cortical activation and improved recovery of extension torque. The results illuminate mechanisms underlying suboptimal cortical activity post-stroke; they enable the identification and parameterization of the most promising targeted neuroplasticity protocols. By providing initial guidance, computational models could facilitate and accelerate the realization of new therapies that improve motor recovery.

Single-trial decoding of movement intentions using functional ultrasound neuroimaging.

New technologies are key to understanding the dynamic activity of neural circuits and systems in the brain. Here, we show that a minimally invasive approach based on ultrasound can be used to detect the neural correlates of movement planning, including directions and effectors. While non-human primates (NHPs) performed memory-guided movements, we used functional ultrasound (fUS) neuroimaging to record changes in cerebral blood volume with 100 µm resolution. We recorded from outside the dura above the posterior parietal cortex, a brain area important for spatial perception, multisensory integration, and movement planning. We then used fUS signals from the delay period before movement to decode the animals' intended direction and effector. Single-trial decoding is a prerequisite to brain-machine interfaces, a key application that could benefit from this technology. These results are a critical step in the development of neuro-recording and brain interface tools that are less invasive, high resolution, and scalable.

How do strength and coordination recovery interact after stroke? A computational model for informing robotic training.

Robotic devices can train strength, coordination, or a combination of both. If a robotic device focuses on coordination, what happens to strength recovery, and vice versa? Understanding this interaction could help optimize robotic training. We developed a computational neurorehabilitation model to gain insight into the interaction between strength and coordination recovery after stroke. In the model, the motor system recovers by optimizing the activity of residual corticospinal cells (focally connected, excitatory and inhibitory) and reticulospinal cells (diffusely connected and excitatory) to achieve a motor task. To do this, the model employs a reinforcement learning algorithm that uses stochastic search based on a reward signal produced by task execution. We simulated two tasks that require strength and coordination: a finger movement task and a bilateral wheelchair propulsion task. We varied the reward signal to value strength versus coordination, determined by a weighting factor. The model predicted a nonlinear relationship between strength and coordination recovery consistent with clinical data obtained for each task. The model also predicted that stroke can cause a competition between strength and coordination recovery, due to a scarcity of focal and inhibitory cells. These results provide a rationale for implementing robotic movement therapy that can adaptively alter the combination of force and coordination training to target desired components of motor recovery.

Planar hand motion guidance using fingertip skin-stretch feedback.

In this paper, we show that a simple haptic device can accurately guide users through planar hand movements. The device guides the user through skin stretch feedback on the fingerpad of the user's index finger. In an angle matching test evaluating two types of stimuli, users are able to discriminate between eight stimulus directions and match the motion of their hand to the stimulus direction with 10 degree accuracy. In two motion guidance tests, haptic cues effectively guide users' arm motions through the full extent of their reachable workspace. Real-time corrective feedback greatly improves user performance, keeping average user hand motions within 12 mm of the prescribed path and within 4 degree of the indicated directions. Additionally, the paper shows that participants exhibit distorted haptic perceptual responses, finding that the distortion causes a response direction bias, but that appropriate haptic feedback can correct for the effect. Such motion guidance has applications in human-machine interaction, such as upper-extremity rehabilitation.