The primary goals of the AshLab are to understand mechanisms of neuroplasticity in the human brain, to develop tools to modulate neuroplasticity, and to augment recovery from neuropsychiatric disease.
I. Advance neuroscientific knowledge about synaptic stability and plasticity in the human brain across development and in neuropsychiatric disease.
How to brain states like attention and emotion regulate learning and plasticity?
Experience tells us and experiments confirm that brain states like attention powerfully regulate learning, and presumably this occurs via modulation of synaptic plasticity in the brain. We interested in investigating these processes in the lab. In a recent study we investigated the role of spatial attention in visual cortical plasticity, and we found evidence for only modest attentional enhancement of a form of EEG-recorded visual cortical plasticity.
How do mechanisms regulating synaptic stability and plasticity go awry in neuropsychiatric conditions?
In preclinical models, we are developing novel PET-based measures of synaptic stability, which can serve as a potential noninvasive biomarker for critical period plasticity and excessive synaptic stability in neuropsychiatric conditions.
II. Develop novel neuroscience-informed therapeutics to rebalance synaptic stability and plasticity in neuropsychiatric conditions.
Our lab is advancing the technology of transcranial focused ultrasound (FUS) as a novel approach to focally target deep brain areas for circuit manipulations. FUS refers to the focusing of ultrasound waves originating from transducers at the scalp to a small point in the brain. FUS can be delivered at safe intensities for direct neuromodulation, as even CNS neurons express mechanosensitive ion channels which are highly sensitive to ultrasound. FUS can also be used for thermal neuromodulation, microbubble-mediated blood-brain barrier opening, and targeted drug release. FUS can achieve a tunable focal spot of 1-30 mm diameter that can be rapidly steered to generate arbitrary stimulation patterns throughout the brain. Seminal initial studies already demonstrate that monoclonal antibodies, drugs, and other biologics which normally do not cross the BBB can be successfully targeted to specific brain regions in human patients to treat neurodegenerative disease, cancer, and Parkinson disease. This approach allows agents that don’t cross the BBB to be used for CNS applications, and furthermore allows targeting to an intended brain area without off target effects in other parts of the brain. Additionally, ultrasound-sensitive nanoparticles developed by our collaborators at Stanford (see Purohit et al., Nature Nanotechnology 2025) and University of Texas (see Wang et al. Nature, 2025) enable FUS-based targeting of drugs and other neural actuators solely to desired brain targets.
What are the effective parameters for neuromodulation with transcranial focused ultrasound?
We have built a highly-optimized paradigm to assess the efficacy of transcranial focused ultrasound in the human brain, using high-SNR EEG steady state visual evoked potentials and rigorous perceptual psychophysics. This helps us identify the FUS parameters that most reliably modulate neural activity.
What is the causal role of the pulvinar nucleus in visual attention and global visual integration?
We are using FUS neuromodulation to investigate the function of the pulvinar, a poorly understood area that is the largest thalamic nucleus in primates.
FUS neuromodulation to facilitate recovery from neuropsychiatric illness
We are planning early-stage clinical trials to use FUS neuromodulation to ameliorate symptoms in posttraumatic stress disorder and autism.
FUS-based targeting of biologics to rebalance synaptic stability and plasticity in the brain
In preclinical models, we are pursuing multiple novel approaches to powerfully modulate synaptic stability with FUS-based targeting of biological actuators. This could lead to completely new mechanistically-informed treatments for a range of psychiatric conditions including PTSD, addiction, autism, chronic pain, epilepsy, and more.