Biology subjects

Sigona, M. K.

Publications and source records attributed to Sigona, M. K..

2 recordsLinked to original sources

bioRxiv2023

Small volume blood-brain barrier opening in macaques with a 1 MHz ultrasound phased array

Focused ultrasound blood-brain barrier (BBB) opening is a promising tool for targeted delivery of therapeutic agents into the brain. The volume of opening determines the extent of therapeutic administration and sets a lower bound on the size of targets which can be selectively treated. We tested a custom 1 MHz array transducer optimized for cortical regions in the macaque brain with the goal of achieving small volume openings. We integrated this device into a magnetic resonance image guided focused ultrasound system and demonstrated twelve instances of small volume BBB opening with average opening volumes of 59 {+/-} 37 mm3 and 184 {+/-} 2 mm3 in cortical and subcortical targets, respectively. We developed real-time cavitation monitoring using a passive cavitation detector embedded in the array and characterized its performance on a bench-top flow phantom mimicking transcranial BBB opening procedures. We monitored cavitation during in-vivo procedures and compared cavitation metrics against opening volumes and safety outcomes measured with FLAIR and susceptibility weighted MR imaging. Our findings show small BBB opening at cortical targets in macaques and characterize the safe pressure range for 1 MHz BBB opening. Additionally, we used subject-specific simulations to investigate variance in measured opening volumes and found high correlation (R2 = 0.8577) between simulation predictions and observed measurements. Simulations suggest the threshold for 1 MHz BBB opening was 0.53 MPa. This system enables BBB opening for drug delivery and gene therapy to be targeted to more specific brain regions.

bioengineering↗

bioRxiv2021

Transcranial Ultrasound Stimulation in Anterior Cingulate Cortex Impairs Information Sampling and Learning in Loss Contexts

Neuronal subgroups in anterior cingulate cortex (ACC) and the anterior striatum (STR) encode the reward structure of a given environment. But whether or how this reward information is used to guide information sampling, optimize decision making, or motivate behavior in cognitively challenging situations has remained elusive. Here, we causally tested these scenarios by transiently disrupting ACC and STR of rhesus monkeys with transcranial ultrasound with a learning task that independently varied cognitive and motivational demands. We found that disrupting the ACC, but not the STR, prolonged information sampling and reduced learning efficiency whenever the motivational payoff was low. These impairments were most pronounced at high cognitive demands and based on an inability to use loss experiences to improve performance. These results provide causal evidence that the ACC is necessary for motivation, to overcome anticipated costs from negative (loss) outcomes, and for cognition, to enhance visual information sampling during adaptive behavior. HIGHLIGHTSO_LITranscranial ultrasound stimulation of the anterior cingulate cortex disrupts learning after loss experience. C_LIO_LIThe ultrasound-induced learning deficit is exacerbated at high cognitive load. C_LIO_LIThe ultrasound-induced learning deficit is accompanied by inefficient fixational information sampling. C_LIO_LIAnterior cingulate cortex causally supports credit assignment of aversive outcomes to visual features. C_LI

neuroscience↗