15 Stimulating the brain with sound: focused ultrasound for neuromodulation

Chris Butler studied medicine at Gonville and Caius College, Cambridge (1991–1994) and then at the University of Edinburgh (1994–1997). He conducted his PhD on the syndrome of transient epileptic amnesia under the supervision of Professor Adam Zeman. He worked as a post-doctoral fellow at the Memory and Aging Center, University of California at San Francisco and moved to Oxford in 2009. He was awarded a Clinician Scientist fellowship from the Medical Research Council in 2013.Transcranial ultrasound stimulation (TUS) is emerging as a potentially powerful, non-invasive technique for focal brain stimulation. TUS uses low intensity focused ultrasound delivered through the skull to cause direct modulation of neuronal function. In animal studies, TUS has been shown to modulate activity in several brain areas, including sensorimotor regions, visual cortex, frontal eye fields, anterior cingulate cortex and thalamic targets, resulting in behavioural as well as electrophysiological changes. Several studies have shown that TUS can be applied safely to healthy human participants to modulate behaviour and neural activity in brain regions including somatosensory, visual, and motor cortex as well as to deeper thalamic nuclei. These data have resulted in TUS emerging as a safe, potent, non-invasive brain stimulation tool, with better spatial accuracy and greater depth than established techniques such as transcranial magnetic or electrical stimulation. I will review these studies and discuss recent work of our own in which we studied, for the first time, TUS effects on higher-order human cortex.We investigated whether TUS can modulate higher-order visual processing both in superficial (middle temporal area (MT)) and deep (fusiform face area (FFA)) regions. Magnetic resonance imaging was used to map skull anatomy and functional regions of interest (MT and FFA) for each participant (n=16). To control for non-specific effects, auditory masking was applied during the tasks. EEG data were collected throughout. Auditory masking reduced subjective stimulation detection to chance level and abolished auditory evoked potentials. Ultrasonic stimulation of MT led to facilitation of visual motion detection in the contralateral hemifield, with no effect upon face identity detection. Stimulation of FFA did not affect visual motion detection performance. We show that TUS can be used in humans to modify behaviour and electrophysiological activity in higher-order visual pathways in a task- specific and anatomically precise manner.

Neonicotinoid and sulfoximine pesticides differentially impair insect escape behavior and motion detection

Insect nervous systems offer unique advantages for studying interactions between sensory systems and behavior, given their complexity with high tractability. By examining the neural coding of salient environmental stimuli and resulting behavioral output in the context of environmental stressors, we gain an understanding of the effects of these stressors on brain and behavior and provide insight into normal function. The implication of neonicotinoid (neonic) pesticides in contributing to declines of nontarget species, such as bees, has motivated the development of new compounds that can potentially mitigate putative resistance in target species and declines of nontarget species. We used a neuroethologic approach, including behavioral assays and multineuronal recording techniques, to investigate effects of imidacloprid (IMD) and the novel insecticide sulfoxaflor (SFX) on visual motion-detection circuits and related escape behavior in the tractable locust system. Despite similar LD50 values, IMD and SFX evoked different behavioral and physiological effects. IMD significantly attenuated collision avoidance behaviors and impaired responses of neural populations, including decreases in spontaneous firing and neural habituation. In contrast, SFX displayed no effect at a comparable sublethal dose. These results show that neonics affect population responses and habituation of a visual motion detection system. We propose that differences in the sublethal effects of SFX reflect a different mode of action than that of IMD. More broadly, we suggest that neuroethologic assays for comparative neurotoxicology are valuable tools for fully addressing current issues regarding the proximal effects of environmental toxicity in nontarget species.

The Right Hemisphere Planum Temporale Supports Enhanced Visual Motion Detection Ability in Deaf People: Evidence from Cortical Thickness

After sensory loss, the deprived cortex can reorganize to process information from the remaining modalities, a phenomenon known as cross-modal reorganization. In blind people this cross-modal processing supports compensatory behavioural enhancements in the nondeprived modalities. Deaf people also show some compensatory visual enhancements, but a direct relationship between these abilities and cross-modally reorganized auditory cortex has only been established in an animal model, the congenitally deaf cat, and not in humans. Using T1-weighted magnetic resonance imaging, we measured cortical thickness in the planum temporale, Heschl’s gyrus and sulcus, the middle temporal area MT+, and the calcarine sulcus, in early-deaf persons. We tested for a correlation between this measure and visual motion detection thresholds, a visual function where deaf people show enhancements as compared to hearing. We found that the cortical thickness of a region in the right hemisphere planum temporale, typically an auditory region, was greater in deaf individuals with better visual motion detection thresholds. This same region has previously been implicated in functional imaging studies as important for functional reorganization. The structure-behaviour correlation observed here demonstrates this area’s involvement in compensatory vision and indicates an anatomical correlate, increased cortical thickness, of cross-modal plasticity.