Citations

The distinct impacts of fouling mechanisms on a carbon fiber microelectrode and an Ag/AgCl reference electrode, affecting their performance in neurotransmitter detection via Fast-scan Cyclic Voltammetry.

OBJECTIVE Conventional frame-based stereotactic systems have circumferential base frames, often necessitating deep brain stimulation (DBS) surgery in two stages: intracranial electrode insertion followed by surgical re-preparation and pulse generator implantation. Some patients do not tolerate awake surgery, underscoring the need for a safe alternative for asleep DBS surgery. A frame-based stereotactic system with a skull-mounted "key" in lieu of a circumferential base frame received US FDA clearance. The authors describe the system’s application for single-stage, asleep DBS surgery in 8 patients at their institution and review its workflow and technical considerations. METHODS Eight patients underwent DBS lead insertion and IPG implantation in a single surgical preparation under general anesthesia using the system. Postoperative CT imaging confirmed lead placement. RESULTS Eight patients underwent implantation of 15 total leads targeting the ventral intermediate nucleus (4 patients), globus pallidus internus (GPi; 3 patients), and subthalamic nucleus (STN; 1 patient). Intraoperative microelectrode recording was conducted for GPi and STN targets. Postoperative CT imaging revealed a mean ± SD radial error of 1.24 ± 0.45 mm (n = 15 leads), without surgical complications. CONCLUSIONS The stereotactic system facilitated safe and effective asleep, single-stage DBS surgery, maintaining traditional lead accuracy standards.

Abstract Tourette syndrome is a childhood-onset neuropsychiatric disorder characterized by intrusive motor and vocal tics that can lead to self-injury and deleterious mental health complications. While dysfunction in striatal dopamine neurotransmission has been proposed to underlie tic behaviour, evidence is scarce and inconclusive. Deep brain stimulation (DBS) of the thalamic centromedian parafascicular complex (CMPf), an approved surgical interventive treatment for medical refractory Tourette syndrome, may reduce tics by affecting striatal dopamine release. Here, we use electrophysiology, electrochemistry, optogenetics, pharmacological treatments and behavioural measurements to mechanistically examine how thalamic DBS modulates synaptic and tonic dopamine activity in the dorsomedial striatum. Previous studies demonstrated focal disruption of GABAergic transmission in the dorsolateral striatum of rats led to repetitive motor tics recapitulating the major symptom of Tourette syndrome. We employed this model under light anaesthesia and found CMPf DBS evoked synaptic dopamine release and elevated tonic dopamine levels via striatal cholinergic interneurons while concomitantly reducing motor tic behaviour. The improvement in tic behaviour was found to be mediated by D2 receptor activation as blocking this receptor prevented the therapeutic response. Our results demonstrate that release of striatal dopamine mediates the therapeutic effects of CMPf DBS and points to striatal dopamine dysfunction as a driver for motor tics in the pathoneurophysiology of Tourette syndrome.

OBJECTIVE Magnetic resonance imaging at 7T offers improved image spatial and contrast resolution for visualization of small brain nuclei targeted in neuromodulation. However, greater image geometric distortion and a lack of compatible instrumentation preclude implementation. In this report, the authors detail the development of a stereotactic image localizer and accompanying imaging sequences designed to mitigate geometric distortion, enabling accurate image registration and surgical planning of basal ganglia nuclei. METHODS Magnetization-prepared rapid acquisition with gradient echo (MPRAGE), fast gray matter acquisition T1 inversion recovery (FGATIR), T2-weighted, and T2*-weighted sequences were optimized for 7T in 9 human subjects to visualize basal ganglia nuclei, minimize image distortion, and maximize target contrast-to-noise and signal-to-noise ratios. Extracranial spatial distortions were mapped to develop a skull-contoured image localizer embedded with spherical silicone fiducials for improved MR image registration and target guidance. Surgical plan accuracy testing was initially performed in a custom-developed MRI phantom (n = 5 phantom studies) and finally in a human trial. RESULTS MPRAGE and T2*-weighted sequences had the best measures among global measures of image quality (3.8/4, p < 0.0001; and 3.7/4, p = 0.0002, respectively). Among basal ganglia nuclei, FGATIR outperformed MPRAGE for globus pallidus externus (GPe) visualization (2.67/4 vs 1.78/4, p = 0.008), and FGATIR, T2-weighted imaging, and T2*-weighted imaging outperformed MPRAGE for substantia nigra visualization (1.44/4 vs 2.56/4, p = 0.04; vs 2.56/4, p = 0.04; vs 2.67/4, p = 0.003). Extracranial distortion was lower in the head’s midregion compared with the base and apex ( 1.17–1.33 mm; MPRAGE and FGATIR, p < 0.0001; T2-weighted imaging, p > 0.05; and T2*-weighted imaging, p = 0.013). Fiducial placement on the localizer in low distortion areas improved image registration (fiducial registration error, 0.79–1.19 mm; p < 0.0001) and targeting accuracy (target registration error, 0.60–1.09 mm; p = 0.04). Custom surgical software and the refined image localizer enabled successful surgical planning in a human trial (fiducial registration error = 1.0 mm). CONCLUSIONS A skull-contoured image localizer that accounts for image distortion is necessary to enable high-accuracy 7T imaging–guided targeting for surgical neuromodulation. These results may enable improved clinical efficacy for the treatment of neurological disease.

Serotonin plays a vital role in drug addiction. Here, using N-shaped fast-scan cyclic voltammetry, we demonstrated the effect of cocaine on the phasic release of serotonin at the nucleus accumbens core. To the best of our knowledge, this has not previously been elucidated. Our results not only reinforce the role of serotonin in the mechanism of action of cocaine but also help to fill a gap in our knowledge and provide a baseline for future studies in cocaine addiction.