Subthalamic Nucleus
subthalamic nucleus
Subthalamic nucleus
Integrative Neuromodulation: from biomarker identification to optimizing neuromodulation
Why do we make decisions impulsively blinded in an emotionally rash moment? Or caught in the same repetitive suboptimal loop, avoiding fears or rushing headlong towards illusory rewards? These cognitive constructs underlying self-control and compulsive behaviours and their influence by emotion or incentives are relevant dimensionally across healthy individuals and hijacked across disorders of addiction, compulsivity and mood. My lab focuses on identifying theory-driven modifiable biomarkers focusing on these cognitive constructs with the ultimate goal to optimize and develop novel means of neuromodulation. Here I will provide a few examples of my group’s recent work to illustrate this approach. I describe a series of recent studies on intracranial physiology and acute stimulation focusing on risk taking and emotional processing. This talk highlights the subthalamic nucleus, a common target for deep brain stimulation for Parkinson’s disease and obsessive-compulsive disorder. I further describe recent translational work in non-invasive neuromodulation. Together these examples illustrate the approach of the lab highlighting modifiable biomarkers and optimizing neuromodulation.
Targeting thalamic circuits rescues motor and mood deficits in PD mice
Although bradykinesia, tremor, and rigidity are hallmark motor defects in Parkinson’s disease (PD) patients, they also experience motor learning impairments and non-motor symptoms such as depression. The neural basis for these different PD symptoms are not well understood. While current treatments are effective for locomotion deficits in PD, therapeutic strategies targeting motor learning deficits and non-motor symptoms are lacking. We found that distinct parafascicular (PF) thalamic subpopulations project to caudate putamen (CPu), subthalamic nucleus (STN), and nucleus accumbens (NAc). While PF-->CPu and PF-->STN circuits are critical for locomotion and motor learning respectively, inhibition of the PF-->NAc circuit induced a depression-like state. While chemogenetically manipulating CPu-projecting PF neurons led to a long-term restoration of locomotion, optogenetic long-term potentiation at PF-->STN synapses restored motor learning behavior in PD model mice. Furthermore, activation of NAc-projecting PF neurons rescued depression-like PD phenotypes. Importantly, we identified nicotinic acetylcholine receptors capable of modulating PF circuits to rescue different PD phenotypes. Thus, targeting PF thalamic circuits may be an effective strategy for treating motor and non-motor deficits in PD.
Clinical and genetic predictors of subthalamic nucleus deep brain stimulation in Parkinson’s disease
Compulsive-like seeking behavior correlates with AMPA receptor rectification in synapses of the subthalamic nucleus in a rat model of cocaine addiction
FENS Forum 2024
Glutamatergic neurons in the subthalamic nucleus regulate arousal and REM sleep
FENS Forum 2024
Interactions between the subthalamic nucleus and the primary motor cortex control parkinsonian motor and nociceptive disorders
FENS Forum 2024
Pathological delta oscillation in the subthalamic nucleus of rats with acute stroke relates to motor disability
FENS Forum 2024
Pathology of the subthalamic nucleus in Parkinson’s disease
FENS Forum 2024
The subthalamic nucleus controls nociceptive integration in the spinal cord and reverses nociceptive hypersensitivity in Parkinson’s disease
FENS Forum 2024
The subthalamic nucleus hyperdirect pathway neural dynamics during cocaine use and 'natural' reward seeking behavior – a pilot study
FENS Forum 2024
Subthalamic nucleus optogenetic inhibition reduces motivation for social interactions
FENS Forum 2024