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

The subthalamic nucleus hyperdirect pathway neural dynamics during cocaine use and 'natural' reward seeking behavior – a pilot study

FENS Forum 2024

Behavioral and electrophysiological characterization of different functional regions of the subthalamic nucleus in healthy non-human primates

Experimental investigation into the role of the subthalamic nucleus (STN) using optogenetics in mice

FOXP1 and nNOS neuronal populations in the adult human, mouse and rat subthalamic nucleus

Investigating the electrical stimulation of subthalamic nucleus for the treatment of cortical stroke

Molecular markers of the prenatal human subthalamic nucleus

Relationship between tonic dopamine level and aperiodic component from local field potentials of the subthalamic nucleus in hemiparkinsonian rats

Reversing escalated cocaine intake with social contact and optogenetic modulation of the subthalamic nucleus

Subthalamic nucleus deep brain stimulation reduces alcohol intake in rats under influence of proximal social factors

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

Subthalamic nucleus optogenetic inhibition reduces motivation for social interactions

FENS Forum 2024