Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation

Abstract

This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson’s disease, Huntington’s disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms.

Antagonistic but Not Symmetric Regulation of Primary Motor Cortex by Basal Ganglia Direct and Indirect Pathways

“…SNr provides GABAergic innervation of the ventrolateral thalamus (VL), which closes the loop via glutamatergic projections to cortex. This anatomical model explains the contributions of the BG to motor control, as well as the mechanisms by which symptoms of Parkinson’s disease are ameliorated by deep brain stimulation (Da Cunha et al, 2015) and is supported by lesion and pharmacological (Mink, 1996) as well as genetic and optogenetic (Bateup et al, 2010; Kravitz et al, 2010) studies.…”

Resting-state functional connectivity modulates the BOLD activation induced by nucleus accumbens stimulation in the swine brain

“…Dysfunctional functional connectivity between the NAc and various brain regions has been implicated in many neuropsychiatric disorders (Da Cunha, et al, 2015). Combining NAc-DBS with functional imaging permits causal relationships between the stimulation and modulation of functional networks to be mapped, thus providing insights into the underlying mechanisms responsible for therapeutic and adverse effects for neuropsychiatric disorders.…”

Computational modeling of neurostimulation in brain diseases

“…DBS in PD is one of the most common treatment options when patients develop disabling motor symptoms, with the subthalamic nucleus (STN) and globus pallidus interna (GPi) being the primary stimulation targets (Miocinovic et al, 2013). However, following its incidental discovery in 1987 (Benabid et al, 1987), the mechanism of action of the DBS therapy is still debated (Da Cunha et al, 2015;DeLong and Wichmann, 2012;Dostrovsky and Lozano, 2002;Lobb, 2014;McIntyre and Hahn, 2010) and its effects are not consistent for all patients. Proposals range from DBS introducing antidromic action potentials stimulating the motor cortex (Li et al, 2012) to DBS changing the large-scale structural connectivity of the brain (van Hartevelt et al, 2014).…”

“…This does not only come with technical drawbacks, such as batteryrecharging issues, but also some potential negative side effects (e.g., confusion, delirium, weight-gain, cognitive impairment) have been noted as a result of the permanent stimulation (Da Cunha et al, 2015). Hence, some effort has been invested in the development of closed-loop on-demand protocols (see Carron et al, 2013;Modolo et al, 2015, for motivation and review).…”