DBS target

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Disorders currently under investigation with deep brain stimulation

See movement disorder

Disorder	Circuit	Postulated circuit dysfunction	DBS target(s) being studied or that could be considered	Stage of study
Parkinson disease, essential tremor or dystonia	Motor	- Beta and theta oscillations - GPi overactivity - STN overactivity - Neuronal bursting	STN, GPi, GPe, VL thalamus, PPN and spinal cord	Standard of care
Major depression	Limbic	- Increased activity in OFC, SCC, amygdala and VS - Failure to downregulate amygdalar activation	SCC, NAcc, habenula and medial forebrain bundle	Phase III
Obsessive–compulsive disorder	Motor and limbic	- OFC hyperactivity - Failure of VS-mediated thalamofrontal inhibition	NAcc, BNST, ITP, ALIC and STN	Phase II/III
Tinnitus	Auditory	- Sensory deafferentation - Thalamocortical dysrhythmia	Auditory pathways and caudate nucleus	Phase I
Tourette syndrome	Motor and limbic	- Overactive direct pathway - Failure of thalamocortical inhibition	GPi and CM–Pf	Phase I
Schizophrenia — positive symptoms	Executive function, cognition and reward	- Thalamocortical dysrhythmia - Failure of saliency networks	Temporal cortex and NAcc	Preclinical
Schizophrenia — negative symptoms	Motivation, reward, cognition and mood	- Mesolimbic and mesocortical dysfunction - Failure to engage anticipatory hedonic system	NAcc, VTA and SCC	Preclinical
Alzheimer disease	Cognitive and memory circuits	- Amyloid-β plaques throughout the brain - Default mode network dysfunction - Cholinergic degeneration - Entorhinal cortex and hippocampal atrophy	Fornix, entorhinal cortex, hippocampus, cingulate, precuneus, frontal cortex and nucleus basalis	Phase II/III
Pain (phantom pain, deafferentation pain, central pain and nociceptive pain)	Sensory systems and interoceptive awareness	- Sensory deafferentation - Abnormal neuronal spontaneous bursting behaviour	Sensory pathways, periventricular and periaqueductal areas, cingulate and insula	Phase I/II
Addiction	Reward	NAcc sensitivity to reward	NAcc	Phase I/II
Anorexia nervosa	Reward and mood	- Frontoparietal disconnection - Parietal hypometabolism - Insular abnormality - SCC overactivity	SCC and NAcc	Phase II
Epilepsy	Various	Abnormal excitability and synchrony	CM thalamus, anterior thalamic nucleus, thalamus and seizure focus	Phase II/III

ALIC, anterior limb of the capsula interna; BNST, bed nucleus of stria terminalis; CM, centromedian; CM–Pf, CM–parafascicular; GPe, globus pallidus externus; GPi, globus pallidus internus; ITP, inferior thalamic peduncle; NAcc, nucleus accumbens; OFC, orbitofrontal cortex; PPN, pedunculopontine nucleus; SCC, subgenual cingulate cortex; STN, subthalamic nucleus; VL, ventral lateral; VS, ventral striatum; VTA, ventral tegmental area.

Target

Indication	Deep brain targets
Parkinson’s disease	Globus pallidus interna, subthalamic nucleus
Dystonia	Globus pallidus interna
Tremor	Ventralis intermedius thalamic nucleus, zona incerta
Depression	Subgenual cingulate cortex, anterior limb of internal capsule
Obsessive-compulsive disorder	Anterior limb of internal capsule
Tourette’s syndrome	Ventromedial thalamus, anterior limb of internal capsule, globus pallidus interna
Epilepsy	Anterior thalamic nucleus, centromedian thalamic nucleus
Cluster headache	Posterior hypothalamus

Reference: FitzGerald 2018

VIM: coordinates atlas

Medial-laterally (X)

14-15 mm from the medial line or
11-11.5 mm from the wall of the third ventricle;

Anteroposteriorly (Y)

3-7 mm anterior to the PC, or
3-4 mm posterior to the mid-commissural point;

Midpoint (Z) at the AC-PC line

GPi

Intercommissural (AC-PC) line

19–21 mm laterally from the midline
2.5 mm in front of the AC-PC midpoint
5 mm below the AC-PC line

STN

X = 11mm
Y = − 2.5mm
Z = − 4.5mm

EMBO Molecular Medicine DBS targets in coronal view In projection circa 5 mm anterior to 1 mm anterior C Mechanisms Of deep brain stimulation DBS targets in coronal view Martin Jakobs et al In projection circa midcommissural point to 6mm behind anterior commissure a b c d e DBS targets in coronal view dACC — Dorsal anterior cingulate cortex • Indication: • Chronic pain • Effect: • Improved affective component of pain Fornix • Indication: • Alzheimer's disease • Effect: • Decreased decline in memory/ improvement of memory SCG — Subcallosal cingulate gyrus • Indication: • Depression • Effect: • Improvement of mood and anxiety ALIC — Anterior limb of internal capsule (ventral capsule/ventral striatum) • Indication: • Depression • OCD• • Effect: • Improvement of mood and anxiety • Improvement of compulsive behavior NACC — Nucleus accumbens (ventral capsule/ ventral striatum) • Indication: • Addiction midcommissural point Thalamic DBS targets a b c Vim — Ventral intermediate thalamus • Indication: • Tremor* • Reduction of tremor STN — Subthalamic nucleus • Indication: • Parkinson's disease • Effect: (motor areas) • • OCD (limbic areas) • Reduction of dystonia • Reduction of rigidity, tremor and bradykinesia • Reduction of compulsive behavior PHyp — Posterior hypothalamus • Indication: • Cluster headache • Effect: • Reduction of cluster headache attacks Right thalamus: Laterosuperior view Medial Anterior • Effect: • Depression • Tourette syndrome • Improvement of craving • Improvement of mood • Improvement of tics ANT VL Pulvinar In projection circa 1 mm anterior anterior commissure to midcommissural point Internal medullary lamina Posterior LHA — Lateral hypothalamic area • Indication: • Obesity Vim FVPM Lateral — Coronal cross section a b c d • Effect: • Increased satiety cm nuclei VPL VPM NBM — Nucleus basalis of Meynert • Indication: • Dementia • Effect: • Reduced decline in memory GPi — Globus pallidus internus • Indication: • Dystonia• a b c d e ANT — Anterior nucleus of the thalamus • Indication: • Epilepsy' • Effect: • Reduction in seizures • Effect: • Parkinson's disease' • Tourette syndrome • Reduction of dystonia • Reduction of rigidity, bradykinesia and dyskinesia • Reduced tics Gpe — Globus pallidus extemus • Indication: • Huntington's disease (in combination with GPi) • Reduced choreatic movements • Decreased cognitive decline (in combination with GPi) Figure 7. • Effect: Overview Of selected targets for DBS. Cm-Voi — Centromedian nucleus, ventro-oralis internus • Indication: • Tourette syndrome • Effect: • Reduction of tics Vim — Ventral intermediate nucleus • Indication: • Tremor* • Effect: • Reduction of tremor VPM/VPL Ventral posteromedial nucleus/ Ventral posterolateral nucleus • Indication: • Neuropathic deafferentation pain • Effect: • Reduction of pain Cm-Pf — Centromedian and parafascicular nuclei • Indication: • Pain and epilepsy • Effect: • Reduction of chronic pain and seizures Location Of DBS targets for established and investigational indications: (A) DBS targets in coronal projection view (rostra' to anterior commlssure), (B) DBS targets in coronal projection view (anterior commissure to midcommissural point), (C) midcommissural point to posterior commissure), and (D) overview of thalamic DBS targets. 12 of 18 EMBO Molecular Medicine | 2019 0 2019 The Authors — Overview of selected targets for DBS. Location of DBS targets for established and investigational indications. (A) DBS targets in coronal projection view (rostral to anterior commissure), (B) DBS targets in coronal projection view (anterior commissure to midcommissural point), (C) midcommissural point to posterior commissure, and (D) overview of thalamic DBS targets.

Pedunculopontine nucleus (PPN)

Upper pons in the dorsolateral portion of the ponto-mesencephalic tegmentum. Its main mass is positioned at the trochlear nucleus level, and is part of the mesenphalic locomotor region (MLR) in the upper brainstem.

In PD patients, GABAergic BG output levels are abnormally increased, and gait disturbances are produced via abnormal increases in SNr-induced inhibition of the MLR.

Good DBS target for Gait and freezing

Anatomical Characterization of the Human Structural Connectivity between the Pedunculopontine Nucleus and Globus Pallidus via Multi-Shell Multi-Tissue Tractography

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