No abstract

Deep brain stimulation (DBS) of the subthalamic nucleus, pallidum, and thalamus is an established therapy for various movement disorders. Limbic targets have also been increasingly explored for their application to neuropsychiatric and cognitive disorders. The brainstem constitutes another DBS substrate, although the existing literature on the indications for and the effects of brainstem stimulation remains comparatively sparse. The objective of this review was to provide a comprehensive overview of the pertinent anatomy, indications, and reported stimulation-induced acute and long-term effects of existing white and grey matter brainstem DBS targets. We systematically searched the published literature, reviewing clinical trial articles pertaining to DBS brainstem targets. Overall, 164 studies describing brainstem DBS were identified. These studies encompassed 10 discrete structures: periaqueductal/periventricular grey (n = 63), pedunculopontine nucleus (n = 48), ventral tegmental area (n = 22), substantia nigra (n = 9), mesencephalic reticular formation (n = 7), medial forebrain bundle (n = 8), superior cerebellar peduncles (n = 3), red nucleus (n = 3), parabrachial complex (n = 2), and locus coeruleus (n = 1). Indications for brainstem DBS varied widely and included central neuropathic pain, axial symptoms of movement disorders, headache, depression, and vegetative state. The most promising results for brainstem DBS have come from targeting the pedunculopontine nucleus for relief of axial motor deficits, periaqueductal/periventricular grey for the management of central neuropathic pain, and ventral tegmental area for treatment of cluster headaches. Brainstem DBS has also acutely elicited numerous motor, limbic, and autonomic effects. Further work involving larger, controlled trials is necessary to better establish the therapeutic potential of DBS in this complex area.

Background: Panic attacks affect a sizeable proportion of the population. The neurocircuitry of panic remains incompletely understood. Objective: To investigate the neuroanatomical underpinnings of panic attacks induced by deep brain stimulation (DBS) through (1) connectomic analysis of an obsessive-compulsive disorder patient who experienced panic attacks during inferior thalamic peduncle DBS; (2) appraisal of existing clinical reports on DBS-induced panic attacks. Methods: Panicogenic, ventral contact stimulation was compared with benign stimulation at other contacts using volume of tissue activated (VTA) modelling. Networks associated with the panicogenic zone were investigated using state-of-the-art normative connectivity mapping. In addition, a literature search for prior reports of DBS-induced panic attacks was conducted. Results: Panicogenic VTAs impinged primarily on the tuberal hypothalamus. Compared to nonpanicogenic VTAs, panicogenic loci were significantly functionally coupled to limbic and brainstem structures, including periaqueductal grey and amygdala. Previous studies found stimulation of these areas can also provoke panic attacks. Conclusions: DBS in the region of the tuberal hypothalamus elicited panic attacks in a single obsessivecompulsive disorder patient and recruited a network of structures previously implicated in panic pathophysiology, reinforcing the importance of the hypothalamus as a hub of panicogenic circuitry.