Network perspectives on the mechanisms of deep brain stimulation

Abstract

Deep brain stimulation (DBS) is an established medical therapy for the treatment of movement disorders and shows great promise for several other neurological disorders. However, after decades of clinical utility the underlying therapeutic mechanisms remain undefined. Early attempts to explain the mechanisms of DBS focused on hypotheses that mimicked an ablative lesion to the stimulated brain region. More recent scientific efforts have explored the wide-spread changes in neural activity generated throughout the stimulated brain network. In turn, new theories on the mechanisms of DBS have taken a systems-level approach to begin to decipher the network activity. This review provides an introduction to some of the network based theories on the function and pathophysiology of the cortico-basal-ganglia-thalamo-cortical loops commonly targeted by DBS. We then analyze some recent results on the effects of DBS on these networks, with a focus on subthalamic DBS for the treatment of Parkinson's disease. Finally we attempt to summarize how DBS could be achieving its therapeutic effects by overriding pathological network activity.

Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases

“…From the theoretical standpoint, interactions observed with rs-fcMRI are sensitive to the influence of polysynaptic connectivity (40,41,91,92). This sensitivity allows the identification of distant and complex network interactions that match well with data suggesting that the effects of brain stimulation are also polysynaptic (4,10,(26)(27)(28)(29)(30)(31)(32)(33). From the practical standpoint, prior work has used rs-fcMRI to predict the propagation of brain stimulation (93)(94)(95), link sites of invasive and noninvasive stimulation in depression (43), and identify biomarkers of the response to therapeutic brain stimulation (36).…”

“…Second, although therapeutic mechanisms remain unknown, invasive and noninvasive brain stimulation share important properties. In both cases, the effects of stimulation propagate beyond the stimulation site to impact a distributed set of connected brain regions (i.e., a brain network) (4,10,(26)(27)(28)(29)(30)(31)(32)(33). Given increasing evidence that these network effects are relevant to therapeutic response (4,(34)(35)(36), it is possible that invasive and noninvasive stimulation of different brain regions actually modify the same brain network to provide therapeutic benefit.…”

Submodularity in Dynamics and Control of Networked Systems

“…An important case is synchronization in the presence of external inputs [32]. External inputs arise in applications including neuroscience, where they represent environmental stimuli [46] or deep brain stimulation [87]. From an engineering standpoint, by introducing external inputs that pin a subset of nodes to a desired phase and frequency, a network that does not synchronize in the absence of inputs can be driven to a synchronized state, thus facilitating stability and performance of the network.…”

Deep brain stimulation: a mechanistic and clinical update

“…Proposed mechanisms of DBS can be grouped into 4 main categories: 1) inhibition of the target, the classic reversible functional lesioning paradigm; 2) activation of the target; 3) combined inhibition and activation; and 4) disruption of pathological oscillations to restore rhythmic activity and synchronization, the "noisy signal hypothesis." 134,141 Recent findings have mostly supported the view that therapeutic effects are related to alterations in ongoing oscillations. In PD, subthalamic nucleus (STN) field potentials have been found to exhibit abnormal phase-amplitude coupling and spike-local field potential (LFP) coupling to primary motor cortex.…”