Penfield’s Prediction: A Mechanism for Deep Brain Stimulation

Abstract

Context: Despite its widespread use, the precise mechanism of action of Deep Brain Stimulation (DBS) therapy remains unknown. The modern urgency to publish more and new data can obscure previously learned lessons by the giants who have preceded us and whose shoulders we now stand upon. Wilder Penfield extensively studied the effects of artificial electrical brain stimulation and his comments on the subject are still very relevant today. In particular, he noted two very different (and seemingly opposite) effects of stimulation within the human brain. In some structures, artificial electrical stimulation has an effect, which mimics ablation, while, in other structures, it produces a stimulatory effect on that tissue.Hypothesis: The hypothesis of this paper is fourfold. First, it proposes that some neural circuits are widely synchronized with other neural circuits, while some neural circuits are unsynchronized and operate independently. Second, it proposes that artificial high-frequency electrical stimulation of a synchronized neural circuit results in an ablative effect, but artificial high-frequency electrical stimulation of an unsynchronized neural circuit results in a stimulatory effect. Third, it suggests a part of the mechanism by which large-scale physiologic synchronization of widely distributed independently processed information streams may occur. This may be the neural mechanism underlying Penfield’s “centrencephalic system,” which he emphasized so many years ago. Fourth, it outlines the specific anatomic distribution of this physiologic synchronization, which Penfield has already clearly delineated as the distribution of his centrencephalic system.Evidence: This paper draws on a brief overview of previous theory regarding the mechanism of action of DBS and on historical, as well as widely known modern clinical data regarding the observed effects of stimulation delivered to various targets within the brain. Basic science investigations, which support the hypothesis are also cited.Conclusion: This paper proposes a novel hypothesis for the mechanism of action of DBS, which was conceptually foreshadowed by Wilder Penfield decades ago.

Selective Activation of Resting-State Networks following Focal Stimulation in a Connectome-Based Network Model of the Human Brain

“…7 ). This study should also serve as a good starting point to investigate repetitive stimulation (e.g., with respect to deep brain stimulation; Murrow, 2014 ) and the spatiotemporal dynamics of brain resonance phenomena ( Spiegler et al, 2011 ).…”

Low frequency deep brain stimulation in the inferior colliculus ameliorates haloperidol-induced catalepsy and reduces anxiety in rats

“…The fact that opposite effects can be obtained stimulating the same site at the same structure only by using different stimulation parameters, raises the question whether this is also the case for other brain structures. Indeed, opposing effects of DBS have already been demonstrated when the electrode is placed in different sites at the same structure [ 27 – 29 ], or when it is misplaced [ 30 ], which is not our case.…”

Entorhinal Cortical Deep Brain Stimulation Rescues Memory Deficits in Both Young and Old Mice Genetically Engineered to Model Alzheimer’s Disease

“…Although these lines of evidence suggest that the procognitive effects of EC-DBS are at least partly mediated by reduction in plaques and enhancement in adult hippocampal neurogenesis, they do not preclude the involvement of other mechanisms. For instance, DBS has been proposed to excite or inhibit local neurons (Kringelbach et al, 2007, Chiken andNambu, 2016), modulate neurotransmission (Chiken and Nambu, 2016), restore disrupted circuit activity (Mayberg et al, 2005,Laxton et al, 2010, or synchronize brain activity (Murrow, 2014). Further studies are required to address these questions.…”