Article

How does deep brain stimulation work? Present understanding and future questions

Emory University, Atlanta, Georgia, United States
Journal of Clinical Neurophysiology (Impact Factor: 1.6). 01/2004; 21(1):40-50. DOI: 10.1097/00004691-200401000-00006
Source: PubMed

ABSTRACT High-frequency deep brain stimulation (DBS) of the thalamus or basal ganglia represents an effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been vaulted forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address the present knowledge of the effects of high frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS. Four general hypotheses have been developed to explain the mechanism(s) of DBS: depolarization blockade, synaptic inhibition, synaptic depression, and stimulation-induced modulation of pathologic network activity. Using the results from microdialysis, neural recording, functional imaging, and neural modeling experiments, the authors address the main hypotheses and attempt to reconcile what have been considered conflicting results from different research modalities.

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    • "Without considering this nonlinear relationship, large deviations between the device-evoked responses and the desired responses are expected. In practice, such deviations can be mitigated by tuning the stimulation parameters (Lauer et al., 2000; O'Suilleabhain et al., 2003; McIntyre et al., 2004; Tellez-Zenteno et al., 2006; Rupp and Gerner, 2007; Albert et al., 2009; McLachlan et al., 2010). This optimization procedure is typically performed manually and empirically, e.g., assuming a static and linear relation between the stimulation pattern and the desired responses, and then searching for the optimal ratio between the stimulation intensity and the outcome responses via a trial-and-error procedure. "
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    Frontiers in Neural Circuits 02/2013; 7:20. DOI:10.3389/fncir.2013.00020 · 2.95 Impact Factor
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    • "These apparently contrasting effects can be reconciled by the observation that DBS is capable of inhibiting the spontaneous firing of STN and simultaneously generate a new pattern of activity (Garcia et al., 2003). This is consistent with the observation that DBS does not have the same impact on the neuronal soma and axon, suggesting that STN DBS could uncouple somatic and axonal activity (Holsheimer et al., 2000; McIntyre et al., 2004). Nevertheless, these observations regarding the effects of high-frequency DBS on neuronal activity (Garcia et al., 2005; Hammond et al., 2008) have failed to provide a satisfactory explanation for the paradoxical effects of DBS on motor function highlighted over a decade ago (Marsden and Obeso, 1994). "
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    Frontiers in Integrative Neuroscience 07/2012; 6:47. DOI:10.3389/fnint.2012.00047
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    • "In the last two decades, DBS has developed into an effective clinical approach to alleviate PD symptoms in certain patients. Yet, in spite of the phenomenal success of DBS in PD and several other neurological disorders (Benabid, 2003; Kringelbach et al., 2007), the biophysical and neuronal mechanisms underlying DBS functioning are still only poorly understood (Benabid, 2003; McIntyre et al., 2004; Kringelbach et al., 2007; Nambu, 2008). Also, it is well established that, while periodic high-frequency stimulation (HFS) of the STN is efficient for the treatment of PD symptoms, periodic low-frequency stimulation (LFS) may even aggravate motor impairment (Eusebio et al., 2008). "
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