Therapeutic mechanisms of high-frequency stimulation in Parkinson’s disease and neural restoration via loop-based reinforcement | Zendy

Sabato Santaniello | Zendy; Michelle M. McCarthy | Zendy; Erwin B. Montgomery | Zendy; John T. Gale | Zendy; Nancy Kopell | Zendy; Sridevi V. Sarma | Zendy

Open Access

Therapeutic mechanisms of high-frequency stimulation in Parkinson’s disease and neural restoration via loop-based reinforcement

Author(s) -

Sabato Santaniello,

Michelle M. McCarthy,

Erwin B. Montgomery,

John T. Gale,

Nancy Kopell,

Sridevi V. Sarma

Publication year - 2015

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.1406549111

Subject(s) - basal ganglia , neuroscience , striatum , stimulation , deep brain stimulation , reinforcement , parkinson's disease , stimulus (psychology) , medium spiny neuron , psychology , dopamine , medicine , disease , central nervous system , social psychology , psychotherapist

Significance We investigated the therapeutic mechanisms of high-frequency stimulation (HFS) in Parkinson’s disease by developing a computational model of the cortico-basal ganglia-thalamo-cortical loop in normal and parkinsonian conditions under the effects of stimulation at several frequencies. We found that the stimulation injected in the loop elicits neural perturbations that travel along multiple pathways with different latencies and rendezvous in striatum (one of the basal ganglia). If the stimulation frequency is high enough, these perturbations overlap (reinforcement) and cause more regular, stimulus-locked firing patterns in striatum. Overlap is maximal at clinically relevant HFS and restores more normal activity in the remaining structures of the loop. This suggests that neural restoration and striatal reinforcement may be a therapeutic merit and mechanism of HFS, respectively.

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