PT  - JOURNAL ARTICLE
AU  - Samira Moorjani
AU  - Sarita Walvekar
AU  - Eberhard E. Fetz
AU  - Steve I. Perlmutter
TI  - Movement-Dependent Electrical Stimulation for Volitional Strengthening of Cortical Connections in Behaving Monkeys
AID  - 10.1101/2021.09.03.458906
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.03.458906
4099  - http://biorxiv.org/content/early/2021/10/09/2021.09.03.458906.short
4100  - http://biorxiv.org/content/early/2021/10/09/2021.09.03.458906.full
AB  - Correlated activity of neurons can lead to long-term strengthening or weakening of the connections between them. In addition, the behavioral context, imparted by execution of physical movements or the presence of a reward, can modulate the plasticity induced by Hebbian mechanisms. In the present study, we have combined behavior and induced neuronal correlations to strengthen connections in the motor cortex of adult behaving monkeys. Correlated activity was induced using an electrical-conditioning protocol in which stimuli gated by voluntary movements were used to produce co-activation of neurons at motor-cortical sites involved in those movements. Delivery of movement-dependent stimulation resulted in small increases in the strength of associated cortical connections immediately after conditioning. Remarkably, when paired with further repetition of the movements that gated the conditioning stimuli, there were substantially larger gains in the strength of cortical connections, that occurred in a use-dependent manner, without delivery of additional conditioning stimulation. In the absence of such movements, little change was observed in the strength of motor-cortical connections. Performance of the motor behavior in the absence of conditioning also did not produce any changes in connectivity. Our results show that combining movement-gated stimulation with further natural use of the “conditioned” pathways after stimulation ends can produce use-dependent strengthening of connections in adult primates, highlighting an important role for behavior in cortical plasticity. Our data also provide strong support for combining movement-gated stimulation with use-dependent physical rehabilitation for strengthening connections weakened by a stroke or spinal-cord injury.Significance Statement We describe an electrical-conditioning protocol in adult behaving monkeys in which stimuli gated by voluntary movements were used to strengthen connections between motor-cortical neurons involved in those movements. Movement-gated stimulation created a plastic landscape in which repetition of the movements that gated conditioning stimuli produced strengthening of cortical connections, in a use-dependent manner, long after stimulation had ended, a finding that is both novel and unique. In the absence of such behavior, little change was observed in the strength of connections. Similarly, movements alone did not produce any changes in connectivity. Our data highlight a critical role for behavior in plasticity and provide strong support for combining movement-gated stimulation with use-dependent rehabilitation for strengthening connections weakened by injury or disease.Competing Interest StatementThe authors have declared no competing interest.