Differential effects of open- and closed-loop intracortical microstimulation on firing patterns of neurons in distant cortical areas

Background Intracortical microstimulation can be used successfully to modulate neuronal activity. Activity-dependent stimulation (ADS), in which action potentials recorded extracellularly from a single neuron are used to trigger stimulation at another cortical location (closed-loop), is an effective treatment for behavioral recovery after brain lesion in rodents. Neurophysiological changes in cortical communication induced by ADS, and how these changes differ from those induced by open-loop random stimulation (RS) are still not clear. Objectives We investigated the ability of ADS and RS to induce changes in firing patterns in distant populations of neurons in healthy anesthetized rats. Methods For this study we used 23 adult Long-Evan rats, recording from a total of 591 neuronal units. Stimulation was delivered to either forelimb or barrel field somatosensory cortex, using either randomly-timed stimulus pulses or ADS triggered from neuronal spikes recorded in the rostral forelimb area (RFA) of the motor cortex. Results Both RS and ADS stimulation protocols rapidly altered spike firing within RFA compared with no stimulation. Changes consisted of increases in mean firing rates and patterns of spike firing as measured by the revised Local Variation metric. ADS was more effective than RS in increasing short-latency evoked spikes during the stimulation periods, by producing a reliable, progressive increase in stimulus-related activity over time. Conclusions These results are critical for understanding the efficacy of electrical microstimulation protocols in altering activity patterns in interconnected brain networks. These data further strengthen the idea that activity-dependent microstimulation, can be used to modulate cortical state and functional connectivity.