Electrical Microstimulation: Mapping Monosynaptic Connectivity & Cortico-Thalamo-Cortical Loops

Abstract: Direct Electrical stimulation (DES) of the brain has been performed for over 100 years, and although some might say it is a crude technique for understanding the detailed mechanisms underlying different neural computations, microstimulation has made significant contributions to our knowledge in both basic and clinical research. Recently there has been resurgence in its use in the context of electrotherapy and neural prostheses. For example, ES has made it possible to at least partially restore hearing to deaf patients by delivering pulses via implanted electrodes to different regions of the cochlea. Stimulation of the basal ganglia is remarkably effective in restoring motor function to Parkinson’s patients, and microstimulation of the geniculostriate visual pathway is regarded by some as a very promising (future) method for making the blind see again. Yet, the methodology still suffers from many fundamental problems; For example, we do not always know exactly what is being stimulated when we pass currents through the tissue; Neither do we know how electrically induced signals propagate in cortex. Moreover stimulation causes activation in a large number of areas even outside the stimulation site, making it difficult to isolate and evaluate the behavioral effects of the stimulated area itself. DES combined with fMRI (DES-fMRI) could – in principle – provide a unique opportunity to gain insights into global signal-propagation, to visualize the networks underlying electrostimulation-induced behaviors, to map neuromodulatory systems, or to develop electrotherapy and neural prosthetic devices. In my talk, I shall discuss findings from recent and on-going work on signal propagation during electrical stimulation in monkeys.  In short, our first findings suggest that DES has an important limitation: It clearly demarcates all monosynaptic targets of a stimulated site, but it largely fails to reveal polysynaptic cortico-cortical connectivity. Behaviors induced by DES or for that matter by transcranial magnetic stimulation (TMS) likely reflect cortico-subcortico-cortical pathways rather than direct cortico-cortical communication. To further optimize the stimulation methodology we have also employed optogenetics, and compared it with DES by stimulating thalamus. Specifically, we compared cell targeted optogenetics and electrical microstimulation in the macaque monkey brain to functionally map the koniocellular lateral geniculate nucleus (LGN) projection to primary visual cortex (V1).  Selective activation of the LGN konio neurons with CamK-specific optogenetics caused selective electrical current inflow in the supra-granular layers of V1. Electrical microstimulation targeted at LGN konio layers revealed the same supra-granular V1 activation pattern as the one elicited by optogenetics. Taken together, these findings establish a selective koniocellular LGN influence on V1 supra-granular layers and indicate comparable capacities of both stimulation methods to isolate thalamo-cortical circuits in the primate brain.