The effects of electrical microstimulation on cortical signal propagation

Abstract

Recurrence 1Electrical stimulation (ES) is used in animals and humans to study potential causal links between neural activity and specific cognitive functions. Recently, it has found increased application in electrotherapy and neural prostheses as well. However, how ES-elicited signals propagate in brain tissues is still unclear. Here we used combined electrostimulation, neurophysiology, microinjection and fMRI to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We find that stimulation of a site in LGN (lateral geniculate nucleus) increases the fMRI signal in the regions of primary visual cortex (V1) receiving input from that site, but suppresses it in the retinotopically matched regions of extrastriate cortex. In agreement with previous observations, intracranial recordings show that immediately after a stimulation pulse a long-lasting inhibition follows a short excitatory response. Following microinjections of GABA (γ-aminobutyric acid) antagonists in V1, LGN stimulation induces positive fMRI signals in all cortical areas. Taken together, our findings suggest that ES disrupts cortico-cortical signal propagation by silencing the output of any neocortical area whose afferents are electrically stimulated.We recently developed and optimized the esfMRI (combined ES and fMRI) methodology for experiments in anesthetized and behaving monkeys 1, 2 . Our first experiments, including fMRI-based estimations of tissue excitability (rheobase and chronaxie measurements), showed that electrical stimulation of the primary visual cortex V1 mainly excites large pyramidal cells and axons, eliciting positive BOLD responses (PBR) in topographically matched regions of extrastriate areas such as V2, V3, V3A, V4, and MT (V5); all monosynaptic targets of the primary visual cortex. These findings are consistent with the well-established anatomical connections between V1 and the extrastriate cortex of macaque monkeys 3 . One puzzling observation in our initial studies was the clear lack of transsynaptic effects during cortical stimulation. In the present study, we stimulated either the LGN or the pulvinar (Pul) in anesthetized and alert monkeys in order to systematically examine the propagation of ES-induced signals.We demonstrate that electrical stimulation of a thalamic site indeed suppresses the neural activity of its projection regions in visual cortex. The strong reduction in BOLD response is likely due to synaptic inhibition and it be can be reversed by injections of GABA antagonists in V1. In agreement with the fMRI results, intracortical recordings show that an electric pulse evokes an action potential followed by a pronounced and long-lasting inhibition. Such disruptive effects of cortical afferent stimulation on the activity of projection neurons have already been reported. Yet, by using the combined physiology, pharmacology and fMRI approach here we illustrate for the first time the extent and generality of ES-induced activity suppression, and we propose that many behavioral e...

Unravelling cerebellar pathways with high temporal precision targeting motor and extensive sensory and parietal networks

“…Th e only conceivable explanation we can think of is that we may have missed hitting the fi bre bundle in the SCP destined for prefrontal cortex. A fi nal note relates to the striking diff erence between the rather limited extent of stimulation eff ects observed aft er electrical stimulation of striate and extrastriate neocortex, confi ned to structures receiving monosynaptic input from the stimulation site 10,11,52 and the widespread polysynaptic stimulation eff ects seen aft er stimulating the DCN. Diff erences in inhibition probably constitute a crucial factor.…”

“…4a,b ). Unlike in cerebral cortex 10,11 , where electrical pulses at frequencies as low as 100 Hz evoke reliable BOLD responses (amplitudes of 3 standard deviation units (SDU), Fig. 5 in ref.…”

“…However, irrespective of the stimulation parameters, our striate and extrastriate cortex stimulation did not result in any transsynaptic propagation of the activity within the neocortex. By contrast, electrical stimulation of subcortical structures such as the optical tract revealed transsynaptic propagation of activity through the thalamus to the neocortex 10 . Synaptic pathways therefore show diff erent degrees of effi cacy in mediating activity evoked by electrical stimulation.…”

“…We decided to readdress the structure of cerebello -cerebral connections by using a novel technique that enabled us to delineate a more comprehensive pattern of cerebello -cerebral projections in an individual. Electrical stimulation, combined with functional magnetic resonance imaging (es-fMRI), is an important tool to study the functional properties of the spatially distributed neuronal networks of the brain 10,11 , and could be ideally suited to readdress the cerebello -cerebral connections. Our earlier studies in the neocortex showed that the evoked blood oxygen level-dependant (BOLD) responses were due to the stimulation of pyramidal axons 11 .…”

Setup and data analysis for functional magnetic resonance imaging of awake cat visual cortex

“…Although it may not be easy to train cats in tasks with a high cognitive load, similar to the work that has been performed in some monkey studies, the cat is more widely available and is a good candidate for fMRI experiments, especially for those combining fMRI with microstimulation [13] , microinjection [58] , pharmacological MRI combined with electrophysiology [59] , or reversible deactivation with a cooling system [60] . Our setup and motion-correction method represent critical first steps toward successful fMRI investigation in the awake cat.…”