Stimulating research
Click to enlarge. Description below.
Since the discovery of the chemical-electrical nature of brain function, scientists have artificially stimulated the brain with electric currents. Over the last decade, this technique has become refined enough to be used in the medical treatment of neurological disorders like Parkinson’s disease.
However, in medical application and basic research alike, one question remained largely unanswered: How do spontaneous and artificially evoked activity interact, and how does the current activity state of the brain influence the eventual effect of a stimulation paradigm? Applications like Deep Brain Stimulation would greatly benefit from an answer, making a new generation of stimulators possible that will adapt their stimulation patterns to brain activity in real-time.
In an article published in the Journal of Neurophysiology, the group of Prof. Ulrich Egert at the Bernstein Center Freiburg presents their findings about the relationship between stimulus and response in generic neuronal networks. The scientists worked in vitro with isolated networks of nerve cells, which are much easier to analyse than a whole brain and have fewer aspects to consider. The authors found that the networks’ answer to a stimulus followed certain rules, making the outcome more predictable. The responses started faster and lasted longer if the network was relatively inactive right before the stimulus started. They further found that the speed at which a stimulus was propagated throughout the network depended on the overall activity state of the network at the moment of stimulation. This was similar to the dependencies in the patterns of spontaneous activity.
Evidence from their experiments leads Egert’s team to believe that one reason for this effect is that excitability of the network decreases temporarily as a consequence of spontaneous activity and they become thus slower and weaker to respond if the subsequent recovery period is short.
In their article, the researchers from Freiburg describe a closed-loop control scheme to induce predictable activity patterns in neuronal networks by electrical stimulation. They implement a predefined timing of stimulation relative to spontaneous activity (see picture). This paradigm not only allowed them to study the stimulus-response interactions, but also enabled more reproducible responses in their experiments. This technique may help to predict the relationship of stimulus and response in neurotechnological devices and thus improve their efficacy.
Original article (subscription required):
Oliver Weihberger, Samora Okujeni, Jarno E. Mikkonen and Ulrich Egert (2013) Quantitative examination of stimulus-response relations in cortical networks in vitro. J Neurophysiol. 109: 1764-1774; published ahead of print December 28, 2012, doi:10.1152/jn.00481.2012
Image caption:
A: Raster plot of more than 2000 stimuli during a closed-loop experiment where stimulation was timed depending on the duration of pre-stimulus inactivity.
B: The variability of responses was lower compared to random timing of stimulation.
C: Response length variability across more than 10 experiments was smaller for stimuli in the closed-loop paradigm (fixed delay) compared to open-loop configuration (fixed IstimI).