A closed-loop experiment
There is great interest in using brain stimulation to alleviate seizure disorders. Some closed-loop studies using EEG recordings to trigger macro-electrode stimuli are underway in animals and humans (Morrell, 2006; Colpan et al., 2007). As a demonstration of NeuroRighter's closed-loop capabilities, we triggered stimulation in epileptic rats based on the detection of interictal spikes, large ∼100 ms LFPs exhibited in most presentations of epilepsy (de Curtis and Avanzini, 2001). Upon each detection, a stimulus pulse was delivered within 4–5 ms, illustrating the ability of the device to close the loop in physiological time scales. While brief pulses of electrical stimulation have been shown to suppress afterdischarges in humans (Lesser et al., 1999), it was not surprising that the small currents used in this experiment (±10 μA) were ineffective in altering the interictal spikes (Figure 3B). They did, however, evoke action potentials (Figure 3A,C). Future studies will test whether stimulation applied with more electrodes to different regions, or with different parameters (rate, pulse width, etc.), is able to effectively control or suppress interictal spikes in animal models. Further details of this experiment are presented in Rolston et al. (2009a).
Figure 3  Closed-loop stimulation responses. (A) Biphasic current-controlled stimuli (cathodic, negative phase first; 400 μs per phase) were delivered to an electrode in CA1 of the hippocampus, and responses were recorded as seen here in CA3. Ten trials of every stimulus amplitude are overlaid in each panel. Stimulus duration is indicated by the red bar. The first action potentials appear at a certain stimulus threshold (≥6 μA, blue arrow), with the latency decreasing as current is increased (green arrowhead). Additional, less consistent action potentials are recruited at high stimulation intensities (purple asterisks). All traces were digitally filtered with the SALPA algorithm (Wagenaar and Potter, 2002). Stimuli were delivered at 1 Hz and in random order (to guard against neural adaptation). (B) The LFP of an electrode in CA3 was monitored for interictal spikes (IISs) and a single 10 μA biphasic current-controlled pulse was delivered to one microelectrode upon IIS detection (red X's in bottom panel). The displayed LFP trace (top panel) is from one electrode of an array implanted in CA1. The large amplitude is typical of LFPs during IISs and seizures. (C) A raster plot of action potentials recorded from all of the 16 electrodes during many IISs is shown, time-locked to the stimulus pulse. Action potentials are evoked by the stimulus at low latency following each pulse. The inset shows sample evoked AP waveforms recorded from one of the 16 electrodes during the experiment. This experiment is further characterized in Rolston et al. (2009a).