Abstracts

Rationale: Cortical stimulation is playing an increasing role in clinical neuroscience in the treatment of epilepsy, stroke and pain. The neuromodulatory effects of cortical stimulation include both excitation and inhibition. As a result, cortical stimulation also influences cerebral hemodynamics, including perfusion and oxygenation, which may vary depending on the stimulation parameters.Methods: Using bipolar tungsten electrodes, the rat sensory neocortex was stimulated at variable frequencies in a pseudo-random fashion at 5 Hz, 10 Hz, 50 Hz, 100 Hz, and 250 Hz at a constant charge (CC) by varying the duration of stimulation. In a separate experiment constant duration (CD) was maintained by stimulating for 2 seconds at each of the frequencies. The amplitude remained constant at 1 mA. Simultaneous field potential (f.p.) recording and ORIS was performed at 570 nm and 610 nm to quantitatively measure total hemoglobin (Hbt) and deoxygenated hemoglobin (Hbr) with a modified Beer-Lambert calculation.Results: For both CC and CD conditions, a large increase in Hbr was recorded at all stimulation frequencies despite a large increase in Hbt. The maximum increase occurred at 10 Hz to 50 Hz for the CC condition while the maximum increase for the CD condition occurred at 50 Hz to 100 Hz (n=6). There was a significant correlation between the duration of stimulation and the duration of the increase in both Hbr and Hbt. However, the duration of initial dip in Hbr was generally slightly shorter than the duration of stimulation. In contrast, the duration of the increase in Hbt was longer than the duration of stimulation by more than 10 seconds, regardless of frequency. A triphasic response in Hbr, characterized by an initial dip, a BOLD signal, and a secondary dip, was commonly observed. Conclusions: These results demonstrate that direct bipolar cortical stimulation causes a large increase in metabolic demand in a cortical neuronal population, resulting in a transient mismatch between perfusion and oximetry signals. Our results also indicate that the duration of stimulation is more important than the frequency in determining the duration of the increase in Hbr and that the relationship between frequency and both Hbt and Hbr is not linear.