Acute modulation of the limbic network with low and high-frequency stimulation of the human fornix

Targeted stimulation of white matter has opened newer perspectives in the field of neuromodulation, towards an attempt to improve memory or as a therapy for epilepsy. Stimulation of the fornix, being a part of the Papez circuit, is likely to modulate the limbic network excitability. However, the stimulation-frequency dependent variability in network excitability is unknown. In the case study, which involved stereo electroencephalographic (SEEG) recording of field potentials in a 48-year old left-handed woman with suspected temporal lobe epilepsy, we demonstrated the network effects of acute low (1 and 10 Hz) and high (50 Hz) frequency electrical stimulation of fornix. Mapping the short-latency evoked responses to forniceal stimulation confirmed the SEEG target localization within the Papez circuit. Low and high-frequency stimulation of the fornix produced opposite effects in the post-stimuli excitability, with the latter causing increased excitability in the limbic network that culminated in a clinical seizure. A distinct spectral peak around 8 Hz confirmed that sensing field potentials from the forniceal white matter is feasible. This is the first case study that provided an insight into how the temporal patterning of forniceal stimulation altered the downstream limbic network excitability.