Cognitive refractory state caused by spontaneous epileptic high frequency oscillations in the human brain
Epileptic brain tissue is often considered pathological and the conventional treatment of patients with uncontrollable seizures is to identify the tissue and aim for its complete resection. However, cognitive deficits ensuing surgical resection of epileptic tissue remains of critical concern. What also remains to be achieved in the current clinical practice of epilepsy is a means by which clinicians can distinguish pathological from physiological high frequency activity, and estimate the extent of healthy functions in the pathological epileptic tissue, and predict, at the individual patient level, if the cortical tissue can be removed without significant functional side effects.
We designed the current study to explore the presence or absence of stimulus-locked physiological high frequency broadband (HFB, 70 - 180 Hz) responses in a given epileptic tissue and determine its relationship with ongoing pathological high frequency oscillations (HFO, 80 - 500 Hz). We also devised a method by which the two activities can be reliably differentiated.
In all subjects, the epileptic brain sites generating abundant pathological HFOs were capable of generating stimulus-locked HFB responses (p < 0.05, FDR-corrected). Using a combination of selected features, pathological HFOs were successfully separated from functional activities with AUC = 0.96.
Potential causal relationship between the pathological HFOs and functional HFBs：pre-stimulus HFOs occurring shortly before (~1s) the presentation of stimulus are more associated with the absence or delay of HFBs. This effect is most significant when HFO occurs [-200~ +100 ms] around the onset of visual stimuli.
The ongoing pathological HFOs significantly impact the subjects’ behavioral performance
Our major findings indicate that brain structures involved with epileptogenicity elicit normal physiological responses to relevant cognitive stimuli. Task induced HFBs in an epileptic tissue are “seized” when spontaneous pathological HFOs occur right before the onset of stimulus. These ongoing pathological HFOs significantly impact the subjects’ behavioral performance. Lastly, we report a computerized method on the basis of which pathological and physiological high frequency activities can be automatically differentiated.