Rationale: Patients with epilepsy often have co-occurring mood changes in association with seizures or comorbid mood disorders. Psychiatric symptoms often impact quality of life more negatively than seizure frequency or severity, even after seizure control is accomplished. Elucidating the relationship between seizures, inter-ictal epileptiform activity, and psychiatric symptoms is complicated by the dynamic nature of these features over time and between individuals. Ecological momentary assessments (EMAs) of psychiatric symptoms combined with ambulatory long-term intracranial electroencephalographic (iEEG) recordings provide the essential tools to understand psychiatric symptoms in patients with epilepsy, and to identify potential targets for their treatment. Methods: Data were collected as part of clinical trial NCT03946618. One human subject with bilateral temporal lobe epilepsy was implanted with the investigational Medtronic Summit RC+S sense and stimulation device with electrodes bilaterally in hippocampus (Hc) and anterior nucleus of the thalamus (ANT). Therapeutic stimulation was delivered to the ANT. Continuous iEEG data from four bipolar sensing channels covering bilateral Hc along the long axis were streamed from the device to a hand-held tablet computer using Epilepsy Personal Assistant Device (EPAD) and a cloud platform for automated analysis and visual review. Seizures and spikes were detected offline and used to determine accurate gold standard seizure diary and inter-ictal epileptiform spike rates. Spike rates were calculated at the most anterior Hc bipolar contacts, proximal to the amygdala, bilaterally. The subject was prompted by EPAD, to complete EMAs randomly at intervals of one to five days between 10:00 AM and 7:00 PM. EMAs included two items addressing sleep quality and the 12-item Immediate Mood Scaler. Beck Depression Inventory, GAD-7, PHQ-9, and Columbia Suicide Severity Rating Scale were completed at in-person visits. Results: The subject completed over nine months of ecological momentary assessments, including a two-month baseline prior to device implantation. Only IMS-12 scores separated by a minimum of two hours were used in this analysis with most scores separated by three days on average. The IMS-12 score was negatively correlated with interictal spike rate at the right anterior Hc contacts (r = -0.522, p = 0.001), but not at the left Hc, during the 30 minute period preceding EMA completion. The IMS-12 score did not correlate with time to next seizure and did not differ between seizure and non-seizure days. Conclusions: These results suggest a long-term association between inter-ictal epileptiform activity and mood state in this individual subject. Interestingly, the spike rate in the left Hc, the side with the higher baseline inter-ictal epileptiform spike rate and the origin of most seizures, did not significantly correlate with mood score. The high seizure frequency in this subject may be a limitation in assessing the relationship between pre-ictal state and mood, as has previously been published. Although the inclusion of n = 1 subject is a limitation and notable consideration for the statistical interpretation of this early analysis, this is the first study to track inter-ictal spike rates and EMAs in a freely behaving human subject long term. Future directions include assessing Hc spectral features and mood state in this subject. Funding: Please list any funding that was received in support of this abstract.: NIH Brain Initiative UH2/3 NS095495 NIH R01NS092882
