Effects of midazolam on high-frequency oscillations in amygdala and hippocampus of epilepsy patients.

High-frequency oscillations (HFOs) are associated with normal brain function, but are also increasingly recognized as potential biomarkers of epileptogenic tissue. Considering the important role of interneuron activity in physiological HFO generation, we studied their modulation by midazolam (MDZ), an agonist of γ-aminobutyric acid type A (GABAA)-benzodiazepine receptors. Here, we analyzed 80 intracranial electrode contacts in amygdala and hippocampus of 13 patients with drug-refractory focal epilepsy who had received MDZ for seizure termination during presurgical monitoring. Ripples (80-250 Hz) and fast ripples (FRs; 250-400 Hz) were compared before and after seizures with MDZ application, and according to their origin either within or outside the individual seizure onset zone (SOZ). We found that MDZ distinctly suppressed all HFOs (ripples and FRs), whereas the reduction of ripples was significantly less pronounced inside the SOZ compared to non-SOZ contacts. The rate of FRs inside the SOZ was less affected, especially in hippocampal contacts. In a few cases, even a marked increase of FRs following MDZ administration was seen. Our results demonstrate, for the first time, a significant HFO modulation in amygdala and hippocampus by MDZ, thus giving insights into the malfunction of GABA-mediated inhibition within epileptogenic areas and its role in HFO generation.

Long-term versus short-term memory deficits for faces in temporal lobe and generalized epilepsy patients.

It is still an open question whether short-term and long-term memory are two anatomically dissociable memory systems working in parallel or whether they are represented by neural circuits within similar cortical areas. Epilepsy may be used as a model to study these memory processes. We hypothesized that a double dissociation of short-term and long-term memory exists in temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE). Immediate and 24-hour face recognition was tested in 10 TLE patients, 9 IGE patients, and 10 healthy controls. TLE patients' immediate recognition was unimpaired, but their memory scores were reduced as compared to healthy controls after 24 hours. In IGE patients, memory was already reduced during immediate recognition. These results are in line with the idea that short-term memory is a transient trace that requires consolidation supported by the medial temporal lobe to change into a more stable status of long-term memory.

Long-term face memory as a measure of right temporal lobe function in TLE: the Alsterdorfer Faces Test.

There is a shortage of neuropsychological tests to assess right temporal lobe memory function in TLE patients. Although right temporal lobe dominance for face memory is well established, neuropsychological studies on face memory in epilepsy surgery candidates have reported mixed results. These latter studies in TLE patients mostly concentrated on immediate face recognition. There is evidence suggesting that increasing test delays raise the sensitivity of neuropsychological face recognition tests to predict face memory decline after right temporal lobectomy. Long-term face recognition may also help in lateralizing right TLE in preoperative patients with little or no hippocampal sclerosis. In this context, we will introduce the Alsterdorfer Faces Test, a computerized long-term face memory test developed in the clinical context of an epilepsy center.

Remembering versus knowing during face recognition in unilateral temporal lobe epilepsy patients with or without hippocampal sclerosis.

Recognition memory involves knowing an item was learned (familiarity) and remembering contextual details about the prior learning episode (recollection). We tested three competing hypotheses about the role of the hippocampus in recollection and familiarity. It mediates either recollection or familiarity, or serves both processes. We further tested whether the left temporal lobe mediates recollection and the right temporal lobe familiarity (modes of processing view), or whether the two temporal lobes mediate remembering material specifically (material specificity view). We investigated 24-h face recognition using the "remember-know" procedure. We studied 23 left and 24 right temporal lobe epilepsy (LTLE/RTLE) patients with and without hippocampal sclerosis (HS+/HS-) and 31 healthy participants. HS+ patients made fewer know responses than HS- patients or healthy participants. RTLE was related to fewer remember responses than LTLE. Our results suggest the hippocampus has a critical role in familiarity. Further, our findings support the material specificity hypothesis of laterality.

Face memory in MRI-positive and MRI-negative temporal lobe epilepsy.

PURPOSE: Effects of MRI-positive (MRI(+)) as compared to MRI-negative (MRI(-)) temporal lobe epilepsy (TLE) on face memory are not yet known. METHODS: We studied 24 MRI(-) (11 right/13 left) and 20 MRI(+) (13 right/7 left) TLE patients, 12 generalized epilepsy patients, and 12 healthy subjects undergoing diagnostic workup with 24-72-h Video-EEG-monitoring. Twenty faces were shown, and had to be recognized from 40 faces immediately and after a 24-h delay. RESULTS: MRI(+) and MRI(-) right TLE (RTLE) patients showed deficits in face recognition compared to controls or generalized epilepsy, consistent with right temporal lobe dominance for face recognition. MRI(+) RTLE patients had deficits in both immediate and delayed recognition, while MRI(-) RTLE patients showed delayed recognition deficits only. The RTLE groups showed comparable delayed recognition deficits. Separate analyses in which the MRI(+) group included patients with hippocampal sclerosis only, did not alter results. Furthermore, MRI(-) RTLE had a worse delayed recognition than MRI(-) left TLE (LTLE). On the other hand, MRI(+) RTLE did not differ from MRI(+) LTLE in delayed recognition. Combining MRI(-) and MRI(+) TLE groups, we found differences between RTLE and LTLE in delayed, but not immediate face recognition. CONCLUSIONS: Our results suggest that a delayed recognition condition might be superior to immediate recognition tests in detecting face memory deficits in MRI(-) RTLE patients. This might explain why former studies in preoperative patients did not observe an immediate face recognition dominance of the right temporal lobe when combining MRI(-) and MRI(+) TLE patients. Our data further point to an important role of the right mesial temporal region in face recognition in TLE.

A novel high channel-count system for acute multisite neuronal recordings.

Multisite recording represents a suitable condition to study microphysiology and network interactions in the central nervous system and, therefore, to understand brain functions. Several different materials and array configurations have been proposed for the development of new probes utilized to record brain activity from experimental animal models. We describe new multisite silicon probes that broaden the currently available application base for neuroscientists. The array arrangement of the probes recording sites was extended to increase their spatial resolution. Probes were integrated with a newly developed electronic hardware and novel software for advanced real-time processing and analysis. The new system, based on 32- and 64-electrode silicon probes, proved very valuable to record field potentials and single unit activity from the olfactory-limbic cortex of the in vitro isolated guinea-pig brain preparation and to acutely record unit activity at multiple sites from the cerebellar cortex in vivo. The potential advantages of the new system in comparison to the currently available technology are discussed.