Dissecting out conscious and unconscious memory (sub)processes within the human medial temporal lobe.

The human medial temporal lobe (MTL) system mediates memories that can be consciously recollected. However, the specific natures of the individual contributions of its various subregions to conscious memory processes remain equivocal. Here we show a functional dissociation between the hippocampus proper and the parahippocampal region in conscious and unconscious memory as revealed by invasive recordings of limbic event-related brain potentials recorded during explicit and implicit word recognition: Only hippocampal and not parahippocampal neural activity exhibits a sensitivity to the implicit versus explicit nature of the recognition memory task. Moreover, only within the hippocampus proper do the neural responses to repeated words differ not only from those to new words but also from each other as a function of recognition success. By contrast parahippocampal (rhinal) responses are sensitive to repetition independent of conscious recognition. These findings thus demonstrate that it is the hippocampus proper among the MTL structures that is specifically engaged during conscious memory processes.

Hippocampal function and visual object processing in temporal lobe epilepsy.

Limbic event-related potentials related to verbal but not to visual recognition memory have been found to be attenuated within the epileptic hippocampus of patients with temporal lobe epilepsy (TLE). To identify hippocampal contributions to visual processing and memory we recorded intracranial ERPs directly from within the epileptic and the non-epileptic hippocampus in 12 patients with unilateral TLE during a visual object decision and naming task. While the non-epileptic hippocampus differentiated reliably between real and nonsense objects, this effect was completely eliminated within the epileptic mesial temporal lobe. This finding suggests that the hippocampus proper contributes to the semantic processing of visual objects and may help to explain visual memory deficits in TLE.

Inferior temporal stream for word processing with integrated mnemonic function.

The participation of the inferior temporal cortex in visual word perception and recognition raises several questions: Is there a directed processing stream proceeding anteriorly by continuous cortical processing? How fast are words processed within such an inferior temporal stream? Does this stream support implicit or explicit memory? To answer these questions, we analyzed the spatio-temporal relationship of event-related potentials, recorded directly from the inferior temporal cortex in epilepsy patients performing a continuous visual word recognition paradigm. Event-related potentials elicited an inferior temporal positivity in a strip along the left collateral sulcus. This potential exhibited a linear (r = 0.74) peak latency progression from posterior to anterior inferior temporal regions (approximately 15 cm/sec), indicating a directed, intracortical processing stream. Peak amplitudes and latencies showed reliable old/new effects with smaller amplitudes and shorter latencies for old as opposed to new words. Although the amplitude-old/new-effect occurred for all repeated words (e.g., implicit memory), the latency-old/new-effect occurred for correctly recognized old words only (e.g., explicit recognition). These results seem to dissociate two distinct mnemonic processes. The graded decrease of mean ITP peak amplitudes and latencies, however, does not allow us to exclude a single trace model as assumed for explicit recognition memory based on familiarity (Mandler [1980]: Psychol Rev 87:252-271). Regardless whether there is a dissociation between implicit and explicit memory in inferior temporal cortex or not, our findings are in accordance with an integrated inferior temporal processing stream for words that performs continuously semantic and mnemonic operations supporting both implicit and explicit memory.

Evidence relating human verbal memory to hippocampal N-methyl-D-aspartate receptors.

Studies in rodents and nonhuman primates have linked the activity of N-methyl-D-aspartate (NMDA) receptors within the hippocampus to animals' performance on memory-related tasks. However, whether these receptors are similarly essential for human memory is still an open question. Here we present evidence suggesting that hippocampal NMDA receptors, most likely within the CA1 region, do participate in human verbal memory processes. Words elicit a negative event-related potential (ERP) peaking around 400 ms within the anterior mesial temporal lobe (AMTL-N400). Ketamine, an NMDA-receptor antagonist, reduces the amplitude of the AMTL-N400 (in contrast to other hippocampal potentials) on initial presentation, eliminates the typical AMTL-N400 amplitude reduction with repetition, and leads to significant memory impairment. Of the various hippocampal subfields, only the density of CA1 neurons correlates with the word-related ERPs that are reduced by ketamine. Altogether, our behavioral, anatomical, and electrophysiological results indicate that hippocampal NMDA receptors are involved in human memory.

Real-time tracking of memory formation in the human rhinal cortex and hippocampus.

A fundamental question about human memory is which brain structures are involved, and when, in transforming experiences into memories. This experiment sought to identify neural correlates of memory formation with the use of intracerebral electrodes implanted in the brains of patients with temporal lobe epilepsy. Event-related potentials (ERPs) were recorded directly from the medial temporal lobe (MTL) as the patients studied single words. ERPs elicited by words subsequently recalled in a memory test were contrasted with ERPs elicited by unrecalled words. Memory formation was associated with distinct but interrelated ERP differences within the rhinal cortex and the hippocampus, which arose after about 300 and 500 milliseconds, respectively. These findings suggest that declarative memory formation is dissociable into subprocesses and sequentially organized within the MTL.

Limbic P300s in temporal lobe epilepsy with and without Ammon's horn sclerosis.

Limbic P300 potentials can be recorded within the mesial temporal lobes of patients with temporal lobe epilepsy (TLE). To delineate possible mechanisms of their generation and pathological alteration, we analysed limbic P300s in 55 TLE patients with and 29 without Ammon's horn sclerosis (AHS) and correlated their amplitudes with neuronal cell counts in 30 histopathological specimens. Limbic P300 amplitudes were reduced on the side of the epileptogenic focus only in patients with AHS. Moreover, in AHS patients, limbic P300 latencies were prolonged bilaterally; and in patients with left-sided AHS, amplitudes were reduced bilaterally. Both findings suggest bilateral functional deficits in TLE with unilateral AHS. Limbic P300 areas correlated significantly with neuronal densities of dentate gyrus granule cells but not hippocampal pyramidal cells in the CA1-4 (cornu ammonis) subfields. This finding points to a potential mechanism for the bilateral effects of unilateral AHS as both dentate gyri exhibit strong reciprocal contralateral connectivity.

Prediction of postoperative seizure control by hippocampal event-related potentials.

PURPOSE: In spite of unequivocal results of the presurgical evaluation, between 10 and 30% of patients with medial temporal lobe epilepsy (MTLE) do not become seizure free by temporal lobe surgery. Because event-related potentials (ERPs) recorded within the hippocampal formation have been shown to be sensitive to the epileptogenic process, we examined whether ERPs can help to improve the prediction of postoperative seizure control. METHODS: We recorded ERPs to words from bilateral intrahippocaampal electrodes by using a visual word-recognition paradigm in 70 patients with unilateral hippocampal pathology and related these measurements to seizure outcome after temporal lobe surgery. RESULTS: Words elicited N400 potentials, which were reduced in amplitude on repetition on the side contralateral to hippocampal sclerosis. This contralateral repetition effect, however, was significantly diminished in the group of patients who experienced seizure recurrence after the operation. Contralateral repetition effects thus permitted correct prediction of postoperative seizure control in 94% of all patients. CONCLUSIONS: Recording ERPs to words within the medial temporal lobes can improve the prediction of postoperative seizure control. Reduced repetition effects contralateral to the side of hippocampal sclerosis may indicate bilateral epileptogenicity.

Limbic ERPs predict verbal memory after left-sided hippocampectomy.

Surgical removal of the dominant medial temporal lobe regions runs a considerable risk of verbal memory deficits which may be compensated for postoperatively by corresponding regions in the non-dominant medial temporal lobe. We examined this possibility by recording event-related potentials (ERPs) to words from the medial temporal lobes of patients with left-sided temporal lobe epilepsy (TLE) undergoing presurgical evaluation. N400 amplitudes in the right anterior medial temporal lobe predicted the postoperative verbal recall performance of individual patients with surprising accuracy, indicating that intracranial recordings can be used to quantify the functional capacities of the right hemisphere that can compensate for the verbal memory deficits after loss of medial temporal lobe structures in the left hemisphere.