Nico Pezer

Neuronal substrates of sensory gating within the human brain

BACKGROUND For the human brain, habituation to irrelevant sensory input is an important function whose failure is associated with behavioral disturbances. Sensory gating can be studied by recording the brains electrical responses to repeated clicks: the P50 potential is normally reduced to the second of two paired clicks but not in schizophrenia patients. To identify its neural correlates, we recorded electrical traces of sensory gating directly from the human hippocampus and neocortex. METHODS Intracranial evoked potentials were recorded using hippocampal depth electrodes and subdural strip and grid electrodes in 32 epilepsy patients undergoing invasive presurgical evaluation. RESULTS We found evidence of sensory gating only in the hippocampus, the temporo-parietal region (Brodmanns areas 22 and 2), and the prefrontal cortex (Brodmanns areas 6 and 24); however, whereas neocortical habituating responses to paired clicks were peaking around 50 msec, responses within the hippocampus proper had a latency of about 250 msec. CONCLUSIONS Consistent with data from animal studies, our findings show that the hippocampus proper contributes to sensory gating, albeit during a time window following neocortical habituation processes. Thus, sensory gating may be a multistep process, with an early phase subserved by the temporo-parietal and prefrontal cortex and a later phase mediated by the hippocampus.

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 Ammons 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.

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.

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.

Prediction of Postoperative Seizure Control by Hippocampal Event‐Related Potentials

Summary: 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.

Heterotopias, cortical dysplasias and glioneural tumors participate in cognitive processing in patients with temporal lobe epilepsy.

Focal brain lesions such as cortical dysplasia and glioneural tumors generate epileptic activity and thus may be synaptically connected with normal cortex. To test this hypothesis, we compared event-related potentials recorded directly from the medial temporal lobe (MTL) and a dysplastic lesion in eight patients with intractable temporal lobe epilepsy. The P3 component, related to visual target detection, showed different peak latencies in four patients and a larger intralesional amplitude compared to established anterior-MTL-generators in two patients. Semantic processing was identified by the N400 component and showed a different latency in four patients and larger intralesional amplitudes in two patients. These results are compatible with the hypothesis that cortical lesions interact with synaptic pathways related to cognitive functions such as visual target detection, and verbal processing.

Hippocampus proper distinguishes between identified and unidentified real-life visual objects: an intracranial ERP study.

Converging evidence indicates that the medial temporal lobe participates not only in memory but also in visual object processing. We investigated hippocampal contributions to visual object identification by recording event-related potentials directly from within the hippocampus during a visual object identification task with spatially filtered pictures of real objects presented at different levels of filtering. Hippocampal responses differentiated between identified and unidentified visual objects within a time window of 200-900 ms after stimulus presentation: identified objects elicited a small negative component peaking around 300 ms (hippocampal-N300) and a large positive component, around 650 ms (hippocampal-P600), while the N300 was increased and the P600 was reduced in amplitude in response to unidentified objects. These findings demonstrate that the hippocampus proper contributes to the identification of visual objects discriminating from the very early between identified and unidentified meaningful visual objects.

Hippocampal response to visual objects is related to visual memory functioning.

The medial temporal lobe participates not only in episodic memory, but also in visual object processing. Here we asked whether these processes are linked within the human hippocampus. To this end, we recorded field potentials directly from the hippocampus proper during a visual object decision task in temporal lobe epilepsy patients with either normal or below normal visual memory performance. Only in patients with normal visual memory, did the hippocampus proper differentiate reliably between real and nonsense objects, whereas neural responses to both kinds of objects were virtually the same in patients whose visual memory performance was reduced. These findings suggest that neural responses to visual objects within the hippocampus proper are directly linked to visual memory performance.

Gender Specific Processing of Eye Contact within the Human Medial Temporal Lobe

Eye contact is a powerful social stimulus for human and non-human primates. However, it is unclear whether brain mechanisms that interpret eye contact are sensitive to gender. Here we show that human brain responses to eye contact are indeed gender specific. Recording event-related potentials directly from the medial temporal lobes, we found that eye contact elicited specific responses in men only when they saw female faces. Conversely, women responded specifically to eye contact only when they saw pictures of men. Thus, the human medial temporal lobes subserve specifically the processing of eye contact with persons of the opposite gender.