Andrew G. Parrent

Impaired familiarity with preserved recollection after anterior temporal-lobe resection that spares the hippocampus

It is well established that the medial-temporal lobe (MTL) is critical for recognition memory. The MTL is known to be composed of distinct structures that are organized in a hierarchical manner. At present, it remains controversial whether lower structures in this hierarchy, such as perirhinal cortex, support memory functions that are distinct from those of higher structures, in particular the hippocampus. Perirhinal cortex has been proposed to play a specific role in the assessment of familiarity during recognition, which can be distinguished from the selective contributions of the hippocampus to the recollection of episodic detail. Some researchers have argued, however, that the distinction between familiarity and recollection cannot capture functional specialization within the MTL and have proposed single-process accounts. Evidence supporting the dual-process view comes from demonstrations that selective hippocampal damage can produce isolated recollection impairments. It is unclear, however, whether temporal-lobe lesions that spare the hippocampus can produce selective familiarity impairments. Without this demonstration, single-process accounts cannot be ruled out. We examined recognition memory in NB, an individual who underwent surgical resection of left anterior temporal-lobe structures for treatment of intractable epilepsy. Her resection included a large portion of perirhinal cortex but spared the hippocampus. The results of four experiments based on three different experimental procedures (remember-know paradigm, receiver operating characteristics, and response-deadline procedure) indicate that NB exhibits impaired familiarity with preserved recollection. The present findings thus provide a crucial missing piece of support for functional specialization in the MTL.

Hippocampal electrical stimulation in mesial temporal lobe epilepsy

Background: Adjustable, reversible therapies are needed for patients with pharmacoresistant epilepsy. Electrical stimulation of the hippocampus has been proposed as a possible treatment for mesial temporal lobe epilepsy (MTLE). Methods: Four patients with refractory MTLE whose risk to memory contraindicated temporal lobe resection underwent implantation of a chronic stimulating depth electrode along the axis of the left hippocampus. The authors used continuous, subthreshold electrical stimulation (90 μsec, 190 Hz) and a double blind, multiple cross-over, randomized controlled design, consisting of three treatment pairs, each containing two 1-month treatment periods. During each treatment pair the stimulator was randomly turned ON 1 month and OFF 1 month. Outcomes were assessed at monthly intervals in a double blind manner, using standardized instruments and accounting for a washout period. The authors compared outcomes between ON, OFF, and baseline periods. Results: Hippocampal stimulation produced a median reduction in seizures of 15%. All but one patient’s seizures improved; however, the results did not reach significance. Effects seemed to carry over into the OFF period, and an implantation effect cannot be ruled out. The authors found no significant differences in other outcomes. There were no adverse effects. One patient has been treated for 4 years and continues to experience substantial long-term seizure improvement. Conclusion: The authors demonstrate important beneficial trends, some long-term benefits, and absence of adverse effects of hippocampal electrical stimulation in mesial temporal lobe epilepsy. However, the effect sizes observed were smaller than those reported in non-randomized, unblinded studies.

Three-dimensional database of subcortical electrophysiology for image-guided stereotactic functional neurosurgery

We present a method of constructing a database of intraoperatively observed human subcortical electrophysiology. In this approach, patient electrophysiological data are standardized using a multiparameter coding system, annotated to their respective magnetic resonance images (MRIs), and nonlinearly registered to a high-resolution MRI reference brain. Once registered, we are able to demonstrate clustering of like interpatient physiologic responses within the thalamus, globus pallidus, subthalamic nucleus, and adjacent structures. These data may in turn be registered to a three-dimensional patient MRI within our image-guided visualization program enabling prior to surgery the delineation of surgical targets, anatomy with high probability of containing specific cell types, and functional borders. The functional data were obtained from 88 patients (106 procedures) via microelectrode recording and electrical stimulation performed during stereotactic neurosurgery at the London Health Sciences Centre. Advantages of this method include the use of nonlinear registration to accommodate for interpatient anatomical variability and the avoidance of digitized versions of printed atlases of anatomy as a common database coordinate system. The resulting database is expandable, easily searched using a graphical user interface, and provides a visual representation of functional organization within the deep brain.

Propofol sedation during awake craniotomy for seizures: patient-controlled administration versus neurolept analgesia.

This prospective study evaluated the safety and efficacy of patient-controlled sedation (PCS) using propofol during awake seizure surgery performed under bupivacaine scalp blocks. Thirty-seven patients were randomized to receive either propofol PCS combined with a basal infusion of propofol (n = 20) or neurolept analgesia using an initial bolus dose of fentanyl and droperidol followed by a fentanyl infusion (n = 17). Both groups received supplemental fentanyl and dimenhydrinate for intraoperative pain and nausea, respectively. Comparisons were made between groups for sedation, memory, and cognitive function, patient satisfaction, and incidence of complications. Levels of intraoperative sedation and patient satisfaction were similar between groups. Memory and cognitive function were well preserved in both groups. The incidence of transient episodes of ventilatory rate depression (<8 bpm) was more frequent among the propofol patients (5 vs 0, P = 0.04), particularly after supplemental doses of opioid. Intraoperative seizures were more common among the neurolept patients (7 vs 0, P = 0.002). PCS using propofol represents an effective alternative to neurolept analgesia during awake seizure surgery performed in a monitored care environment. (Anesth Analg 1997;84:1285-91)

Stereotactic amygdalohippocampotomy for the treatment of medial temporal lobe epilepsy.

Summary: Purpose: This study was carried out to assess the safety and efficacy of stereotactic ablation of the amygdala and hippocampus for the treatment of medial temporal lobe epilepsy.

Morbidity associated with the use of intracranial electrodes for epilepsy surgery

BACKGROUND Invasive monitoring for the investigation of medically intractable epilepsy may be associated with undesirable morbidity. We performed a review of our recent experience to determine the incidence of major complications. METHODS We reviewed the clinical records of all patients who underwent invasive EEG monitoring at our institution between 2000 and 2004. RESULTS One-hundred and sixteen patients (57 males, 59 females) with a mean age of 32 years of age underwent intracranial placement of electrodes for epilepsy surgery investigation. Subdural strips were placed in 115 patients with a mean of eight strips per patient. Subdural grids were inserted in 11 patients and depth electrodes in five. Fourteen of the 15 patients with grids or depth electrodes also had strips. Coverage was unilateral in 37 patients and bilateral in 79 patients. Electrodes were placed over the frontal lobe in 78 cases, temporal in 93, parietal in 24, and occipital in 27 patients. The average duration of investigation was 12.3 days (range 3-29). The evaluation led to the performance of a surgical resection in 85 patients (74%). Complications were seen in four patients with subdural strips (3%), and in two patients with grids (13%), characterized by clinical infection, intracranial hemorrhage, aseptic meningitis, transient neurological deficits, and status epilepticus. Mortality was nil. CONCLUSIONS In comparison with previously published literature on the topic, the major complication rate in this group of patients appears to be low.

Bilateral hippocampal stimulation for intractable temporal lobe epilepsy: impact on seizures and memory.

The effect of continuous electrical stimulation of the hippocampus bilaterally on seizures and memory was assessed in two subjects with seizures from both mesial temporal lobes who were not candidates for resective epilepsy surgery. A double blind, randomized, controlled, cross‐over trial design was utilized. Two electrodes with four contacts each were implanted along the axis of the hippocampus bilaterally. Simultaneous stimulation of all electrodes contacts was either on or off during each 3‐month interval. Seizure frequency decreased by 33% in the two patients during stimulation and remained lower by 25% for the 3 months after stimulation was turned off before returning to baseline (p < 0.01). No consistent change in objective or subjective measures of memory occurred. No other adverse effects occurred. Seizure frequency is reduced both during and for a period after bilateral hippocampal stimulation, but the overall impact in this study is not as robust as has been previously reported.

Propofol sedation during awake craniotomy for seizures: electrocorticographic and epileptogenic effects.

This prospective study evaluated the effects of propofol sedation on the incidence of intraoperative seizures and the adequacy of electrocorticographic (ECoG) recordings during awake craniotomy performed for the management of refractory epilepsy.Thirty patients scheduled for temporal or frontal lobectomy for epilepsy under bupivacaine scalp block were randomized to receive patient-controlled propofol sedation (PCS) combined with a basal infusion of propofol (n = 15) or neurolept analgesia using an initial bolus dose of fentanyl (0.7 micro g/kg) and droperidol (0.04 mg/kg) followed by a fentanyl infusion (n = 15). Propofol administration was suspended 15 min before ECoG recording in the PCS group. The occurrence of inappropriate intraoperative seizures was noted and, based on blind review, the adequacy of ECoG recordings was compared. A higher incidence of intraoperative seizures was noted among the neurolept patients (6 vs 0, P = 0.008). Intraoperatively, ECoG recordings were adequate to proceed with resection in both groups. Evidence of low spike activity on ECoG did not correlate with the type of sedation administered. Higher frequency background ECoG activity was noted among patients who received propofol, but this did not interfere with ECoG interpretation. The use of propofol sedation does not appear to interfere with ECoG during epilepsy surgery, provided administration is suspended at least 15 min before recording. (Anesth Analg 1997;84:1280-4)

Double dissociation of selective recollection and familiarity impairments following two different surgical treatments for temporal-lobe epilepsy.

Research has firmly established that the integrity of the medial temporal lobe (MTL) is critical for recognition memory. This ability is supported by recollection, which involves recovery of contextual details of a past stimulus encounter, and familiarity assessment, which leads to awareness of prior occurrence without such recovery. Dual-process models of MTL organization posit that recollection and familiarity are supported by the hippocampus and perirhinal cortex, respectively. Alternatively, it has been argued that both structures support these recognition processes similarly as part of a more integrated declarative memory system; from this perspective, reported selective recollection impairments with circumscribed hippocampal lesions may reflect differential sensitivity to overall memory strength, rather than a deficit in a distinct recognition process. Findings from past neuropsychological research remain inconsistent and controversial, in part due to biases in patient selection, variability in clinical etiology, and limited lesion documentation. Here, we administered a verbal recognition-memory task in combination with remember-know judgements to 10 individuals who had undergone left- or right-sided stereotactic amygdalo-hippocampotomy as a surgical treatment for intractable temporal-lobe epilepsy. Comparisons with healthy control participants revealed isolated impairments in recollection with preserved familiarity, regardless of hemispheric site of lesion. In addition, we show that this impairment can be observed at a comparable level of memory strength (i.e., overall recognition performance) as the selective familiarity impairment we previously described in N.B.--an individual who underwent a tailored surgical resection of the left anterior temporal lobe with hippocampal sparing for treatment of temporal-lobe epilepsy. By revealing a double dissociation concerning temporal-lobe mechanisms for recollection and familiarity, this evidence argues against a unitary, strength-based account of MTL organization.

Segmentation of thalamic nuclei using a modified k-means clustering algorithm and high-resolution quantitative magnetic resonance imaging at 1.5 T

Patient outcome in minimally invasive stereotactic neurosurgical procedures depends on the ability to accurately locate the desired functional region within the deep brain while avoiding the surrounding anatomy. Due to the lack of sufficient contrast within this region in pre-operatively acquired MR images, electrophysiological exploration and histological atlases are currently required to define the surgical target within the thalamus in the treatment of many motor-control disorders. In this paper we introduce a method for segmenting the individual thalamic nuclei based on high-resolution quantitative magnetic resonance images, providing improved target visualization. The method was tested using whole-brain T1 and T2 data acquired from four healthy individuals. Accuracy of the segmentation results was assessed by comparing the center-of-mass coordinates of the segmented nuclei, with coordinates obtained from a classic histological atlas registered to these images. Strong agreement was found, with an average Euclidean distance difference of less than 4.5 mm averaged across all nuclei and all individuals. Reproducibility of the method, determined by calculating the percent similarity of segmentation results derived from data acquired from repeated scan sessions, was greater than 85%. These results illustrate the ability to accurately and reliably segment the primary nuclei of the thalamus and suggest that the method may have utility in the study of individual nuclear regions in disease state as well as for planning deep-brain surgical procedures.