Hippocampal adequacy versus functional reserve: predicting memory functions following temporal lobectomy.

While decrements in memory following temporal lobectomy for intractable epilepsy remain a major neurocognitive complication of surgical intervention, it has been difficult to identify patients who are most at risk for developing decrements in their memory functions following surgery. Two different models of hippocampal functioning have been posited to account for postsurgical memory losses: hippocampal reserve versus functional adequacy. This article briefly examines the basis of the traditional model of hippocampal reserve, which suggests that it is the reserve or capacity of the contralateral hippocampus to support memory after surgery that determines whether changes in memory function will be observed. A more in-depth review of emerging data from studies of function (baseline neuropsychological testing and intracarotid amytal procedure) and structure (histologic cell densities and MRI volumetrics) supporting a functional adequacy model of hippocampal functioning is then presented. Data from these latter studies provide strong convergent support for the view that the risk for memory decrements following mesial temporal lobe epilepsy surgery is inversely related to the functional adequacy of the tissue to be resected. Data reviewed here have broad implications for the field of neuropsychology. Not only do the data reported in this article challenge some of the basic tenets of our understanding of the role of the hippocampus in memory functioning, but they illustrate the importance of ongoing research, critical reevaluation of basic concepts, and the importance of self-scrutiny in light of new technologies.     

Allocentric spatial memory activation of the hippocampal formation measured with fMRI

Hippocampal activation was investigated, comparing allocentric and egocentric spatial memory. Healthy participants were immersed in a virtual reality circular arena, with pattern-rendered walls. In a viewpoint-independent task, they moved toward a pole, which was then removed. They were relocated to another position and had to move to the prior location of the pole. For viewpoint-dependent memory, the participants were not moved to a new starting point, but the patterns were rotated to prevent them from indicating the final position. Hippocampal and parahippocampal activation were found in the viewpoint-independent memory encoding phase. Viewpoint-dependent memory did not result in such activation. These results suggest differential activation of the hippocampal formation during allocentric encoding, in partial support of the spatial mapping hypothesis as applied to humans.     

Allocentric and egocentric reference frames in the processing of three-dimensional haptic space

In an earlier experiment we showed that selective attention plays a critical role in rabbit eye blink conditioning (Steele-Russell et al. in Exp Brain Res 173:587–602, 2006). The present experiments are concerned to examine the extent to which visual recognition processes are a separate component from the motor learning that is also involved in conditioning. This was achieved by midline section of the optic chiasma which disconnected the direct retinal projections via the brainstem to the cerebellar oculomotor control system. By comparing both normal and chiasma-sectioned rabbits it was possible to determine the dependence or independence of conditioning on the motor expression of the eye blink response during training. Both normal and chiasma-sectioned animals were tested using a multiple test battery to determine the effect of this redirection of the visual input pathways on conditioning. All animals were first tested for any impairment in visual capability following section of the optic chiasma. Despite the loss of 90% of retinal ganglion cell fibres, no visual impairment for either intensity or pattern vision was seen in the chiasma animals. Also no difference was seen in nictitating membrane (NM) conditioning to an auditory signal between normal and chiasma animals. Testing for motor learning to a visual signal, the chiasma rabbits showed a complete lack of any NM conditioning. However the sensory tests of visual conditioning showed that chiasma-sectioned animals had completely normal sensory recognition learning. These results show that NM Pavlovian conditioning involves anatomically separate and independent sensory recognition and motor output components of the learning. This research was supported by S&W research grants ID# 1810 to ISR and ID# 7985 to JAC.     

Traditional and computerized assessment procedures applied to the evaluation of memory change after temporal lobectomy.

After establishing that 40 temporal lobectomy patients (20 right, 20 left) demonstrated the same pattern of memory compromise as has been reported in prior studies, we examined the sensitivity of computerized tests of everyday memory skills to the cognitive change associated with temporal resection. Multiple cognitive deficits occur after left, but not after right, temporal lobectomies. Memory impairment after surgery is not limited to traditionally structured memory tests but is also evident on tasks designed to simulate activities of daily life.     

Differences between nouns and verbs after anterior temporal lobectomy

To test the claim that lesions of left anterior and middle temporal cortical structures specifically impair processing of nouns but not verbs, 56 left-hemisphere-language-dominant patients who had undergone anterior temporal lobectomy (ATL) completed tasks assessing confrontation naming of pictured objects and actions, generation of synonyms for nouns and verbs, and semantic lexical judgments about nouns and verbs. Compared with right ATL patients, left ATL patients were impaired across different tasks that assessed naming and comprehension of high-imageability as well as low-imageability nouns. These groups did not differ, however, in verb naming or comprehension on most tasks. Results are consistent with the hypothesized specialization of left temporal lobe structures for processing nouns and suggest that naming problems commonly seen after left ATL extend beyond difficulties with retrieving object names and may be related to subtle disturbances in comprehension of the meanings underlying nominal word forms.     

Allocentric spatial and tactile memory impairments in rats with dorsal caudate lesions are affected by preoperative behavioral training

Rats with caudate lesions and pretrained for 36 trials demonstrated impaired performance on the "reference memory" or invariant aspect of a 12-arm radial maze and normal performance on the "working memory" or variable aspect of the maze. Rats with caudate lesions and no pretraining were also impaired on an invariant tactile discrimination in a T maze, but they were not impaired on the variable goal-arm choice of the T maze. More extensive preoperative training ameliorated behavioral deficits of rats with caudate lesions in the T maze and radial arm maze. Results showed that behavioral impairment after damage to the caudate is not restricted to egocentric tasks as previously suggested, but the caudate seems to be involved in the initial acquisition of information that is invariant over many trials.     

Horizontal otolith-ocular responses in humans after unilateral vestibular deafferentation

We studied horizontal eye movements evoked by lateral whole body translation in nine patients who underwent vestibular nerve section. Preoperatively, all had preserved caloric function on both sides. Testing was performed before, 1 week and 6–10 weeks after surgery. Patients were seated upright in an electrically powered car running on a linear track. The car executed acceleration steps of 0.24 g, randomly to the left and right in the dark. The normal response consisted of a bidirectionally symmetrical nystagmus with compensatory slow phases. Response asymmetry of the slow-phase velocity of the desaccaded and averaged eye position signal was less than 13% in normals (n = 21). Before surgery, patients’ responses were mostly symmetrical. Postoperatively, responses were diminished or absent with head acceleration towards the operated ear in all patients, causing a marked asymmetry which averaged 56% after correction for spontaneous nystagmus. On follow-up, responses regained symmetry. Thus, early after vestibular nerve section, a single utricle produces a normal LVOR only with ipsilateral head translation. Therefore, afferents for the LVOR seem to originate from the mid-lateral area of the macula, where hair cells are stimulated in their on-direction during ipsilateral head translation. Compensation may depend on recovery of the off-directional responses from lateral hair cells of the remaining utricle. Received: 9 December 1996 / Accepted: 15 July 1997     

Detection of changes in material-specific memory following temporal lobectomy using the Wechsler Memory Scale-Revised.

To determine the utility of the Wechsler Memory Scale-Revised (WMS-R) in measuring material-specific memory changes, within-subject comparisons of the Verbal-Visual Memory Index discrepancy and discrepancy scores using short-term and delayed Logical Memory and Visual Reproduction subtests from the WMS-R were studied prior to and following temporal lobectomy among 30 patients with left temporal lobectomy, 30 with right temporal lobectomy, and 50 epileptic, non-surgical controls. The groups were matched on age, sex, handedness, age at seizure onset, duration of epilepsy, and presurgical Verbal and Performance IQ; the right temporal group had a higher mean educational level (p <.05). All surgical patients were left hemisphere dominant for speech; those who had persistent postoperative seizures were excluded from study. On retesting, left temporal lobectomy was associated with a marked change in short-term and delayed memory discrepancy scores primarily due to a drop in verbal memory. Right temporal lobectomy was not associated with a drop in visual memory, suggesting that the WMS-R appears to reflect decrements in material-specific memory following left but not right temporal lobectomy. The nonsurgical controls showed increases in both short-term and delayed memory discrepancy scores due to increases in short-term and delayed verbal memory. Relative to these controls, the absence of comparable increases in verbal memory among the right temporal patients suggests that right temporal lobectomy may be associated with risk to verbal memory.     

Different vulnerability in female's spatial behaviour after unilateral hippocampal inactivation

This study was aimed to determine the effect of unilateral hippocampal inactivation on spatial memory retrieval in male and female Wistar rats. Subjects were chronically implanted with a stainless-steel cannula that enabled unilateral intrahippocampal injections of tetrodotoxin, a sodium channel blocker. Rats were trained during eight consecutive days on the Morris water maze task. On day 1, subjects received a visible platform session. From day 2 to day 7 the hidden platform was located in North quadrant and on day 8 the hidden platform changed to the opposite location. Subjects were randomly distributed into four groups: male saline, male TTX, female saline, female TTX. Saline or TTX was applied 30min before training but only on days 7 and 8. Results showed that males outperform females during the initial training (days 2-6). After TTX injection, both male and female rats were impaired. However, a detailed analysis revealed that the impairment in females was more pronounced, both during the retrieval session (day 7) as well as during reversal (day 8). This data points to a different role of the hippocampus or a different distribution of memories in both sexes.     

The effects of unilateral and bilateral ECT on verbal and visual spatial memory

Investigated the effects of unilateral left (UL), unilateral right (UR), and bilateral (B) ECT on the performance of right-handed male patients on the Wechsler Memory Scale and two tests of the Williams battery, which provided eight independent measures of verbal memory and two of visual-spatial memory. Patients were tested three times: (1) within 1 week prior to ECT; (2) within 30 minutes after the sixth ECT; (3) 10 days after the sixty ECT. Double blind procedures were maintained carefully. Results showed a significant loss on second testing followed by a significant improvement 10 days later for all ECT groups compared with matched controls. There was some tendency for the UR group to show the least impairment on verbal measures and the UL group to show the least impairment on visual-spatial memory test of the WMS, but most of the differences between UL and UR groups and between each of these and the B group were not significant. The most sensitive test in differentiating among the ECT groups was the brief Verbal Learning subtest of the Williams battery.     

Morpho-functional changes of neurons in temporal cortex in comparison with spatial memory in bulbectomized mice after treatment with minerals and ascorbates

The effect of antioxidant mixture of mineralascorbates (MA) on the status of neurons of brain temporal cortex and behavior of mice after olfactory bulbectomy (BE) was studied, as it was previously shown by us that these animals were characterized by a deficit of spatial memory and development of neurodegenerative process in brain structures, which are affected by Alzheimer disease. Disorganization of cytoarchitectonics of temporal cortex with the deletion of its layers as a result of dystrophy of pyramidal neurons and foci of their complete disappearance were shown 1 month after BE. The increased number of neurons with the phenomena of karyopyknosis, karyolysis and vacuolysis was observed with a concomitant reduction in neuronal density. Addition of MA to the diet for three weeks prevented the development of deterioration of spatial memory in mice after BE and protected the neurons of brain temporal cortex from the degenerative changes. The results obtained suggest the possibility of realization of prophylaxis aimed at the prevention of the development of Alzheimer-type neurodestructive processes.     

Effect of low-intensity hippocampal stimulation on spatial versus working memory in rats

A series of experiments was performed to investigate differing predictions from the spatial mapping hypothesis of hippocampal function proposed by O'Keefe and Nadel (1978) and the working memory hypothesis proposed more recently by Olton and his colleagues (Olton, Becker, & Handelmann, 1979). Each of two groups of rats was trained to use a different strategy to locate a submerged platform in a tank of opaque water. The MAP group used a spatial mapping strategy to reach a platform in a fixed location over trials; whereas the CUE group used a guidance strategy, which involved following a cue that signaled the location of a randomly placed platform on each trial. Following acquisition, one-half of each group was given low-level unilateral electrical stimulation of the dentate gyrus and immediately tested on the water maze task. The results of Experiment 1 showed that both the MAP and CUE groups were impaired by stimulation. However, it was observed that there was an inadvertent spatial element involved in the CUE task. When this element was eliminated in Experiment 3, the same CUE animals were not affected by a second series of stimulation trials, whereas the MAP animals continued to show impairment. These results are interpreted as strongly supporting the cognitive mapping hypothesis, while at the same time providing little support for the working memory hypothesis of hippocampal function.     

Immunological memory in humans

Specificity and memory are the defining characteristics of adaptive immune responses. Vaccines are predicated on the existence of immune memory, and the robustness of immune memory is a primary determinant of vaccine efficacy. How is immune memory maintained? Much progress has been made in this area over the past several years, and new human studies have added key insights into the longevity of B and T cell immune memory in the absence of antigen.     

Minimal model to document psychometric change after standard anterior temporal lobectomy for intractable seizure disorder

Neuropsychological assessment of persons with epilepsy is recommended whenever neurosurgery is considered as an alternative therapy for seizure disorders refractory to ordinary medical management. Although psychological assessment is common in centers specialized in the care of epilepsy patients, standardized protocols are not common. This study addresses the question of the optimal minimal test battery necessary to differentiate groups of right-handed patients with refractory, complex partial seizure disorder who receive either right or left anterior temporal lobectomy or no surgery. No variable differentiated the groups before surgery. Only Logical Memory-Immediate of the Wechsler Memory Scale differentiated the groups following surgery. This finding is consistent with the literature.     

Preservation and loss of spatial memory in aged rats and humans: implications for the analysis of memory dysfunction in dementia

Research with laboratory rats and humans demonstrating that the usual age-related deficits in spatial working memory can be attenuated or eliminated by prior training earlier in adult life is reviewed and possible mechanisms for this phenomenon are considered. A new technique for measuring remote memory for spatial information in humans is described and preliminary results with demented patients are discussed.     

The role of rat dorsomedial prefrontal cortex in working memory for egocentric responses

By using extracellular recordings of field potential, the exact pathway by which the endogenous ACh influencing the induction of long-term potentiation (LTP) in CA1 area was analysed in slices of rat hippocampus. The results showed that: (1) the application of (-) huperzine A, an AChE inhibitor extracted from Chinese herb Qian Ceng Ta (Huperzia Serrata), could enhance the induction of LTP, while this drug showed little effect on the second components of multiple population spikes that were recorded in Mg(2+)-free medium and had proven to be N-methyl-D-aspartate (NMDA) receptor-mediated response; and (2) scopolamine, a muscarinic receptor antagonist, could significantly suppressed the induction of LTP, while most of the suppressive effect of scopolamine was blocked when slices were pretreated by bicuculline, a gamma-aminobutyric acid (GABA(A)) receptor antagonist. These results suggest that endogenous ACh potentiates the induction of LTP through the inhibition of GABAergic interneurons that modulate pyramidal neurons, but not through the activation of NMDA receptors located on pyramidal neurons.     

Topographic segregation and convergence of verbal, object, shape and spatial working memory in humans

This functional magnetic resonance imaging study investigates commonalties and differences in working memory (WM) processes employing different types of stimuli. We specifically sought to characterize topographic convergence and segregation with respect to prefrontal cortex involvement using verbal, spatial, real object and shape memory items in a two-back WM task. Both the dorsolateral and ventrolateral prefrontal cortices are conjointly activated across all stimulus types. No stimulus-specific differences in the activation patterns of the prefrontal cortex could be demonstrated giving support to the view of an amodal prefrontal involvement during WM processes. However, extra-frontal regions specialized on feature processing and involved in the preprocessing of the stimuli were selectively activated by these different subtypes of WM. These selectively activated regions are assigned to parts of the ventral and dorsal stream.