Sex differences in the medial temporal lobe during encoding and recognition of pseudowords and abstract designs.

Sex differences in various cognitive abilities have been demonstrated in terms of performance differentials and, more recently, in differences in activation patterns during fMRI. Hemispheric lateralization is sometimes accentuated in sex differences; e.g., women demonstrating greater activation of the left hemisphere than men during verbal tasks. We were interested in whether this phenomenon applies to memory for words and designs (i.e., material specific memory). Using analogous verbal (pseudowords) and nonverbal (abstract designs) encoding and recognition tasks completed back-to-back in a 3T scanner, we found that women tend to show exaggerated left hippocampal activation during certain stages of encoding and recognition of verbal information, compared with men. Likewise (although to a lesser extent), men showed more right hippocampal activation than women did during the abstract design learning task. These results have important implications for the generalization of fMRI memory study results, for example to clinical populations such as patients undergoing epilepsy surgery.

Intracarotid amobarbital procedure and etomidate speech and memory test.

The intracarotid amobarbital procedure (IAP) has for over 50 years been an important component of the presurgical investigation of patients with epilepsy who are candidates for surgical intervention as treatment for their seizures. Owing to increasing frequency and duration of amobarbital shortages, alternatives for this drug have been sought and implemented, but until now only the drug was changed, while the basic procedure remained essentially the same as that used with amobarbital. This paper describes the Montreal Neurological Institute experience using etomidate in place of amobarbital and introducing a significant change in the procedure: after an initial bolus injection, an infusion is used to maintain the level of hemianesthesia during critical test times. Results of 28 patients tested with this procedure are compared to results from 40 patients tested in the standard IAP.

Surgical treatment of independent bitemporal lobe epilepsy defined by invasive recordings.

OBJECTIVES: Bitemporal lobe epilepsy is commonly encountered in the evaluation of pharmacoresistant epilepsy. Yet the role of surgery in the management of these patients is unclear. This study evaluates the impact of surgery on seizure tendency and quality of life, as well as prognostic indicators in individuals with proven ictal onset bitemporal lobe epilepsy. METHODS: The study population comprised all patients who underwent temporal lobe surgery over a 10 year period and had ictal onset bitemporal lobe epilepsy identified with intracranial electrode monitoring. Patients with extratemporal seizure generators were excluded. Subjects were divided into a favourable or less favourable group based on the results of surgery on seizure tendency. RESULTS: 11 subjects were studied with a mean 5.9 years of post-surgical follow-up. Six subjects constituted the favourable outcome group. Four had a less favourable outcome and continued to have frequent seizures after surgery; however, three with less favourable seizure reduction subjectively reported improvement in quality of life after surgery as a result of reduced seizure frequency and severity, and reduced medications. No single preoperative factor was significantly different between the groups, including ictal EEG laterality, epilepsy duration, age at surgery, age at seizure onset and mesial temporal atrophy. CONCLUSIONS: Surgical resection is an important treatment option for medically intractable bitemporal epilepsy. The proportion of seizures arising from one temporal lobe is not reliable as a single indicator to prognosticate the results of surgery on seizure tendency. In addition, individuals who achieved only palliation by reducing seizure frequency experienced improvement in quality of life.

Functional dissociation between fornix and hippocampus in spatial conditional learning.

Do lesions of the fornix or the hippocampus impair the performance of spatial conditional associative learning tasks, and to what extent does damage to these brain structures result in comparable deficits in this type of spatial behavior? The available evidence is not clear. In the present study, rats with lesions of the fornix, hippocampus, and normal control animals were trained on two spatial-visual conditional learning tasks in which they had to form arbitrary associations between visual stimuli and the context in which these stimuli were embedded. In one condition, rats were required to choose stimulus X in place A and stimulus Y in place B, and there was no overlap in the contents of the two scenes. In the other condition, the animal approached the same scene from two different directions and had to select stimulus X when the scene was viewed from perspective A and to select stimulus Y when the scene was viewed from perspective B. Rats with fornix transection were able to learn both conditional tasks at a rate comparable to that of normal control animals, but rats with hippocampal damage were severely impaired under both conditions. The findings extend the range of tasks known to be sensitive to damage of the hippocampus. In addition, the results argue that the fornix is not necessary for the acquisition of certain spatial conditional learning tasks and that this brain structure cannot be used as an indicator of hippocampal dysfunction under all learning situations.

Contribution of the anterior thalamic nuclei to conditional learning in rats.

The anterior thalamic region is intimately linked anatomically and functionally with the hippocampus, which is critical for various forms of spatial learning. Rats with lesions to the anterior thalamic nuclei and a control group were trained on a visual-spatial conditional associative learning task in which they had to learn to go to one of two locations depending on the particular visual cue presented on each trial; the rats approached the cues from different directions. The animals were subsequently tested on a spatial working memory task, the eight-arm radial maze. Performance on both these tasks had previously been shown to be impaired by hippocampal lesions. Rats with anterior thalamic damage were able to acquire the conditional associative task at a rate comparable to that of the control animals, but were impaired on the radial maze task. The finding of a dissociation between the effects of lesions of the anterior thalamic nuclei on two different classes of behavior known to be associated with hippocampal function suggest that while different neural stations within the extended hippocampal circuit may all play a role in spatial learning, the role of each of these regions in such learning may be more selective than previously considered.

Memory and the medial temporal lobe: hemispheric specialization reconsidered.

The role of the medial temporal lobe in learning and memory has been well established in research on humans and other animals. In humans, clinical and neuroimaging studies typically suggest material-specific lateralization in which the left and right temporal lobes are associated with verbal and nonverbal memory, respectively. It is often assumed that the temporal lobes are functionally alike, differing only in terms of the content to be learned. Here we present data that challenge this notion, showing that the type of material used during a memory task can influence fMRI activation patterns beyond the expected left-verbal/right-nonverbal dichotomy. Our results also suggest some degree of functional asymmetry in the medial temporal lobe that is independent of material type, pointing to underlying processing differences between the left and right temporal lobes.

Etomidate speech and memory test (eSAM): a new drug and improved intracarotid procedure.

BACKGROUND: The intracarotid amobarbital procedure (IAP) is an important part of comprehensive investigation of patients who are candidates for surgical treatment of epilepsy. Owing to repeated and lengthy shortages of amobarbital, causing delays in elective surgery, attempts have been made to find a suitable alternative anesthetic. The authors report their experience using etomidate, a widely used agent for the induction of anesthesia. METHODS: Sixteen consecutive patients requiring IAP to evaluate memory or to lateralize speech underwent the procedure using etomidate. Prior to the procedure a catheter was placed in the internal carotid artery and an angiogram was performed. EEG was recorded and read online by an electroencephalographer. An anesthetist injected the drug, administered by bolus followed by an infusion, which was maintained until each speech measure had been sampled and new memory items had been introduced. The infusion was then stopped and testing continued as in a standard IAP. RESULTS: In all cases (30 hemispheres) contralateral hemiplegia followed injection. EEG slow waves were observed in every injected hemisphere, with some contralateral slowing anteriorly in 18. Global aphasia with preserved attention and cooperation followed dominant-hemisphere injections. These phenomena remained during infusion, and upon its termination returned gradually to baseline over a period of about 4 minutes. CONCLUSIONS: Etomidate is a viable alternative to amobarbital, and its administration by bolus followed by infusion offers an improvement over the traditional intracarotid amobarbital procedure. Cognitive tests can be performed during an assured hemianesthesia of the injected hemisphere.

Gustatory agnosia.

OBJECTIVE: To report the assessment of a patient exhibiting gustatory agnosia. METHODS: Preoperative and postoperative neuropsychological, neuroimaging, and chemosensory evaluations were performed in a 39-year-old woman undergoing surgical treatment for intractable epilepsy. RESULTS: Preoperative MRIs showed bilateral (right > left) atrophy in the medial temporal lobes and complete atrophy of the left insula. Evaluation of gustatory function revealed normal suprathreshold intensity estimation, affective evaluation, and detection thresholds but elevated recognition thresholds. A functional neuroimaging study showed activation to stimulation of aversive taste in the left amygdala. Surgical treatment entailed resection from the left medial temporal lobe that included the region of amygdala that had responded to taste. Postoperatively, detection, naming, and intensity estimation for taste remained normal, but the patient was unable to recognize different tastes (sweet, sour, salty, and bitter). A second evaluation 2.5 years after her surgery revealed no change in taste ability. CONCLUSION: The anteromedial temporal lobe has an important role in recognizing taste quality.

Egocentric conditional associative learning: effects of restricted lesions to the hippocampo-mammillo-thalamic pathway.

Rats with lesions of the hippocampus, the mammillary region, the anterior thalamic nuclei, and normal control animals were trained on a conditional associative learning task in which they had to learn to make one of two motor responses (i.e., turn left or right), depending on which one of two visual cues was presented. Damage to the hippocampus severely impaired performance of this task. By contrast, rats with lesions of the mammillary region or the anterior thalamic nuclei were able to acquire the task at a rate comparable to that of the normal animals. These findings demonstrate that hippocampal lesions impair the ability to form arbitrary associations between visual cues and kinesthetic responses (body turns) and, furthermore, suggest that the hippocampus does not rely on input from its major subcortical targets for learning such visual-kinesthetic associations.

Effects of lesions to the hippocampus or the fornix on allocentric conditional associative learning in rats.

Rats with lesions of the fornix, the hippocampus, or normal control animals were trained on a visual-spatial conditional associative learning task in which they had to learn to go to a particular location based on the presence of a specific visual cue; the rats approached the cues from different directions. Animals with damage of the fornix were able to learn the task at a rate comparable to that of the control animals. The performance of the hippocampal rats was significantly impaired as compared with the control group. Both the fornix and the hippocampal animals were significantly impaired on a spatial working memory task, the eight-arm radial maze. These findings suggest that, under certain conditions, a functional dissociation exists between the effects of damage to the fornix or the hippocampus and that the fornix may be only selectively involved in spatial learning and memory.

Selectivity of the spatial learning deficit after lesions of the mammillary region in rats.

Rats with lesions of the mammillary region (MB-R) or a control group (C) were trained on a visual-spatial conditional associative learning task in which they had to learn to go to one of two locations depending on the particular visual cue presented on each trial; the rats approached the cues from different directions. The animals were subsequently tested on a spatial working memory task, the eight-arm radial maze. Rats with damage to the MB-R were able to acquire the conditional associative task at a rate comparable to that of the C animals. By contrast, lesions of the MB-R led to a severe impairment on the radial maze. The present finding of a dissociation between the effects of MB-R lesions on two different classes of behavior suggest that the spatial learning deficit following damage of this region may be specific to remembering one or more places over a given time but not the ability to form associations between visual and spatial stimuli.

The effects of lesions to the anterior thalamic nuclei on object-place associations in rats.

Rats with lesions of the anterior nuclei of the thalamus were trained postoperatively on two spatial conditional associative learning tasks. In the first task, the rats were required to choose one or the other of two objects depending on the location in which they were found. In the second task, the animals learned to turn left or right depending on which one of two visual cues was presented. A third experiment examined the effects of damage to the anterior thalamic nuclei on the eight-arm radial maze, a spatial working memory task. Damage of the anterior thalamic nuclei impaired performance on the radial maze task and the conditional task requiring associations between objects and their location. By contrast, rats with anterior thalamic lesions were able to acquire, at a rate comparable with that of operated control animals, the conditional task requiring associations between objects and body turns. These findings suggest that lesions to the anterior thalamic nuclei result in a general impairment in learning about allocentric spatial information without disrupting the learning of egocentric spatial information.

Conditional associative learning and the hippocampal system.

Rats with lesions of the fornix, the dorsal hippocampus, or a control operation were trained on a spatial-visual conditional associative learning task in which they had to learn to associate particular locations with specific visual stimuli. Animals with damage of the fornix were able to learn the task at a rate comparable to that of the control animals, but the performance of the hippocampal rats was significantly impaired in comparison with that of both the control and the fornix groups. In a second experiment, lesions to the fornix or the dorsal hippocampus significantly impaired performance on a spatial working memory task, the eight-arm radial maze. These findings suggest that the interaction between the hippocampus and subcortical structures via the fornix may be critical only for certain types of spatial learning and memory.

Memory and the region of the mammillary bodies.

The contribution of the mammillary region to several classes of learning and memory has been reviewed. There is considerable evidence that lesions of this region of the brain impair performance on tasks that require memory for locations that an animal has visited, but that the deficit depends both on the amount of damage within the region and the difficulty of the task. Such lesions, however, do not appear to impair performance on a variety of spatial conditional associative learning tasks which require the animal to form an association between a place or a scene and a stimulus embedded within it. In addition, damage to the region of the mammillary bodies does not impair the ability to learn a variety of non-spatial memory tasks. These studies suggest that the mammillary region may play a selective role in certain types of spatial learning and memory.

Performance of healthy subjects and patients with resection from the anterior temporal lobe on matched tests of verbal and visuoperceptual learning.

We examined the equivalence of three matched forms of the Rey Auditory Verbal Learning Test (RAVLT) and three parallel forms of a new nonverbal analog, the Aggie Figures Learning Test (AFLT). One hundred and fourteen healthy subjects, primarily college students, were administered corresponding forms of the two tasks. For both tasks the three forms proved to be well-matched; as well, overall performance on the RAVLT was comparable to that on the AFLT. The two tasks were also administered to 23 patients with anterior resection from the left or right temporal lobe (ATL). Findings showed that right ATL patients were significantly impaired on the learning trials of the AFLT as compared to their learning on the RAVLT; they showed little forgetting of figures or words over a 20-min delay interval. By contrast, left ATL patients showed severe forgetting of words as compared to figures, but their learning curve for the RAVLT did not differ from that on the AFLT.

Functional anatomy of visuomotor skill learning in human subjects examined with positron emission tomography.

The present study was designed to examine patterns of regional cerebral blood flow (CBF) associated with the learning of a repeated visuomotor sequence both in the early and late phases of the acquisition process. In addition, changes in blood flow related to the implicit versus explicit aspects of learning such a skill were investigated. Fourteen normal control subjects were scanned while performing the task (i) in both early and advanced learning stages of the visuomotor sequence; (ii) after having acquired explicit knowledge of the sequences; and (iii) in two control conditions (perceptual and random sequence). Subtraction of the random condition from the highly learned condition revealed specific areas of activity in the right ventral striatum and dentate nucleus of the cerebellum. Blood flow changes in the right hemisphere were also seen in the medial posterior parietal and prestriate regions, as well as in the anterior cingulate cortex. Finally, once the subjects had acquired explicit knowledge of the embedded sequence that was presented in the highly learned condition, increased CBF activity was observed only in the mid-ventrolateral frontal area in the right hemisphere. These findings confirm that both the striatum and the cerebellum are involved in the implicit acquisition of a visuomotor skill, especially in the advanced stages of the learning process, and furthermore that the ventrolateral prefrontal cortex contributes preferentially to the declarative aspect of this task.

The effects of lesions to the mammillary region and the hippocampus on conditional associative learning by rats.

Rats with extensive lesions to the mammillary body region, the hippocampus, or rats which had received a control operation were trained postoperatively on two visuo-spatial conditional associative learning tasks in which they had to learn to associate spatial cues with particular visual/auditory stimuli. The animals were subsequently trained on a spatial working memory task, the eight-arm radial maze. Rats with lesions to the mammillary body region were able to acquire the conditional associative learning tasks at a rate comparable to that of operated control animals, whereas those with hippocampal lesions were not. By contrast, rats with a lesion of the mammillary body region or the hippocampus were significantly impaired in comparison with the operated control animals in the radial maze. The findings suggest that lesions to the mammillary body region impair spatial working memory without affecting the capacity to associate particular exteroceptive cues with spatial locations.

Memory impairments following lesions to the mammillary region of the rat.

The contribution of the mammillary region to learning and memory was investigated. It was demonstrated that lesions of this region impair performance on tasks that require memory for spatial information but that the deficit depends both on the amount of damage within the region and the difficulty of the task. A dissociation in the effect of such lesions on performance of comparable spatial and non-spatial memory tasks was shown. In contrast to the deficits observed on spatial memory tasks, the acquisition and retention of a complex non-spatial memory task was not impaired after extensive damage to the mammillary region. Such lesions also did not impair performance in a conditioned taste aversion task. These experiments suggest that the mammillary region may be selectively involved in spatial learning and memory.

Memory for Places and the Region of the Mamillary Bodies in Rats.

Rats with extensive lesions of the mamillary bodies and the immediately adjoining areas exhibited a severe impairment on two spatial memory tasks. In the first task, the animals had to retrieve food from each one of eight separate locations within the daily test session. In the second task, the animals were allowed to visit a particular location and retrieve food from it and, after a variable delay, they had to select between returning to the location they had already visited and a new location that now contained the food. Rats with lesions of the mamillary region were able to perform the task with minimal delay, but their performance was impaired as the delay increased. Finally, rats with mamillary lesions were not impaired in learning a visual discrimination task or its reversal. The results show that extensive damage in the mamillary region can lead to significant and long lasting spatial memory impairments.