Viviane Sziklas

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 Adjunctive Topiramate on Cognitive Function in Patients with Epilepsy

Summary:  Purpose: We investigated possible cognitive effects of topiramate (TPM) in polypharmacy on patients with intractable epilepsy.

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.

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.

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.

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.

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 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.

Spatial conditional associative learning: effects of thalamo-hippocampal disconnection in rats.

Unilateral lesions to the anterior thalamic nuclei (ATN) and the hippocampus (H) were made in opposite hemispheres in the rat to examine whether these brain structures form part of a functional neural pathway underlying spatial learning and memory. In the first experiment, rats were tested on a spatial-visual conditional associative task in which they had to learn to approach one of two stimuli depending on the spatial context in which the stimuli were embedded. The rats were subsequently trained on delayed forced alternation, a spatial working memory task known to be sensitive to the effects of ATNxH damage. Rats with ATNxH lesions were impaired in the acquisition of both tasks in comparison with normal control animals. The findings support the idea that the anterior thalamic nuclei and the hippocampus are critical components of an anatomical system subserving spatial memory and suggest that these brain regions work in a dependent fashion during the performance of certain spatial learning tasks.

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.