Biomedical subjects
Charles Pierrot-Deseilligny
Publications and source records attributed to Charles Pierrot-Deseilligny.
The prefrontal substrate of reflexive saccade inhibition in humans.
BACKGROUND: Prefrontal dysfunction in neuropsychiatric disorders such as schizophrenia has been shown to impair inhibition of reflexive saccadic eye movements; however, it is unclear whether reflexive saccade inhibition can be attributed to a distinct subregion of the human prefrontal cortex. METHODS: We tested 15 patients with acute unilateral ischemic lesions of the prefrontal cortex and 20 control subjects with an antisaccade task. Lesions were reconstructed using Talairach coordinates, and possible candidate regions for reflexive saccade inhibition were identified. RESULTS: Significantly increased antisaccade error rates were observed in patients with lesions affecting a region in mid-dorsolateral prefrontal cortex or the white matter between this region and the anterior portions of the internal capsule. Antisaccade error rates of patients with lesions outside this region were normal. These findings were largely independent of lesion volume, postlesion delay, and subject age. CONCLUSIONS: Our findings suggest that inhibition of reflexive saccades depends on a circumscribed subregion of the human dorsolateral prefrontal cortex. This region closely corresponds to Brodmann area 46 as defined by recent cytoarchitectonic studies. Increased antisaccade error rates in patients with prefrontal pathology may be explained by dysfunction of this region.
Cortical mechanisms of saccade generation from execution to decision.
Several cortical areas are involved in the control of ocular motor behavior, but little is known about the cognitive processes occurring prior to saccade triggering. The use of functional brain imaging allows a better understanding of the networks involved specifically in distinct processes of saccade generation. The use of sophisticated visual stimulation paradigms in functional imaging studies suggests that the decision process of where to look when faced with visual alternatives is subserved by a prefrontoparietal network, including the dorsolateral prefrontal cortex.
[Eye movement: from basic semiology to cognitive neuroscience].
Eye movements are an integral part of visual function. They are particularly well developed in frontal-eyed predator species. The abducens nuclei ensure lateral ocular motor synergy, while the oculomotor nuclei control vertical eye movements and convergence. The two main types of conjugate eye movement--saccades (image switching) and slow movements (image stabilization)--are controlled by specific brainstem premotor structures (respectively reticular and vestibular). Upstream of the brainstem, the cortical and subcortical pathways involved in eye movements are gradually being elucidated. Saccades are being used as a motor model to study the different cognitive processes, such as spatial memory, prediction and decision, involved in general movement preparation. The classical approaches based on lesion analysis, combined with transcranial magnetic stimulation and functional cerebral imaging, are contributing to our understanding of how the brain functions. Eye movements can be used for bedside diagnostic purposes, but also for sophisticated laboratory studies designed to explore the universe of cognition.
[The control of gaze (3). Neurological defects].
Eye movements serve vision, which has two different aims: changing images using saccades, i.e. rapid eye movements, and stabilizing new images on the retina using slow eye movements. Eye movements are performed by ocular motor nuclei in the brainstem, on which supranuclear pathways--originating in the cerebral cortex, cerebellum and vestibular structures--converge. It is useful for the neurologist to know the clinical abnormalities of eye movements visible at the bedside since such signs are helpful for localization. Eye movement paralysis may be nuclear or infranuclear (nerves), involving all types of eye movements, i.e. saccades as well as the vestibulo-ocular reflex (VOR), or supranuclear, in which case the VOR is usually preserved. Lateral eye movements are organized in the pons, with paralysis of adduction (and preservation of convergence) when the lesion affects the medial longitudinal fasciculus (internuclear ophthalmoplegia), paralysis of conjugate lateral eye movements when the lesion affects the abducens nucleus (VI) and the "one-and-a-half" syndrome when both these structures are involved. Vertical eye movements are organized in the midbrain, with ipsilateral oculomotor (III) paralysis and contralateral paralysis of the superior rectus muscle when the third nerve nucleus is unilaterally damaged, supranuclear upward gaze paralysis when the posterior commissure is unilaterally damaged and supranuclear downward gaze paralysis (often coupled with upward gaze paralysis) when the mesencephalic reticular formations are bilaterally damaged. Numerous types of abnormal eye movements exist, of which nystagmus is the most frequent and usually due to damage to peripheral or central vestibular pathways. Cerebral hemispheric or cerebellar damage results in subtle eye movement abnormalities at the bedside, in general only detected using eye movement recordings, because of the multiplicity of eye movement pathways at these levels and their reciprocal compensation in the case of a lesion. Lastly, eye movements can also help the neuroscientist to understand the organization of the brain. They are a good model of motricity allowing us, using eye movement recordings, to study the afferent pathways of the cortical areas that trigger them, and thus to analyze relatively complex neuropsychological processes such as visuo-spatial integration, spatial memory, motivation and the preparation of motor programs.
Eye movement control by the cerebral cortex.
PURPOSE OF REVIEW: This review focuses on eye movement control by the cerebral cortex, mainly in humans. Data have emerged based on the important contribution of recent techniques such as transcranial magnetic stimulation and functional magnetic resonance imaging, which provide complementary results to those of the classical lesion and electrical stimulation studies. RECENT FINDINGS: The location of the human frontal eye field and its role in pursuit eye movement control were recently detailed. Cumulative evidence for the role of the dorsolateral prefrontal cortex in unwanted reflexive saccade inhibition, short-term spatial memory and prediction suggests that this area controls decisional processes governing ocular motor behaviour. The organization of spatial memory in the dorsolateral prefrontal cortex (short-term), the parahippocampal cortex (medium-term) and the hippocampal formation (long-term) is also reviewed with the results of recent transcranial magnetic stimulation studies. The relatively complicated anatomy of the posterior parietal cortex in humans is briefly described followed by some additional results concerning the location of the parietal eye field - within the posterior half of the intraparietal sulcus - and its role in visuo-spatial integration and attention. The other areas involved in spatial attention are also examined in the light of several recent contributing reports. Lastly, there are also new functional magnetic resonance imaging findings concerning the posterior cingulate cortex, which appears to be mainly involved in the control of externally guided eye movements and attentional mechanisms. SUMMARY: Many new findings on the organization of saccades and pursuit eye movements at the cortical level have recently been reported. Furthermore, eye movements are increasingly used as a tool to elucidate relatively complex neuropsychological processes such as attention, spatial memory, motivation and decisional processes, and a considerable number of reports dealing with these questions have been observed.
Information processing in long delay memory-guided saccades: further insights from TMS.
The performance of memory-guided saccades with two different delays (3 s and 30 s of memorisation) was studied in eight subjects. Single pulse transcranial magnetic stimulation (TMS) was applied simultaneously over the left and right dorsolateral prefrontal cortex (DLPFC) 1 s after target presentation. In both delays, stimulation significantly increased the percentage of error in amplitude of memory-guided saccades. Furthermore, the interfering effect of TMS was significantly higher in the short delay compared to that of the long delay paradigm. The results are discussed in the context of a mixed model of spatial working memory control including two components: First, serial information processing with a predominant role of the DLPFC during the early period of memorisation and, second, parallel information processing, which is independent from the DLPFC, operating during longer delays.
Neuropsychiatric disturbances in presumed late-onset cobalamin C disease.
BACKGROUND: Combined methylmalonic aciduria and homocystinuria cobalamin C type (cobalamin C disease) is an inborn metabolic disorder consisting of an impaired intracellular synthesis of the 2 active forms of vitamin B12 (cobalamin), namely, adenosylcobalamin and methylcobalamin, that results in increased levels of methylmalonic acid and homocysteine in the blood and urine. Most patients present in the first year of life with systemic, hematological, and neurological abnormalities. Late-onset forms are rare and had not been comprehensively characterized. They could be easily misdiagnosed. OBJECTIVE: To describe clinical and biochemical features of the disease in 2 siblings affected with presumed late-onset cobalamin C disease. DESIGN: Case report and review of the literature. SETTING: Neurological intensive care unit of a university hospital. OBSERVATION: We describe 2 patients with neurological deterioration due to presumed cobalamin C disease. A 16-year-old girl was initially seen with psychosis and severe progressive neuropathy requiring mechanical ventilatory support and her 24-year-old sister had a 2-year disease course of subacute combined degeneration of the spinal cord. A metabolic workup displayed increased methylmalonic acid levels, severe hyperhomocysteinemia, and low plasma methionine levels. The diagnosis was then confirmed by demonstration of impaired synthesis of adenosylcobalamin and methylcobalamin in cultured skin fibroblasts and Epstein-Barr virus-infected lymphocytes. Under specific treatment the younger sister's condition dramatically improved. CONCLUSIONS: Although complementation studies have not been conducted, it is most likely these patients had cobalamin C disease. This study emphasizes the possibility of late-onset disease with purely neurological manifestations. Left untreated, this treatable condition can lead to death or irreversible damage to the nervous system. Screening for intracellular vitamin B12 dysmetabolism should, therefore, be considered in the investigation of adults with unexplained neurological disease, particularly when they are initially seen with a clinical picture suggestive of vitamin B12 deficiency.
Intraoperative frontal eye field stimulation elicits ocular deviation and saccade suppression.
Cortical stimulation is a useful way of elucidating the cortical control of eye movements. The aim of this study was to determine the type of eye movements evoked in response to intraoperative electrical stimulation of the frontal eye field (FEF) region in a fully awake patient during surgery for a frontal lobe glioma. A train of low-intensity electrical pulses within an area in the precentral gyrus evoked contraversive smooth eye movements (SEM) recorded electro-oculographically. Stimulation of an anterior sub-region of this electrically determined FEF disclosed both SEM and suppression of self-paced saccades. However, electrical stimulation of this region evoked no saccades in agreement with pre-operative fMRI using a self-paced saccade paradigm, which did not show activation within the ipsilateral FEF. In humans, intraoperative FEF stimulation may elicit recordable contraversive SEM, and interfere with oculomotor behaviour, suppressing self-paced saccades.
Cortical control of spatial memory in humans: the visuooculomotor model.
We review current knowledge of the cortical control of spatial memory, studied using visuooculomotor paradigms. Spatial memory is an essential cognitive process that can be involved in preparing motor responses. Our knowledge of spatial memory in humans recently has progressed thanks to the use of ocular saccades as a convenient model of motor behavior. Accuracy of memory-guided saccades, made to the remembered locations of visual targets, is a reflection of spatial memory. For the performance of memory-guided saccades with brief delays (up to 15-20 seconds), that is, involving short-term spatial memory, lesion studies have shown that the posterior parietal cortex, the dorsolateral prefrontal cortex, and the frontal eye field play significant roles. Studies of memory-guided saccades using transcranial magnetic stimulation have suggested that the right posterior parietal cortex is involved at the initial stage (<300 milliseconds) of visuospatial integration, whereas the dorsolateral prefrontal cortex in both hemispheres controls the following phase of short-term memorization, the frontal eye field mainly serving to trigger saccades. The new concept of a medium-term spatial memory has emerged from a behavioral study of memory-guided saccades in normal subjects, showing a paradoxical spontaneous improvement of spatial memory after delays of approximately 20 seconds. Lesion studies have shown that the parahippocampal cortex could specifically control this medium-term spatial memory. Last, different experimental and clinical arguments suggest that, after a few minutes, the hippocampal formation finally takes over the control of spatial memory for long-term spatial memorization. Therefore, spatial memory involved in the memorization of visual items could be successively controlled by the dorsolateral prefrontal cortex (short-term spatial memory), the parahippocampal cortex (medium-term spatial memory), and the hippocampal formation (long-term spatial memory), depending on specific periods of times. The applicability of this simple visuooculomotor model of spatial memory to other types of stimuli and general motoricity has yet to be confirmed.
Time-dependent hierarchical organization of spatial working memory: a transcranial magnetic stimulation study.
The performance of memory-guided saccades with two different delays (3 and 30 s of memorization) was studied in seven healthy subjects. Double-pulse transcranial magnetic stimulation (dTMS) with an interstimulus interval of 100 ms was applied over the right dorsolateral prefrontal cortex (DLPFC) early (1 s after target presentation) and late (28 s after target presentation). Early stimulation significantly increased in both delays the percentage of error in amplitude (PEA) of contralateral memory-guided saccades compared to the control experiment without stimulation. dTMS applied late in the delay had no significant effect on PEA. Furthermore, we found a significantly smaller effect of early stimulation in the long-delay paradigm. These results suggest a time-dependent hierarchical organization of the spatial working memory with a functional dominance of DLPFC during the early memorization, independent from the memorization delay. For a long memorization delay, however, working memory seems to have an additional, DLPFC-independent component.