1 Institut National de la Santé et de
la Recherche Médicale U. 289 and Service de Neurologie,
Hôpital de la Salpêtrière, F-75651 Paris
Cedex 13, France; and 2 Klinik für
Neurologie, Charité, ...D-10117 Berlin, Germany
Ploner, Christoph J.,
Sophie Rivaud-Péchoux,
Bertrand M. Gaymard,
Yves Agid, and
Charles Pierrot-Deseilligny.
Errors of Memory-Guided Saccades in Humans With Lesions of the
Frontal Eye Field and the Dorsolateral Prefrontal Cortex. J. Neurophysiol. 82: 1086-1090, 1999. Behavioral
studies in monkeys and humans suggest that systematic and variable
errors of memory-guided saccades reflect distinct neuronal computations
in primate spatial memory. We recorded memory-guided saccades with a
2-s delay in three patients with unilateral ischemic lesions of the
frontal eye field and in three patients with unilateral ischemic
lesions of the frontal eye field and the dorsolateral prefrontal
cortex. Results suggest that systematic errors of memory-guided saccades originate in the frontal eye field and variable errors in the
dorsolateral prefrontal cortex. These data are the first human lesion
data to support the hypothesis that these regions provide functionally
distinct contributions to spatial short-term memory.
OBJECTIVE:To describe the relation between gaze and posture/gait control in Parkinson disease (PD) and to determine the role of the mesencephalic locomotor region (MLR) and cortex-MLR connection in ...saccadic behavior because this structure is a major area involved in both gait/postural control and gaze control networks.
METHODS:We recruited 30 patients with PD with or without altered postural control and 25 age-matched healthy controls (HCs). We assessed gait, balance, and neuropsychological status and separately recorded gait initiation and eye movements (visually guided saccades and volitional antisaccades). We identified correlations between the clinical and physiologic parameters that best characterized patients with postural instability. We measured resting-state functional connectivity in 2 pathways involving the frontal oculomotor cortices and the MLR and sought correlations with saccadic behavior.
RESULTS:Patients with PD with postural instability showed altered antisaccade latencies that correlated with the stand-walk-sit time (r = 0.78, p < 0.001) and the duration of anticipatory postural adjustments before gait initiation (r = 0.61, p = 0.001). Functional connectivity between the pedunculopontine nucleus (PPN) and the frontal eye field correlated with antisaccade latency in the HCs (r = −0.54, p = 0.02) but not in patients with PD.
CONCLUSIONS:In PD, impairment of antisaccade latencies, a simple and robust parameter, may be an indirect marker correlated with impaired release of anticipatory postural program. PPN alterations may account for both antisaccade and postural impairments.
Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm characterized by proliferation of tumor histiocytes that involves multiple organs including central nervous system. The ...physiopathologic process underlying degenerative neuro-LCH (i.e., DN-LCH) remains imperfectly settled. Since the main clinical features of DN-LCH are cerebellar ataxia and dysexecutive syndrome, eye movements might be disrupted and may help in disease diagnosis and monitoring. We retrospectively analyzed the medical records of twenty DN-LCH patients investigated using eye movement recording (EMR) in our hospital between 2015 and 2018. DN-LCH patients exhibited (i) abnormal gain in visually guided saccades including hypermetric saccades and excessive gain variability -45.0%-, (ii) increased mean antisaccade error rates -66.7%-, (iii) altered smooth pursuit -50.0%-, and (iv) excessive number of square wave jerks-25%- and gaze-evoked nystagmus. Our study suggests that DN-LCH patients present a peculiar pattern of eye movement impairments supporting cerebellar and prefrontal dysfunctions. As a non-invasive method, EMR could therefore be a useful tool for quantitative monitoring of DN-LCH patients. Further studies are warranted to support our findings.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The significance of cannabinoid signaling for human cognition and motor control is still poorly understood. Here, we have investigated acute behavioral effects of oral δ-9-tetrahydrocannabinol (THC) ...with oculomotor paradigms in 12 healthy human subjects. Compared to baseline testing: (i) THC increased latencies of reflexive visually guided saccades, while their accuracy was not affected; (ii) latencies of memory-guided saccades were unaffected, but THC modulated accuracy of these eye movements by increasing average gain and gain variability; (iii) frequency of anticipated memoryguided saccades and antisaccade errors was increased; (iv) the saccade amplitude/peak velocity relationships were not affected. These results show that THC acts on selected aspects of saccade control, namely spatial attention shifts, fine tuning of volitional saccades, spatial working memory and inhibition of inappropriate saccades. The pattern of effects suggests modulation of neuronal activity in substantia nigra pars reticulata and/or dorsolateral prefrontal cortex and sparing of the eye fields and the final motor pathway for saccades. Behaviorally, our findings reflect the distribution of CB-1 cannabinoid receptors in the human neocortex, basal ganglia and brainstem and provide evidence for participation of the cannabinoidergic system in high level control of saccades and associated cognitive functions. Saccadic eye movements may provide an objective measure of motor and cognitive effects of cannabinoids.
Richard F. Lewis 1 ,
Bertrand M. Gaymard 1 , and
Rafael J. Tamargo 2
1 Department of Neurology and 2 Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland ...21287
Lewis, Richard F., Bertrand M. Gaymard, and Rafael J. Tamargo. Efference copy provides the eye position information required for visually guided reaching. J. Neurophysiol. 80: 1605-1608, 1998. The contribution of extraocular muscle (EOM) proprioception to the eye position signal used to transform retinotopic visual information to a craniotopic reference frame remains uncertain. In this study we examined the effects of unilateral and bilateral proprioceptive deafferentation of the EOMs on the accuracy of reaching movements directed to visual targets. No significant changes occurred in the mean accuracy (constant error) or variance (variable error) of pointing after unilateral or bilateral deafferentation. We concluded that in normal animals efference copy provides sufficient information about orbital eye position to code space in craniotopic coordinates.
Fragile X-associated tremor ataxia syndrome (FXTAS) is defined by FMR1 premutation, cerebellar ataxia, intentional tremor, and middle cerebellar peduncle (MCP) hyperintensities. We delineate the ...clinical, neurophysiologic, and morphologic characteristics of FXTAS.
Clinical, morphologic (brain MRI, (123)I-ioflupane SPECT), and neurophysiologic (tremor recording, nerve conduction studies) study in 22 patients with FXTAS, including 4 women.
A total of 43% of patients had no family history of fragile X syndrome (FXS), which contrasts with previous FXTAS series. A total of 86% of patients had tremor and 81% peripheral neuropathy. We identified 3 electroclinical tremor patterns: essential-like (35%), cerebellar (29%), and parkinsonian (12%). Two electrophysiologic patterns evocative of non-length-dependent (56%) and length-dependent sensory neuropathy (25%) were identified. Corpus callosum splenium (CCS) hyperintensity was as frequent (68%) as MCP hyperintensities (64%). Sixty percent of patients had parkinsonism and 47% abnormal (123)I-ioflupane SPECT. Unified Parkinson's Disease Rating Scale motor score was correlated to abnormal (123)I-ioflupane SPECT (p = 0.02) and to CGG repeat number (p = 0.0004). Scale for the assessment and rating of ataxia correlated with dentate nuclei hyperintensities (p = 0.03) and CCS hyperintensity was a marker of severe disease progression (p = 0.04).
We recommend to include in the FXTAS testing guidelines both CCS hyperintensity and peripheral neuropathy and to consider them as new major radiologic and minor clinical criterion, respectively, for the diagnosis of FXTAS. FXTAS should also be considered in women or when tremor, MCP hyperintensities, or family history of FXS are lacking. Our study broadens the spectrum of tremor, peripheral neuropathy, and MRI abnormalities in FXTAS, hence revealing the need for revised criteria.
Neuroimagery findings have shown similar cerebral networks associated with imagination and execution of a movement. On the other hand, neuropsychological studies of parietal-lesioned patients suggest ...that these networks may be at least partly distinct. In the present study, normal subjects were asked to either imagine or execute auditory-cued hand movements. Compared with rest, imagination and execution showed overlapping networks, including bilateral premotor and parietal areas, basal ganglia and cerebellum. However, direct comparison between the two experimental conditions showed that specific cortico-subcortical areas were more engaged in mental simulation, including bilateral premotor, prefrontal, supplementary motor and left posterior parietal areas, and the caudate nuclei. These results suggest that a specific neuronal substrate is involved in the processing of hand motor representations.
Abstract Background Blurred near vision is a common non-motor symptom in patients with Parkinson's disease (PD), however detailed characterization of vergence eye movements (VEM) is lacking. Methods ...Convergence and divergence were examined in 18 patients with PD and 18 control subjects using infrared video-oculography. VEM metrics analyzed included latency, velocity and accuracy, in vertical and horizontal planes. Results The latency of convergence and divergence was significantly increased in PD subjects. Additionally, divergence was slow and hypometric, while other convergence metrics were similar to controls. Conclusion We provide evidence in favor of disrupted VEM in PD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background
Ketamine, a non-competitive
N
-methyl-
d
-aspartic acid antagonist, has been widely used for anaesthetic purposes. At sub-anaesthetic dosage, it induces a dissociative state similar to ...schizophrenia. The discovery of this effect on dissociative state has led to its use as a pharmacological model of schizophrenia and has also been responsible for its illegal use as a recreational drug. Whereas the former has provided invaluable information, the latter has demonstrated that repeated administration of ketamine induces tolerance. Surprisingly, a review of the relevant literature shows that tolerance to sub-anaesthetic doses of ketamine is largely unreported in neuropharmacological studies.
Methods
In order to investigate this caveat, we have performed a post hoc analysis of the behavioural effects induced by repeated injections of sub-anaesthetic doses of ketamine observed in five consecutive monkeys performing two oculomotor tasks. Ketamine effects were quantified by the animals' performances and latencies in a prosaccade and an antisaccade task, two oculomotor paradigms that are impaired after ketamine administration.
Results
Although the result of the initial injections confirmed a clear behavioural effect of ketamine injections in all monkeys, subsequent administrations showed that a tolerance eventually appeared in all monkeys. The profile of this tolerance exhibited however a large inter-subject variability.
Conclusions
Psychopharmacological experiments using ketamine as a pharmacological model of psychosis should therefore consider the kinetic and time course of these effects in each individuals and take them into account in the design of experimental protocols.
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DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10–60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of ...FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability.
We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor.
A higher frequency of expanded allele carriers in index cases with ataxia was significant only above 300 GAA repeats (10.1%, n = 85) compared with controls (1.1%, n = 5) (p < 0.0001) whereas GAA250–299 alleles were detected in 1.7% of both groups. Eight of 14 index cases with GAA250-299 repeats had other causal pathogenic variants (4/14) and/or discordance of co-segregation (5/14), arguing against GAA causality. We compared the clinical signs in 127 GAA≥300 carriers to cases with non-expanded GAA ataxia resulting in defining a key phenotype triad: onset after 45 years, downbeat nystagmus, episodic ataxic features including diplopia; and a frequent absence of dysarthria. All maternally transmitted alleles above 100 GAA were unstable with a median expansion of +18 repeats per generation (r2 = 0.44; p < 0.0001). In comparison, paternally transmitted alleles above 100 GAA mostly decreased in size (−15 GAA (r2 = 0.63; p < 0.0001)), resulting in the transmission bias observed in SCA27B pedigrees.
SCA27B diagnosis must consider both the phenotype and GAA expansion size. In carriers of GAA250-299 repeats, the absence of documented familial transmission and a presentation deviating from the key SCA27B phenotype, should prompt the search for an alternative cause. Affected fathers have a reduced risk of having affected children, which has potential implications for genetic counseling.
This work was supported by the Fondation pour la Recherche Médicale, grant number 13338 to JLM, the Association Connaître les Syndrome Cérébelleux – France (to GS) and by the European Union’s Horizon 2020 research and innovation program under grant agreement No 779257 (“SOLVE-RD” to GS). DP holds a Fellowship award from the Canadian Institutes of Health Research (CIHR). SK received a grant (01GM1905C) from the Federal Ministry of Education and Research, Germany, through the TreatHSP network. This work was supported by the Australian Government National Health and Medical Research Council grants (GNT2001513 and MRFF2007677) to MB and PJL.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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