Alain Vighetto

Early Amygdala Reaction to Fear Spreading in Occipital, Temporal, and Frontal Cortex: A Depth Electrode ERP Study in Human

The amygdala involvement in fear processing has been reported in behavioral, electrophysiological, and functional imaging studies. However, the literature does not provide precise data on the temporal course of facial emotional processing. Intracranial event-related potentials to facial expressions were recorded in epileptic patients implanted with depth electrodes during a presurgical evaluation. Specific potentials to fear beginning 200 ms poststimulus were observed in amygdala, both individually in two patients and in a ten patient population study. These potentials occurred 100 ms earlier than potentials to disgust recorded in insula in a previous study. Potentials to fear were confined in amygdala during a first transient period and then, during a second period of sustained activity, spread to occipito-temporal, anterior temporal, and orbitofrontal cortex in two patients. This study clarifies the temporal course of the involvement of these structures known to be part of a neural network recruited to process emotional information.

Impaired social cognition in mild Alzheimer disease

Abnormal decoding of social information has been associated with the conversion from prodromal Alzheimers disease (AD) to dementia. Since the distributed neural networks involved in face processing are differentially affected in prodromal and dementia states of AD and in Fronto-Temporal Dementia (FTD), we hypothezed a differential impairment in face processing in these populations. Facial expression, gender and gaze direction decoding abilities were examined in patients with probable amnesic Mild Cognitive Impairment (aMCI, N = 10) fulfilling criteria for prodromal AD, in patients with mild and moderate AD (N = 10) as well as in FTD patients (N = 10) and in a group of age- and sex-matched healthy comparison subjects (N = 10). Gender recognition was preserved in all groups. Compared to controls, patients with mild or moderate AD were impaired in expression recognition and FTD patients were impaired in expression and gaze direction determination, whereas MCI patients were not impaired at all.

Correlations between soluble α/β forms of amyloid precursor protein and Aβ38, 40, and 42 in human cerebrospinal fluid

Cerebrospinal fluid (CSF) biomarkers are now widely used for diagnosis of Alzheimer disease (AD) in atypical clinical forms, for differential and early diagnosis, or for stratification of patients in clinical trials. Among these biomarkers, different forms of amyloid peptides (Aβ) produced by the cleavage of a transmembrane precursor protein called APP (amyloid precursor protein) have a major role. Aβ peptides exist in different length the most common ones having 40 (Aβ40), 42 (Aβ42), or 38 (Aβ38) amino acids in length. APP processing by gamma-secretase releases also an amino-terminal secreted fragment called sAβPP-beta while an alternative nonamyloidogenic cleavage of APP, through an alpha-secretase, liberates another fragment called sAβPP-alpha. To decipher the molecular and pathological mechanisms leading to the production and the detection of these entities is essential for the comprehension and the prevention of AD. In this report, we present the results of the multiplex measurement of CSF Aβ38, Aβ40, Aβ42, sAβPP-alpha, and sAβPP-beta in 60 patients mostly with dementia eventually segregated between neurochemical dementia diagnostic (NDD) positive and negative groups. The NDD classification was based on our routine Tau, P-tau(181), and Aβ(42) cutoff values. We confirmed previous findings regarding the correlation between sAβPP-alpha and sAβPP-beta, as well as the potential interest of these new biomarkers. We also studied the correlation between sAβPPs and Aβ peptides, as well as between Aβ peptides themselves. We observed a strong correlation between Aβ38 and sAβPP-beta which suggested that the production of this peptide was in direct relation with β secretase activities. We also reported a strong correlation between Aβ38 and Aβ40, while Aβ42 was correlated to these fragments only in nonpathological situations. These results enlighten the complex relationships between these molecular markers in both physiological and pathological situations. Our results are important for the further use of these analytes for AD diagnosis as well as for validating the cell biological hypotheses of APP processing and Aβ fragment production.

Phosphorus and proton magnetic resonance spectroscopy in episodic ataxia type 2.

Localized phosphorus (31P) and proton (1H) magnetic resonance spectroscopy was performed in the cerebellum and the occipital lobe of 6 patients with episodic ataxia type 2. From use of 31P magnetic resonance spectroscopy, untreated patients showed decreased high‐energy phosphate ratios in the cerebrum, and increased pH in the cerebellum and cerebrum, which normalized under acetazolamide. 1H magnetic resonance spectra demonstrated high lactate peaks in 3 of the 6 patients. These metabolic alterations, probably induced by the calcium channelopathy, may characterize episodic ataxia type 2. Ann Neurol 1999;46:256–259

Pre-saccadic perceptual facilitation can occur without covert orienting of attention

The pre-motor theory of attention suggests that the mechanisms involved in target selection for eye movements are the same as those for spatial attention shifts. The pre-saccadic facilitation of perceptual discrimination at the location of a saccadic goal (paradigm of Deubel and Schneider, 1996) has been considered as an argument for this theory. We compared letter discrimination performance in a saccade (overt attention - pre-saccadic facilitation) and a fixation (covert attention) task in a patient with right posterior parietal damage and 4 controls. In the overt attention condition, the patient was instructed by a central cue to make a saccade to a target located at a peripheral location. During the saccade latency (in a period of time of 250 msec following the presentation of the cue), a letter was presented at the target location. Accuracy of leftward saccades was impaired compared to rightward saccades. To evaluate letter discrimination performance in this saccade task (i.e., the presence of pre-saccadic facilitation), we selected only those leftward saccades that were equivalent in accuracy (and latency) to the rightward ones. Within these selected trials, the patient was able to discriminate letters equally well in both visual fields. In contrast, he performed at chance level during the fixation task (covert attention condition) for letters presented at the same peripheral location with the same timing with respect to the cue presentation. The patient could thus discriminate the letter presented at 8° of visual eccentricity while he was preparing a saccade, whereas he was unable to perceive the letter in the fixation task. Remarkably, in the left visual field, letter discrimination was impossible even when a letter was presented as close as 2.5° of visual eccentricity in the fixation task. Altogether, these results suggest that pre-saccadic perceptual facilitation does not rely on the same processes as those of covert attention, as tested by fixation task. Instead, we propose that pre-saccadic perceptual facilitation results from a form of attention specific to action, which could correspond to a pre-saccadic remapping process.

Decreased sAβPPβ, Aβ38, and Aβ40 cerebrospinal fluid levels in frontotemporal dementia.

To improve the etiological diagnosis of neurodegenerative dementias like Alzheimers disease (AD) or frontotemporal dementia (FTD), we evaluated the value of individual and combined measurements of the following relevant cerebrospinal fluid (CSF) biomarkers: Tau, 181p-Tau, Aβ38, Aβ40, Aβ42, sAβPPα, and sAβPPβ. This study conducted in two centers included patients with FTD (n = 34), AD (n = 52), as well as a control group of persons without dementia (CTRL, n = 42). Identical clinical criteria and pre-analytical conditions were used while CSF biomarkers were measured using commercial single and multiplex quantitative immunoassays. Thorough statistical analyses, including ROC curves, logistic regressions, and decision trees, were performed. We validated in AD the specific increase of p-Tau levels and the decrease of Aβ42 levels, two biological hallmarks of this disease. Tau concentrations were highest in AD and intermediate in FTD when compared to CTRL. The most interesting results were obtained by focusing on amyloid biomarkers as we found out in FTD a significant decrease of sAβPPβ, Aβ38, and Aβ40 levels. Aβ38 in particular was the most useful biomarker to differentiate FTD subjects from the CTRL population. Combining p-Tau and Aβ38 led us to correctly classifying FTD patients with sensitivity at 85% and specificity at 82%. Significant changes in amyloid biomarkers, particularly for Aβ38, are therefore seen in FTD. This could be quite useful for diagnosis purposes and it might provide additional evidence on the interrelationship between Tau and AβPP biology which understanding is essential to progress towards optimal therapeutic and diagnostic approaches of dementia.

Secondary deterioration of visual field during cabergoline treatment for macroprolactinoma

Objective  During dopaminergic agonist treatment for macroprolactinoma, tumour shrinkage can be accompanied by secondary deterioration of the visual field in rare instances. The aim of the present study was to evaluate the incidence of symptomatic or asymptomatic delayed visual loss associated with chiasmal herniation during long‐term cabergoline treatment of macroprolactinomas and to report our experience of its management.

Contraversive Eye Deviation During Stimulation of the Subthalamic Region

Contraversive eye deviation (CED) is most often observed intraoperatively during subthalamic nucleus implantation for Parkinsons disease and considered to result from wrong electrode positioning. We report on a woman, bilaterally implanted in the subthalamic nucleus for severe Parkinsons disease disclosing long‐lasting CED only when the stimulators were activated separately. Clinical examination and eye movements recording in this patient showed that CED occurred when stimulation was applied at the site and at similar intensity used for the best antiparkinsonian effect. These results suggest that the subthalamic area may be involved in orienting movements, either through the subthalamic nucleus itself or the fibers from the Frontal Eye Fields. Interestingly, this report shows that CED may be corrected by bilateral stimulation and that CED may not necessarily implicate electrode repositioning.

Saccadic lateropulsion in Wallenberg syndrome: a window to access cerebellar control of saccades?

Saccadic lateropulsion is characterized by an undershoot of contralaterally directed saccades, an overshoot of ipsilaterally directed saccades and an ipsilateral deviation of vertical saccades. In Wallenberg syndrome, it is thought to result from altered signals in the olivo-cerebellar pathway to the oculomotor cerebellar network. In the current study we aimed to determine whether saccadic lateropulsion results from a cerebellar impairment of motor related signals or visuo-spatial related signals. We studied the trajectory, the accuracy, the direction and the amplitude of a variety of vertical and oblique saccades produced by five patients and nine control subjects. Some results are consistent with previous data suggesting altered motor related signals. Indeed, the horizontal error of contralesional saccades in patients increased with the desired horizontal saccade size. Furthermore, the initial directional error measured during the saccadic acceleration phase was smaller than the global directional error, suggesting that the eye trajectory curved progressively. However, some other results suggest that the processes that specify the horizontal spatial goal of the saccades might be impaired in the patients. Indeed, the horizontal error of ipsilesional saccades in patients did not change significantly with the desired horizontal saccade size. In addition, when comparing saccades with similar intended direction, it was found that the directional error was inversely related to the vertical saccade amplitude. Thus we conclude that the cerebellum might be involved both in controlling the motor execution of saccades and in determining the visuo-spatial information about their goal.

Oscillopsies : approches physiopathologique et thérapeutique

Oscillopsia is an illusion of an unstable visual world. It is associated with poor visual acuity and is a disabling and stressful symptom reported by numerous patients with neurological disorders. The goal of this paper is to review the physiology of the systems subserving stable vision, the various pathophysiological mechanisms of oscillopsia and the different treatments available. Visual stability is conditioned by two factors. First, images of the seen world projected onto the retina have to be stable, a sine qua non condition for foveal discriminative function. Vestibulo-ocular and optokinetic reflexes act to stabilize the retinal images during head displacements; ocular fixation tends to limit the occurrence of micro ocular movements during gazing; a specific system also acts to maintain the eyes stable during eccentric gaze. Second, although we voluntary move our gaze (body, head and eye displacements), the visual world is normally perceived as stable, a phenomenon known as space constancy. Indeed, complex cognitive processes compensate for the two sensory consequences of gaze displacement, namely an oppositely-directed retinal drift and a change in the relationship between retinal and spatial (or subject-centered) coordinates of the visual scene. In patients, oscillopsia most often results from abnormal eye movements which cause excessive motion of images on the retina, such as nystagmus or saccadic intrusions or from an impaired vestibulo-ocular reflex. Understanding the exact mechanisms of impaired eye stability may lead to the different treatment options that have been documented in recent years. Oscillopsia could also result from an impairment of spatial constancy mechanisms that in normal condition compensate for gaze displacements, but clinical data in this case are scarce. However, we suggest that some visuo-perceptive deficits consecutive to temporo-parietal lesions resemble oscillopsia and could result from a deficit in elaborating spatial constancy.