Lydia Yahia-Cherif

High nigral iron deposition in LRRK2 and Parkin mutation carriers using R2* relaxometry

The goal of this work was to investigate iron deposition in the basal ganglia and thalamus in symptomatic and asymptomatic leucine‐rich repeat kinase 2 (LRRK2) and Parkin‐associated Parkinsons disease (PD), using R2* relaxometry rate.

Age-related decline in the responsiveness of motor cortex to plastic forces reverses with levodopa or cerebellar stimulation

The plasticity of motor cortex is integral for motor memory and skills acquisition but it declines with aging. Forty healthy volunteers, across 6 decades, were tested to examine the (a) age-dependency of motor cortex responsiveness to plasticity induction, as measured from the response to paired associative stimulation (PAS) and the (b) effect of aging on the cerebellar modulation of motor cortex response to PAS. We examined if reduced dopaminergic transmission was involved in the age-related decline of response to PAS by retesting 10 of the older subjects after a single dose of levodopa. There was a substantial decline in the motor cortex response to PAS with aging, which was restored by levodopa in the older subjects. The cerebellar modulation of motor cortex response to PAS was less vulnerable to aging and a single session of cerebellar inhibition reinstated the cortical responsiveness in older subjects. Both levodopa and cerebellar inhibition can be tested for their ability to enhance motor skills acquisition and motor performance in the elderly individuals.

Radiofrequency signal affects alpha band in resting electroencephalogram

The aim of the present work was to investigate the effects of the radiofrequency (RF) electromagnetic fields (EMFs) on human resting EEG with a control of some parameters that are known to affect alpha band, such as electrode impedance, salivary cortisol, and caffeine. Eyes-open and eyes-closed resting EEG data were recorded in 26 healthy young subjects under two conditions: sham exposure and real exposure in double-blind, counterbalanced, crossover design. Spectral power of EEG rhythms was calculated for the alpha band (8-12 Hz). Saliva samples were collected before and after the study. Salivary cortisol and caffeine were assessed by ELISA and HPLC, respectively. The electrode impedance was recorded at the beginning of each run. Compared with the sham session, the exposure session showed a statistically significant (P < 0.0001) decrease of the alpha band spectral power during closed-eyes condition. This effect persisted in the postexposure session (P < 0.0001). No significant changes were detected in electrode impedance, salivary cortisol, and caffeine in the sham session compared with the exposure one. These results suggest that GSM-EMFs of a mobile phone affect the alpha band within spectral power of resting human EEG.

Amygdala processing of social cues from faces: an intracrebral EEG study

The amygdala is a key structure for monitoring the relevance of environmental stimuli. Yet, little is known about the dynamics of its response to primary social cues such as gaze and emotion. Here, we examined evoked amygdala responses to gaze and facial emotion changes in five epileptic patients with intracerebral electrodes. Patients first viewed a neutral face that would then convey social cues: it turned either happy or fearful with or without gaze aversion. This social cue was followed by a laterally presented target, the detection of which was faster if it appeared in a location congruent with the averted gaze direction. First, we observed pronounced evoked amygdala potentials to the initial neutral face. Second, analysis of the evoked responses to the cue showed an early effect of gaze starting at 123 ms in the right amygdala. Differential effects of fearful vs happy valence were individually present but more variable in time and therefore not observed at group-level. Our study is the first to demonstrate such an early effect of gaze in the amygdala, in line with its particular behavioral relevance in the spatial attention task.

Magnetic Resonance Imaging Biomarkers to Assess Substantia Nigra Damage in Idiopathic Rapid Eye Movement Sleep Behavior Disorder

Objectives Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered to be a prodromal stage of Parkinsons disease (PD). At PD onset, 40 to 70% of the dopaminergic neurons in the substantia nigra (SN) are already lost. Thus, milder SN damage is expected in participants with iRBD. We aimed to quantify SN damage in participants with iRBD using multimodal magnetic resonance imaging (MRI) and to determine biomarker efficacy in preclinical Parkinsonism. Methods Nineteen participants with iRBD and 18 controls underwent 3-Tesla MRI, including diffusion tensor imaging, neuromelanin (NM)-sensitive imaging, and T2* mapping. Regions of interest in the SN area were drawn in NM-sensitive and T2-weighted images. The volume and normalized signal intensity in NM-sensitive images, R2*, and diffusion tensor measures were quantified in the SN. Additionally, two raters performed visual analysis of the SN using the NM-sensitive images. Results Participants with iRBD showed a reduction in the NM-sensitive volume and signal intensity and a decrease in fractional anisotropy (FA) versus controls, but showed no differences in axial, radial, or mean diffusivity or in R2*. For NM-sensitive volume and signal intensity, the receiver operating characteristic analysis discriminated between participants with iRBD and controls with a diagnostic accuracy of 0.86 and 0.79, respectively, whereas the accuracy was 0.77 for FA. The three biomarkers had a combined accuracy of 0.92. The fraction of participants correctly characterized by visual assessment was 0.81. Conclusions NM-sensitive imaging and FA allowed for the detection of SN damage in participants with iRBD with good diagnostic accuracy. These measures may represent valuable biomarkers for prodromal Parkinsonism.

Longitudinal changes in functional connectivity of cortico-basal ganglia networks in manifests and premanifest huntington's disease.

Huntingtons disease (HD) is a genetic neurological disorder resulting in cognitive and motor impairments. We evaluated the longitudinal changes of functional connectivity in sensorimotor, associative and limbic cortico‐basal ganglia networks. We acquired structural MRI and resting‐state fMRI in three visits one year apart, in 18 adult HD patients, 24 asymptomatic mutation carriers (preHD) and 18 gender‐ and age‐matched healthy volunteers from the TRACK‐HD study. We inferred topological changes in functional connectivity between 182 regions within cortico‐basal ganglia networks using graph theory measures. We found significant differences for global graph theory measures in HD but not in preHD. The average shortest path length (L) decreased, which indicated a change toward the random network topology. HD patients also demonstrated increases in degree k, reduced betweeness centrality bc and reduced clustering C. Changes predominated in the sensorimotor network for bc and C and were observed in all circuits for k. Hubs were reduced in preHD and no longer detectable in HD in the sensorimotor and associative networks. Changes in graph theory metrics (L, k, C and bc) correlated with four clinical and cognitive measures (symbol digit modalities test, Stroop, Burden and UHDRS). There were no changes in graph theory metrics across sessions, which suggests that these measures are not reliable biomarkers of longitudinal changes in HD. preHD is characterized by progressive decreasing hub organization, and these changes aggravate in HD patients with changes in local metrics. HD is characterized by progressive changes in global network interconnectivity, whose network topology becomes more random over time. Hum Brain Mapp 37:4112–4128, 2016.

Motor cortex plasticity can indicate vulnerability to motor fluctuation and high L-DOPA need in drug-naïve Parkinson's disease.

INTRODUCTION Motor cortex plasticity is reported to be decreased in Parkinsons disease in studies which pooled patients in various stages of the disease. Whether the early decrease in plasticity is related to the motor signs or is linked to the future development of motor complications of treatment is unclear. The aim of the study was to test if motor cortex plasticity and its cerebellar modulation are impaired in treatment-naïve Parkinsons disease, are related to the motor signs of the disease and predict occurrence of motor complications of treatment. METHODS Twenty-nine denovo patients with Parkinsons disease were longitudinally assessed for motor complications for four years. Using transcranial magnetic stimulation, the plasticity of the motor cortex and its cerebellar modulation were measured (response to paired-associative stimulation alone or preceded by 2 active cerebellar stimulation protocols), both in the untreated state and after a single dose of L-DOPA. Twenty-six matched, healthy volunteers were tested, only without L-DOPA. RESULTS Patients and healthy controls had similar proportions of responders and non-responders to plasticity induction. In the untreated state, the more efficient was the cerebellar modulation of motor cortex plasticity, the lower were the bradykinesia and rigidity scores. The extent of the individual plastic response to paired associative stimulation could indicate a vulnerability to develop early motor fluctuation but not dyskinesia. CONCLUSIONS Measuring motor cortex plasticity in denovo Parkinsons disease could be a neurophysiological parameter that may help identify patients with greater propensity for early motor fluctuations.

Gaze perception induces early attention orienting effects in occipito-parietal regions

&NA; Others eye gaze is a powerful attention orienting cue that can change our perception of objects in the environment. Here, we seek to characterize the influence of attention orienting by eye gaze on the neural processing of visual targets. We used a Posner‐like cueing paradigm to investigate with magnetoencephalography the brain responses associated with target processing. We analyzed the cerebral sources of the evoked responses to visual targets that were validly or invalidly cued by eye gaze. The effect of attention orienting was reflected in faster reaction times to valid than invalid targets. At the brain level, we showed an early influence of attention orienting by gaze with enhanced brain responses for invalid relative to valid targets. This influence was maximum contra‐laterally to the target, with a right hemisphere dominance. Responses to targets presented in the left visual field were modulated between 91 and 400 ms in the right posterior parietal and occipital cortices. Responses to targets presented in the right visual field were modulated between 174 and 218 ms in the left superior parietal cortex. Our results confirm previous EEG studies that demonstrated early influence of attention orienting by gaze on target processing and provide evidence for the sources of this effect in occipito‐parietal regions. This early influence may reflect the first stage of the perceptual changes induced by social attention. HighlightsWe examined neuromagnetic responses to targets in a task of attention cueing by gaze.We showed an early influence of eye gaze cueing on brain responses to targets.The sources of this effect were located in occipital and parietal cortices.

Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate Idiopathic Parkinson Disease

BACKGROUND AND PURPOSE: Several new MR imaging techniques have shown promising results in patients with Parkinson disease; however, the comparative diagnostic values of these measures at the individual level remain unclear. Our aim was to compare the diagnostic value of MR imaging biomarkers of substantia nigra damage for distinguishing patients with Parkinson disease from healthy volunteers. MATERIALS AND METHODS: Thirty-six patients and 20 healthy volunteers were prospectively included. The MR imaging protocol at 3T included 3D T2-weighted and T1-weighted neuromelanin-sensitive images, diffusion tensor images, and R2* mapping. T2* high-resolution images were also acquired at 7T to evaluate the dorsal nigral hyperintensity sign. Quantitative analysis was performed using ROIs in the substantia nigra drawn manually around the area of high signal intensity on neuromelanin-sensitive images and T2-weighted images. Visual analysis of the substantia nigra neuromelanin-sensitive signal intensity and the dorsolateral nigral hyperintensity on T2* images was performed. RESULTS: There was a significant decrease in the neuromelanin-sensitive volume and signal intensity in patients with Parkinson disease. There was also a significant decrease in fractional anisotropy and an increase in mean, axial, and radial diffusivity in the neuromelanin-sensitive substantia nigra at 3T and a decrease in substantia nigra volume on T2* images. The combination of substantia nigra volume, signal intensity, and fractional anisotropy in the neuromelanin-sensitive substantia nigra allowed excellent diagnostic accuracy (0.93). Visual assessment of both substantia nigra dorsolateral hyperintensity and neuromelanin-sensitive images had good diagnostic accuracy (0.91 and 0.86, respectively). CONCLUSIONS: The combination of neuromelanin signal and volume changes with fractional anisotropy measurements in the substantia nigra showed excellent diagnostic accuracy. Moreover, the high diagnostic accuracy of visual assessment of substantia nigra changes using dorsolateral hyperintensity analysis or neuromelanin-sensitive signal changes indicates that these techniques are promising for clinical practice.