The cost of attentional reorienting on conscious visual perception: an MEG study.

How do attentional networks influence conscious perception? To answer this question, we used magnetoencephalography in human participants and assessed the effects of spatially nonpredictive or predictive supra-threshold peripheral cues on the conscious perception of near-threshold Gabors. Three main results emerged. (i) As compared with invalid cues, both nonpredictive and predictive valid cues increased conscious detection. Yet, only predictive cues shifted the response criterion toward a more liberal decision (i.e. willingness to report the presence of a target under conditions of greater perceptual uncertainty) and affected target contrast leading to 50% detections. (ii) Conscious perception following valid predictive cues was associated to enhanced activity in frontoparietal networks. These responses were lateralized to the left hemisphere during attentional orienting and to the right hemisphere during target processing. The involvement of frontoparietal networks occurred earlier in valid than in invalid trials, a possible neural marker of the cost of re-orienting attention. (iii) When detected targets were preceded by invalid predictive cues, and thus reorienting to the target was required, neural responses occurred in left hemisphere temporo-occipital regions during attentional orienting, and in right hemisphere anterior insular and temporo-occipital regions during target processing. These results confirm and specify the role of frontoparietal networks in modulating conscious processing and detail how invalid orienting of spatial attention disrupts conscious processing.

Longitudinal Monitoring of Microstructural Alterations in Cerebral Ischemia with in Vivo Diffusion-weighted MR Spectroscopy.

Background The time course of cellular damage after acute ischemic stroke (IS) is currently not well known, and specific noninvasive markers of microstructural alterations linked to inflammation are lacking, which hinders the monitoring of anti-inflammatory treatment. Purpose To evaluate the temporal pattern of neuronal and glial microstructural changes after stroke using in vivo single-voxel diffusion-weighted MR spectroscopy. Materials and Methods In this prospective longitudinal study, participants with IS and healthy volunteers (HVs) underwent MRI at 3.0 T. In participants with IS, apparent diffusion coefficients (ADCs) and concentrations of total N-acetyl-aspartate (tNAA), total creatine (tCr), and total choline (tCho) were measured in volumes of interest (VOIs), including the lesion VOI (VOIles) and the contralateral VOI (VOIcl) at 2 weeks, 1 month, and 3 months after IS. HVs were examined once, with VOIs located in the same brain regions as participants with IS. Within- and between-group differences and longitudinal changes were examined using linear mixed-effects models. Results Twenty participants with IS (mean age, 61 years ± 13 [SD]; 12 women) and 20 HVs (mean age, 59 years ± 13; 12 women) were evaluated. No differences in ADCs or concentrations were observed in VOIcl between HVs and participants with IS. In participants with IS, the ADC of tCr was higher in VOIles than in VOIcl at 1 month (+14.4%, P = .004) and 3 months after IS (+19.0%, P < .001), while the ADC of tCho was higher only at 1 month (+16.7%, P = .001). No difference in the ADC of tNAA was observed between the two VOIs at any time point. tNAA and tCr concentrations were lower in VOIles than in VOIcl and were stable over time (approximately -50% and -30%, respectively; P < .001). Conclusion High diffusivity of choline-containing compounds and total creatine (tCr) in the ischemic lesion 1 month after ischemic stroke (IS) indicates glial morphologic changes, suggesting that active inflammation is still ongoing at this time point. High tCr diffusivity up to 3 months after IS likely reflects the presence of astrogliosis at the chronic stage of cerebral ischemia. Clinical trial registration no. NCT02833961 © RSNA, 2022 Online supplemental material is available for this article.

Deep Learning-Based Neuromelanin MRI Changes of Isolated REM Sleep Behavior Disorder.

BACKGROUND: Isolated REM sleep behavior disorder (iRBD) is considered a prodromal stage of parkinsonism. Neurodegenerative changes in the substantia nigra pars compacta (SNc) in parkinsonism can be detected using neuromelanin-sensitive MRI. OBJECTIVE: To investigate SNc neuromelanin changes in iRBD patients using fully automatic segmentation. METHODS: We included 47 iRBD patients, 134 early Parkinson's disease (PD) patients and 55 healthy volunteers (HVs) scanned at 3 Tesla. SNc regions-of-interest were delineated automatically using convolutional neural network. SNc volumes, volumes corrected by total intracranial volume, signal-to-noise ratio (SNR) and contrast-to-noise ratio were computed. One-way general linear models (GLM) analysis of covariance (ANCOVA) was conducted while adjusting for age and sex. RESULTS: All SNc measurements differed significantly between the three groups (except SNR in iRBD). Changes in iRBD were intermediate between those in PD and HVs. CONCLUSIONS: Using fully automated SNc segmentation method and neuromelanin-sensitive imaging, iRBD patients showed neurodegenerative changes in the SNc at a lower level than in PD patients. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Antisaccade, a predictive marker for freezing of gait in Parkinson's disease and gait/gaze network connectivity.

Freezing of gait is a challenging sign of Parkinson's disease associated with disease severity and progression and involving the mesencephalic locomotor region. No predictive factor of freezing has been reported so far. The primary objective of this study was to identify predictors of freezing occurrence at 5 years. In addition, we tested whether functional connectivity of the mesencephalic locomotor region could explain the oculomotor factors at baseline that were predictive of freezing onset. We performed a prospective study investigating markers (parkinsonian signs, cognitive status and oculomotor recordings, with a particular focus on the antisaccade latencies) of disease progression at baseline and at 5 years. We identified two groups of patients defined by the onset of freezing at 5 years of follow-up; the 'Freezer' group was defined by the onset of freezing in the ON medication condition during follow-up (n = 17), while the 'non-Freezer' group did not (n = 8). Whole brain resting-state functional MRI was recorded at baseline to determine how antisaccade latencies were associated with connectivity of the mesencephalic locomotor region networks in patients compared to 25 age-matched healthy volunteers. Results showed that, at baseline and compared to the non-Freezer group, the Freezer group had equivalent motor or cognitive signs, but increased antisaccade latencies (P = 0.008). The 5-year course of freezing of gait was correlated with worsening antisaccade latencies (P = 0.0007). Baseline antisaccade latencies was also predictive of the freezing onset (χ2 = 0.008). Resting state connectivity of mesencephalic locomotor region networks correlated with (i) antisaccade latency differently in patients and healthy volunteers at baseline; and (ii) the further increase of antisaccade latency at 5 years. We concluded that antisaccade latency is a predictive marker of the 5-year onset of freezing of gait. Our study suggests that functional networks associated with gait and gaze control are concurrently altered during the course of the disease.

The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease.

In Parkinson's disease, there is a progressive reduction in striatal dopaminergic function, and loss of neuromelanin-containing dopaminergic neurons and increased iron deposition in the substantia nigra. We tested the hypothesis of a relationship between impairment of the dopaminergic system and changes in the iron metabolism. Based on imaging data of patients with prodromal and early clinical Parkinson's disease, we assessed the spatiotemporal ordering of such changes and relationships in the sensorimotor, associative and limbic territories of the nigrostriatal system. Patients with Parkinson's disease (disease duration < 4 years) or idiopathic REM sleep behaviour disorder (a prodromal form of Parkinson's disease) and healthy controls underwent longitudinal examination (baseline and 2-year follow-up). Neuromelanin and iron sensitive MRI and dopamine transporter single-photon emission tomography were performed to assess nigrostriatal levels of neuromelanin, iron, and dopamine. For all three functional territories of the nigrostriatal system, in the clinically most and least affected hemispheres separately, the following was performed: cross-sectional and longitudinal intergroup difference analysis of striatal dopamine and iron, and nigral neuromelanin and iron; in Parkinson's disease patients, exponential fitting analysis to assess the duration of the prodromal phase and the temporal ordering of changes in dopamine, neuromelanin or iron relative to controls; and voxel-wise correlation analysis to investigate concomitant spatial changes in dopamine-iron, dopamine-neuromelanin and neuromelanin-iron in the substantia nigra pars compacta. The temporal ordering of dopaminergic changes followed the known spatial pattern of progression involving first the sensorimotor, then the associative and limbic striatal and nigral regions. Striatal dopaminergic denervation occurred first followed by abnormal iron metabolism and finally neuromelanin changes in the substantia nigra pars compacta, which followed the same spatial and temporal gradient observed in the striatum but shifted in time. In conclusion, dopaminergic striatal dysfunction and cell loss in the substantia nigra pars compacta are interrelated with increased nigral iron content.

Longitudinal Changes in Neuromelanin MRI Signal in Parkinson's Disease: A Progression Marker.

BACKGROUND: Development of reliable and accurate imaging biomarkers of dopaminergic cell neurodegeneration is necessary to facilitate therapeutic drug trials in Parkinson's disease (PD). Neuromelanin-sensitive MRI techniques have been effective in detecting neurodegeneration in the substantia nigra pars compacta (SNpc). The objective of the current study was to investigate longitudinal neuromelanin signal changes in the SNpc in PD patients. METHODS: In this prospective, longitudinal, observational case-control study, we included 140 PD patients and 64 healthy volunteers divided into 2 cohorts. Cohort I included 99 early PD patients (disease duration, 1.5 ± 1.0 years) and 41 healthy volunteers analyzed at baseline (V1), where 79 PD patients and 32 healthy volunteers were rescanned after 2.0 ± 0.2 years of follow-up (V2). Cohort II included 41 progressing PD patients (disease duration, 9.3 ± 3.7 years) and 23 healthy volunteers at V1, where 30 PD patients were rescanned after 2.4 ± 0.5 years of follow-up. Subjects were scanned at 3 T MRI using 3-dimensional T1-weighted and neuromelanin-sensitive imaging. Regions of interest were delineated manually to calculate SN volumes, volumes corrected by total intracranial volume, signal-to-noise ratio, and contrast-to-noise ratio. RESULTS: Results showed (1) significant reduction in volume and volume corrected by total intracranial volume between visits, greater in progressing PD than nonsignificant changes in healthy volunteers; (2) no significant effects of visit for signal intensity (signal-to-noise ratio); (3) significant interaction in volume between group and visit; (4) greater volume corrected by total intracranial volume at baseline in female patients and greater decrease in volume and increase in the contrast-to-noise ratio in progressing female PD patients compared with male patients; and (5) correlations between neuromelanin SN changes and disease severity and duration. CONCLUSIONS: We observed a progressive and measurable decrease in neuromelanin-based SN signal and volume in PD, which might allow a direct noninvasive assessment of progression of SN loss and could represent a target biomarker for disease-modifying treatments. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Automated Categorization of Parkinsonian Syndromes Using Magnetic Resonance Imaging in a Clinical Setting.

BACKGROUND: Machine learning algorithms using magnetic resonance imaging (MRI) data can accurately discriminate parkinsonian syndromes. Validation in patients recruited in routine clinical practice is missing. OBJECTIVE: The aim of this study was to assess the accuracy of a machine learning algorithm trained on a research cohort and tested on an independent clinical replication cohort for the categorization of parkinsonian syndromes. METHODS: Three hundred twenty-two subjects, including 94 healthy control subjects, 119 patients with Parkinson's disease (PD), 51 patients with progressive supranuclear palsy (PSP) with Richardson's syndrome, 35 with multiple system atrophy (MSA) of the parkinsonian variant (MSA-P), and 23 with MSA of the cerebellar variant (MSA-C), were recruited. They were divided into a training cohort (n = 179) scanned in a research environment and a replication cohort (n = 143) examined in clinical practice on different MRI systems. Volumes and diffusion tensor imaging (DTI) metrics in 13 brain regions were used as input for a supervised machine learning algorithm. To harmonize data across scanners and reduce scanner-dependent effects, we tested two types of normalizations using patient data or healthy control data. RESULTS: In the replication cohort, high accuracies were achieved using volumetry in the classification of PD-PSP, PD-MSA-C, PSP-MSA-C, and PD-atypical parkinsonism (balanced accuracies: 0.840-0.983, area under the receiver operating characteristic curves: 0.907-0.995). Performances were lower for the classification of PD-MSA-P, MSA-C-MSA-P (balanced accuracies: 0.765-0.784, area under the receiver operating characteristic curve: 0.839-0.871) and PD-PSP-MSA (balanced accuracies: 0.773). Performance using DTI was improved when normalizing by controls, but remained lower than that using volumetry alone or combined with DTI. CONCLUSIONS: A machine learning approach based on volumetry enabled accurate classification of subjects with early-stage parkinsonism, examined on different MRI systems, as part of their clinical assessment. © 2020 International Parkinson and Movement Disorder Society.

Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson's disease.

This study aimed to investigate the spatiotemporal changes in neuromelanin-sensitive MRI signal in the substantia nigra and their relation to clinical scores of disease severity in patients with early or progressing Parkinson's disease and patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) exempt of Parkinsonian signs compared to healthy control subjects. Longitudinal T1-weighted anatomical and neuromelanin-sensitive MRI was performed in two cohorts, including patients with iRBD, patients with early or progressing Parkinson's disease, and control subjects. Based on the aligned substantia nigra segmentations using a study-specific brain anatomical template, parametric maps of the probability of a voxel belonging to the substantia nigra were calculated for patients with various degrees of disease severity and controls. For each voxel in the substantia nigra, probability map of controls, correlations between signal-to-noise ratios on neuromelanin-sensitive MRI in patients with iRBD and Parkinson's disease and clinical scores of motor disability, cognition and mood/behaviour were calculated. Our results showed that in patients, compared to the healthy control subjects, the volume of the substantia nigra was progressively reduced for increasing disease severity. The neuromelanin signal changes appeared to start in the posterolateral motor areas of the substantia nigra and then progressed to more medial areas of this region. The ratio between the volume of the substantia nigra in patients with Parkinson's disease relative to the controls was best fitted by a mono-exponential decay. Based on this model, the pre-symptomatic phase of the disease started at 5.3 years before disease diagnosis, and 23.1% of the substantia nigra volume was lost at the time of diagnosis, which was in line with previous findings using post-mortem histology of the human substantia nigra and radiotracer studies of the human striatum. Voxel-wise patterns of correlation between neuromelanin-sensitive MRI signal-to-noise ratio and motor, cognitive and mood/behavioural clinical scores were localized in distinct regions of the substantia nigra. This localization reflected the functional organization of the nigrostriatal system observed in histological and electrophysiological studies in non-human primates (motor, cognitive and mood/behavioural domains). In conclusion, neuromelanin-sensitive MRI enabled us to assess voxel-wise modifications of substantia nigra's morphology in vivo in humans, including healthy controls, patients with iRBD and patients with Parkinson's disease, and identify their correlation with nigral function across all motor, cognitive and behavioural domains. This insight could help assess disease progression in drug trials of disease modification.

Multimodal Magnetic Resonance Imaging Quantification of Brain Changes in Progressive Supranuclear Palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is a neurodegenerative clinically heterogeneous disorder, formal diagnosis being based on postmortem histological brain examination. OBJECTIVE: We aimed to perform a precise in vivo staging of neurodegeneration in PSP using quantitative multimodal MRI. The ability of MRI biomarkers to differentiate PSP from PD was also evaluated. METHODS: Eleven PSP patients were compared to 26 age-matched healthy controls and 51 PD patients. Images were acquired at 3 Tesla (three-dimensional T1 -weighted, diffusion tensor, and neuromelanin-sensitive images) and 7 Tesla (three-dimensional-T2 * images). Regions of interest included the cortical areas, hippocampus, amygdala, basal ganglia, basal forebrain, brainstem nuclei, dentate nucleus, and cerebellum. Volumes, mean diffusivity, and fractional anisotropy were measured. In each region, a threshold value for group categorization was calculated, and four grades of change (0-3) were determined. RESULTS: PSP patients showed extensive volume decreases and diffusion changes in the midbrain, SN, STN, globus pallidus, basal forebrain, locus coeruleus, pedunculopontine nucleus, and dentate nucleus, in close agreement with the degrees of impairment in histological analyses. The predictive factors for the separation of PSP and healthy controls were, in descending order, the neuromelanin-based SN volume; midbrain fractional anisotropy; volumes of the midbrain, globus pallidus, and putamen; and fractional anisotropy in the locus coeruleus. The best predictors for separating PSP from PD were the neuromelanin-based volume in the SN, fractional anisotropy in the pons, volumes of the midbrain and globus pallidus, and fractional anisotropy in the basal forebrain. CONCLUSIONS: These results suggest that it is possible to evaluate brain neurodegeneration in PSP noninvasively, even in small brainstem nuclei, in close agreement with previously published histological data. © 2019 International Parkinson and Movement Disorder Society.

Multimodal magnetic resonance imaging investigation of basal forebrain damage and cognitive deficits in Parkinson's disease.

BACKGROUND: Cognitive deficits in Parkinson's disease (PD) may result from damage in the cortex as well as in the dopaminergic, noradrenergic, and cholinergic inputs to the cortex. Cholinergic inputs to the cortex mainly originate from the basal forebrain and are clustered in several regions, called Ch1 to Ch4, that project to the hippocampus (Ch1-2), the olfactory bulb (Ch3), and the cortex and amygdala (Ch4). OBJECTIVE: We investigated changes in basal forebrain and their role in cognitive deficits in PD. METHODS: We studied 52 nondemented patients with PD (Hoehn & Yahr 1-2) and 25 age-matched healthy controls using diffusion and resting state functional MRI. RESULTS: PD patients had a loss of structural integrity within the Ch1-2 and Ch3-4 nuclei of the basal forebrain as well as in the fornix. Tractography showed that the probability of anatomical connection was decreased in PD between Ch3-4 and the associative prefrontal cortex, occipital cortex, and peri-insular regions. There was a reduction in functional connectivity between Ch1-2 and the bilateral hippocampi and parahippocampal gyri, the left middle and superior temporal gyri, and the left fusiform gyrus and between Ch3-4 and the right inferior frontal gyrus and the right and left thalamus. In Ch1-2, loss of structural integrity and connectivity correlated with scores at the memory tests, whereas changes in Ch3-4 correlated with scores of global cognition and executive functions. CONCLUSION: This study highlights the association between deficits of different cholinergic nuclei of the basal forebrain and the extent of cognitive impairments in nondemented PD patients. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Pedunculopontine network dysfunction in Parkinson's disease with postural control and sleep disorders.

BACKGROUND: The objective of this study was to investigate pedunculopontine nucleus network dysfunctions that mediate impaired postural control and sleep disorder in Parkinson's disease. METHODS: We examined (1) Parkinson's disease patients with impaired postural control and rapid eye movement sleep behavior disorder (further abbreviated as sleep disorder), (2) Parkinson's disease patients with sleep disorder only, (3) Parkinson's disease patients with neither impaired postural control nor sleep disorder, and (4) healthy volunteers. We assessed postural control with clinical scores and biomechanical recordings during gait initiation. Participants had video polysomnography, daytime sleepiness self-evaluation, and resting-state functional MRIs. RESULTS: Patients with impaired postural control and sleep disorder had longer duration of anticipatory postural adjustments during gait initiation and decreased functional connectivity between the pedunculopontine nucleus and the supplementary motor area in the locomotor network that correlated negatively with the duration of anticipatory postural adjustments. Both groups of patients with sleep disorder had decreased functional connectivity between the pedunculopontine nucleus and the anterior cingulate cortex in the arousal network that correlated with daytime sleepiness. The degree of dysfunction in the arousal network was related to the degree of connectivity in the locomotor network in all patients with sleep disorder, but not in patients without sleep disorder or healthy volunteers. CONCLUSIONS: These results shed light on the functional neuroanatomy of pedunculopontine nucleus networks supporting the clinical manifestation and the interdependence between sleep and postural control impairments in Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society.

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

Huntington's 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. © 2016 Wiley Periodicals, Inc.

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.

Single-voxel (1)H spectroscopy in the human hippocampus at 3 T using the LASER sequence: characterization of neurochemical profile and reproducibility.

The hippocampus is crucial for long-term episodic memory and learning. It undergoes structural change in aging and is sensitive to neurodegenerative and psychiatric diseases. MRS studies have seldom been performed in the hippocampus due to technical challenges. The reproducibility of MRS in the hippocampus has not been evaluated at 3 T. The purpose of the present study was to quantify the concentration of metabolites in a small voxel placed in the hippocampus and evaluate the reproducibility of the quantification. Spectra were measured in a 2.4 mL voxel placed in the left hippocampus covering the body and most of the tail of the structure in 10 healthy subjects across three different sessions and quantified using LCModel. High-quality spectra were obtained, which allowed a reliable quantification of 10 metabolites including glutamate and glutamine. Reproducibility of MRS was evaluated with coefficient of variation, standard errors of measurement, and intraclass correlation coefficients. All of these measures showed improvement with increased number of averages. Changes of less than 5% in concentration of N-acetylaspartate, choline-containing compounds, and total creatine and of less than 10% in concentration of myo-inositol and the sum of glutamate and glutamine can be confidently detected between two measurements in a group of 20 subjects. A reliable and reproducible neurochemical profile of the human hippocampus was obtained using MRS at 3 T in a small hippocampal volume.

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

OBJECTIVES: 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 Parkinson's disease (PD), using R2* relaxometry rate. METHODS: Twenty subjects with genetic PD (four symptomatic and two asymptomatic Parkin subjects, nine symptomatic and five asymptomatic LRRK2 subjects) were compared with 20 patients with idiopathic PD (IPD) and 20 healthy subjects. Images were obtained at 3 teslas, using multi-echo T2 and T2* sequences. R2 and R2* values were calculated in the substantia nigra (SN), the striatum, the globus pallidus, and the thalamus. RESULTS: The R2* values in the SN were increased in IPD and mutation-carrying patients as compared with controls and in mutation-carrying patients as compared with IPD. Asymptomatic mutation carriers showed higher R2* values than controls and did not differ from IPD patients. No changes were seen in the other structures or in R2 values. CONCLUSION: These results are consistent with increased iron load in LRRK2- and Parkin-mutation carriers. The increased R2* in asymptomatic PD-mutation carriers suggests that iron deposition occurs early during the preclinical phase of the disease. R2* measurements may be used as markers for investigating nigrostriatal damage in preclinical mutation-carrying patients.

Brain dynamic neurochemical changes in dystonic patients: a magnetic resonance spectroscopy study.

Measurements of the concentrations of γ-aminobutyric acid (GABA) and glutamate in the motor cortices and lentiform nuclei of dystonic patients using single-voxel (1)H magnetic resonance spectroscopy (MRS) have yielded conflicting results so far. This study aimed to investigate dynamic changes in metabolite concentrations after stimulation of the motor cortices in patients with upper limb dystonia. Using single-voxel MRS at 3 T, the concentrations of GABA, glutamate plus glutamine, and N-acetylaspartate were measured bilaterally in the primary sensorimotor cortex, lentiform nucleus, and occipital region before and after 5-Hz transcranial magnetic stimulation (TMS) over the dominant motor cortex. Data obtained from 15 patients with upper limb primary dystonia were compared with data obtained from 14 healthy volunteers. At baseline, there was no group difference in concentration of metabolites in any region. rTMS induced a local (in the stimulated motor cortex) decrease of N-acetylaspartate (P < .006) to the same extent in healthy volunteers and patients. GABA concentrations were modulated differently, however, decreasing mildly in patients and increasing mildly in healthy volunteers (P = .05). There were no remote effects in the lentiform nucleus in either group. The stimulation-induced changes in metabolite concentrations have been interpreted in view of the increased energy demand induced by rTMS. The dynamics of the GABA concentration were specifically impaired in dystonic patients. Whether these changes reflect changes in the extrasynaptic or synaptic GABA component is discussed.

Theta band brainwaves in human resting EEG modulated by mobile phone radiofrequency.

PURPOSE: Wireless communication has become an integral part of our lives. The growing number of antennas in our environment and the expanding use of mobile phones (MPs) are increasing the population's exposure to electromagnetic fields. The present study aimed to examine the potential impact of MPs radiofrequency electromagnetic fields (RF-EMF) exposure on the brainwaves of the resting electroencephalogram (EEG) in humans. MATERIALS AND METHODS: Twenty-one healthy volunteers were exposed to Global System for Mobile communications (GSM) signal at 900 MHz MP RF-EMF. The maximum specific absorption rate (SAR) of the MP averaged on 10 g tissue and 1 g tissue were measured at 0.49 W/kg, 0.70 W/kg, respectively. RESULTS: Results showed that while delta and beta rhythms of resting EEG were not affected, theta brainwaves were significantly modulated during exposure to RF-EMF related to MPs. For the first time, it was shown that this modulation is dependent on the eye condition, i.e. closed or open. CONCLUSIONS: This study strongly suggests that acute exposure to RF-EMF alters the EEG theta rhythm at rest. Long-term exposure studies are required to explore the effect of this disruption in high-risk or sensitive populations.

Assessment of Electrical Brain Activity of Healthy Volunteers Exposed to 3.5 GHz of 5G Signals within Environmental Levels: A Controlled-Randomised Study.

Following the recent deployment of fifth-generation (5G) radio frequencies, several questions about their health impacts have been raised. Due to the lack of experimental research on this subject, the current study aimed to investigate the bio-physiological effects of a generated 3.5 GHz frequency. For this purpose, the wake electroencephalograms (EEG) of 34 healthy volunteers were explored during two "real" and "sham" exposure sessions. The electromagnetic fields were antenna-emitted in an electrically shielded room and had an electrical field root-mean-square intensity of 2 V/m, corresponding to the current outdoor exposure levels. The sessions were a maximum of one week apart, and both contained an exposure period of approximately 26 min and were followed by a post-exposure period of 17 min. The power spectral densities (PSDs) of the beta, alpha, theta, and delta bands were then computed and corrected based on an EEG baseline period. This was acquired for 17 min before the subsequent phases were recorded under two separate conditions: eyes open (EO) and eyes closed (EC). A statistical analysis showed an overall non-significant change in the studied brain waves, except for a few electrodes in the alpha, theta, and delta spectra. This change was translated into an increase or decrease in the PSDs, in response to the EO and EC conditions. In conclusion, this studhy showed that 3.5 GHz exposure, within the regulatory levels and exposure parameters used in this protocol, did not affect brain activity in healthy young adults. Moreover, to our knowledge, this was the first laboratory-controlled human EEG study on 5G effects. It attempted to address society's current concern about the impact of 5G exposure on human health at environmental levels.

Brain dysfunction in gait disorders of Caribbean atypical Parkinsonism and progressive supranuclear palsy patients: A comparative study.

INTRODUCTION: Gait disorders and falls occur early in progressive supranuclear palsy (PSP-RS) and Caribbean atypical parkinsonism (Caribbean AP). However, the link between these signs and brain lesions has never been explored in these patient populations. Here, we investigate and compare the imaging factors that relate to gait and balance disorders in Caribbean AP and PSP-RS patients. METHODS: We assessed gait and balance using clinical scales and gait recordings in 16 Caribbean AP and 15 PSP-RS patients and 17 age-matched controls. We measured the grey and white matter brain volumes on 3 T brain MRI images. We performed a principal component analysis (PCA) including all the data to determine differences and similarities between groups, and explore the relationship between gait disorders and brain volumes. RESULTS: Both Caribbean AP patients and PSP-RS have marked gait and balance disorders with similar severity. In both groups, gait and balance disorders were found to be most strongly related to structural changes in the lateral cerebellum, caudate nucleus, and fronto-parietal areas. In Caribbean AP patients, gait disorders were also related to additional changes in the cortex, including frontal, insular, temporal and cuneus lobes, whereas in PSP-RS patients, additional white matter changes involved the mesencephalon and parahippocampal gyrus. CONCLUSION: Gait and balance disorders in Caribbean AP patients are mainly related to dysfunction of cortical brain areas involved in visuo-sensorimotor processing and self-awareness, whereas these signs mainly result from premotor-brainstem-cerebellar network dysfunction in PSP-RS patients, brain areas involved in initiation and maintenance of locomotor pattern and postural adaptation.

Human resting-state EEG and radiofrequency GSM mobile phone exposure: the impact of the individual alpha frequency.

PURPOSE: With the extensive use of mobile phone (MP), several studies have been realized to investigate the effects of radiofrequency electromagnetic fields (RF-EMF) exposure on brain activity at rest via electroencephalography (EEG), and the most consistent effect has been seen on the alpha band power spectral density (PSD). However, some studies reported an increase or a decrease of the PSD, while others showed no effect. It has been suggested that these differences might partly be due to a variability of the physiological state of the brain between subjects. So, the aim of this study was to investigate the alpha band modulation, exploring the impact of the alpha band frequency ranges applied in the PSD analysis. MATERIALS AND METHODS: Twenty-one healthy volunteers took part to the study with a double-blind, randomized and counterbalanced crossover design, during which eyes-open (EO) and eyes-closed (EC) resting-state EEG was recorded. The exposure system was a sham or a real GSM (global system for mobile) 900 MHz MP (pulse modulated at 217 Hz, mean power of 250 mW and 2 W peak, with a maximum specific absorption rate of 0.70 W/kg on 1 g tissue). The experimental protocol presented a baseline recording phase without MP exposure, an exposure phase during which the exposure system was placed against the left ear, and the post-exposure phase without MP. EEG data from baseline and exposure phases were analyzed and PSD was computed for the alpha band in the fixed range of 8-12 Hz and for the individual alpha band frequency range (IAF). RESULTS: Results showed a trend in decrease or increase of EEG power of both alpha oscillations during exposure in relation to EC and EO recording conditions, respectively, but not reaching statistical significance. Findings did not provide evidence for a different sensitivity to RF-EMF MP related to individual variability in the frequency of the alpha band. CONCLUSION: In conclusion, these results did not show alpha band activity modulation during resting-state under RF-EMF. It might be argued the need of a delay after the exposure in order to appreciate an EEG spectral power modulation related to RF-EMF exposure.