Investigating the discrimination ability of 3D convolutional neural networks applied to altered brain MRI parametric maps.

Convolutional neural networks (CNNs) are gradually being recognized in the neuroimaging community as a powerful tool for image analysis. Despite their outstanding performances, some aspects of CNN functioning are still not fully understood by human operators. We postulated that the interpretability of CNNs applied to neuroimaging data could be improved by investigating their behavior when they are fed data with known characteristics. We analyzed the ability of 3D CNNs to discriminate between original and altered whole-brain parametric maps derived from diffusion-weighted magnetic resonance imaging. The alteration consisted in linearly changing the voxel intensity of either one (monoregion) or two (biregion) anatomical regions in each brain volume, but without mimicking any neuropathology. Performing ten-fold cross-validation and using a hold-out set for testing, we assessed the CNNs' discrimination ability according to the intensity of the altered regions, comparing the latter's size and relative position. Monoregion CNNs showed that the larger the modified region, the smaller the intensity increase needed to achieve good performances. Biregion CNNs systematically outperformed monoregion CNNs, but could only detect one of the two target regions when tested on the corresponding monoregion images. Exploiting prior information on training data allowed for a better understanding of CNN behavior, especially when altered regions were combined. This can inform about the complexity of CNN pattern retrieval and elucidate misclassified examples, particularly relevant for pathological data. The proposed analytical approach may serve to gain insights into CNN behavior and guide the design of enhanced detection systems exploiting our prior knowledge.

Developmental dyslexia, developmental coordination disorder and comorbidity discrimination using multimodal structural and functional neuroimaging.

Developmental dyslexia (DD) and developmental coordination disorder (DCD) are two common neurodevelopmental disorders with a high co-occurrence rate. This led several authors to postulate that the two disorders share, at least partially, similar neural underpinning. However, even though several studies examined brain differences between typically developing (TD) children and children with either DD or DCD, no previous study directly compared DD, DCD and children with both disorders (COM) using neuroimaging. We acquired structural and resting-state functional MRI images of 136 children (TD = 42, DD = 45, DCD = 20, COM = 29). Difference between TD children and the other groups was assessed using univariate analysis of structural indexes including grey and white matter volumes and functional indexes quantifying activity (fraction of the amplitude of the low frequency fluctuations), local and global connectivity. Regional differences in structural and functional brain indexes were then used to train machine learning models to discriminate among DD, DCD and COM and to find the most discriminant regions. While no imaging index alone discriminated between the three groups, grouping grey and white matter volumes (structural model) or activity, local and global connectivity (functional model) made possible to discriminate among the DD, DCD and COM groups. The most important discrimination was obtained using the functional model, with regions in the cerebellum and the temporal lobe being the most discriminant for DCD and DD children, respectively. Results further showed that children with both DD and DCD have subtle but identifiable brain differences that can only be captured using several imaging indexes pertaining to both brain structure and function.

Insular functional connectivity in migraine with aura.

INTRODUCTION: Insula plays an integrating role in sensory, affective, emotional, cognitive and autonomic functions in migraine, especially in migraine with aura (MA). Insula is functionally divided into 3 subregions, the dorsoanterior, the ventroanterior and the posterior insula respectively related to cognition, emotion, and somatosensory functions. This study aimed at investigating functional connectivity of insula subregions in MA. METHODS: Twenty-one interictal patients with MA were compared to 18 healthy controls (HC) and 12 interictal patients with migraine without aura (MO) and were scanned with functional MRI during the resting state. Functional coupling of the insula was comprehensively tested with 12 seeds located in the right and left, dorsal, middle, ventral, anterior and posterior insula, by using a seed-to-voxel analysis. RESULTS: Seed-to-voxel analysis revealed, in MA, a strong functional coupling of the right and left antero-dorsal insula with clusters located in the upper cerebellum. The overlap of these cerebellar clusters corresponded to the vermis VI. These functional couplings were not correlated to duration of MA, frequency of MA attacks nor time since last MA attack, and were not found in MO. DISCUSSION: The anterior insula and superior cerebellum, including vermis VI, are components of the central Autonomic Nervous System (ANS) network. As these regions are involved in the control of cardiovascular parasympathetic tone, we hypothesize that this connectivity may reflect the cardiovascular features of MA. CONCLUSION: The anterior dorsal insula is connected with vermis VI in MA patients in the resting state. This connectivity may reflect the cardiovascular features of MA. TRIAL REGISTRATION: NCT02708797.

Atypical connectivity in the cortico-striatal network in NF1 children and its relationship with procedural perceptual-motor learning and motor skills.

INTRODUCTION: Neurofibromatosis type 1 (NF1) is considered a model of neurodevelopmental disorder because of the high frequency of learning deficits, especially developmental coordination disorder. In neurodevelopmental disorder, Nicolson and Fawcett formulated the hypothesis of an impaired procedural learning system that has its origins in cortico-subcortical circuits. Our aim was to investigate the relationship between cortico-striatal connectivity and procedural perceptual-motor learning performance and motor skills in NF1 children. METHODS: Seventeen NF1 and 18 typically developing children aged between 8 and 12 years old participated in the study. All were right-handed and did not present intellectual or attention deficits. In all children, procedural perceptual-motor learning was assessed using a bimanual visuo-spatial serial reaction time task (SRTT) and motor skills using the Movement Assessment Battery for Children (M-ABC). All participants underwent a resting-state functional MRI session. We used a seed-based approach to explore cortico-striatal connectivity in somatomotor and frontoparietal networks. A comparison between the groups' striato-cortical connectivity and correlations between connectivity and learning (SRTT) and motor skills (M-ABC) were performed. RESULTS: At the behavioral level, SRTT scores are not significantly different in NF1 children compared to controls. However, M-ABC scores are significantly impaired within 9 patients (scores below the 15th percentile). At the cerebral level, NF1 children present a higher connectivity in the cortico-striatal regions mapping onto the right angular gyrus compared to controls. We found that the higher the connectivity values between these regions, differentiating NF1 and controls, the lower the M-ABC scores in the whole sample. No correlation was found for the SRTT scores. CONCLUSION: NF1 children present atypical hyperconnectivity in cortico-striatal connections. The relationship with motor skills could suggest a sensorimotor dysfunction already found in children with developmental coordination disorder. These abnormalities are not linked to procedural perceptual-motor learning assessed by SRTT.

Brain-age estimation accuracy is significantly increased using multishell free-water reconstruction.

Although free-water diffusion reconstruction for diffusion-weighted imaging (DWI) data can be applied to both single-shell and multishell data, recent finding in synthetic data suggests that the free-water indices from single-shell acquisition should be interpreted with care, as they are heavily influenced by initialization parameters and cannot discriminate between free-water and mean diffusivity modifications. However, whether using a longer multishell acquisition protocol significantly improve reconstruction for real human MRI data is still an open question. In this study, we compare canonical diffusion tensor imaging (DTI), single-shell and multishell free-water imaging (FW) indices derived from a short, clinical compatible diffusion protocol (b = 500 s/mm2 , b = 1,000 s/mm2 , 32 directions each) on their power to predict brain age. Age was chosen as it is well-known to be related to widespread modification of the white matter and because brain-age estimation has recently been found to be relevant to several neurodegenerative diseases. We used a previously developed and validated data-driven whole-brain machine learning pipeline to directly compare the precision of brain-age estimates in a sample of 89 healthy males between 20 and 85 years old. We found that multishell FW outperform DTI indices in estimating brain age and that multishell FW, even when using low (500 ms2 ) b-values secondary shell, outperform single-shell FW. Single-shell FW led to lower brain-age estimation accuracy even of canonical DTI indices, suggesting that single-shell FW indices should be used with caution. For all considered reconstruction algorithms, the most discriminant indices were those measuring free diffusion of water in the white matter.

Are morphological and structural MRI characteristics related to specific cognitive impairments in neurofibromatosis type 1 (NF1) children?

INTRODUCTION: NF1 children have cognitive disorders, especially in executive functions, visuospatial, and language domains, the pathophysiological mechanisms of which are still poorly understood. MATERIALS AND METHODS: A correlation study was performed from neuropsychological assessments and brain MRIs of 38 NF1 patients and 42 controls, all right-handed, aged 8-12 years and matched in age and gender. The most discriminating neuropsychological tests were selected to assess their visuospatial, metaphonological and visuospatial working memory abilities. The MRI analyses focused on the presence and location of Unidentified Bright Objects (UBOs) (1), volume analysis (2) and diffusion analysis (fractional anisotropy and mean diffusivity) (3) of the regions of interest including subcortical structures and posterior fossa, as well as shape analysis of subcortical structures (4). The level of attention, intelligence quotient, age and gender of the patients were taken into account in the statistical analysis. Then, we studied how diffusion and volumes parameters were associated with neuropsychological characteristics in NF1 children. RESULTS: NF1 children present different brain imaging characteristics compared to the control such as (1) UBOs in 68%, (2) enlarged total intracranial volume, involving all subcortical structures, especially thalamus, (3) increased MD and decreased FA in thalamus, corpus callosum and hippocampus. These alterations are diffuse, without shape involvement. In NF1 group, brain microstructure is all the more altered that volumes are enlarged. However, we fail to find a link between these brain characteristics and neurocognitive scores. CONCLUSION: While NF1 patients have obvious pathological brain characteristics, the neuronal substrates of their cognitive deficits are still not fully understood, perhaps due to complex and multiple pathophysiological mechanisms underlying this disorder, as suggested by the heterogeneity observed in our study. However, our results are compatible with an interpretation of NF1 as a diffuse white matter disease.

Functional and Structural Integrity of Frontoparietal Connectivity in Traumatic and Anoxic Coma.

OBJECTIVES: Recovery from coma might critically depend on the structural and functional integrity of frontoparietal networks. We aimed to measure this integrity in traumatic brain injury and anoxo-ischemic (cardiac arrest) coma patients by using an original multimodal MRI protocol. DESIGN: Prospective cohort study. SETTING: Three Intensive Critical Care Units affiliated to the University in Toulouse (France). PATIENTS: We longitudinally recruited 43 coma patients (Glasgow Coma Scale at the admission < 8; 29 cardiac arrest and 14 traumatic brain injury) and 34 age-matched healthy volunteers. Exclusion criteria were disorders of consciousness lasting more than 30 days and focal brain damage within the explored brain regions. Patient assessments were conducted at least 2 days (5 ± 2 d) after complete withdrawal of sedation. All patients were followed up (Coma Recovery Scale-Revised) 3 months after acute brain injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Functional and structural MRI data were recorded, and the analysis was targeted on the posteromedial cortex, the medial prefrontal cortex, and the cingulum. Univariate analyses and machine learning techniques were used to assess diagnostic and predictive values. Coma patients displayed significantly lower medial prefrontal cortex-posteromedial cortex functional connectivity (area under the curve, 0.94; 95% CI, 0.93-0.95). Cardiac arrest patients showed specific structural disturbances within posteromedial cortex. Significant cingulum architectural disturbances were observed in traumatic brain injury patients. The machine learning medial prefrontal cortex-posteromedial cortex multimodal classifier had a significant predictive value (area under the curve, 0.96; 95% CI, 0.95-0.97), best combination of subregions that discriminates a binary outcome based on Coma Recovery Scale-Revised). CONCLUSIONS: This exploratory study suggests that frontoparietal functional disconnections are specifically observed in coma and their structural counterpart provides information about brain injury mechanisms. Multimodal MRI biomarkers of frontoparietal disconnection predict 3-month outcome in our sample. These findings suggest that fronto-parietal disconnection might be particularly relevant for coma outcome prediction and could inspire innovative precision medicine approaches.

Neuroplasticity and brain reorganization associated with positive outcomes of multidisciplinary rehabilitation in progressive multiple sclerosis: A fMRI study.

BACKGROUND: Multiple sclerosis (MS) is characterized by a range of symptoms, including motor, sensorimotor and cognitive impairments, that limit the quality of life. A multidisciplinary rehabilitation approach in people affected by multiple sclerosis was recently reported to improve the functional abilities of MS patients in daily activities. The purpose of the study was to assess the effect of multidisciplinary rehabilitation on the whole brain of MS patients by means of functional magnetic resonance imaging (fMRI). METHODS: Thirty individuals affected by MS (49.9 ± 12.1 years; disease duration: 16.0 ± 8.5 years) with a medium-high severity of disease were enrolled. The fMRI examination assessed a range of action-related tasks involving passive movement, mental simulation of action and miming of action triggered by external stimuli, such as object photography. The three tasks were performed using each arm separately. The fMRI acquisitions were performed at T1 (inclusion in the study), T2 (3 months later, at the start of rehabilitation) and T3 (after 3 months of multidisciplinary rehabilitation). RESULTS: The fMRI results revealed a significant reduction in the activity of brain areas related to task-specific networks as well as the activation of cerebral regions not usually involved in task-specific related network, such as the medial prefrontal area. CONCLUSIONS: The effectiveness of multidisciplinary rehabilitation on activity and participation has been established in previous studies. Our study sheds new light on the effect of such treatment on brain reorganization.

Intrinsic Cortico-Subcortical Functional Connectivity in Developmental Dyslexia and Developmental Coordination Disorder.

Developmental dyslexia (DD) and developmental coordination disorder (DCD) are distinct diagnostic disorders. However, they also frequently co-occur and may share a common etiology. It was proposed conceptually a neural network framework that explains differences and commonalities between DD and DCD through impairments of distinct or intertwined cortico-subcortical connectivity pathways. The present study addressed this issue by exploring intrinsic cortico-striatal and cortico-cerebellar functional connectivity in a large (n = 136) resting-state fMRI cohort study of 8-12-year-old children with typical development and with DD and/or DCD. We delineated a set of cortico-subcortical functional circuits believed to be associated with the brain's main functions (visual, somatomotor, dorsal attention, ventral attention, limbic, frontoparietal control, and default-mode). Next, we assessed, using general linear and multiple kernel models, whether and which circuits distinguished between the groups. Findings revealed that somatomotor cortico-cerebellar and frontoparietal cortico-striatal circuits are affected in the presence of DCD, including abnormalities in cortico-cerebellar connections targeting motor-related regions and cortico-striatal connections mapping onto posterior parietal cortex. Thus, DCD but not DD may be considered as an impairment of cortico-subcortical functional circuits.

Neural modifications in lower limb amputation: an fMRI study on action and non-action oriented body representations.

The loss of sensorimotor and visual information that follows limb amputation is known to affect both the action-oriented (body schema, BS) and non-action oriented (NA) body representations. However, the neural underpinnings of these effects have not yet been fully understood. We investigated the neural correlates of body representations in a group of 9 healthy right-handed individuals with left lower limb amputation (LLA) and 11 healthy age-matched controls (HC) by using event-related functional magnetic resonance imaging. Participants were scanned while performing mental rotation of body parts (i.e. hand, foot and eye) and objects (i.e. a rear-view mirror). Although the performance of LLA were similar to that of HC, they showed a different activation profile in relation to both BS and to NA within a wide range of brain areas. The bilateral intraparietal sulcus was less activated in LLA than HC, whereas the bilateral anterior insula as well as the fusiform body area, the precentral gyrus, the supplementary motor area in the left hemisphere and the inferior occipital gyrus in the right hemisphere were more activated during the mental rotation of left stimuli in the LLA. Also, the left EBA showed higher activation during the mental rotation of the foot than that of the eye in the LLA but not in the HC. Our results are consistent with the hypothesis that left LLA yields to a modification in the body representation network even when it does not lead to clear behavioral deficits.

Significant Decrease in Hippocampus and Amygdala Mean Diffusivity in Treatment-Resistant Depression Patients Who Respond to Electroconvulsive Therapy.

Introduction: The hippocampus plays a key role in depressive disorder, and the amygdala is involved in depressive disorder through the key role that it plays in emotional regulation. Electroconvulsive therapy (ECT) may alter the microstructure of these two regions. Since mean diffusivity (MD), is known to be an indirect marker of microstructural integrity and can be derived from diffusion tensor imaging (DTI) scans, we aim to test the hypothesis that treatment-resistant depression (TRD) patients undergoing bilateral (BL) ECT exhibit a decrease of MD in their hippocampus and amygdala. Methods: Patients, between 50 and 70 years of age, diagnosed with TRD were recruited from the University Hospital of Toulouse and assessed clinically (Hamilton Depression Rating Scale, HAM-D) and by DTI scans at three time points: baseline, V2 (during treatment), and V3 within 1 week of completing ECT. Results: We included 15 patients, who were all responders. The left and right hippocampi and the left amygdala showed a significant decrease in MD at V3, compared to baseline [respectively: ß = -2.78, t = -1.97, p = 0.04; ß = -2.56, t = -2, p = 0.04; ß = -2.5, t = -2.3, p = 0.04, false discovery rate (FDR) corrected]. MD did not decrease in the right amygdala. Only the left amygdala was significantly associated with a reduction in HAM-D (ρ = 0.55, p = 0.049, FDR corrected). Conclusion: MD is an indirect microstructural integrity marker, which decreases in the hippocampus and the left amygdala, during BL ECT in TRD populations. This could be interpreted as a normalization of microstructural integrity in these structures.

Grey Matter changes in treatment-resistant depression during electroconvulsive therapy.

INTRODUCTION: 20-30% of depressed patients experience Treatment Resistant Depression (TRD). Electroconvulsive Therapy (ECT) remains the treatment of choice for TRD. However, the exact mechanism of ECT remains unclear. We aim to assess grey matter changes in patients with TRD undergoing bilateral ECT treatment at different points during and after treatment. METHODS: Patients are recruited at the University Hospital of Toulouse. Eligibility criteria include a diagnosis of TRD and an age between 50 and 70 years old. Patients received clinical assessments (Hamilton Depression Rating Scale) and structural scans (MRI) at three points: baseline (within 48 h before the first ECT); V2 (after the first ECT considered effective); and V3 (within 1 week of completing ECT). RESULTS: At baseline, controls had significantly higher cortical thickness than patients in the fusiform gyrus, the inferior, middle and superior temporal gyrus, the parahippocampal gyrus and the transverse temporal gyrus (respectively: t(35)=2.7, p = 0.02; t(35)=2.89, p = 0.017; t(35)=3.1, p = 0.015; t(35)=3.6, p = 0.009; t(35)=2.37, p = 0.031; t(35)=2.46, p = 0.03). This difference was no longer significant after ECT. We showed an increase in cortical thickness in superior temporal gyrus between (i) baseline and V3 (t(62)=-3.43 p = 0.009) and (ii) V2 and V3 (t(62)=-3.42 p = 0.009). We showed an increase in hippocampal volume between (i) baseline and V3 (t(62)=-5.23 p < 0.001) and (ii) V2 and V3 (t(62)=-5.3 p < 0.001). CONCLUSION: We highlight that there are grey matter changes during ECT treatment in a population with TRD compared to a healthy control population. These changes seem to occur after several rounds of ECT.

Discriminating between neurofibromatosis-1 and typically developing children by means of multimodal MRI and multivariate analyses.

Neurofibromatosis Type 1 leads to brain anomalies involving both gray and white matter. The extent and granularity of these anomalies, together with their possible impact on brain activity, is still unknown. In this multicentric cross-sectional study we submitted a sample of 42 typically developing and 38 neurofibromatosis-1 children to a multimodal MRI assessment including T1, diffusion weighted and resting state functional sequences. We used a pipeline involving several features selection steps coupled with multivariate statistical analysis (supporting vector machine) to discriminate between the two groups while having interpretable models. We used MRI indexes measuring macro (gray matter volume) and microstructural (fractional anisotropy, mean diffusivity) characteristics of the brain, as well as indexes of brain activity (fractional amplitude of low frequency fluctuations) and connectivity (local and global correlation) at rest. We found that structural indexes could discriminate between the two groups, with the mean diffusivity leading to performance as high as the combination of all structural indexes combined (accuracy = 0.86), while functional indexes had worse performances. The MRI signature of NF1 brain pathology is a combination of gray and white matter abnormalities, as measured with gray matter volume, fractional anisotropy, and mean diffusivity.

Can the Cognitive Phenotype in Neurofibromatosis Type 1 (NF1) Be Explained by Neuroimaging? A Review.

Neurofibromatosis type 1 (NF1) is one of the most frequent monogenetic disorders. It can be associated with cognitive dysfunctions in several domains such as executive functioning, language, visual perception, motor skills, social skills, memory and/or attention. Neuroimaging is becoming more and more important for a clearer understanding of the neural basis of these deficits. In recent years, several studies have used different imaging techniques to examine structural, morphological and functional alterations in NF1 disease. They have shown that NF1 patients have specific brain characteristics such as Unidentified Bright Objects (UBOs), macrocephaly, a higher volume of subcortical structures, microstructure integrity alterations, or connectivity alterations. In this review, which focuses on the studies published after the last 2 reviews of this topic (in 2010 and 2011), we report on recent structural, morphological and functional neuroimaging studies in NF1 subjects, with special focus on those that examine the neural basis of the NF1 cognitive phenotype. Although UBOs are one of the most obvious and visible elements in brain imaging, correlation studies have failed to establish a robust and reproducible link between major cognitive deficits in NF1 and their presence, number or localization. In the same vein, the results among structural studies are not consistent. Functional magnetic resonance imaging (fMRI) studies appear to be more sensitive, especially for understanding the executive function deficit that seems to be associated with a dysfunction in the right inferior frontal areas and the middle frontal areas. Similarly, fMRI studies have found that visuospatial deficits could be associated with a dysfunction in the visual cortex and especially in the magnocellular pathway involved in the processing of low spatial frequency and high temporal frequency. Connectivity studies have shown a reduction in anterior-posterior "long-range" connectivity and a deficit in deactivation in default mode network (DMN) during cognitive tasks. In conclusion, despite the contribution of new imaging techniques and despite relative advancement, the cognitive phenotype of NF1 patients is not totally understood.

Connectivity of the Human Number Form Area Reveals Development of a Cortical Network for Mathematics.

The adult brain contains cortical areas thought to be specialized for the analysis of numbers (the putative number form area, NFA) and letters (the visual word form area, VWFA). Although functional development of the VWFA has been investigated, it is largely unknown when and how the NFA becomes specialized and connected to the rest of the brain. One hypothesis is that NFA and VWFA derive their special functions through differential connectivity, but the development of this differential connectivity has not been shown. Here, we mapped the resting state connectivity of NFA and VWFA to the rest of the brain in a large sample (n = 437) of individuals (age 3.2-21 years). We show that within NFA-math network and within VWFA-reading network the strength of connectivity increases with age. The right NFA is significantly connected to the right intraparietal cortex already at the earliest age tested (age 3), before formal mathematical education has begun. This connection might support or enable an early understanding of magnitude or numerosity In contrast, the functional connectivity from NFA to the left anterior intraparietal cortex and to the right dorsolateral prefrontal cortex is not different from the functional connectivity of VWFA to these regions until around 12-14 years of age. The increase in connectivity to these regions was associated with a gradual increase in mathematical ability in an independent sample. In contrast, VWFA connects significantly to Broca's region around age 6, and this connectivity is correlated with reading ability. These results show how the differential connectivity of the networks for mathematics and reading slowly emerges through years of training and education.

Action and Non-Action Oriented Body Representations: Insight from Behavioural and Grey Matter Modifications in Individuals with Lower Limb Amputation.

OBJECTIVE: Following current model of body representations, we aimed to systematically investigate the association between brain modifications, in terms of grey matter loss, and body representation deficits, in terms of alterations of the body schema (BS) and of non-action oriented body representations (NA), in individuals with lower limb amputation (LLA). METHOD: BS and NA (both semantic and visuospatial NA) were evaluated in 11 healthy controls and in 14 LLA, considering the impact of clinical variables such as prosthesis use. The association between BS and NA deficits and grey matter loss was also explored in LLA by using Voxel Based Morphometry analysis. RESULTS: LLA's performance was fine in terms of semantic NA, while it showed behavioural impairments both in BS and visuospatial NA as compared to healthy controls. Interestingly the visuospatial NA performance was related to the amount of prosthesis use. NA deficits in terms of visuospatial body map processing were associated with grey matter reduction in left (lobule VIII) and right (crus II) cerebellum, while BS deficits were associated with grey matter reduction in right anterior cingulate cortex and the bilateral cuneus. No significant association was detected for semantic NA. CONCLUSION: The study of BS and NA representations after limb loss has informed our understanding of the different dynamics (i.e., adjustments to body change) of such representations, supporting current cognitive models of body representation. The clinical relevance of present findings is also discussed.

MRI supervised and unsupervised classification of Parkinson's disease and multiple system atrophy.

BACKGROUND: Multimodal MRI approach is based on a combination of MRI parameters sensitive to different tissue characteristics (eg, volume atrophy, iron deposition, and microstructural damage). The main objective of the present study was to use a multimodal MRI approach to identify brain differences that could discriminate between matched groups of patients with multiple system atrophy, Parkinson's disease, and healthy controls. We assessed the 2 different MSA variants, namely, MSA-P, with predominant parkinsonism, and MSA-C, with more prominent cerebellar symptoms. METHODS: Twenty-six PD patients, 29 MSA patients (16 MSA-P, 13 MSA-C), and 26 controls underwent 3-T MRI comprising T2*-weighted, T1-weighted, and diffusion tensor imaging scans. Using whole-brain voxel-based MRI, we combined gray-matter density, T2* relaxation rates, and diffusion tensor imaging scalars to compare and discriminate PD, MSA-P, MSA-C, and healthy controls. RESULTS: Our main results showed that this approach reveals multiparametric modifications within the cerebellum and putamen in both MSA-C and MSA-P patients, compared with PD patients. Furthermore, our findings revealed that specific single multimodal MRI markers were sufficient to discriminate MSA-P and MSA-C patients from PD patients. Moreover, the unsupervised analysis based on multimodal MRI data could regroup individuals according to their clinical diagnosis, in most cases. CONCLUSIONS: This study demonstrates that multimodal MRI is able to discriminate patients with PD from those with MSA with high accuracy. The combination of different MR biomarkers could be a great tool in early stage of disease to help diagnosis. © 2018 International Parkinson and Movement Disorder Society.

Cerebellar grey matter modifications in lower limb amputees not using prosthesis.

Plastic brain changes following peripheral deafferentation, in particular those following limb amputations, are well-documented, with significant reduction of grey matter (GM) in the sensory-motor cerebral areas representing the amputated limb. However, few studies have investigated the role played by the use of a prosthesis in these structural brain modifications. Here we hypothesized that using a functional prosthesis that allows individuals to perform actions may reduce grey matter reduction. We investigated the brain structural reorganization following lower limb amputation by using a Voxel Based Morphometry (VBM) analysis of structural magnetic resonance imaging (MRI) in 8 right-handed individuals with lower limb amputation (LLA) fitted with prostheses (LLAwp), compared to 6 LLA who had never used a prosthesis (LLAnp). 14 age-matched healthy controls were also enrolled (HC). We did not find any significant effect when comparing LLAwp and HC. However we found a decreased GM volume in the bilateral cerebellum in LLAnp compared with HC. These results suggest that prosthesis use prevents GM decrease in the cerebellum after lower limb amputation.

Transcranial Electric Stimulation Can Impair Gains during Working Memory Training and Affects the Resting State Connectivity.

Transcranial electric stimulation (tES) is a promising technique that has been shown to improve working memory (WM) performance and enhance the effect of cognitive training. However, experimental set up and electrode placement are not always determined based on neurofunctional knowledge about WM, leading to inconsistent results. Additional research on the effects of tES grounded on neurofunctional evidence is therefore necessary. Sixty young, healthy, volunteers, assigned to six different groups, participated in 5 days of stimulation or sham treatment. Twenty-five of these subjects also participated in MRI acquisition. We performed three experiments: In the first one, we evaluated tES using either direct current stimulation (tDCS) with bilateral stimulation of the frontal or parietal lobe; in the second one, we used the same tDCS protocol with a different electrode placement (i.e., supraorbital cathode); in the third one, we used alternating currents (tACS) of 35 Hz, applied bilaterally to either the frontal or parietal lobes. The behavioral outcome measure was the WM capacity (i.e., number of remembered spatial position) during the 5 days of training. In a subsample of subjects we evaluated the neural effects of tDCS by measuring resting state connectivity with functional MRI, before and after the 5 days of tDCS and visuo-spatial WM training. We found a significant impairment of WM training-related gains associated with parietal tACS and frontal tDCS. Five days of tDCS stimulation was also associated with significant change in resting state connectivity revealed by multivariate pattern analysis. None of the stimulation paradigms resulted in improved WM performance or enhanced WM training gains. These results show that tES can have negative effects on cognitive plasticity and affect resting-state functional connectivity.

Does aging affect the formation of new topographical memories? Evidence from an extensive spatial training.

A decline in navigational abilities is a consistent feature of aging. Although many studies focused on recall of navigational information, the impact of time and type of learning on recall has received little attention. We submitted older adults and young participants to an extensive training of an ecological environment, from both route and survey perspectives. Then, we tested participants' learning using from both route and survey perspectives. Although older adults benefit from the extensive training, they did not reach the same performance of the young participants. Despite this main effect of age, the effect of the type of learning was the same in the two groups. Congruence between type of learning and recall led to better performance in both groups. We discuss these findings in the light of cognitive models of human navigation and aging. Useful suggestions about how these findings may inform a specific cognitive intervention in older adults are also provided.