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1.  Fronto-Tectal White Matter Connectivity Mediates Facilitatory Effects of Non-invasive Neurostimulation on Visual Detection 
NeuroImage  2013;82:344-354.
The causal ability of pre-target FEF activity to modulate visual detection for perithreshold stimuli has been recently demonstrated in humans by means of non-invasive neurostimulation. Yet in spite of the network-distributed effects of these type of techniques, the white matter (WM) tracts and distant visual nodes contributing to such behavioral impact remain unknown. We hereby used individual data from a group of healthy human subjects, who received time-locked pulses of active or sham Transcranial Magnetic Stimulation (TMS) to the right Frontal Eye Field (FEF) region, and experienced increases in visual detection sensitivity. We then studied the extent to which interindividual differences in visual modulation might be dependent on the WM patterns linking the targeted area to other regions relevant for visuo-attentional behaviors. We report a statistically significant correlation between the probability of connection in a right fronto-tectal pathway (FEF-Superior Colliculus) and the modulation of visual sensitivity during a detection task. Our findings support the potential contribution of this pathway and the superior colliculus in the mediation of visual performance from frontal regions in humans. Furthermore, we also show the ability of a TMS/DTI correlational approach to contribute to the disambiguation of the specific long-range pathways driving network-wide neurostimulatory effects on behavior, anticipating their future role in guiding a more efficient use of focal neurostimulation.
PMCID: PMC3779842  PMID: 23707586
Frontal Eye Field; Cortico-tectal projections; Visuo-Spatial Attention; Neuroanatomy; Transcranial Magnetic Stimulation; Diffusion Tensor Imaging
2.  Damage to the medial motor system in stroke patients with motor neglect 
Background and objectives: Motor neglect (MN) is a clinically important condition whereby patients with unilateral brain lesions fail to move their contralateral limbs, despite normal muscle strength, reflexes, and sensation. MN has been associated with various lesion sites, including the parietal and frontal cortex, the internal capsule, the lenticulostriate nuclei, and the thalamus. In the present study, we explored the hypothesis that MN depends on a dysfunction of the medial motor system by performing a detailed anatomical analysis in four patients with MN.
Methods: Ten patients participated in the study: four with MN, four with left visual neglect but without MN, and three patients with left hemiplegia without MN. We used specific scales for clinical and neuropsychological assessment. We drew the lesion borders directly onto the original brain images of each patient, and plotted the lesions on anatomical atlases for gray and white matter.
Results: Lesion locations were highly heterogeneous in our MN patients, and included frontal and parietal sites, basal ganglia, and white matter. The only consistently damaged structure across all MN patients was the cingulum bundle, a major pathway of the medial motor system important for motor initiative, and a key connection with limbic structures crucial for motivational aspects of actions. Three MN patients with additional damage to lateral fronto-parietal networks had also signs of contralesional visual neglect. The cingulum bundle was intact in all the control patients with visual neglect or hemiplegia.
Conclusions: Cingulum damage may induce MN through unilateral dysfunction of the medial motor system. Additional lateral fronto-parietal dysfunction can result in the association with visual neglect.
PMCID: PMC4052665  PMID: 24966826
motor neglect; visual neglect; medial motor system; cingulum bundle; parieto-frontal network
3.  White Matter atrophy in Alzheimer Disease variants 
In comparison to late-onset Alzheimer’s disease (LO-AD, onset > 65), early age-of-onset Alzheimer’s disease (EO-AD, onset<65 years) more often presents with language, visuospatial and/or executive impairment, often occurring earlier than a progressive memory deficit. The logopenic variant of primary progressive aphasia (lv-PPA) and the posterior cortical atrophy (PCA) have recently been described as possible atypical variants of EO-AD. Lv-PPA is characterized by isolated language deficit, while PCA is characterized by predominant visuospatial deficits. Severe hemispheric grey matter (GM) atrophy associated with EO-AD, lv-PPA and PCA has been described, but regional patterns of white matter (WM) damage are still poorly understood.
Using structural MRI and voxel-based morphometry, we investigated WM damage in 16 EO-AD, 13 PCA, 10 lv-PPA, and 14 LO-AD patients at presentation, and 72 age-matched controls.
In EO-AD, PCA and lv-PPA patients, WM atrophy was centered on lateral temporal and parietal regions, including cingulum and posterior corpus callosum. Compared to controls, lv-PPA patients showed a more severe left parietal damage, and PCA showed a more severe occipital atrophy. Moreover, EO-AD had greater cingulum atrophy compared with LO-AD. LO-AD showed WM damage in medial temporal regions and less extensive hemispheric involvement.
Patterns of WM damage in EO-AD, lv-PPA and PCA are consistent with the clinical syndromes and GM atrophy patterns. WM injury in AD atypical variants may contribute to symptoms and disease pathogenesis.
PMCID: PMC3717610  PMID: 23021625
Alzheimer’s disease; white matter damage; cerebral network; age of onset; VBM
4.  Music Recognition in Frontotemporal Lobar Degeneration and Alzheimer Disease 
To compare music recognition in patients with frontotemporal dementia, semantic dementia, Alzheimer disease, and controls and to evaluate the relationship between music recognition and brain volume.
Recognition of familiar music depends on several levels of processing. There are few studies about how patients with dementia recognize familiar music.
Subjects were administered tasks that assess pitch and melody discrimination, detection of pitch errors in familiar melodies, and naming of familiar melodies.
There were no group differences on pitch and melody discrimination tasks. However, patients with semantic dementia had considerable difficulty naming familiar melodies and also scored the lowest when asked to identify pitch errors in the same melodies. Naming familiar melodies, but not other music tasks, was strongly related to measures of semantic memory. Voxel-based morphometry analysis of brain MRI showed that difficulty in naming songs was associated with the bilateral temporal lobes and inferior frontal gyrus, whereas difficulty in identifying pitch errors in familiar melodies correlated with primarily the right temporal lobe.
The results support a view that the anterior temporal lobes play a role in familiar melody recognition, and that musical functions are affected differentially across forms of dementia.
PMCID: PMC3691095  PMID: 21617528
Pitch; Melody; temporal lobe; auditory perception
5.  Language networks in semantic dementia 
Brain  2009;133(1):286-299.
Cognitive deficits in semantic dementia have been attributed to anterior temporal lobe grey matter damage; however, key aspects of the syndrome could be due to altered anatomical connectivity between language pathways involving the temporal lobe. The aim of this study was to investigate the left language-related cerebral pathways in semantic dementia using diffusion tensor imaging-based tractography and to combine the findings with cortical anatomical and functional magnetic resonance imaging data obtained during a reading activation task. The left inferior longitudinal fasciculus, arcuate fasciculus and fronto-parietal superior longitudinal fasciculus were tracked in five semantic dementia patients and eight healthy controls. The left uncinate fasciculus and the genu and splenium of the corpus callosum were also obtained for comparison with previous studies. From each tract, mean diffusivity, fractional anisotropy, as well as parallel and transverse diffusivities were obtained. Diffusion tensor imaging results were related to grey and white matter atrophy volume assessed by voxel-based morphometry and functional magnetic resonance imaging activations during a reading task. Semantic dementia patients had significantly higher mean diffusivity, parallel and transverse in the inferior longitudinal fasciculus. The arcuate and uncinate fasciculi demonstrated significantly higher mean diffusivity, parallel and transverse and significantly lower fractional anisotropy. The fronto-parietal superior longitudinal fasciculus was relatively spared, with a significant difference observed for transverse diffusivity and fractional anisotropy, only. In the corpus callosum, the genu showed lower fractional anisotropy compared with controls, while no difference was found in the splenium. The left parietal cortex did not show significant volume changes on voxel-based morphometry and demonstrated normal functional magnetic resonance imaging activation in response to reading items that stress sublexical phonological processing. This study shows that semantic dementia is associated with anatomical damage to the major superior and inferior temporal white matter connections of the left hemisphere likely involved in semantic and lexical processes, with relative sparing of the fronto-parietal superior longitudinal fasciculus. Fronto-parietal regions connected by this tract were activated normally in the same patients during sublexical reading. These findings contribute to our understanding of the anatomical changes that occur in semantic dementia, and may further help to explain the dissociation between marked single-word and object knowledge deficits, but sparing of phonology and fluency in semantic dementia.
PMCID: PMC2801321  PMID: 19759202
semantic dementia; semantic knowledge; diffusion tensor-based tractography; functional MRI; voxel-based morphometry
6.  Neuroimaging in Dementia 
Seminars in neurology  2008;28(4):467-483.
Although dementia is a clinical diagnosis, neuroimaging often is crucial for proper assessment. Magnetic resonance imaging (MRI) and computed tomography (CT) may identify nondegenerative and potentially treatable causes of dementia. Recent neuroimaging advances, such as the Pittsburgh Compound-B (PIB) ligand for positron emission tomography imaging in Alzheimer’s disease, will improve our ability to differentiate among the neurodegenerative dementias. High-resolution volumetric MRI has increased the capacity to identify the various forms of the frontotemporal lobar degeneration spectrum and some forms of parkinsonism or cerebellar neurodegenerative disorders, such as corticobasal degeneration, progressive supranuclear palsy, multiple system atrophy, and spinocerebellar ataxias. In many cases, the specific pattern of cortical and subcortical abnormalities on MRI has diagnostic utility. Finally, among the new MRI methods, diffusion-weighted MRI can help in the early diagnosis of Creutzfeldt-Jakob disease. Although only clinical assessment can lead to a diagnosis of dementia, neuroimaging is clearly an invaluable tool for the clinician in the differential diagnosis.
PMCID: PMC2647854  PMID: 18843575
MRI; PET; Pittsburgh Compound-B; dementia; neurodegenerative disease

Results 1-6 (6)