The resilience of the developing reading system: multi-modal evidence of incident and recovery after a pediatric stroke.

Decades of neuroscientific findings have elucidated the highly specialized brain areas involved in reading, especially along the ventral occipitotemporal stream where the critical step of recognizing words occurs. We report on a 14-year-old female with temporary dyslexia after a left ventral occipitotemporal ischemic stroke. Our longitudinal multimodal findings show that the resolution of the reading impairment was associated with heightened activity in the left posterior superior and inferior temporal gyri. Our findings highlight the role of the left inferior temporal gyrus in reading and the importance of perilesional and ipsilateral cortical areas for functional recovery after childhood stroke.

Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology.

Post-mortem studies show that focal anterior temporal lobe (ATL) neurodegeneration is most often caused by frontotemporal lobar degeneration TDP-43 type C pathology. Clinically, these patients are described with different terms, such as semantic variant primary progressive aphasia (svPPA), semantic dementia (SD), or right temporal variant frontotemporal dementia (FTD) depending on whether the predominant symptoms affect language, semantic knowledge for object or people, or socio-emotional behaviors. ATL atrophy presents with various degrees of lateralization, with right-sided cases considered rarer even though estimation of their prevalence is hampered by the paucity of studies on well-characterized, pathology-proven cohorts. Moreover, it is not clear whether left and right variants show a similar distribution of atrophy within the ATL cross-sectionally and longitudinally. Here we study the largest cohort to-date of pathology-proven TDP-43-C cases diagnosed during life as svPPA, SD or right temporal variant FTD. We analyzed clinical, cognitive, and neuroimaging data from 30 cases, a subset of which was followed longitudinally. Guided by recent structural and functional parcellation studies, we constructed four bilateral ATL regions of interest (ROIs). The computation of an atrophy lateralization index allowed the comparison of atrophy patterns between the two hemispheres. This led to an automatic, imaging-based classification of the cases as left-predominant or right-predominant. We then compared the two groups in terms of regional atrophy patterns within the ATL ROIs (cross-sectionally) and atrophy progression (longitudinally). Results showed that 40% of pathology proven cases of TDP-43-C diagnosed with a temporal variant presented with right-lateralized atrophy. Moreover, the findings of our ATL ROI analysis indicated that, irrespective of atrophy lateralization, atrophy distribution within both ATLs follows a medial-to-lateral gradient. Finally, in both left and right cases, atrophy appeared to progress to the contralateral ATL, and from the anterior temporal pole to posterior temporal and orbitofrontal regions. Taken together, our findings indicate that incipient right predominant ATL atrophy is common in TDP-43-C pathology, and that distribution of damage within the ATLs appears to be the same in left- and right- sided variants. Thus, regardless of differences in clinical phenotype and atrophy lateralization, both temporal variants of FTD should be viewed as a spectrum presentation of the same disease.

Application of quantitative DTI metrics in sporadic CJD.

Diffusion Weighted Imaging is extremely important for the diagnosis of probable sporadic Jakob-Creutzfeldt disease, the most common human prion disease. Although visual assessment of DWI MRI is critical diagnostically, a more objective, quantifiable approach might more precisely identify the precise pattern of brain involvement. Furthermore, a quantitative, systematic tracking of MRI changes occurring over time might provide insights regarding the underlying histopathological mechanisms of human prion disease and provide information useful for clinical trials. The purposes of this study were: 1) to describe quantitatively the average cross-sectional pattern of reduced mean diffusivity, fractional anisotropy, atrophy and T1 relaxation in the gray matter (GM) in sporadic Jakob-Creutzfeldt disease, 2) to study changes in mean diffusivity and atrophy over time and 3) to explore their relationship with clinical scales. Twenty-six sporadic Jakob-Creutzfeldt disease and nine control subjects had MRIs on the same scanner; seven sCJD subjects had a second scan after approximately two months. Cortical and subcortical gray matter regions were parcellated with Freesurfer. Average cortical thickness (or subcortical volume), T1-relaxiation and mean diffusivity from co-registered diffusion maps were calculated in each region for each subject. Quantitatively on cross-sectional analysis, certain brain regions were preferentially affected by reduced mean diffusivity (parietal, temporal lobes, posterior cingulate, thalamus and deep nuclei), but with relative sparing of the frontal and occipital lobes. Serial imaging, surprisingly showed that mean diffusivity did not have a linear or unidirectional reduction over time, but tended to decrease initially and then reverse and increase towards normalization. Furthermore, there was a strong correlation between worsening of patient clinical function (based on modified Barthel score) and increasing mean diffusivity.

Functional connectivity during resting-state functional MR imaging: study of the correspondence between independent component analysis and region-of-interest-based methods.

BACKGROUND AND PURPOSE: The connectivity across brain regions can be evaluated through fMRI either by using ICA or by means of correlation analysis of time courses measured in predefined ROIs. The purpose of this study was to investigate quantitatively the correspondence between the connectivity information provided by the 2 techniques. MATERIALS AND METHODS: In this study, resting-state fMRI data from 40 healthy participants were independently analyzed by using spatial ICA and ROI-based analysis. To assess the correspondence between the results provided by the 2 methods, for all combinations of ROIs, we compared the time course correlation coefficient with the corresponding "ICA coactivation index." RESULTS: A strongly significant correspondence of moderate intensity was found for 20 ICA components (r = 0.44, P < .001). Repeating the analysis with 10, 15, 25, 30, 35, and 40 components, we found that the correlation remained but was weaker (r = 0.35-0.41). CONCLUSIONS: There is a significant but not complete correspondence between the results provided by ICA and ROI-based analysis of resting-state data.

Decreased diffusivity in the caudate nucleus of presymptomatic huntington disease gene carriers: which explanation?

BACKGROUND AND PURPOSE: The neostriatum is known to be affected in HD. In this work, our aim was to determine whether microstructural and volumetric alterations occur in the neostriatum of presymptomatic HD gene carriers and in patients with early-stage HD. MATERIALS AND METHODS: We studied a group of 15 presymptomatic gene carriers who were far from the estimated symptom onset (16% probability of developing the disease within 5 years), a group of 9 patients with early symptomatic HD, and 2 groups of age-matched controls. Volumetric MR imaging and DWIs were acquired, and statistical analyses were performed on the volumes of the caudate nucleus and putamen and on the corresponding MD measurements. RESULTS: Neostriatal volumes were significantly smaller in both presymptomatic HD gene carriers and symptomatic patients with respect to controls. However, whereas the diffusivity in the caudate nucleus was increased in the symptomatic patients, it was decreased in the presymptomatic gene carriers. CONCLUSIONS: Altered diffusivity and reduced volume of the caudate nucleus in presymptomatic HD gene carriers indicate that the neostriatum is affected well before the onset of symptoms. The observed initial decrease and subsequent increase of MD might be related to the combined effect of increased oligodendroglial population, putatively a developmental abnormality, and incipient neurodegeneration.

Diffusion tensor imaging shows different topographic involvement of the thalamus in progressive supranuclear palsy and corticobasal degeneration.

BACKGROUND AND PURPOSE: In progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), postmortem studies show different topographic involvement of the thalamus, basal ganglia, and their cortical connections. Diffusion tensor imaging (DTI) is an MR imaging technique sensitive to gray and white matter microstructure integrity. This study was performed to determine whether DTI may demonstrate microstructural differences between PSP and CBD, particularly within the thalamus and its cortical connections. MATERIALS AND METHODS: Nine patients with probable PSP, 11 with probable CBD, and 7 controls formed the study group. Apparent diffusion coefficient average (ADC(ave)) and fractional anisotropy (FA) values were measured in regions of interest positioned in the ventrolateral (motor), medial, anterior, and posterior regions of the thalami, basal ganglia, fronto-orbital white matter, cingulum, supplementary motor area (SMA), and precentral and postcentral gyri in patients and controls. RESULTS: In PSP, ADC(ave) values were increased in several areas: the thalamus, particularly in its anterior and medial nuclei; cingulum; motor area; and SMA. FA values were particularly decreased in the fronto-orbital white matter, anterior cingulum, and motor area. In CBD, ADC(ave) was increased in the motor thalamus, in the precentral and postcentral gyri, ipsilateral to the affected frontoparietal cortex, and in the bilateral SMA. FA was mainly decreased in the precentral gyrus and SMA, followed by the postcentral gyrus and cingulum. CONCLUSIONS: In patients with PSP, thalamic involvement was diffuse and prevalent in its anterior part, whereas in CBD involvement was asymmetric and confined to the motor thalamus. DTI may be useful in the differential diagnosis of these 2 parkinsonian disorders.

Functional-MRI evaluation of pain processing in chronic migraine with medication overuse.

Withdrawal is the first step for treating patients with chronic migraine and medication overuse. Recent studies confirmed common elements in personality between these patients and subjects addicted; some neuroimaging researches showed that abnormalities revealed are related to a specific cerebral pattern and that they can return to the normal state after withdrawal. Aim of the study was to submit a group of patients suffering from chronic migraine and medication overuse (the diagnosis was made according to Silberstein-Lipton criteria) to a withdrawal, to evaluate by f-MRI the presence of specific cerebral patterns before treatment and their possible changes after withdrawal. f-MRI seems to be a useful technique to obtain information on particular neuronal changes of the pain network involved in this type of patients. The activated areas are congruent with some data of the literature and the data emerged are discussed according to preceding reports.

Elevating tensor rank increases anisotropy in brain areas associated with intra-voxel orientational heterogeneity (IVOH): a generalised DTI (GDTI) study.

Rank-2 tensors are unable to represent multi-modal diffusion associated with intra-voxel orientational heterogeneity (IVOH), which occurs where axons are incoherently oriented, such as where bundles intersect or diverge. Under this condition, they are oblate or spheroidally shaped, resulting in artefactually low anisotropy, potentially masking reduced axonal density, myelinisation and integrity. Higher rank tensors can represent multi-modal diffusion, and suitable metrics such as generalised anisotropy (GA) and scaled entropy (SE) have been introduced. The effect of tensor rank was studied through simulations, and analysing high angular resolution diffusion imaging (HARDI) data from two volunteers, fit with rank-2, rank-4 and rank-6 tensors. The variation of GA and SE as a function of rank was investigated through difference maps and region of interest (ROI)-based comparisons. Results were correlated with orientation distribution functions (ODF) reconstructed with q-ball, and with colour-maps of the principal and second eigenvectors. Simulations revealed that rank-4 tensors are able to represent multi-modal diffusion, and that increasing rank further has a minor effect on measurements. IVOH was detected in subcortical regions of the corona radiata, along the superior longitudinal fasciculus, in the radiations of the genu of the corpus callosum, in peritrigonal white matter and along the inferior fronto-occipital and longitudinal fascicula. In these regions, elevating tensor rank increased anisotropy. This was also true for the corpus callosum, cingulum and anterior limb of the internal capsule, where increasing tensor rank resulted in patterns that, although mono-modal, were more anisotropic. In these regions the second eigenvector was coherently oriented. As rank-4 tensors have only 15 distinct elements, they can be determined without acquiring a large number of directions. By removing artefactual underestimation of anisotropy, their use may increase the sensitivity to pathological change.

Diffusion tensor imaging of spinocerebellar ataxias types 1 and 2.

BACKGROUND AND PURPOSE: Structural MR imaging does not enable reliable differentiation of spinocerebellar ataxia (SCA) types 1 and 2 (SCA1 and SCA2), and imaging may be normal during the first years after the onset of symptoms. We aimed at determining whether measurements of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) may enable their differentiation. MATERIALS AND METHODS: We enrolled 14 patients with SCA1, 11 with SCA2, and 9 age-matched controls. Diffusion tensor imaging (DTI) was performed on a 1.5T scanner, with b = 1000s/mm2 and 12 directions. ADC and FA were measured by means of regions of interest, positioned in the corticospinal tract at the level of the cerebral peduncle and at the level of the pons, in the transverse pontine fibers, in the superior and middle cerebellar peduncle, and in the hemispheric cerebellar white matter. RESULTS: With respect to controls, the ADC was significantly elevated in the middle cerebellar peduncle and in hemispheric white matter in SCA1, and in all regions under consideration in SCA2. It was significantly higher in SCA2 than in SCA1 in all regions under consideration. With respect to controls, the FA was significantly reduced in all regions under consideration in SCA1 and in SCA2. It was significantly lower in SCA2 than in SCA1 in the transverse pontine fibers and in the corticospinal tract at the level of the cerebral peduncle. Correlations with clinical scores were found. CONCLUSIONS: DTI did not enable differentiation between SCA1 and SCA2. However, strongly significant differences between the 2 subtypes and with respect to controls and correlations with clinical scores were found.