Paolo Vitali

Training-induced brain remapping in chronic aphasia: a pilot study.

Background. The neural correlates of training-induced improvements of cognitive functions after brain damage remain still scarcely understood. In the specific case of aphasia, although several investigations have addressed the issue of the neural substrates of functional recovery, only a few studies have attempted to assess the impact of language training on the damaged brain. Aims. The main goal of this study was to examine the neurobiological correlates of improved picture-naming performance in 2 aphasic patients who received intensive and specific training for a chronic and severe phonological anomia. Methods. In both participants, picture-naming performance was assessed before and after phonological cueing training. Training-induced changes in patients’ performance were correlated to brain activity patterns as revealed by pre- and post-training event-related functional magnetic resonance imaging scanning. Results. Training-induced improvement was observed concurrently with changes in the brain activation patterns. Better performance was observed in the patient with the smaller lesion, partially sparing Broca’s area, who showed a left perilesional reactivation. Conversely, the patient with complete destruction of Broca’s area showed a posttraining activation in the right mirror frontal region. Conclusions. The results show that, even in the chronic stage, phonological strategies may improve impaired naming and induce cerebral reorganization.

Generating animal and tool names: An fMRI study of effective connectivity

The present fMRI study of semantic fluency for animal and tool names provides further evidence for category-specific brain activations, and reports task-related changes in effective connectivity among defined cerebral regions. Two partially segregated systems of functional integration were highlighted: the tool condition was associated with an enhancement of connectivity within left hemispheric regions, including the inferior prefrontal and premotor cortex, the inferior parietal lobule and the temporo-occipital junction; the animal condition was associated with greater coupling among left visual associative regions. These category-specific functional differences extend the evidence for anatomical specialization to lexical search tasks, and provide for the first time evidence of category-specific patterns of functional integration in word-retrieval.

Neuroimaging in Dementia

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 Alzheimers 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.

Comparing CSF biomarkers and brain MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease.

SummaryWe assessed the diagnostic utility of 3 CSF biomarkers—14-3-3 protein, total tau (T-tau), and neuron-specific enolase (NSE)—from the same lumbar puncture to distinguish between participants with neuropathologically confirmed sporadic Creutzfeldt-Jakob disease (sCJD, n = 57) and controls with nonprion rapidly progressive dementia (npRPD, n = 41). Measures of diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value, as well as logistic regression and area under the receiver operator curve (AUC), were used to assess the ability of these CSF biomarkers, alone or concomitantly, to predict diagnosis. In a subcohort with available MRI (sCJD n = 57, npRPD = 32), we compared visual assessment of diffusion-weighted imaging MRI sequences to these CSF biomarkers. MRI was the best predictor, with an AUC of 0.97 (confidence interval [CI] 0.92–1.00) and a diagnostic accuracy of 97% (CI 90%–100%). Of the CSF biomarkers, T-tau had a higher diagnostic accuracy (79.6%) than 14-3-3 (70.4%, CI for difference 8.7%, 9.7%; p = 0.048) or NSE (71.4%, CI for difference 7.6%, 8.7%; p = 0.03).

Generalization of the effects of phonological training for anomia using structural equation modelling: A multiple single-case study

Structural Equation Modelling analysis of three longitudinal er-fMRI sessions was used to test the impact of phonological training and of the generalization process on the pattern of brain connectivity during overt picture naming in two chronic anomic patients. Phonological training yielded a positive effect on the trained material. Six months after the training, a generalization of the positive impact on the untrained items was also observed. Connectivity analysis showed that training and generalization effects shared paralleled cortical patterns of functional integration. These findings may represent the neurophysiological correlate of the training-induced cognitive strategies for the compensation of anomia.

CHARACTERIZING RADIOLOGY REPORTS IN PATIENTS WITH FRONTOTEMPORAL DEMENTIA

Frontotemporal lobar degeneration (FTLD) is a common early onset dementing condition.1 The subtypes of FTLD, behavioral variant frontotemporal dementia (bvFTD), and semantic dementia (SemD) have distinctive imaging patterns that separate them from healthy aging, Alzheimer disease (AD), and from each other.2–4 The bvFTD causes frontotemporal tissue loss while SemD displays selective atrophy of the anterior temporal lobes. We performed a retrospective analysis of MRI atrophy patterns in 40 patients with bvFTD.5 ### Methods. #### Participants. All patients evaluated between 1999 and 2006 at the UCSF Memory and Aging Center who consented to research, met the Neary research criteria for FTD,5 and had an MRI scan within 1 year of presentation were included (figure e-1 on the Neurology ® Web site at www.neurology.org). The referring diagnosis in patients’ records and the radiologist’s findings and impression on the first scan were recorded. Thirty-four scans were performed in academic settings and 6 in private centers. #### Standard protocol approvals, registrations, and patient consents. We received ethics approval from the UCSF Research ethical standards committee on human experimentation and informed consent was obtained from all participants. #### Test methods. Nine categories were identified based on the radiologist’s reports of the 40 patients: 1) bvFTD, 2) white matter/ischemic disease, 3) AD, 4) normal pressure hydrocephalus (NPH)/hydrocephalus, 5) mitochondrial/metabolic, 6) encephalomalacia, …

White matter involvement in sporadic Creutzfeldt-Jakob disease

Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P = 0.002), axial (P = 0.0003) and radial (P = 0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (P < 0.05, corrected for multiple comparisons), with a generally symmetric pattern of involvement in sporadic Creutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P = 0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter abnormality either on T2-weighted or diffusion-weighted images. Widespread reduction in white matter mean diffusivity, however, was apparent visibly on the quantitative attenuation coefficient maps compared to healthy control subjects. Neuropathological analysis showed diffuse astrocytic gliosis and activated microglia in the white matter, rare prion deposition and subtle subcortical microvacuolization, and patchy foci of demyelination with no evident white matter axonal degeneration. Decreased mean diffusivity on attenuation coefficient maps might be associated with astrocytic gliosis. We show for the first time significant global reduced mean diffusivity within the white matter in sporadic Creutzfeldt-Jakob disease, suggesting possible primary involvement of the white matter, rather than changes secondary to neuronal degeneration/loss.

Two insular regions are differentially involved in behavioral variant FTD and nonfluent/agrammatic variant PPA.

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and the behavioral variant frontotemporal dementia (bvFTD) are focal neurodegenerative disorders belonging to the FTD-spectrum clinical syndromes. NfvPPA is characterized by effortful speech and/or agrammatism and left frontal atrophy, while bvFTD is characterized by social-emotional dysfunction often accompanied by right-lateralized frontal damage. Despite their contrasting clinical presentations, both disorders show prominent left anterior insula atrophy. We investigated differential patterns of insular sub-region atrophy in nfvPPA and bvFTD. Based on knowledge of insular connectivity and physiology, we hypothesized that the left superior precentral region of the dorsal anterior insula (SPGI) would be more atrophic in nvfPPA due to its critical role in motor speech, whereas the ventral anterior region would be more atrophied in bvFTD reflecting its known role in social-emotional-autonomic functions. Early stage nfvPPA and bvFTD patients matched for disease severity, age, gender and education and healthy controls participated in the study. Detailed clinical history, neurological examination, neuropsychological screening evaluation, and high-resolution T1-weighted brain magnetic resonance imaging (MRI) were collected. Voxel-based morphometry (VBM) was applied to perform group comparisons across the whole brain and in bilateral insula region of interest (ROI). Correlation analyses between insular sub-region atrophy and relevant clinical features were performed. Whole brain group comparisons between nfvPPA and bvFTD showed the expected predominantly left or right anterior insular atrophy pattern. ROI analysis of bilateral insula showed that the left SPGI was significantly more atrophied in nfvPPA compared to bvFTD, while the bilateral ventral anterior and right dorsal anterior insula sub-regions were more atrophied in bvFTD than nfvPPA. Only left SPGI volume correlated with speech production abilities, while left and right ventral anterior insula volumes correlated with ratings of aberrant eating behavior. These two FTD clinical variants show different patterns of insular sub-region atrophy in the left precentral dorsal anterior and bilateral ventral anterior regions, providing further evidence for the role of these sub-regions in speech production and social-emotional function.

Cerebral Microbleed Causing an Acute Stroke-like Episode in a CADASIL Patient.

Cerebral microbleeds (CMBs), visualized on gradient-recalled echo (GRE) T2 or susceptibility-weighted imaging magnetic resonance imaging (MRI) sequences, and thought to reflect minor leakage from fragile arterial micro-vessels, are classically considered to be clinically silent. They are frequent incidental findings in MRI scans of healthy subjects, especially in the elderly population and even more prevalent in patients with acute ischemic and hemorrhagic stroke. However, increasing evidence has called into question the asymptomatic nature of CMBs. In particular, they appear to be associated with an increased risk of incident ischemic and hemorrhagic strokes as well as recurrent strokes. Greater controversy surrounds the possibility that CMBs can cause acute stroke-like episodes. In fact, CMBs are often associated with a degree of surrounding tissue necrosis; however, in theory, the brain tissue damaged by an acutely developing CMB is too small to produce focal neurological symptoms. Nevertheless, a few case reports of acute focal deficits with negative diffusionweighted imaging (DWI) brain-MRI sequences seem to suggest that a strategically located CMB could, indeed, cause an acute stroke syndrome. These few published reports have invariably described patients with classical risk factors for small vessel disease.

Proper name anomia in poststroke aphasics: evidence from a multiple-case study

We aimed to characterize difficulties in famous face naming in three poststroke aphasic patients with a lesion limited to the left mid-posterior temporal language regions, sparing the anterior temporal lobe. The patients did not present semantic deficits specific to known people. Nonetheless, they showed difficulties naming famous buildings in addition to famous faces, but they were comparable to healthy controls in generating proper names. Our results support the critical role of the mid-posterior temporal language regions in the lexical retrieval of proper names, namely from pictorial stimuli, in absence of semantic impairments.