Maria Vittoria Spampinato

Medial temporal lobe epilepsy is associated with neuronal fibre loss and paradoxical increase in structural connectivity of limbic structures

Background It has been hypothesised that seizure induced neuronal loss and axonal damage in medial temporal lobe epilepsy (MTLE) may lead to the development of aberrant connections between limbic structures and eventually result in the reorganisation of the limbic network. In this study, limbic structural connectivity in patients with MTLE was investigated, using diffusion tensor MRI, probabilistic tractography and graph theory based network analysis. Methods 12 patients with unilateral MTLE and hippocampal sclerosis (five left and seven right MTLE) and 26 healthy controls were studied. The connectivity of 10 bilateral limbic regions of interest was mapped with probabilistic tractography, and the probabilistic fibre density between each pair of regions was used as the measure of their weighted structural connectivity. Binary connectivity matrices were then obtained from the weighted connectivity matrix using a range of fixed density thresholds. Graph theory based properties of nodes (degree, local efficiency, clustering coefficient and betweenness centrality) and the network (global efficiency and average clustering coefficient) were calculated from the weight and binary connectivity matrices of each subject and compared between patients and controls. Results MTLE was associated with a regional reduction in fibre density compared with controls. Paradoxically, patients exhibited (1) increased limbic network clustering and (2) increased nodal efficiency, degree and clustering coefficient in the ipsilateral insula, superior temporal region and thalamus. There was also a significant reduction in clustering coefficient and efficiency of the ipsilateral hippocampus, accompanied by increased nodal degree. Conclusions These results suggest that MTLE is associated with reorganisation of the limbic system. These results corroborate the concept of MTLE as a network disease, and may contribute to the understanding of network excitability dynamics in epilepsy and MTLE.

Stroke Assessment With Diffusional Kurtosis Imaging

Background and Purpose— Despite being the gold standard technique for stroke assessment, conventional diffusion MRI provides only partial information about tissue microstructure. Diffusional kurtosis imaging is an advanced diffusion MRI method that yields, in addition to conventional diffusion information, the diffusional kurtosis, which may help improve characterization of tissue microstructure. In particular, this additional information permits the description of white matter (WM) in terms of WM-specific diffusion metrics. The goal of this study is to elucidate possible biophysical mechanisms underlying ischemia using these new WM metrics. Methods— We performed a retrospective review of clinical and diffusional kurtosis imaging data of 44 patients with acute/subacute ischemic stroke. Patients with a history of brain neoplasm or intracranial hemorrhages were excluded from this study. Region of interest analysis was performed to measure percent change of diffusion metrics in ischemic WM lesions compared with the contralateral hemisphere. Results— Kurtosis maps exhibit distinct ischemic lesion heterogeneity that is not apparent on apparent diffusion coefficient maps. Kurtosis metrics also have significantly higher absolute percent change than complementary conventional diffusion metrics. Our WM metrics reveal an increase in axonal density and a larger decrease in the intra-axonal (Da) compared with extra-axonal diffusion microenvironment of the ischemic WM lesion. Conclusions— The well-known decrease in the apparent diffusion coefficient of WM after ischemia is found to be mainly driven by a significant drop in the intra-axonal diffusion microenvironment. Our results suggest that ischemia preferentially alters intra-axonal environment, consistent with a proposed mechanism of focal enlargement of axons known as axonal swelling or beading.

Social contracts and precautions activate different neurological systems: An fMRI investigation of deontic reasoning

We conducted an event-related, functional MRI investigation of 12 males and 12 females reasoning about conditional deontic rules, rules regulating peoples behavior. We employed two different types of rules: social contracts and nonsocial, precautionary rules. Although the rules and the demands of the task were matched in terms of their logical structure, reasoning about social contracts and precautions activated a different constellation of neurological structures. The regions differentially activated by social contracts included dorsomedial PFC (BA 6/8), bilateral ventrolateral PFC (BA 47), the left angular gyrus (BA 39), and left orbitofrontal cortex (BA 10). The regions differentially activated by precautions included bilateral insula, the left lentiform nucleus, posterior cingulate (BA 29/31), anterior cingulate (BA 24) and right postcentral gyrus (BA 3). Collectively, reasoning about prescriptive rules activated the dorsomedial PFC (BA 6/8). The results reinforce the view that human reasoning is not a unified phenomenon, but is content-sensitive.

Cerebral Blood Volume Measurements by Perfusion-Weighted MR Imaging in Gliomas : Ready for Prime Time in Predicting Short-Term Outcome and Recurrent Disease?

BACKGROUND AND PURPOSE: Current classification and grading of primary brain tumors has significant limitations. Our aim was to determine whether the relative cerebral volume (rCBV) measurements in gliomas may serve as an adjunct to histopathologic grading, with a hypothesis that rCBV values are more accurate in predicting 1-year survival and recurrence. MATERIALS AND METHODS: Thirty-four patients with gliomas (WHO grade I-IV, 27 astrocytomas, 7 tumors with oligodendroglial components) underwent contrast-enhanced MR rCBV measurements before treatment. The region of interest and the single pixel with the maximum CBV value within the tumors were normalized relative to the contralateral normal tissue (rCBVmean and rCBVmax, respectively). Karnofsky performance score and progression-free survival (PFS) were recorded. Receiver operating characteristic curves and Kaplan-Meier survival analysis were conducted for CBV and histologic grade (WHO grade). RESULTS: Significant correlations were detected only when patients with oligodendrogliomas and oligoastrocytomas were excluded. The rCBVmean and rCBVmax in the astrocytomas were 3.5 ± 2.9 and 3.7 ± 2.7. PFS correlated with rCBV parameters (r = −0.54 to −0.56, P ≤ .009). WHO grade correlated with rCBV values (r = 0.65, P ≤ .0002). rCBVmax >4.2 was found to be a significant cutoff value for recurrence prediction with 77.8% sensitivity and 94.4% specificity (P = .0001). rCBVmax ≤3.8 was a significant predictor for 1-year survival (93.7% sensitivity, 72.7% specificity, P = .0002). The relative risk for shorter PFS was 11.1 times higher for rCBVmax >4.2 (P = .0006) and 6.7 times higher for WHO grade >II (P = .05). The combined CBV−WHO grade classification enhanced the predictive value for recurrence/progression (P < .0001). CONCLUSIONS: rCBV values in astrocytomas but not tumors with oligodendroglial components are predictive for recurrence and 1-year survival and may be more accurate than histopathologic grading.

Politics on the brain: an FMRI investigation.

Abstract We assessed political attitudes using the Implicit Association Test (IAT) in which participants were presented with faces and names of well-known Democrat and Republican politicians along with positive and negative words while undergoing functional MRI. We found a significant behavioral IAT effect for the face, but not the name, condition. The fMRI face condition results indicated that ventromedial and anterior prefrontal cortices were activated during political attitude inducement. Amygdala and fusiform gyrus were activated during perceptual processing of familiar faces. Amygdala activation was also associated with measures of strength of emotion. Frontopolar activation was positively correlated with an implicit measure of bias and valence strength (how strongly the participants felt about the politicians), while strength of affiliation with political party was negatively correlated with lateral PFC, lending support to the idea that two distinct but interacting networks—one emphasizing rapid, stereotypic, and emotional associative knowledge and the other emphasizing more deliberative and factual knowledge—co-operate in the processing of politicians. Our findings of ventromedial PFC activation suggests that when processing the associative knowledge concerned with politicians, stereotypic knowledge is activated, but, in addition, the anterior prefrontal activations indicate that more elaborative, reflective knowledge about the politician is activated.

Novel White Matter Tract Integrity Metrics Sensitive to Alzheimer Disease Progression

BACKGROUND AND PURPOSE: Along with cortical abnormalities, white matter microstructural changes such as axonal loss and myelin breakdown are implicated in the pathogenesis of Alzheimer disease. Recently, a white matter model was introduced that relates non-Gaussian diffusional kurtosis imaging metrics to characteristics of white matter tract integrity, including the axonal water fraction, the intra-axonal diffusivity, and the extra-axonal axial and radial diffusivities. MATERIALS AND METHODS: This study reports these white matter tract integrity metrics in subjects with amnestic mild cognitive impairment (n = 12), Alzheimer disease (n = 14), and age-matched healthy controls (n = 15) in an effort to investigate their sensitivity, diagnostic accuracy, and associations with white matter changes through the course of Alzheimer disease. RESULTS: With tract-based spatial statistics and region-of-interest analyses, increased diffusivity in the extra-axonal space (extra-axonal axial and radial diffusivities) in several white matter tracts sensitively and accurately discriminated healthy controls from those with amnestic mild cognitive impairment (area under the receiver operating characteristic curve = 0.82–0.95), while widespread decreased axonal water fraction discriminated amnestic mild cognitive impairment from Alzheimer disease (area under the receiver operating characteristic curve = 0.84). Additionally, these white matter tract integrity metrics in the body of the corpus callosum were strongly correlated with processing speed in amnestic mild cognitive impairment (r = |0.80–0.82|, P < .001). CONCLUSIONS: These findings have implications for the course and spatial progression of white matter degeneration in Alzheimer disease, suggest the mechanisms by which these changes occur, and demonstrate the viability of these white matter tract integrity metrics as potential neuroimaging biomarkers of the earliest stages of Alzheimer disease and disease progression.

Apolipoprotein E and Gray Matter Volume Loss in Patients with Mild Cognitive Impairment and Alzheimer Disease

PURPOSE To examine the influence of apoliprotein E ε4 allele (APOE4) carrier status on disease progression by evaluating the rate of regional gray matter (GM) volume loss and disease severity in patients with newly diagnosed Alzheimer disease (AD) and stable amnestic mild cognitive impairment (MCI). MATERIALS AND METHODS This study was approved by the institutional review board and was HIPAA compliant. All subjects or their legal representatives gave informed consent for participation. Ninety-five subjects (63 male; average age, 77.1 years; age range, 58-91 years; 51 APOE4 carriers; 44 noncarriers) with either documented MCI to AD conversion or stable amnestic MCI underwent three yearly magnetic resonance imaging examinations. Voxel-based morphometry for image postprocessing and Clinical Dementia Rating (CDR) scale for cognitive assessment were used. RESULTS In APOE4 carriers, GM volume loss affected the hippocampi, temporal and parietal lobes, right caudate nucleus, and insulae in patients with MCI to AD conversion and the insular and temporal lobes in patients in whom MCI was stable. In subjects who were not APOE4 carriers, there was no significant GM volume change. There were no differences in CDR scores between APOE4 carriers and noncarriers. CONCLUSION APOE4 carriers with cognitive decline undergo faster GM atrophy than do noncarriers. The involvement of APOE4 in the progression of hippocampal atrophy, neocortical atrophy, or both has potential important implications for diagnosis and therapeutic approaches in patients with AD and should be considered in clinical trials. The present results and the results of prior studies indicate that the rate of hippocampal and neocortical atrophy is greater in association with APOE4 in nondemented elderly subjects, subjects with MCI, and those with AD.

Integral calculus problem solving : an fMRI investigation

Only a subset of adults acquires specific advanced mathematical skills, such as integral calculus. The representation of more sophisticated mathematical concepts probably evolved from basic number systems; however its neuroanatomical basis is still unknown. Using fMRI, we investigated the neural basis of integral calculus while healthy participants were engaged in an integration verification task. Solving integrals activated a left-lateralized cortical network including the horizontal intraparietal sulcus, posterior superior parietal lobe, posterior cingulate gyrus, and dorsolateral prefrontal cortex. Our results indicate that solving of more abstract and sophisticated mathematical facts, such as calculus integrals, elicits a pattern of brain activation similar to the cortical network engaged in basic numeric comparison, quantity manipulation, and arithmetic problem solving.

Thrombosed fetal dural sinus malformation diagnosed with magnetic resonance imaging.

BACKGROUND: Dural sinus malformations are rare congenital forms of dural arteriovenous shunt. Our goal is to describe prenatal ultrasonography and magnetic resonance imaging (MRI) findings of a thrombosed midline dural venous malformation. CASE: Second-trimester fetal ultrasonography and MRI demonstrated a large T2-hypointense mass centered at the level of the torcular Herophili consistent with complete thrombosis of a dural sinus malformation. A follow-up third-trimester MRI showed decreased thrombus size and no parenchymal injury. A neurologically intact newborn was delivered. CONCLUSION: Dural sinus malformations can lead to fetal intracranial thrombosis. Prenatal imaging is useful to establish the diagnosis of dural sinus malformations and to plan perinatal management and treatment options.

The frontopolar cortex mediates event knowledge complexity: a parametric functional MRI study

Event knowledge is organized on the basis of goals that enable the selection of specific event sequences to organize everyday life activities. Although the medial prefrontal cortex represents event knowledge, little is known about its role in mediating event knowledge complexity. We used functional MRI to investigate the patterns of brain activation while healthy volunteers were engaged in the task of evaluating the complexity (i.e. numbers of events) of daily life activities selected on the basis of normative data. Within a left frontoparietal network, we isolated the medial frontopolar cortex as the only region that showed a linear relationship between changes in the blood oxygen level-dependent signal and changes in event knowledge complexity. Our results specify the importance of the medial frontopolar cortex in subserving event knowledge that is required to build and execute complex behavior.