Margherita Di Paola

In vivo structural neuroanatomy of corpus callosum in Alzheimer's disease and mild cognitive impairment using different MRI techniques: a review.

The corpus callosum (CC), which connects the two cerebral hemispheres, is the largest white matter fiber bundle in the human brain. This structure presents a peculiar myelination pattern: it has small diameter fibers, located in the genu, which myelinate much later in normal development, and large diameter fibers of the splenium, which myelinate early in development. Although the pathology of AD mainly involves the cerebral gray matter structure, there is evidence that white matter may also be involved. To illustrate callosal white matter changes in AD pathology, in this review we summarize in vivo imaging studies in humans, focusing on region of interest, voxel-based morphometry, diffusion-weighted imaging, and diffusion tensor imaging techniques. Our aims were to identify where in the CC, when in the different stages of AD, and how callosal changes can be detected with different MRI techniques. Results showed that changes in the anterior (genu and anterior body) as well as in the posterior (isthmus and splenum) portions of the CC might already be present in the early stages of AD. These findings support the hypothesis that two mechanisms, Wallerian degeneration and myelin breakdown, might be responsible for the region-specific changes detected in AD patients. Wallerian degeneration affects the posterior CC subregion, which receives axons directly from those brain areas (temporo-parietal lobe regions) primarily affected by the AD pathology. Instead, the myelin breakdown process affects the later-myelinating CC subregion and explains the earlier involvement of the genu in CC atrophy.

Prefrontal–thalamic–cerebellar gray matter networks and executive functioning in schizophrenia

OBJECTIVE Poor executive functioning is a core deficit in schizophrenia and has been linked to frontal lobe alterations. We aimed to identify (1) prefrontal cerebral areas in which decreased volume is linked to executive dysfunction in schizophrenia; and (2) areas throughout the brain that are volumetrically related to the prefrontal area identified in the first analysis, thus detecting more extended volumetric networks associated with executive functioning. METHOD Fifty-three outpatients with schizophrenia and 62 healthy controls, matched for age, gender and handedness, were recruited. High-resolution images were acquired on a 1.5 tesla scanner and regional gray and white matter volumes were analyzed by voxel-based morphometry within SPM5 (statistical parametric mapping, University College London, UK). Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST). RESULTS Twenty-one patients with poor executive functioning showed reduced dorsolateral prefrontal and anterior cingulate gray matter volume as compared to 30 patients with high WCST performance, with a maximum effect in the left dorsolateral prefrontal cortex. Left dorsolateral prefrontal gray matter volume predicted WCST performance after controlling for possible confounding effects of global cognitive functioning, verbal attention span, negative symptoms, illness duration and education. In this area, both patient groups had less gray matter than healthy controls. Left dorsolateral prefrontal gray matter volume was positively related to dorsal prefrontal, anterior cingulate and parietal gray matter volume; and negatively related to thalamic, cerebellar, pontine and right parahippocampal gray matter volume. CONCLUSIONS Volumetric alterations in prefrontal-thalamic-cerebellar gray matter networks may lead to executive dysfunction in schizophrenia.

Combined volumetry and DTI in subcortical structures of mild cognitive impairment and Alzheimer's disease patients.

The aim of this work was to investigate the hypothesis that multimodal MRI is able to detect the progressive disruption of volume and microstructure of subcortical structures in patients with amnestic mild cognitive impairment (a-MCI) and mild Alzheimers disease (AD) in comparison with healthy controls (CTRL). We combined volumetric and diffusion tensor imaging (DTI) techniques in a cross-sectional study including 30 a-MCI, 30 AD patients, and 30 age-matched CTRL. We employed a fully automated model-based segmentation algorithm on 3 Tesla MRI anatomical images and accurate coregistration of DTI to anatomical images to extract regional values of DTI parameters. Both the hippocampi significantly and progressively decreased in volume from CTRL through MCI to AD. Both the thalami showed a progressive and significant decrease in volume from CTRL to AD. Mean diffusivity (MD) values increased progressively across the three groups in the bilateral hippocampus, amygdala, and in the right caudate. No differences in fractional anisotropy (FA) values were found. Two distinct but overlapping patterns of progression of structural (i.e., atrophy) and microstructural (i.e., MD increase) damage were observed. Particularly, the pattern of atrophy was mirrored by the increasing value of the averaged MD, which provided a further indicator of subtle tissue disruption in the hippocampal structure in mild AD patients. Combining different MRI modalities can allow identifying sensitive indicators of the subtle pathogenic mechanisms that occur in subcortical areas of AD patients.

Callosal atrophy in mild cognitive impairment and Alzheimer's disease: different effects in different stages

Alzheimers Disease (AD) is a neurodegenerative disorder that mainly affects grey matter (GM). Nevertheless, a number of investigations have documented white matter (WM) pathology associated with AD. The corpus callosum (CC) is the largest WM fiber bundle in the human brain. It has been shown to be susceptible to atrophy in AD mainly as a correlate of Wallerian degeneration of commissural nerve fibers of the neocortex. The aim of this study was to investigate which callosal regions are affected and whether callosal degeneration is associated with the stage of the disease. For this purpose, we analyzed high-resolution MRI data of patients with amnesic mild cognitive impairment (MCI) (n=20), mild AD (n=20), severe AD (n=10), and of healthy controls (n=20). Callosal morphology was investigated applying two different structural techniques: mesh-based geometrical modeling methods and whole-brain voxel-based analyses. Our findings indicate significant reductions in severe AD patients compared to healthy controls in anterior (genu and anterior body) and posterior (splenium) sections. In contrast, differences between healthy controls and mild AD patients or amnesic MCI patients were less pronounced and did not survive corrections for multiple comparisons. When correlating anterior and posterior WM density of the CC with GM density of the cortex in the severe AD group, we detected significant positive relationships between posterior sections of the CC and the cortex. We conclude that callosal atrophy is present predominantly in the latest stage of AD, where two mechanisms might contribute to WM alterations in severe AD: the Wallerian degeneration in posterior subregions and the myelin breakdown process in anterior subregions.

Differential involvement of the left frontal and temporal regions in verb naming: A tDCS treatment study

PURPOSE In aphasic patients, some studies have already emphasized the efficacy of transcranial direct current stimulation (tDCS) during the treatment of noun retrieval deficits. To date, in the same population, there are have been no studies addressing tDCS effects in the recovery of verb retrieval deficits. In this study, we wanted to test the potential of tDCS to improve verb production in a group of aphasic patients. METHODS Seven chronic subjects participated in an intensive language training for their difficulties in action naming. Each subject was treated with tDCS (20 min., 1 mA) over the left hemisphere in three different conditions: anodic tDCS over Wernickes area, anodic tDCS and sham stimulation over Brocas area. Each experimental condition was performed in five consecutive daily sessions over three weeks with 6 days of intersession interval. RESULTS In all patients, results showed a significantly better response accuracy during the anodic tDCS over Brocas area with respect to the other two conditions which still persisted at one month after the end of the treatment suggesting a long-term effect on the recovery of their verb retrieval deficits. CONCLUSION These findings further confirm that tDCS represents a useful new therapeutic interventions for the rehabilitation of lexical deficits in aphasic patients.

White Matter Microstructure and Apathy Level in Amnestic Mild Cognitive Impairment

In this study, we assess white matter microstructural deficit correlates of apathy level in 20 patients with amnestic mild cognitive impairment by means of diffusion tensor imaging. Mean diffusivity correlated positively with apathy level in the right temporal portion of the uncinate, middle longitudinal and inferior longitudinal fasciculi and in the parathalamic white matter, the fornix and the posterior cingulum of the right hemisphere. Fractional anisotropy results confirmed evidence of disconnection associated with apathy in all white matter areas except the middle longitudinal fasciculus. These results support the view that alterations in the neural mechanisms underlying apathy level occur in the early phase of degenerative dementias.

The role of semantic distance in category-specific impairments for living things: Evidence from a case of semantic dementia ☆

In this paper, we describe a patient (LI) suffering from semantic dementia who showed a category-specific naming impairment for living things over and above the effects of several nonsemantic confounding variables. We investigated the characteristics of LIs impairment to address the following three issues raised in three different accounts of category-specific impairments: (i) the role of an imbalance in the loss of sensory compared to nonsensory features (assumed by the Sensory Functional Theory [Warrington, E. K., & Shallice, T. (1984). Category-specific semantic impairments. Brain, 107, 829-859]); (ii) the role of cross domain differences in Feature Correlation (assumed by the Conceptual Structure Account [Moss, H., Tyler, L. K., & Devlin, J. T. (2002). The emergence of category-specific deficits in a distributed semantic system. In: E. M. E. Forde & G. W. Humphreys (Eds.), Category Specificity in Brain and Mind (pp. 115-147). New York: Psychology Press]); (iii) the role of semantic distance (proposed by Cree and McRae [Cree, G. S., & McRae, K. (2003). Analyzing the factors underlying the structure and computation of the meaning of chipmunk, cherry, chisel, cheese, and cello (and many other such concrete nouns). Journal of Experimental Psychology: General, 132, 163-201]). We found that semantic distance was the only factor causally linked to LIs poorer performance on living things. In fact, her naming performance was less accurate on items that had many semantic neighbours, which is typical of living things. On the contrary, a feature listing task revealed that the features available to LI were not predicted by their level of correlation, as expected by the Conceptual Structure Account. Finally, at variance with the Sensory Functional Theory, although LI quoted sensory features less accurately than nonsensory ones, this did not give rise to a disproportionate loss of semantic features in the living domain.

Prolonged rock climbing activity induces structural changes in cerebellum and parietal lobe

This article analyzes whether climbing, a motor activity featured by upward movements by using both feet and hands, generation of new strategies of motor control, maintenance of not stable equilibrium and adoption of long‐lasting quadrupedal posture, is able to modify specific brain areas. MRI data of 10 word‐class mountain climbers (MC) and 10 age‐matched controls, with no climbing experience were acquired. Combining region‐of‐interest analyses and voxel‐based morphometry we investigated cerebellar volumes and correlation between cerebellum and whole cerebral gray matter. In comparison to controls, world‐class MC showed significantly larger vermian lobules I‐V volumes, with no significant difference in other cerebellar vermian lobules or hemispheres. The cerebellar enlargement was associated with an enlargement of right medial posterior parietal area. The specific features of the motor climbing skills perfectly fit with the plastic anatomical changes we found. The enlargement of the vermian lobules I–V seems to be related to highly dexterous hand movements and to eye‐hand coordination in the detection of and correction of visuomotor errors. The concomitant enlargement of the parietal area is related to parallel work in predicting sensory consequences of action to make movement corrections. Motor control and sensory‐motor prediction of actions make the difference between survive or not at extreme altitude. Hum Brain Mapp 34:2707–2714, 2013.

Bihemispheric stimulation over left and right inferior frontal region enhances recovery from apraxia of speech in chronic aphasia

Several studies have already shown that transcranial direct current stimulation (tDCS) is a useful tool for enhancing recovery in aphasia. However, all tDCS studies have previously investigated the effects using unihemisperic stimulation. No reports to date have examined the role of bihemispheric tDCS on aphasia recovery. Here, eight aphasic persons with apraxia of speech underwent intensive language therapy in two different conditions: real bihemispheric anodic ipsilesional stimulation over the left Brocas area and cathodic contralesional stimulation over the right homologue of Brocas area, and a sham condition. In both conditions, patients underwent concurrent language therapy for their apraxia of speech. The language treatment lasted 10 days (Monday to Friday, then weekend off, then Monday to Friday). There was a 14‐day intersession interval between the real and the sham conditions. In all patients, language measures were collected before (T0), at the end of (T10) and 1 week after the end of (F/U) treatment. Results showed that after simultaneous excitatory stimulation to the left frontal hemisphere and inhibitory stimulation to the right frontal hemisphere regions, patients exhibited a significant recovery not only in terms of better accuracy and speed in articulating the treated stimuli but also in other language tasks (picture description, noun and verb naming, word repetition, word reading) which persisted in the follow‐up session. Taken together, these data suggest that bihemispheric anodic ipsilesional and cathodic contralesional stimulation in chronic aphasia patients may affect the treated function, resulting in a positive influence on different language tasks.

Tractography of the Corpus Callosum in Huntington’s Disease

White matter abnormalities have been shown in presymptomatic and symptomatic Huntington’s disease (HD) subjects using Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) methods. The largest white matter tract, the corpus callosum (CC), has been shown to be particularly vulnerable; however, little work has been done to investigate the regional specificity of tract abnormalities in the CC. Thus, this study examined the major callosal tracts by applying DTI-based tractography. Using TrackVis, a previously defined region of interest tractography method parcellating CC into seven major tracts based on target region was applied to 30 direction DTI data collected from 100 subjects: presymptomatic HD (Pre-HD) subjects (n = 25), HD patients (n = 25) and healthy control subjects (n = 50). Tractography results showed decreased fractional anisotropy (FA) and increased radial diffusivity (RD) across broad regions of the CC in Pre-HD subjects. Similar though more severe deficits were seen in HD patients. In Pre-HD and HD, callosal FA and RD were correlated with Disease Burden/CAG repeat length as well as motor (UHDRSI) and cognitive (URDRS2) assessments. These results add evidence that CC pathways are compromised prior to disease onset with possible demyelination occurring early in the disease and suggest that CAG repeat length is a contributing factor to connectivity deficits. Furthermore, disruption of these callosal pathways potentially contributes to the disturbances of motor and cognitive processing that characterize HD.