Nuria Bargalló

Multiple DTI index analysis in normal aging, amnestic MCI and AD. Relationship with neuropsychological performance

White matter (WM) damage has been reported in Alzheimers Disease (AD) and Mild Cognitive Impairment (MCI) in diffusion tensor imaging (DTI) studies. It is, however, unknown how the investigation of multiple tensor indexes in the same patients, can differentiate them from normal aging or relate to patients cognition. Forty-six individuals (15 healthy, 16 a-MCI and 15 AD) were included. Voxel-based tract based spatial-statistics (TBSS) was used to obtain whole-brain maps of main WM bundles for fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA) and mean diffusivity (MD). FA reductions were evidenced among AD patients with posterior predominance. A-MCI patients displayed reduced mean FA in these critical regions, compared to healthy elders. MD increases were widespread in both groups of patients. Interestingly, a-MCI patients exhibited DR increases in overlapping areas of FA shrinkages in AD, whereas DA increases were only observed in AD. Gray matter atrophy explained most DTI differences, except those regarding MD in both groups as well as DR increases in posterior associative pathways among a-MCI cases. FA values were the only DTI measure significantly related to memory performance among patients. Present findings suggest that most DTI-derived changes in AD and a-MCI are largely secondary to gray matter atrophy. Notably however, specific DR signal increases in posterior parts of the inferior fronto-occipital and longitudinal fasciculi may reflect early WM compromise in preclinical dementia, which is independent of atrophy. Finally, global measures of integrity, particularly orientation coherence (FA) of diffusion, appear to be more closely related to the cognitive profile of our patients than indexes reflecting water movement parallel (DA) and perpendicular (DR) to the primary diffusion direction.

Sustained attention impairment correlates to gray matter decreases in first episode neuroleptic-naive schizophrenic patients

Impaired sustained attention seems to be a specific neuropsychological deficit that is closely linked to schizophrenia. Voxel based morphometry has emerged as a useful tool for the detection of subtle gray matter (GM) abnormalities. The aim of our study was to identify the cerebral regions related to the Identical-Pair version of the Continuous Performance Test (CPT-IP) performance in schizophrenic patients. The study included 13 right-handed, male, first-episode, paranoic, neuroleptic-naive schizophrenic patients and 13 matched controls. High-resolution whole-brain MR images were segmented and analyzed for the whole brain and for regions of interest (ROI) using SPM99. Furthermore, the correlation between CPT-IP performance and GM density was examined. Volumetric analysis of the thalami was also carried out. GM density analysis shown decreases in patients in anterior cingulate gyrus, left inferior frontal, right claustrum, left pulvinar, and dorsomedial bilateral thalamic nuclei, and caudate nuclei as well as left hippocampus and parahippocampal gyrus. Thalamic ROIs revealed a strong correlation between groups differences. The thalamic GM density allowed a good individual classification. GM increases were detected in left insula, superior temporal gyrus, and putamen nucleus, and right supramarginal gyrus. Schizophrenic patients showed smaller left and right thalamic volumes. We found that GM density of the left thalamic nucleus, left angular, and supramarginal gyrus, and left inferior frontal and postcentral gyri correlated significantly with CPT-IP performance in patients but not in controls. Moreover, the restricted ROIs regression was strongly significant for both left and right thalamus. In summary, we provide evidence for the involvement of thalamic, inferior-parietal, and frontal regions in the attentional deficits observed in schizophrenic patients.

Modulation of large-scale brain networks by transcranial direct current stimulation evidenced by resting-state functional MRI

BACKGROUND Brain areas interact mutually to perform particular complex brain functions such as memory or language. Furthermore, under resting-state conditions several spatial patterns have been identified that resemble functional systems involved in cognitive functions. Among these, the default-mode network (DMN), which is consistently deactivated during task periods and is related to a variety of cognitive functions, has attracted most attention. In addition, in resting-state conditions some brain areas engaged in focused attention (such as the anticorrelated network, AN) show a strong negative correlation with DMN; as task demand increases, AN activity rises, and DMN activity falls. OBJECTIVE We combined transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) to investigate these brain network dynamics. METHODS Ten healthy young volunteers underwent four blocks of resting-state fMRI (10-minutes), each of them immediately after 20 minutes of sham or active tDCS (2 mA), on two different days. On the first day the anodal electrode was placed over the left dorsolateral prefrontal cortex (DLPFC) (part of the AN) with the cathode over the contralateral supraorbital area, and on the second day, the electrode arrangement was reversed (anode right-DLPFC, cathode left-supraorbital). RESULTS After active stimulation, functional network connectivity revealed increased synchrony within the AN components and reduced synchrony in the DMN components. CONCLUSIONS Our study reveals a reconfiguration of intrinsic brain activity networks after active tDCS. These effects may help to explain earlier reports of improvements in cognitive functions after anodal-tDCS, where increasing cortical excitability may have facilitated reconfiguration of functional brain networks to address upcoming cognitive demands.

Neuroanatomical correlates of impaired decision-making and facial emotion recognition in early Parkinson’s disease

Decision‐making and recognition of emotions are often impaired in patients with Parkinson’s disease (PD). The orbitofrontal cortex (OFC) and the amygdala are critical structures subserving these functions. This study was designed to test whether there are any structural changes in these areas that might explain the impairment of decision‐making and recognition of facial emotions in early PD. We used the Iowa Gambling Task (IGT) and the Ekman 60 faces test which are sensitive to the integrity of OFC and amygdala dysfunctions in 24 early PD patients and 24 controls. High‐resolution structural magnetic resonance images (MRI) were also obtained. Group analysis using voxel‐based morphometry (VBM) showed significant and corrected (P < 0.05 FEW‐small volume correction) gray matter (GM) loss in the right amygdala and bilaterally in the OFC in PD patients. Volumetric analyses were also performed but did not yield significant differences between groups. Left lateral GM volume in OFC showed a slight correlation with the IGT, and bilateral OFC GM was strongly correlated with Ekman test performance in PD patients. We conclude that: (i) impairment in decision‐making and recognition of facial emotions occurs at the early stages of PD, (ii) these neuropsychological deficits are accompanied by degeneration of OFC and amygdala, and (iii) bilateral OFC reductions are associated with impaired recognition of emotions, and GM volume loss in left lateral OFC is related to decision‐making impairment in PD.

Assessment of cortical degeneration in patients with Parkinson's disease by voxel-based morphometry, cortical folding, and cortical thickness.

Noninvasive brain imaging methods provide useful information on cerebral involution and degenerative processes. Here we assessed cortical degeneration in 20 nondemented patients with Parkinsons disease (PD) and 20 healthy controls using three quantitative neuroanatomical approaches: voxel‐based morphometry (VBM), cortical folding (BrainVisa), and cortical thickness (FreeSurfer). We examined the relationship between global and regional gray matter (GM) volumes, sulcal indices, and thickness measures derived from the previous methods as well as their association with cognitive performance, age, severity of motor symptoms, and disease stage. VBM analyses showed GM volume reductions in the left temporal gyrus in patients compared with controls. Cortical folding measures revealed significant decreases in the left frontal and right collateral sulci in patients. Finally, analysis of cortical thickness showed widespread cortical thinning in right lateral occipital, parietal and left temporal, frontal, and premotor regions. We found that, in patients, all global anatomical measures correlated with age, while GM volume and cortical thickness significantly correlated with disease stage. In controls, a significant association was found between global GM volume and cortical folding with age. Overall these results suggest that the three different methods provide complementary and related information on neurodegenerative changes occurring in PD, however, surface‐based measures of cortical folding and especially cortical thickness seem to be more sensitive than VBM to identify regional GM changes associated to PD. Hum Brain Mapp, 2012.

Brain connectivity during resting state and subsequent working memory task predicts behavioural performance

Brain regions simultaneously activated during any cognitive process are functionally connected, forming large-scale networks. These functional networks can be examined during active conditions [i.e., task-functional magnetic resonance imaging (fMRI)] and also in passive states (resting-fMRI), where the default mode network (DMN) is the most widely investigated system. The role of the DMN remains unclear, although it is known to be responsible for the shift between resting and focused attention processing. There is also some evidence for its malleability in relation to previous experience. Here we investigated brain connectivity patterns in 16 healthy young subjects by using an n-back task with increasing levels of memory load within the fMRI context. Prior to this working memory (WM) task, participants were trained outside fMRI with a shortened test version. Immediately after, they underwent a resting-state fMRI acquisition followed by the full fMRI n-back test. We observed that the degree of intrinsic correlation within DMN and WM networks was maximal during the most demanding n-back condition (3-back). Furthermore, individuals showing a stronger negative correlation between the two networks under both conditions exhibited better behavioural performance. Interestingly, and despite the fact that we considered eight different resting-state fMRI networks previously identified in humans, only the connectivity within the posteromedial parts of the DMN (precuneus) prior to the fMRI n-back task predicted WM execution. Our results using a data-driven probabilistic approach for fMRI analysis provide the first evidence of a direct relationship between behavioural performance and the degree of negative correlation between the DMN and WM networks. They further suggest that in the context of expectancy for an imminent cognitive challenge, higher resting-state activity in the posteromedial parietal cortex may be related to increased attentional preparatory resources.

Decreased cerebral activation during CPT performance: structural and functional deficits in schizophrenic patients

Voxel-based morphometry (VBM) allows the output of structural data in a Statistical Parametric Map of the brain in the same way that the SPM can do with functional data. Using functional magnetic resonance (fMR), we studied brain activation in 14 patients with schizophrenia and 14 matched normal controls. We found significant hypoactivation in patients in several regions, especially in the right hemisphere, in the dorsolateral frontal and temporal regions and in the inferior parietal. Subcortically, we found strong hypoactivity in the thalamus. The optimized VBM method revealed gray matter (GM) abnormalities in the bilateral supramarginal gyrus and cingulate cortex, and in the right inferior temporal regions. Three regions involved in attentional processes showed both structural and functional deficits: the thalamus, the anterior cingulate and the inferior parietal. The results suggest that these regions may be involved in the attentional deficit in schizophrenia.

Cerebral atrophy in Parkinson's disease patients with visual hallucinations

Although visual hallucinations (VH) are relatively frequent in Parkinsons disease (PD) patients, their neural substrates are only known from neuropathological and functional magnetic resonance studies. The aim of this study was to investigate possible structural brain changes on MRI in non‐demented PD patients with VH using voxel‐based morphometry. Eighteen PD patients with VH were compared to 20 patients with PD without VH and 21 healthy controls. Compared with both controls and the non‐hallucinating PD group, PD patients with VH had grey matter volume reductions in the lingual gyrus and superior parietal lobe. Structural changes in these areas involved in higher visual processing may be important in understanding the VH and visual deficits in PD patients.

Decreased Regional Brain Volume and Cognitive Impairment in Preterm Children at Low Risk

OBJECTIVE: To investigate whether preterm children with low risk for neurodevelopmental deficits show long-term changes in gray matter (GM) and white matter (WM) volumes compared with term children and to relate these changes to cognitive outcome. METHODS: MRI was used to evaluate 20 preterm children who were determined to be at low risk for neurodevelopmental deficits and were born between 30 and 34 weeks’ gestational age without major neonatal morbidity or cerebral pathology in the neonatal period and 22 matched, term control subjects. Volumetric images were analyzed by means of voxel-based morphometry to identify regional cerebral alterations. Children also underwent cognitive and behavioral/emotional assessments. RESULTS: Preterm children showed global and regional GM volume reductions in several brain areas, including temporal and parietal lobes and concomitant WM volume reductions in the same areas, although only the left temporal regions achieved statistical significance. Global intellectual performance in the preterm group was significantly decreased compared with control subjects. Neither behavioral nor emotional problems were found in the preterm group. In the whole sample, we found a positive correlation between GM volume bilaterally in the middle temporal and in the postcentral gyri with IQ. Positive correlations were observed between GM and gestational age at birth in parietal and temporal cerebral regions and with WM in parietal regions. CONCLUSION: Preterm birth has an important impact on the neurodevelopmental and cognitive outcome of children at 9 years of age, being a risk factor for decreased regional cortical GM and WM even in preterm children with low risk for neurodevelopmental deficits.

Hippocampal head atrophy predominance in Parkinson's disease with hallucinations and with dementia.

We studied regional gray matter density in the hippocampus in Parkinson’s disease (PD) patients. We obtained magnetic resonance scans in 44 PD patients (PD patients with dementia (PDD) = 9, non-demented PD patients with visual hallucinations (PD + VH) = 16, and PD patients without dementia and without visual hallucinations (PD - VH) = 19) and 56 controls matched for age and years of education. A region of interest (ROI) of the hippocampus following voxel-based morphometry (VBM) procedures was used to perform group comparisons, single-case individual analysis and correlations with learning scores. Group comparisons showed that PDD patients and PD+VH patients had significant hippocampal gray matter loss compared to controls. In PDD patients, hippocampal gray matter loss involved the entire hippocampus and in PD+VH this reduction was mainly confined to the hippocampal head. 78 % of PDD patients, 31 % of PD+VH patients and 26 % of PD-VH patients had hippocampal head gray matter loss when compared to controls. These results suggest that in PD the neurodegenerative process in the hippocampus starts in the head of this structure and later spreads to the tail and that, in addition, memory impairment assessed by Rey’s Auditory Verbal Learning Test (RAVLT) correlates with hippocampal head gray matter loss.