Carme Junqué

The role of prefrontal regions in the Stroop task.

The Stroop is a classical paradigm that presumably involves the inhibition of automatic responses and is frequently used to assess the frontal lobe functions. We investigated the effect of discrete prefrontal lesions in a Stroop task. A sample of 32 patients with frontal lesions were matched with normal controls by sex, age and years of education. Significant differences between patients and controls were found for errors but not for reaction time. Regression analysis showed that the region most related to errors was the right prefrontal lateral cortex. Left lobectomies did not impair the Stroop performance. Our results favour the role of the right prefrontal cortex in sustained attention, and disagree with the conception of the left prefrontal cortex having a role in the inhibition of verbal automatic responses.

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.

Impact of the COMT Val108/158 Met and DAT genotypes on prefrontal function in healthy subjects.

Two limiting factors of dopamine activity are the catechol-o-methyltransferase (COMT) and the dopamine transporter (DAT), which terminate dopamine activity by degradation and uptake, respectively. Genetic variants of COMT and DAT have been related to the enzymatic activity and protein availability, respectively. The Met allele of the COMT Val108/158 Met polymorphism has been associated to lower enzymatic activity and the 9-repeat allele of the DAT 40 base-pair (bp) variable number of tandem repeat (VNTR) polymorphism has been related to lower protein availability. Genotypes for COMT and DAT were determined in a sample of 75 healthy subjects, who underwent functional magnetic resonance imaging (fMRI) while performing an N-back task. To further assess the effects of the genotypes on cognition, subjects were administered the Wisconsin Card Sorting Test (WCST) and the Continuous Performance Test (CPT). Analysis of fMRI data revealed an additive effect of these two genes on brain activation in an N-back task, with subjects homozygous for the Val and the 9-repeat alleles showing the highest activation for the same level of performance. Moreover, the Val allele was related to higher number of perseverative errors on the WCST and with a higher number of commission errors on the CPT. The 10-repeat allele was associated with faster reaction times but also with a higher number of commission errors. Our results support a role of the COMT Val108/158 Met and the DAT 40 bp VNTR in both brain activation and cognition.

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.

Diffusion weighted imaging distinguishes the vegetative state from the minimally conscious state

The vegetative (VS) and minimally conscious (MCS) states are currently distinguished on the basis of exhibited behaviour rather than underlying pathology. Although previous histopathological studies have documented different degrees of diffuse axonal injury as well as damage to the thalami and brainstem regions in VS and MCS, these differences have not been assessed in vivo, and therefore, do not provide a measurable pathological marker to aid clinical diagnosis. Currently, the diagnostic decision-making process is highly subjective and prone to error. Indeed, previous work has suggested that up to 43% of patients in this group may be misdiagnosed. We used diffusion tensor imaging (DTI) to study the neuropathology of 25 vegetative and minimally conscious patients in vivo and to identify measures that could potentially distinguish the patients in these two groups. Mean diffusivity (MD) maps of the subcortical white matter, brainstem and thalami were generated. The MCS and VS patients differed significantly in subcortical white matter and thalamic regions, but appeared not to differ in the brainstem. Moreover, the DTI results predicted scores on the Coma Recovery Scale (p<0.001) and successfully classified the patients in to their appropriate diagnostic categories with an accuracy of 95%. The results suggest that this method may provide an objective and highly accurate method for classifying these challenging patient populations and may therefore complement the behavioural assessment to inform the diagnostic decision making process.

A Role for the Default Mode Network in the Bases of Disorders of Consciousness

Functional connectivity in the default mode network (DMN) is known to be reduced in patients with disorders of consciousness, to a different extent depending on their clinical severity. Nevertheless, the integrity of the structural architecture supporting this network and its relation with the exhibited functional disconnections are very poorly understood. We investigated the structural connectivity and white matter integrity of the DMN in patients with disorders of consciousness of varying clinical severity.

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.

Amygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging.

It has been suggested that the pathophysiology of panic disorder (PD) may involve abnormalities in several brain structures, including the amygdala. To date, however, no study has used quantitative structural neuroimaging techniques to examine amygdalar anatomy in this disorder. Volumetric magnetic resonance imaging (MRI) studies of the amygdalas, hippocampi, and temporal lobes were conducted in 12 drug-free, symptomatic PD patients (six females and six males), and 12 case-matched healthy comparison subjects. Volumetric MRI data were normalized for brain size. PD patients were found to have smaller left-sided and right-sided amygdalar volumes than controls. No differences were found in either hippocampi or temporal lobes. These findings provide new evidence of changes in amygdalar structure in PD and warrant further anatomical and MRI brain studies of patients with this disorder.

Cerebrospinal tau, phospho‐tau, and beta‐amyloid and neuropsychological functions in Parkinson's disease

Alzheimers disease (AD)‐pathology may play a role in Parkinsons disease (PD)‐related dementia (PDD). The aim of this study was to assess cerebrospinal fluid (CSF) levels of tau, phospho‐tau, and beta‐amyloid, proposed AD biomarkers, and their relationship with cognitive function in PD. Forty PD patients [20 nondemented (PDND); 20 PDD] and 30 controls underwent CSF tau, phospho‐tau, and beta‐amyloid analysis using specific ELISA techniques. All PD patients and 15 controls underwent neuropsychological testing of fronto‐subcortical (attention, fluency) and neocortical (memory, naming, visuoperceptive) functions. CSF markers levels were compared between groups, and compared and correlated with neuropsychological measures in PDND and PDD separately and as a continuum (PD). CSF tau and phospho‐tau were higher in PDD than in PDND and controls (P < 0.05). CSF beta‐amyloid ranged from high (controls) to intermediate (PDND) and low (PDD) levels (P < 0.001). In all PD and PDD patients, high CSF tau and phospho‐tau were associated with impaired memory and naming. In PDND, CSF beta‐amyloid was related with phonetic fluency. These findings suggest underlying AD‐pathology in PDD in association with cortical cognitive dysfunction, and that low CSF beta‐amyloid in PDND patients with impaired phonetic fluency can constitute an early marker of cognitive dysfunction.