Cortical thinning associated with mild cognitive impairment in Parkinson's disease.

The aim of this study was to investigate patterns of cortical atrophy associated with mild cognitive impairment in a large sample of nondemented Parkinson's disease (PD) patients, and its relation with specific neuropsychological deficits. Magnetic resonance imaging (MRI) and neuropsychological assessment were performed in a sample of 90 nondemented PD patients and 32 healthy controls. All underwent a neuropsychological battery including tests that assess different cognitive domains: attention and working memory, executive functions, memory, language, and visuoperceptual-visuospatial functions. Patients were classified according to their cognitive status as PD patients without mild cognitive impairment (MCI; n = 43) and PD patients with MCI (n = 47). Freesurfer software was used to obtain maps of cortical thickness for group comparisons and correlation with neuropsychological performance. Patients with MCI showed regional cortical thinning in parietotemporal regions, increased global atrophy (global cortical thinning, total gray matter volume reduction, and ventricular enlargement), as well as significant cognitive impairment in memory, executive, and visuospatial and visuoperceptual domains. Correlation analyses showed that all neuropsychological tests were associated with cortical thinning in parietotemporal regions and to a lesser extent in frontal regions. These results provide neuroanatomic support to the concept of MCI classified according to Movement Disorders Society criteria. The posterior pattern of atrophy in temporoparietal regions could be a structural neuroimaging marker of cognitive impairment in nondemented PD patients. All of the neuropsychological tests reflected regional brain atrophy, but no specific patterns were seen corresponding to impairment in distinct cognitive domains.

Progressive changes in a recognition memory network in Parkinson's disease.

BACKGROUND: In a previous functional MRI (fMRI) study, we found that patients with Parkinson's disease (PD) presented with dysfunctions in the recruitment of recognition memory networks. We aimed to investigate the changes in these networks over time. METHODS: We studied 17 PD patients and 13 age and sex matched healthy subjects. In both groups fMRI (recognition memory paradigm) and neuropsychological assessments were obtained at baseline and at follow-up. To analyse changes over time in functional networks, model free (independent component analysis) analyses of the fMRI data were carried out. Then, a cross correlation approach was used to assess the changes in the strength of functional connectivity. RESULTS: At follow-up, patients showed reduced recruitment of one network, including decreased activation in the orbitofrontal cortices, middle frontal gyri, frontal poles, anterior paracingulate cortex, superior parietal lobes and left middle temporal gyrus, as well as decreased deactivation in the anterior paracingulate gyrus and precuneus. Cross correlation analyses over time showed a decrease in the strength of functional connectivity between the middle frontal gyrus and the superior parietal lobe in PD patients. CONCLUSIONS: Model free fMRI and cross correlation connectivity analyses were able to detect progressive changes in functional networks involved in recognition memory in PD patients at early disease stages and without overt clinical deterioration. Functional connectivity analyses could be useful to monitor changes in brain networks underlying neuropsychological deficits in PD.

Does verbal and gestural expression ability predict comprehension ability in cerebral palsy?

Some people with cerebral palsy have motor and associated impairments that may hinder verbal and gestural expression to various extents. This study explores whether the ability to produce verbal or gestural expressions may be related to the comprehension of verbal communications and gestures. The influence of severity of motor impairment, general cognitive performance, and age on comprehension ability was also explored. Forty people with cerebral palsy were assigned to different groups according to their verbal and gestural expression abilities. A neuropsychological assessment of comprehension abilities and general cognitive performance was carried out. Multiple linear regression analysis was applied to identify the possible influence of expression abilities on comprehension abilities and also to detect the possible contribution of severity of motor impairment, general cognitive performance, and age. Results indicate that verbal and gestural comprehension was mainly predicted by general cognitive performance. Severity of motor impairment and age did not contribute to predicting comprehension abilities. Only verbal grammar comprehension was significantly predicted by verbal expression ability. Verbal expression ability may be an important marker for cerebral palsy therapies. In non-ambulant patients with bilateral cerebral palsy, impaired gestural expression should not be taken as an indicator of impaired gestural comprehension.

Dysfunctions of cerebral networks precede recognition memory deficits in early Parkinson's disease.

We aimed to investigate changes in the verbal recognition memory network in patients with early Parkinson's disease (PD) without overt recognition memory alteration. Verbal recognition memory was assessed in 24 PD patients in early stages of the disease and a control group of 24 healthy subjects during fMRI data acquisition. Participants were presented with a list of 35 words before imaging, and later during fMRI scanning they were required to recognize these previously presented words. Both model-based (FEAT) and model-free (MELODIC) analyses of the fMRI data were carried out with FSL software. Memory was also assessed by means of Rey's Auditory Verbal Learning Test (RAVLT). PD patients showed no difference in the fMRI recognition memory task and recognition memory assessed by the RAVLT compared to healthy controls. Model-based analysis did not show significant differences between groups. On the other hand, model-free analysis identified components that fitted the task-model and were common to all the participants, as well as components that differed between PD and healthy controls. PD patients showed decreased task-related activations in areas involved in the recognition memory network and decreased task-related deactivations in the default mode network in comparison with controls. In conclusion, model-free fMRI analysis detected alterations in functional cerebral networks involved in a verbal memory task in PD patients without evident recognition memory deficit.

Diffusion tensor imaging differences relate to memory deficits in diffuse traumatic brain injury.

BACKGROUND: Memory is one of the most impaired functions after traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to determine the structural basis of memory deficit. We correlated fractional anisotropy (FA) of the fasciculi connecting the main cerebral regions that are involved in declarative and working memory functions. METHODS: Fifteen patients with severe and diffuse TBI and sixteen healthy controls matched by age and years of education were scanned. The neuropsychological assessment included: Letter-number sequencing test (LNS), 2-back task, digit span (forwards and backwards) and the Rivermead profilet. DTI was analyzed by a tract-based spatial statics (TBSS) approach. RESULTS: Whole brain DTI analysis showed a global decrease in FA values that correlated with the 2-back d-prime index, but not with the Rivermead profile. ROI analysis revealed positive correlations between working memory performance assessed by 2-back d-prime and superior longitudinal fasciculi, corpus callosum, arcuate fasciculi and fornix. Declarative memory assessed by the Rivermead profile scores correlated with the fornix and the corpus callosum. CONCLUSIONS: Diffuse TBI is associated with a general decrease of white matter integrity. Nevertheless deficits in specific memory domains are related to different patterns of white matter damage.

Olfactory impairment in Parkinson's disease and white matter abnormalities in central olfactory areas: A voxel-based diffusion tensor imaging study.

Olfactory dysfunction is known to occur before the appearance of the classical motor signs in Parkinson's disease (PD) and diffusion tensor imaging (DTI) studies in PD have reported fractional anisotropy (FA) reductions in the early disease stages. We aimed to investigate the relationship between olfactory dysfunction and white matter (WM) FA of central olfactory areas in early PD. Twenty-four patients at Hoehn and Yahr stages I and II and 24 healthy controls matched by age, gender and years of education participated in this study. DTI was acquired at a 3 Tesla scanner and odor identification was assessed using the University of Pennsylvania Smell Identification Test (UPSIT). We performed FA voxelwise group comparisons in the central olfactory structures using tract-based spatial statistics (TBSS) and correlation analyses between FA values in these central olfactory areas and UPSIT scores. Patients with severe microsmia (UPSIT between 19 and 25) and anosmia (UPSIT lower or equal to 18) had lower FA values than PD patients with mild/moderate or no olfactory dysfunction (UPSIT between 26 and 40) and healthy controls in the WM adjacent to gyrus rectus. In addition, patients with anosmia had reduced FA in the WM surrounding primary olfactory areas in comparison with healthy controls. FA values in the WM adjacent to primary olfactory cortex and right gyrus rectus correlated with UPSIT scores in the PD group. This study demonstrates, for the first time, that microstructural WM reductions are present in the central olfactory system of early stage PD patients and that these reductions are associated with reduced ability to smell.

Hippocampal underactivation in an fMRI study of word and face memory recognition in schizophrenia.

Schizophrenia is a major mental disorder which is characterized by several cognitive deficits. Investigations of the neural basis of memory dysfunctions using neuroimaging techniques suggest that the hippocampus plays an important role in declarative memory impairment. The goal of this study was to investigate possible dysfunctions in cerebral activation in schizophrenic patients during both word and face recognition memory tasks. We tested 22 schizophrenics and 24 controls matched by gender, age, handedness and parental socioeconomic status. Compared to healthy volunteers, patients with schizophrenia showed decreased bilateral hippocampal activation during word and face recognition tasks. The whole brain analysis also showed a pattern of cortical and subcortical hypoactivation for both verbal and non-verbal recognition. This study provides further evidence of hippocampal involvement in declarative memory impairments of schizophrenia.

Neuropsychologic impairment in bilateral cerebral palsy.

The lower-than-average cognitive performance of individuals with bilateral cerebral palsy found in previous studies does not always refer to an abnormal performance or clinically significant impairment. We aimed to establish the percentage of persons with bilateral cerebral palsy who present neuropsychologic impairment, and its relationship to perinatal data and motor signs. Forty children, adolescents, and adults (age range, 6-38 years; 15 females and 25 males) with bilateral cerebral palsy were neuropsychologically assessed. Vocabulary was impaired in 85% of participants, language comprehension in 13-48%, visuoperceptual abilities in 60%, visuospatial abilities in 90%, short-term memory in 21-58%, declarative memory in 47-67%, and praxis comprehension in 20%, with executive deficits in 58-74%. Perinatal data (intrauterine growth and birth weight) contributed to explaining memory impairment. Among cerebral palsy subtypes (spastic, mixed, and dyskinetic), forms of impairment differed only in short-term verbal memory. No persons with dyskinetic cerebral palsy experienced impairment in immediate memory or working visual memory. We conclude that visuospatial deficit is the most frequent impairment in people with bilateral cerebral palsy. Moreover, short-term memory impairment seems sensitive to perinatal complications, and differs among bilateral cerebral palsy subtypes.

A longitudinal fMRI study of working memory in severe TBI patients with diffuse axonal injury.

Traumatic brain injury (TBI) patients have working memory deficits and altered patterns of brain activation during this function. The evolution of the impairment has not been examined to date. This study investigated longitudinal changes in brain activation during a working memory task. Twelve patients with severe and diffuse TBI and ten healthy matched controls were fMRI scanned twice at a 6-month interval during an n-back task (0-, 2- and 3-back). All the TBI patients selected presented signs of diffuse axonal injury on CT but had no evidence of focal lesions on MRI clinical examination. Significant changes in brain activation over time were observed in patients, but not in controls. During the first examination, though both groups engaged bilateral fronto-parietal regions known to be involved in working memory, activation of the right superior frontal gyrus was low in the TBI group. However, the difference between TBI and controls had decreased significantly after 6 months. A factor analysis confirmed the greater increase in activation in the right superior frontal cortex in the TBI group than in healthy controls, leading to normalization of the brain activation pattern. In conclusion, this longitudinal study provides evidence of a progressive normalization of the working memory activation pattern after diffuse axonal injury in severe TBI, coinciding with an improvement in performance on this function.

Cerebral response to speech in vegetative and minimally conscious states after traumatic brain injury.

PRIMARY OBJECTIVE: To study cerebral response in a functional magnetic resonance imaging (fMRI) task of speech perception in a sample of patients in vegetative state (VS) and minimally conscious state (MCS) after traumatic brain injury. METHODS: Three patients in VS, four patients in MCS and 19 healthy volunteers were enrolled for the study. All subjects underwent an fMRI task of passive listening of narratives played forward and backward, alternated with periods of silence. This study analysed cerebral response to language and to complex sound processing in the healthy subjects' group and in each patient, using SPM5. RESULTS: One patient in VS and one in MCS showed cerebral responses to language and to complex sound very similar to those shown by the healthy volunteers. Two more patients, one in VS and one in MCS, showed significant responses to complex sound only. Finally, one patient in VS and one patient in MCS failed to show significant activation in response to either stimulus. CONCLUSIONS: Some patients in VS and MCS can preserve cerebral responses to language and auditory stimuli. fMRI may be useful to identify these responses, which may pass unnoticed in a bedside examination.

Corpus callosum size and neuropsychologic impairment in adolescents who were born preterm.

Prematurity is associated with cerebral abnormalities that might account for poorer cognitive performance. The aim of our study was to investigate the correlations between corpus callosum reductions and neuropsychologic performance in adolescents who were born preterm. Twenty-five subjects born before 33 weeks' gestation were compared with 25 subjects born at term and of similar age, gender, and sociocultural status. All subjects underwent magnetic resonance imaging and neuropsychologic examinations. Premature subjects performed worse than controls in global cognitive functioning, verbal memory, and verbal fluency. Corpus callosum measurements showed a global reduction owing mainly to thinning in the splenium, posterior midbody, and genu. Corpus callosum size significantly correlated with gestational age, Wechsler Performance IQ, and memory performance. These results suggest that cerebral growth during infancy does not compensate for corpus callosum reduction and that this reduction reflects neuropsychologic deficit. The cognitive impairment can arise from the paucity of the complex interneuronal connections owing to fiber damage, particularly myelinated fibers.

Functional networks and structural connectivity of visuospatial and visuoperceptual working memory.

Neural correlates of working memory (WM) in healthy subjects have been extensively investigated using functional MRI (fMRI). However it still remains unclear how cortical areas forming part of functional WM networks are also connected by white matter fiber bundles, and whether DTI measures, used as indices of microstructural properties and directionality of these connections, can predict individual differences in task performance. fMRI data were obtained from 23 healthy young subjects while performing one visuospatial (square location) and one visuoperceptual (face identification) 2-back task. Diffusion tensor imaging (DTI) data were also acquired. We used independent component analysis (ICA) of fMRI data to identify the main functional networks involved in WM tasks. Voxel-wise DTI analyses were performed to find correlations between structural white matter and task performance measures, and probabilistic tracking of DTI data was used to identify the white matter bundles connecting the nodes of the functional networks. We found that functional recruitment of the fusiform and the inferior frontal cortex was specific for the visuoperceptual working memory task, while there was a high overlap in brain activity maps in parietal and middle frontal areas for both tasks. Axial diffusivity and fractional anisotropy, of the tracts connecting the fusiform with the inferior frontal areas correlated with processing speed in the visuoperceptual working memory task. Although our findings need to be considered as exploratory, we conclude that both tasks share a highly-overlapping pattern of activity in areas of frontal and parietal lobes with the only differences in activation between tasks located in the fusiform and inferior frontal regions for the visuoperceptual task. Moreover, we have found that the DTI measures are predictive of the processing speed.

Postsurgical cerebral perfusion changes in idiopathic normal pressure hydrocephalus: a statistical parametric mapping study of SPECT images.

UNLABELLED: Our goal was to study cerebral blood flow (CBF) changes after surgery in a group of 15 patients with idiopathic normal pressure hydrocephalus (NPH). METHODS: We used hexamethylpropyleneamine oxime SPECT and statistical parametric mapping (SPM), an image analysis method that does not require prior selection of regions of interest. RESULTS: Our study showed areas of significant increase in perfusion in specific regions of both frontal lobes and the right parietal lobe. Regions of increased perfusion were found in the left prefrontal dorsolateral areas (Brodmann's areas 9 and 45 or 47), right frontal premotor area (Brodmann's area 44), right medial prefrontal region (Brodmann's area 10 or 32), right frontal white matter area (superior longitudinalis fasciculus), and right basal ganglia (lenticular nucleus, putamen, and globus pallidus). In the right hemisphere, another region of increased perfusion was found in the inferior parietal lobule (Brodmann's area 40). The 2 areas most related to clinical improvement were Brodmann's area 32 and the frontal part of the left lobule of Reil insula. CONCLUSION: The results obtained with the SPM method of image analysis confirm and expand on previous CBF literature in NPH, with specific CBF regions located in frontal and parietal areas that improve after surgery in idiopathic NPH.

Medial temporal MR spectroscopy is related to memory performance in normal adolescent subjects.

In addition to the study of pathological conditions, magnetic resonance spectroscopy can provide useful information about brain-behavior relationships in normal subjects. Recently, there have been reports of correlations between N-acetylaspartate (NAA) values and cognitive functions in normal adults. We tested the possible specific relationship between the NAA/choline (Cho) ratio in the medial temporal lobe and memory performance in normal adolescents. The medial temporal NAA/Cho ratio was unrelated to age, gender and general intelligence but presented a clear correlation with several memory measures. In the regression analysis two memory variables (RAVLT learning and a face-name recognition task) explained 55.6% of NAA/Cho variance. We conclude that NAA values in the medial temporal lobe are related to memory abilities but not to global intelligence in normal adolescent subjects.

Basal ganglia N-acetylaspartate correlates with the performance in the procedural task 'Tower of Hanoi' of neuroleptic-naive schizophrenic patients.

We tested the hypothesis that basal ganglia dysfunction may be related to procedural learning impairment in schizophrenia. We determined the N-acetylaspartate/choline (NAA/Cho) ratio in the left striatal area in 11 young first-episode antipsychotic-naive patients and matched controls. Procedural learning was assessed by the four-disk version of the Tower of Hanoi. Analysis of variance showed that the number of moves and the execution time had a significant group effect (P=0.02, P<0.0001, respectively). Correlation analysis between procedural learning and the NAA/Cho ratio showed a negative significant correlation only in patients, measured by both time (P=0.006) and by moves (P=0.001). In summary, we found that schizophrenic patients have impaired procedural learning, and that this impairment is related to basal ganglia metabolism.

Neuropsychologic differences between bilateral dyskinetic and spastic cerebral palsy.

This study compared the neuropsychologic performance of 30 adolescents and adults with bilateral dyskinetic, mixed, and spastic cerebral palsy aged between 16 and 38 years. The sample was relatively homogeneous in terms of motor severity; no patients were able to walk unaided. In all subjects, we evaluated the general function of nonverbal reasoning and the following specific neuropsychologic areas: language, visual perception, memory, praxis, and frontal functions. Individuals with dyskinetic cerebral palsy had better auditory comprehension, visuospatial abilities, immediate visual memory, and working verbal memory than those with spastic cerebral palsy. Frontal function was the only cognitive function on which subjects with dyskinetic cerebral palsy had lower scores. We conclude that the neuropsychologic profiles of dyskinetic and spastic cerebral palsy are different.

Long-term declarative memory deficits in diffuse TBI: correlations with cortical thickness, white matter integrity and hippocampal volume.

We investigated structural brain damage in subjects who had suffered severe and diffuse traumatic brain injury (TBI), and examined its relationship with declarative memory impairment. Cortical thickness, diffusion tensor imaging (DTI), and volumetric and shape data of the hippocampus were assessed in a group of 26 adults with severe TBI in the chronic stage and 22 healthy matched controls. Declarative memory was evaluated by Rey's Auditory Verbal Learning Test (RAVLT). TBI patients performed significantly worse than controls on all RAVLT measures. The group comparison for cortical thickness and DTI revealed a pattern of widespread atrophy in TBI patients. In the TBI group DTI measures correlated with cortical thickness in the prefrontal and parietal regions, including the precuneus. Declarative memory correlated with both cortical thickness and DTI measures. However, although hippocampal volume was significantly decreased in TBI patients, no correlations were found. Multiple regression analysis of all the structural measures revealed that decreases in Fractional anisotropy (FA) and thinning of the left parietal region were the best predictors of memory impairment. In conclusion, cortical thickness reductions in the left hemisphere and a lack of white matter integrity are the main contributors to long-term impairment in declarative memory among patients suffering from severe and diffuse TBI. In this study the hippocampus did not make a significant contribution to memory dysfunctions, suggesting that damage to this structure is compensated for by other regions, with the definitive sequelae being mainly explained by alterations in cortico-subcortical connectivity.

Neuroanatomical correlates of olfactory loss in normal aged subjects.

In non-demented older persons, smell dysfunction, measured premortem, has been associated with postmortem brain degeneration similar to that of Alzheimer's disease. We hypothesized that distinct measures of gray and white matter integrity evaluated through magnetic resonance imaging (MRI) techniques could detect degenerative changes associated with age-related olfactory dysfunction. High-resolution T1-weighted images and diffusion-tensor images (DTI) of 30 clinically healthy subjects aged 51-77 were acquired with a 3-Tesla MRI scanner. Odor identification performance was assessed by means of the University of Pennsylvania Smell Identification Test (UPSIT). UPSIT scores correlated with right amygdalar volume and bilateral perirhinal and entorhinal cortices gray matter volume. Olfactory performance also correlated with postcentral gyrus cortical thickness and with fractional anisotropy and mean diffusivity levels in the splenium of the corpus callosum and the superior longitudinal fasciculi. Our results suggest that age-related olfactory loss is accompanied by diffuse degenerative changes that might correspond to the preclinical stages of neurodegenerative processes.

White matter/gray matter contrast changes in chronic and diffuse traumatic brain injury.

Signal-intensity contrast of T1-weighted magnetic resonance imaging scans has been associated with tissue integrity and reported as a sign of neurodegenerative changes in diseases such as Alzheimer's disease. After severe traumatic brain injury (TBI), progressive structural changes occur in white (WM) and gray matter (GM). In the current study, we assessed the signal-intensity contrast of GM and WM in patients with diffuse TBI in the chronic stage to (1) characterize the regional pattern of WM/GM changes in intensity contrast associated with traumatic axonal injury, (2) evaluate possible associations between this measure and diffusion tensor image (DTI)/fractional anisotropy (FA) for detecting WM damage, and (3) investigate the correlates of both measures with cognitive outcomes. Structural T1 scans were processed with FreeSurfer software to identify the boundary and calculate the WM/GM contrast maps. DTIs were processed with the FMRIB software library to obtain FA maps. The WM/GM contrast in TBI patients showed a pattern of reduction in almost all of the brain, except the visual and motor primary regions. Global FA values obtained from DTI correlated with the intensity contrast of all associative cerebral regions. WM/GM contrast correlated with memory functions, whereas FA global values correlated with tests measuring memory and mental processing speed. In conclusion, tissue-contrast intensity is a very sensitive measure for detecting structural brain damage in chronic, severe and diffuse TBI, but is less sensitive than FA for reflecting neuropsychological sequelae, such as impaired mental processing speed.

Resting-state functional magnetic resonance imaging activity and connectivity and cognitive outcome in traumatic brain injury.

IMPORTANCE: The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of the brain substrates of cognitive outcome after traumatic axonal injury. This knowledge may contribute to improve clinical management and rehabilitation programs. OBJECTIVE: To study functional magnetic resonance imaging abnormalities in signal amplitude and brain connectivity at rest and their relationship to cognitive outcome in patients with chronic and severe traumatic axonal injury. DESIGN: Observational study. SETTING: University of Barcelona and Hospital Clinic de Barcelona, Barcelona, and Institut Guttmann-Neurorehabilitation Hospital, Badalona, Spain. PARTICIPANTS: Twenty patients with traumatic brain injury (TBI) were studied, along with 17 matched healthy volunteers. INTERVENTIONS: Resting-state functional magnetic resonance imaging and diffusion tensor imaging data were acquired. After exploring group differences in amplitude of low-frequency fluctuations (ALFF), we studied functional connectivity within the default mode network (DMN) by means of independent component analysis, followed by a dual regression approach and seed-based connectivity analyses. Finally, we performed probabilistic tractography between the frontal and posterior nodes of the DMN. MAIN OUTCOMES AND MEASURES: Signal amplitude and functional connectivity during the resting state, tractography related to DMN, and the association between signal amplitudes and cognitive outcome. RESULTS: Patients had greater ALFF in frontal regions, which was correlated with cognitive performance. Within the DMN, patients showed increased connectivity in the frontal lobes. Seed-based connectivity analyses revealed augmented connectivity within surrounding areas of the frontal and left parietal nodes of the DMN. Fractional anisotropy of the cingulate tract was correlated with increased connectivity of the frontal node of the DMN in patients with TBI. CONCLUSIONS AND RELEVANCE: Increased ALFF is related to better cognitive performance in chronic TBI. The loss of structural connectivity produced by damage to the cingulum tract explained the compensatory increases in functional connectivity within the frontal node of the DMN.