Relationships between movement initiation times and movement-related cortical potentials in Parkinson's disease

Movement-related cortical potentials recorded from the scalp reveal increasing cortical activity occurring prior to voluntary movement. Studies of set-related cortical activity recorded from single neurones within premotor and supplementary motor areas in monkeys suggest that such premovement activity may act to prime activity of appropriate motor units in readiness to move, thereby facilitating the movement response. Such a role of early stage premovement activity in movement-related cortical potentials was investigated by examining the relationship between premovement cortical activity and movement initiation or reaction times. Parkinson's disease and control subjects performed a simple button-pressing reaction time task and individual movement-related potentials were averaged for responses with short compared with long reaction times. For Parkinson's disease subjects but not for the control subjects, early stage premovement cortical activity was significantly increased in amplitude for faster reaction times, indicating that there is indeed a relationship between premovement cortical activity amplitude and movement initiation or reaction times. In support of studies of set-related cortical activity in monkeys, it is therefore suggested that early stage premovement activity reflects the priming of appropriate motor units of primary motor cortex, thereby reducing movement initiation or reaction times. (C) 1999 Elsevier Science B.V. All rights reserved.

A medial to lateral shift in pre-movement cortical activity in hemi-Parkinson's disease

Objective: Recent evidence suggests that cortical activity associated with voluntary movement is relatively shifted from medial to lateral premotor areas in Parkinson's disease. This shift occurs bilaterally even for unilateral responses. It is not clear whether the shift in processing reflects an overall change in movement strategy, thereby involving alternate cortical areas, or reflects a compensatory change whereby, given the appropriate conditions, less impaired cortical areas are able to provide a similar function in compensation for those areas which are more impaired. This issue was examined in patients with hemi-Parkinson's disease, in whom basal ganglia impairment is most pronounced in one hemisphere. Methods: Fourteen patients with hemi-Parkinson's disease and 15 age-matched control subjects performed a Go/NoGo finger movement task and the contingent negative variation (CNV) was recorded from 21 scalp positions. Results and conclusions: Maximal CNV amplitudes were found over central medial regions for control subjects, but were shifted more frontally for Parkinson's disease patients, reduced in amplitude over the midline and lateralized towards the side ipsilateral to the greatest basal ganglia impairment. This shift in cortical activity from medial to lateral areas in Parkinson's disease patients appears to reflect a compensatory mechanism operating predominantly on the side of greatest basal ganglia impairment. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Identifying rate-limiting nodes in large-scale cortical networks for visuospatial processing: an illustration using fMRI

With the advent of functional neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), we have gained greater insight into the neural correlates of visuospatial function. However, it may not always be easy to identify the cerebral regions most specifically associated with performance on a given task. One approach is to examine the quantitative relationships between regional activation and behavioral performance measures. In the present study, we investigated the functional neuroanatomy of two different visuospatial processing tasks, judgement of line orientation and mental rotation. Twenty-four normal participants were scanned with fMRI using blocked periodic designs for experimental task presentation. Accuracy and reaction time (RT) to each trial of both activation and baseline conditions in each experiment was recorded. Both experiments activated dorsal and ventral visual cortical areas as well as dorsolateral prefrontal cortex. More regionally specific associations with task performance were identified by estimating the association between (sinusoidal) power of functional response and mean RT to the activation condition; a permutation test based on spatial statistics was used for inference. There was significant behavioral-physiological association in right ventral extrastriate cortex for the line orientation task and in bilateral (predominantly right) superior parietal lobule for the mental rotation task. Comparable associations were not found between power of response and RT to the baseline conditions of the tasks. These data suggest that one region in a neurocognitive network may be most strongly associated with behavioral performance and this may be regarded as the computationally least efficient or rate-limiting node of the network.

Progressive dysgraphia in a case of posterior cortical atrophy

Dysgraphia (agraphia) is a common feature of posterior cortical atrophy (PCA). However, detailed analyses of these spelling and writing impairments are infrequently conducted. LM is a 59-year-old woman with dysgraphia associated with PCA. She presented with a two-year history of decline in her writing and dressmaking skills. A 3D T-1-weighted MRI scan confirmed selective bi-parietal atrophy, with relative sparing of the hippocampi and other cortical regions. Analyses of LM's preserved and impaired spelling abilities indicated mild physical letter distortions and a significant spelling deficit characterised by letter substitutions, insertions, omissions, and transpositions that was systematically sensitive to word length while insensitive to real word versus nonword category, word frequency, regularity, imagery, grammatical class and ambiguity. Our findings suggest a primary graphemic buffer disorder underlies LM's spelling errors, possibly originating from disruption to the operation of a fronto-parietal network implicated in verbal working memory.

A medial to lateral shift in premovement cortical activity in hemi-Parkinson's disease: Studies of event-related potentials and whole-scalp magneto encephalography

Cortical activity associated with voluntary movement is shifted from medial to lateral premotor areas in Parkinson's disease. This occurs bilaterally, even for unilateral movements. We have used both EEG and MEG to further investigate medial and lateral premotor activity in patients with hemi-Parkinson's disease, in whom basal ganglia impairment is most pronounced in one hemisphere. The CNV, recorded from 21 scalp positions in a Go/NoGo task, was maximal over central medial regions in control subjects. For hemi-Parkinson's disease subjects, activity was shifted more frontally, reduced in the midline and lateralised towards the side of greatest basal ganglia impairment. With 143 channel whole-scalp magneto encephalography (MEG) we are further examining asymmetries in supplementary motor/premotor cortical activity prior to self-paced voluntary movement. In preliminary results, one hemi-Parkinson's disease patient with predominantly left-side symptoms showed strong medial activity consistent with a dominant source in the left supplementary motor area (SMA). Three patients showed little medial activity, but early bilateral sources within lateral premotor cortex. Results suggest greater involvement of lateral premotor rather than the SMA prior to movement in Parkinson's disease and provide evidence for asymmetric function of the SMA in hemi- Parkinson's disease, with reduced activity on the side of greatest basal ganglia deficit.

Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia

This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood and adult-onset schizophrenia, bipolar disorder, attention-deficit/ hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages. (C) 2004 Published by Elsevier Inc.

An fMRI study indicating increased cortical recruitment during a cognitive interference task in Huntington's disease patients

We used an event related fMRI design to study the BOLD response in Huntington’s disease (HD) patients during performance of a Simon interference task. We hypothesised that HD patients will demonstrate significantly slower RTs than controls, and that there will be significant differences in the pattern of brain activation between groups. Seventeen HD patients and 15 age and sex matched controls were scanned using 3T GE scanner (FOV = 24 cm2; TE = 40 ms; TR = 3 s; FA = 60°; slice thickness = 6 mm; in-plane resolution = 1.88x1.88 mm2). The task involved two activation conditions, namely congruent (for example, left pointing arrow appearing on the left side of the screen) and incongruent (for example, left pointing arrow appearing on the right side of the screen), and a baseline condition. Each stimulus was presented for 2500 ms followed by a blank screen for 500 ms. Subjects were instructed to press a button using the same hand as indicated by the direction of the arrow head and were given 3000 ms to respond. Data analysis was performed using SPM2 with a random effects analysis model. For each subject parameter estimates for combined task conditions (congruent and incongruent combined) were calculated. Comparisons such as these, based on block designs, have superior statistical power for detecting subtle changes in the BOLD response anywhere in the brain. The activations reported are significant at PFDR_corr

Texture Image Analysis in Differentiating Malignant from Benign Adrenal Cortical Tumors in Children and Adults

Objective: To investigate the possible role of chromatin texture parameters, nuclear morphology, DNA ploidy and clinical functional status in discriminating benign from malignant adrenocortical tumors (ACT). Patients and Methods: Forty-eight cases of clinically benign (n=40) and clinically malignant (n=8) ACT with a minimum of 5-years` follow-up were evaluated for chromatin texture parameters (run length, standard deviation, configurable run length, valley, slope, peak and other 21 Markovian features that describe the distribution of the chromatin in the nucleus), nuclear morphology (nuclear area, nuclear perimeter, nuclear maximum and minumum diameter, nuclear shape), and DNA ploidy. Nuclear parameters were evaluated in Feulgen-stained 5 mu m paraffin-sections analyzed using a CAS 200 image analyzer. Results: Since ACTs present different biological features in children and adults, patients were divided into two groups: children (<= 15 years) and adults (>15 years). In the group of children DNA ploidy presented a marginal significance (p=0.05) in discriminating ACTs. None of the parameters discriminated between malignant and benign ACT in the adult group. Conclusion: ACTs are uncommon and definitive predictive criteria for malignancy remain uncertain, particularly in children. Our data point to DNA content evaluated by image analysis as a new candidate tool for this challenging task. Texture image analysis did not help to differentiate malignant from benign adrenal cortical tumors in children and adults.

The influence of lean mass in trabecular and cortical bone in juvenile onset systemic lupus erythematosus

The aim of this study was to evaluate risk factors for low bone mineral density (BMD) and vertebral fractures, in juvenile systemic lupus (JSLE). Thirty-one consecutive patients with JSLE were compared with 31 gender- and age-matched healthy controls. BNID and body composition from all participants were measured using dual-energy X-ray absorptiometry. Vertebral fractures were defined as a reduction of >= 20% of the vertebral height for all patients. Lumbar spine and total femur BMD was significantly decreased in patients compared with controls (P = 0.021 and P = 0.023, respectively). A high frequency of vertebral fractures (22.58%) was found in patients with JSLE. Analysis of body composition revealed lower lean mass (P = 0.033) and higher fat mass percentage (P = 0.003) in patients than in controls. Interestingly, multiple linear regression using BMD as a dependent variable showed a significant association with lean mass in lumbar spine (R(2) = 0.262; P = 0.004) and total femur (R(2) = 0.419, P = 0.0001), whereas no association was observed with menarche age, SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology, and glucocorticoid. This study indicates that low BMD and vertebral fractures are common in JSLE, and the former is associated with low lean mass, suggesting that muscle rehabilitation may be an additional target for bone therapeutic approach.

Cortical Thickness Reduction of Normal Appearing Cortex in Patients with Polymicrogyria

OBJECTIVE To examine cortical thickness and volumetric changes in the cortex of patients with polymicrogyria, using an automated image analysis algorithm. METHODS Cortical thickness of patients with polymicrogyria was measured using magnetic resonance imaging (MRI) cortical surface-based analysis and compared with age-and sex-matched healthy subjects. We studied 3 patients with disorder of cortical development (DCD), classified as polymicrogyria, and 15 controls. Two experienced neuroradiologists performed a conventional visual assessment of the MRIs. The same data were analyzed using an automated algorithm for tissue segmentation and classification. Group and individual average maps of cortical thickness differences were produced by cortical surface-based statistical analysis. RESULTS Patients with polymicrogyria showed increased thickness of the cortex in the same areas identified as abnormal by radiologists. We also identified a reduction in the volume and thickness of cortex within additional areas of apparently normal cortex relative to controls. CONCLUSIONS Our findings indicate that there may be regions of reduced cortical thickness, which appear normal from radiological analysis, in the cortex of patients with polymicrogyria. This finding suggests that alterations in neuronal migration may have an impact in the cortical formation of the cortical areas that are visually normal. These areas are associated or occur concurrently with polymicrogyria.

Use of SVM Methods with Surface-Based Cortical and Volumetric Subcortical Measurements to Detect Alzheimer`s Disease

Here, we examine morphological changes in cortical thickness of patients with Alzheimer`s disease (AD) using image analysis algorithms for brain structure segmentation and study automatic classification of AD patients using cortical and volumetric data. Cortical thickness of AD patients (n = 14) was measured using MRI cortical surface-based analysis and compared with healthy subjects (n = 20). Data was analyzed using an automated algorithm for tissue segmentation and classification. A Support Vector Machine (SVM) was applied over the volumetric measurements of subcortical and cortical structures to separate AD patients from controls. The group analysis showed cortical thickness reduction in the superior temporal lobe, parahippocampal gyrus, and enthorhinal cortex in both hemispheres. We also found cortical thinning in the isthmus of cingulate gyrus and middle temporal gyrus at the right hemisphere, as well as a reduction of the cortical mantle in areas previously shown to be associated with AD. We also confirmed that automatic classification algorithms (SVM) could be helpful to distinguish AD patients from healthy controls. Moreover, the same areas implicated in the pathogenesis of AD were the main parameters driving the classification algorithm. While the patient sample used in this study was relatively small, we expect that using a database of regional volumes derived from MRI scans of a large number of subjects will increase the SVM power of AD patient identification.

Cognitive performance is related to cortical grey matter volumes in early stages of schizophrenia: A population-based study of first-episode psychosis

Background: Neuropsychological deficits have been reported in association with first-episode psychosis (FEP). Reductions in grey matter (GM) volumes have been documented in FEP subjects compared to healthy controls. However, the possible inter-relationship between the findings of those two lines of research has been scarcely investigated. Objective: To investigate the relationship between neuropsychological deficits and GM volume abnormalities in a population-based sample of FEP patients compared to healthy controls from the same geographical area. Methods: FEP patients (n = 88) and control subjects (n = 86) were evaluated by neuropsychological assessment (Controlled Oral Word Association Test, forward and backward digit span tests) and magnetic resonance imaging using voxel-based morphometry. Results: Single-group analyses showed that prefrontal and temporo-parietal GM volumes correlated significantly (p < 0.05, corrected) with cognitive performance in FEP patients. A similar pattern of direct correlations between neocortical GM volumes and cognitive impairment was seen in the schizophrenia subgroup (n = 48). In the control group, cognitive performance was directly correlated with GM volume in the right dorsal anterior cingulate cortex and inversely correlated with parahippocampal gyral volumes bilaterally. Interaction analyses with ""group status"" as a predictor variable showed significantly greater positive correlation within the left inferior prefrontal cortex (BA46) in the FEP group relative to controls, and significantly greater negative correlation within the left parahippocampal gyrus in the control group relative to FEP patients. Conclusion: Our results indicate that cognitive deficits are directly related to brain volume abnormalities in frontal and temporo-parietal cortices in FEP subjects, most specifically in inferior portions of the dorsolateral prefrontal cortex. (C) 2009 Elsevier B.V. All rights reserved.

Malformations of Cortical Development in Patients With Mid line Facial Defects and Ocular Hypertelorism

Objectives: We studied the neuroimaging and neurophysiological aspects of 17 patients with midline facial defects with ocular hypertelorism (MFDH). Methods: The investigation protocol included a previous semistructured questionnaire about family history; gestational, neonatal, and postnatal development; and dysmorphologic and neurologic evaluation. Recognized monogenic disorders and individuals with other well-known conditions were excluded. All patients had high resolution magnetic resonance imaging (MRI) with multiplanar reconstruction (MPR) and routine electroencephalograms (EEGs). Results: We detected abnormalities in five patients whose MRIs had been previously reported as normal. MRI showed central nervous system (CNS) structural abnormalities in all patients, which included commissural alterations in 16/17 (94%), malformations of cortical development in 10/17 (58%), disturbances of neural tube closure in 7/17(42%), and posterior fossa anomalies in 6/17 (35%). Some patients had more than one type of malformation occurring at different stages of the embryonary process. EEGs showed epileptiform activity in 4/17 (24%) and background abnormalities in 5/17 (29%) of patients. Conclusion: This study clearly demonstrated the presence of structural and functional neurologic alterations related to MFDH. Therefore, the CNS anomalies cannot be considered incidental findings but an intrinsic part of this condition, which could be related to environmental effects and/or genetic mutations. These findings would provide a basis for future investigations on MFDH and should also be considered when planning rehabilitation.