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Neurosecretion and brain peptides. Implications for brain functions and neurological disease.
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[Magnetic resonance--more than just images! New MR techniques improve diagnosis, therapeutic control and assessment of brain function].
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[Biological motivations in systemic organization of brain function].
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Magnetic resonance imaging mapping of brain function. Human visual cortex.
Magnetic resonance imaging (MRI) studies of human brain activity are described. Task-induced changes in brain cognitive state were measured using high-speed MRI techniques sensitive to changes in cerebral blood volume (CBV), blood flow (CBF), and blood oxygenation. These techniques were used to generate the first functional MRI maps of human task activation, by using a visual stimulus paradigm. The methodology of MRI brain mapping and results from the investigation of the functional organization and frequency response of human primary visual cortex (V1) are presented.
The role of diffusion tensor imaging in establishing the proximity of tumor borders to functional brain systems: implications for preoperative risk assessments and postoperative outcomes.
Diffusion Tensor Imaging (DTI) is a new MRI imaging technique sensitive to directional movements of water molecules, induced by tissue barriers. This provides a new form of contrast that allows the identification of functional white matter tracts within the brain, and has been proposed as a technique suitable for presurgical planning in brain tumor patients. Resection of primary brain tumors improves survival, functional performance, and the effectiveness of adjuvant therapies, provided that surgically-induced neurological deficits can be avoided. Diffusion Tensor Imaging (DTI) has the potential to establish spatial relationships between eloquent white matter and tumor borders, provide information essential to preoperative planning, and improve the accuracy of surgical risk assessments preoperatively. We present our experience in a series of 28 brain tumor patients where the integration of functional magnetic resonance imaging (fMRI) and DTI data was used to determine key anatomic spatial relationships preoperatively. Twice as many functional systems were localized to within 5 mm of tumor borders when DTI and fMRI were utilized for preoperative planning, compared to that afforded by fMRI alone. Our results show that the combined use of fMRI and DTI can provide a better estimation of the proximity of tumor borders to eloquent brain systems sub-serving language, speech, vision, motor and premotor functions. Additionally, a low regional complication rate (4%) observed in our series suggests that preoperative planning with these combined techniques may improve surgical outcomes compared to that previously reported in the literature. Larger studies specifically designed to establish the accuracy and predictive value of DTI in brain tumor patients are warranted to substantiate our preliminary observations.
Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson's disease model.
Neurophysiological studies of the brain in normal and Parkinson's disease (PD) patients have indicated intricate connections for basal ganglia-induced control of signaling into the motor cortex. To investigate if similar mechanisms are controlling function in the primate brain (Macaca fascicularis) after MPTP-induced neurotoxicity, we conducted PET studies of cerebral blood flow, oxygen and glucose metabolism, dopamine transporter, and D2 receptor function. Our observations after MPTP-induced dopamine terminal degeneration of the caudate and putamen revealed increased blood flow (15%) in the globus pallidus (GP), while blood flow was moderately decreased (15-25%) in the caudate, putamen, and thalamus and 40 % in the primary motor cortex (PMC). Oxygen extraction fraction was moderately increased (10-20%) in other brain areas but the thalamus, where no change was observable. Oxygen metabolism was increased in the GP and SMA (supplementary motor area including premotor cortex, Fig. 3) by a range of 20-40% and decreased in the putamen and caudate and in the PMC. Glucose metabolism was decreased in the caudate, putamen, thalamus, and PMC (range 35-50%) and enhanced in the GP by 15%. No change was observed in the SMA. In the parkinsonian primate, [(11)C]CFT (2beta-carbomethoxy-3beta-(4-fluorophenyltropane) dopamine transporter binding was significantly decreased in the putamen and caudate (range 60-65%). [(11)C]Raclopride binding of dopamine D(2) receptors did not show any significant changes. These experimental results obtained in primate studies of striato-thalamo-cortico circuitry show a similar trend as hypothetized in Parkinson's disease-type degeneration.
Insights into brain function through the examination of art: the influence of neurodegenerative diseases.
There has been intense interest in determining how the visual brain processes the outside world, and in identifying the neuroanatomical correlates of the ability to create art. Comparing art production before and after illness onset permits some speculation on the function of selective brain regions affected by the neurodegenerative process. In this review of cases of neurodegenerative illness in visual artists, the evolution of abstraction may be argued to either reflect an enhancement of previous skills or, that the emergence of abstraction, when it was previously absent, is a manifestation of cognitive and visuo-spatial decline. We present examples of each, illustrating both perspectives and suggest that the two opposing views may not be mutually exclusive.
Mapping cognitive brain function with modern high-resolution electroencephalography.
High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. While electroencephalography (EEG) provides temporal resolution in the millisecond range, which would seem to make it an ideal complement to other imaging modalities, traditional EEG technology and practice provides insufficient spatial detail to identify relationships between brain electrical events and structures and functions that are visualized by magnetic resonance imaging (MRI) or positron emission tomography (PET). Recent advances overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical information from each subject's MRI, and by correcting the distortion that is caused by volume conduction of EEG signals through the skull and scalp. Along with its ability to record how brains think when performing everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.
Practice-related changes in human brain functional anatomy during nonmotor learning.
Practice of a novel task leads to improved performance. The brain mechanisms associated with practice-induced improvement in performance are largely unknown. To address this question we have examined the functional anatomy of the human brain with positron emission tomography (PET) during the naive and practiced performance of a simple verbal response selection task (saying an appropriate verb for a visually presented noun). As a control state, subjects were asked to repeat the visually presented nouns. Areas of the brain most active during naive performance (anterior cingulate, left prefrontal and left posterior temporal cortices, and the right cerebellar hemisphere), compared to repeating the visually presented nouns, were all significantly less active during practiced performance. These changes were accompanied by changes in the opposite direction in sylvian-insular cortex bilaterally and left medial extrastriate cortex. In effect, brief practice made the cortical circuitry used for verbal response selection indistinguishable from simple word repetition. Introduction of a novel list of words reversed the learning-related effects. These results indicate that two distinct circuits can be used for verbal response selection and normal subjects can change the brain circuits used during task performance following less than 15 min of practice. One critical factor in determining the circuitry used appears to be the degree to which a task is learned or automatic.
Global dimensional complexity of multi-channel EEG indicates change of human brain functional state after a single dose of a nootropic drug.
Viewing the multi-channel EEG as a sequence of momentary field maps corresponds to the concept of a trajectory in K-dimensional state space (K = number of channels). This approach permits a quantitative, single value measure of complexity of the brain state trajectory, the global correlation dimension that describes the ensemble characteristics of all recorded channels. In 5 normal volunteers, 4 records of 16-channel resting EEG were obtained during each of 4 randomized sessions (double blind design) after a single dose of placebo or 2.9 g or 4.8 g or 9.6 g piracetam. The global correlation dimension of a 40 sec epoch from each record was estimated, using 50 computational runs with 8192 point pairs. The results were combined for the two intermediate doses and averaged over repeated records. The dimensionality decreased from placebo (median = 5.89) to low dose (median = 5.72) to high dose (median = 5.59), significant in a Friedman ANOVA at P < 0.02, with significant differences between placebo vs. high and low vs. high dose. Thus, the subtle change of brain global functional state after a single dose of piracetam is reflected by the non-linear measure of global dimensional complexity of the multi-channel EEG.
The continuous performance test, identical pairs version (CPT-IP): III. Brain functioning during performance of numbers and shapes subtasks.
The numbers and shapes subtasks of the CPT-IP are difficulty-matched measures of independent aspects of attentional skill that have been used to differentiate the impairments of schizophrenics and major depressives. Previous studies suggest that they tap into lateralized aspects of attentional performance. To investigate this hypothesis, seven subjects free of psychiatric illness were presented with these CPT-IP subtasks during a SPECT procedure. Subtasks--4-digit number strings and nonsense shapes--were administered on successive weeks, in counterbalanced order, simultaneous with administration of 10 mCi 99mTc HMPAO. Scanning took place after 10 min of test performance. Quantitative data were extracted from each scan via a semi-automated region of interest (ROI) analysis which defined eight cortical and four subcortical ROI on each of five transverse slices. Data for each ROI were normalized and compared between task conditions. Results indicate that the two tasks produce different patterns of functioning within two general areas of the brain. First, during Numbers task performance, left-sided activity was increased on multiple transverse slices in an anterior subcortical region that incorporated the anterior cingulate, frontal white matter, and much of the basal ganglia. Left-sided activity was also increased in a posterior subcortical region including the left side of the thalamus. Lateralization of function, defined as relative activity on the left and right sides, changed within these regions across tasks, but primarily as a result of the contribution of increased or decreased activity on the left side alone. Second, relative perfusion to occipital regions, bilaterally, was more extensive during the Shapes task. These results suggest that subtle alterations in stimulus parameters can affect activation patterns in regions that are critically associated with task performance. They also suggest that the Numbers task may provide more robust activation of anterior attention systems, that may better discriminate the functioning of these systems in normal and psychopathological groups.
[Clinical application of functional mapping: the present state of the art and its future prospects: (series 7) magneto-encephalographic study of higher brain function].
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A default mode of brain function.
A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.
Functional brain networks in Parkinson's disease.
With the advent of new methods of network analysis, we have utilized metabolic data acquired through positron emission tomography (PET) to identify disease-related patterns of functional pathology in the movement disorders. In Parkinson's disease (PD), we have used [(18)F]-fluorodeoxyglucose (FDG)/PET to identify a disease-related regional metabolic covariance pattern characterized by lentiform and thalamic hypermetabolism associated with regional metabolic decrements in the lateral premotor cortex, the supplementary motor area, the dorsolateral prefrontal cortex, and the parieto-occipital association regions. The expression of this network is modulated in a predictable fashion by levodopa therapy and by stereotaxic interventions for PD.We have extended this network analytical approach from studies of glucose metabolism in the resting state to dynamic studies of brain activation during motor performance. These PET studies utilized [(15)O]-water (H(2) (15)O) to measure cerebral blood flow activation responses during the execution of simple and complex motor tasks. In addition to the modulation of abnormal resting metabolic networks, effective PD therapy can enhance brain activation responses during motor execution, with specific regional associations with improvements in timing and spatial accuracy.This approach is also useful in identifying specific brain networks mediating the learning of sequential information. We have found that the normal relationship between brain networks and learning performance are altered in the earliest stages of PD with a functional shift from striatal to cortical processing. Brain activation PET studies during therapeutic interventions for PD demonstrate how normal brain-behavior relationships can be restored with successful therapy. Thus, functional brain imaging with network analysis can provide insights into the mechanistic basis of basal ganglia disorders and their treatment.
A new approach to spatial covariance modeling of functional brain imaging data: ordinal trend analysis.
In neuroimaging studies of human cognitive abilities, brain activation patterns that include regions that are strongly interactive in response to experimental task demands are of particular interest. Among the existing network analyses, partial least squares (PLS; McIntosh, 1999; McIntosh, Bookstein, Haxby, & Grady, 1996) has been highly successful, particularly in identifying group differences in regional functional connectivity, including differences as diverse as those associated with states of awareness and normal aging. However, we address the need for a within-group model that identifies patterns of regional functional connectivity that exhibit sustained activity across graduated changes in task parameters. For example, predictions of sustained connectivity are commonplace in studies of cognition that involve a series of tasks over which task difficulty increases (Baddeley, 2003). We designed ordinal trend analysis (OrT) to identify activation patterns that increase monotonically in their expression as the experimental task parameter increases, while the correlative relationships between brain regions remain constant. Of specific interest are patterns that express positive ordinal trends on a subject-by-subject basis. A unique feature of OrT is that it recovers information about functional connectivity based solely on experimental design variables. In particular, there is no requirement by OrT to provide either a quantitative model of the uncertain relationship between functional brain circuitry and subject variables (e.g., task performance and IQ) or partial information about the regions that are functionally connected. In this letter, we provide a step-by-step recipe of the computations performed in the new OrT analysis, including a description of the inferential statistical methods applied. Second, we describe applications of OrT to an event-related fMRI study of verbal working memory and H(2)15O-PET study of visuo-motor learning. In sum, OrT has potential applications to not only studies of young adults and their cognitive abilities, but also studies of normal aging and neurological and psychiatric disease.
Reduced functional brain activity response in cognitively intact apolipoprotein E epsilon4 carriers.
The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.
Automated Talairach atlas labels for functional brain mapping.
An automated coordinate-based system to retrieve brain labels from the 1988 Talairach Atlas, called the Talairach Daemon (TD), was previously introduced [Lancaster et al., 1997]. In the present study, the TD system and its 3-D database of labels for the 1988 Talairach atlas were tested for labeling of functional activation foci. TD system labels were compared with author-designated labels of activation coordinates from over 250 published functional brain-mapping studies and with manual atlas-derived labels from an expert group using a subset of these activation coordinates. Automated labeling by the TD system compared well with authors' labels, with a 70% or greater label match averaged over all locations. Author-label matching improved to greater than 90% within a search range of +/-5 mm for most sites. An adaptive grey matter (GM) range-search utility was evaluated using individual activations from the M1 mouth region (30 subjects, 52 sites). It provided an 87% label match to Brodmann area labels (BA 4 & BA 6) within a search range of +/-5 mm. Using the adaptive GM range search, the TD system's overall match with authors' labels (90%) was better than that of the expert group (80%). When used in concert with authors' deeper knowledge of an experiment, the TD system provides consistent and comprehensive labels for brain activation foci. Additional suggested applications of the TD system include interactive labeling, anatomical grouping of activation foci, lesion-deficit analysis, and neuroanatomy education.