The inferential impact of global signal covariates in functional neuroimaging analyses.
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The Bereitschaftspotential (BP) was recorded at 56 scalp positions when 17 healthy subjects performed brisk extensions of the right index finger. Aim of the study was to contribute to our understanding of the physiology underlying the BP and, in particular, to specify the situation at BP onset. For this purpose, the spatial pattern of the BP was analyzed in short time intervals (35 and/or 70 ms) starting 2.51 s before movement onset. For each time segment a spherical model of the BP was calculated by using spline interpolation. Then the spatial distribution of the electric potential at the scalp surface was transformed into a spatial distribution of current source densities (CSD map). Onset times of the BP and onset times of initial CSD-activity ranged between 2.23 and 1.81 s before movement onset. We selected a time window between 1.6 and 1.5 s before movement onset in order to analyze the spatial CSD pattern in each subject. In 10 subjects there was a significant current sink in the scalp area located over medial-wall motor areas (pre-SMA, SMA proper and anterior cingulate cortex: electrode positions C1, C2, FCz, Cz) in the absence of a significant current sink over the primary motor cortex (MI: electrode positions C3, CP3, and CP5). In three subjects significant current sinks were present at both sites and in another three subjects a current sink only over the lateral motor cortex was observed. In one subject no significant current sinks were measured. It is concluded that there is a large group of subjects (13/17) in whom BP at onset is associated with a current sink over medial-wall motor areas. At a later time interval (0.6 to 0.5 s before movement onset), significant current sinks were found in 13 subjects in medial and in 10 subjects in lateral recordings. These data were considered to be consistent with the hypothesis that, at least in a majority of subjects, medial-wall motor areas are activated earlier than lateral motor areas when organizing the initiation of a simple self-paced movement. Surface-recordings of the EEG do not allow further specification of cortical areas, which contribute to the current sinks. But in context with the current literature of the electrophysiology of nonhuman primates and of brain imaging in humans it is suggested that SMA and anterior cingulate cortex contribute to the current sink, the fronto-central midline, and that the primary motor cortex (MI) contributes to the current sink in the scalp area, which is located above MI and closely posterior to it.
Generalization can be defined quantitatively and can be used to assess the performance of principal component analysis (PCA). The generalizability of PCA depends on the number of principal components retained in the analysis. We provide analytic and test set estimates of generalization. We show how the generalization error can be used to select the number of principal components in two analyses of functional magnetic resonance imaging activation sets.
The repeated testing of a null univariate hypothesis in each of many sites (either regions of interest or voxels) is a common approach to the statistical analysis of brain functional images. Procedures, such as the Bonferroni, are available to maintain the Type I error of the set of tests at a specified level. An initial assumption of these methods is a "global null hypothesis," i.e., the statistics computed on each site are assumed to be generated by null distributions. This framework may be too conservative when a significant proportion of the sites is affected by the experimental manipulation. This report presents the development of a rigorous statistical procedure for use with a previously reported graphical method, the P plot, for estimation of the number of "true" null hypotheses in the set. This estimate can then be used to sharpen existing multiple comparison procedures. Performance of the P plot method in the multiple comparison problem is investigated in simulation studies and in the analysis of autoradiographic data.
In this paper, we examined three vector quantization (VQ) methods used for the unsupervised classification (clustering) of functional magnetic resonance imaging (fMRI) data. Classification means that each brain volume element (voxel), according to a given scanning raster, was assigned to one group of voxels based on similarity of the fMRI signal patterns. It was investigated how the VQ methods can isolate a cluster that describes the region involved in a particular brain function. As an example, word processing was stimulated by a word comparison task. VQ analysis methodology was verified using simulated fMRI response patterns. It was demonstrated in detail that VQ based on global rather than local optimization of the objective function yielded a higher performance. Performance was measured in statistically relevant series of VQ attempts using several indices for goodness, reliability and efficiency of VQ solutions. Furthermore, it was shown that a poor local optimization caused either an underestimation or an overestimation of the stimulus-induced brain activation. However, this was not observed if the cluster analysis was based upon a global optimization strategy.
Lesion studies show a wide range of sensorimotor functions that can be selectively disturbed in patients with parietal lobe damage. This is illustrated by the selective impairment of unimodal or polymodal sensorimotor transformations in patients with apraxia. These clinically apparent deficits of goal-directed motor behavior are complimented by more subtle sensorimotor transformation disorders such as mirror agnosia and ataxia that can only be disclosed by special tests. Imaging studies further exemplify the prominent role of the parietal cortex as a sensorimotor interface and provide new information about the interrelationship between perception and action. Action observation activates premotor cortex, but parietal cortex is also recruited whenever an action involves objects. This emphasizes the significance of parietal cortex for goal-directed motor behavior. The intact comprehension of the meaning of gestures or of tool use shows the preservation of the cognitive aspects of motor behavior as long as lesions are restricted to the parietal lobe.
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Radiosurgery relies critically on medical imaging modalities. Leksell Gamma Knife (LGK) radiosurgery presents the highest requirements in terms of imaging accuracy as the treatment is applied in a single high-dose session with no other spatial control than medical imaging. The advent of new imaging modalities opens challenges for LGK planning strategies. The integration of stereotactic PET in LGK represents an example of such application of modern multimodality imaging in radiosurgery. Our experience consists of 80 patients treated with the combination of MR/CT and PET guidance. In order to analyze the specific contribution of PET findings, we developed a classification reflecting the strategy used to define the target volume. When combining PET and MR information, 102 target volumes were defined, because some patients presented with multiple lesions or multifocal tumor areas. Abnormal PET uptake was found in 86% of the lesions, and this information altered significantly the MR-defined tumor in 73%. In conclusion, integration of PET in radiosurgery provides additional information opening new perspectives for the treatment of brain tumors. The use of a standardized classification allows to assess the relative role of PET. A similar approach could be useful and may serve as a template for the evaluation of the integration of other new imaging modalities in radiosurgery.
To assess the extent of overlap between clinically diagnosed patients with progressive supranuclear palsy (PSP) and corticobasal ganglionic degeneration (CBGD) we compared clinical scores for rigidity, bradykinesia, supranuclear gaze abnormalities, hemineglect and limb apraxia, postural instability, neck rigidity, and limb dystonia in 15 patients with a degenerative rigid-akinetic syndrome at presentation and at follow-up 3 to 120 months later. Only the presence of hemineglect, usually in combination with limb apraxia, was a reliable and early clinical factor for discriminating between these two conditions. These symptoms were present at admission in all 4 CBGD patients but not in any of the 11 PSP patients either at presentation or later during serial examinations. Though supranuclear ophthalmoplegia, neck rigidity, and postural instability were already observed in most CBGD patients at presentation, their scores remained low compared to those for PSP patients over the longterm. CT-scans and MRI were helpful in supporting clinically-based diagnoses made at presentation in that the vast majority of the PSP patients exhibited various degrees of midbrain atrophy and 50 percent of the CBGD patients exhibited asymmetric pericentral cortical atrophy.
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Twenty-eight children with intractable seizures who subsequently underwent a temporal lobectomy were studied by electroencephalogram (EEG), prolonged video EEG telemetry, computed tomography (CT), magnetic resonance imaging (MRI), and single photon emission computed tomography (SPECT) for the localization of epileptogenic foci. MRI showed abnormalities indicating epileptogenic foci in 21/25 patients and a increased signal intensity in 7/11 patients with mesial temporal sclerosis (MTS). SPECT showed corresponding abnormalities in 17/22 patients, including an interictal decrease in regional cerebral blood flow corresponding to the epileptogenic zone in 15. CT showed localized abnormalities in 16/28. All 12 patients with benign, slow-growing neoplasms showed an abnormality on CT scan. In children, MRI is essential in localizing epileptogenic abnormalities, especially MTS and cortical dysplasia. SPECT contributes to the localization of epileptogenic foci, which are often coincident with EEG abnormalities, particularly in single pathology. CT depicts benign neoplasms with calcification in the temporal lobe, which are likely to provoke complex partial seizures.
In stereotactic radiosurgery, thin external beams of ionizing radiation concentrated in a single dose onto a sharply defined target are employed to treat lesions within the brain, avoiding doses which may produce unwanted damage to the surrounding healthy tissue. The dynamic irradiation technique used with the linear accelerator employs variable arcs of irradiation rotating around the isocenter of the target. The technique of stereotactic magnetic resonance (MR) guided radiosurgery is supported by a dedicated computerized system for treatment planning simulation. The system, based on a personal computer, allows the acquisition, reconstruction, and visualization of the target volume from MR images, and permits calculation and visualization of a three-dimensional dose distribution directly superimposed upon MR images of the lesion. The desired goal of destroying neoplastic tissue without damaging cerebral parenchyma is of particular importance in children. Consequently, adapting the three-dimensional isodose profiles to the morphology of the lesion to be treated is crucial. From this, the importance of the computer simulation is evident, as it permits one to go deeply into the study of isodose distribution, changing beam collimation, and the number and amplitude of arcs of irradiation.
Based on the published literature and on our own experiences in the imaging of lissencephalies with ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) we propose a strategy for the use of the different methods depending on the clinical symptoms and the age of the patient. In newborns and babies with suspected lissencephaly ultrasound should be used as the first method. If there is a cortical malformation and a more thorough examination seems necessary, CT can be used in type I lissencephaly. However, due to its excellent grey-white matter contrast MRI is the best method for imaging of lissencephalies. Especially in the diagnosis of type II lissencephaly, MRI is definitely superior to CT and US, and so it should be used in all patients with Walker-Warburg syndrome and other congenital muscular dystrophies as well as in all doubtful cases. It must always be remembered that the extent of the cortical dysplasias is quite variable, as is the presence of further malformations.
A 35-year-old female patient suffering from epilepsy was examined during status epilepticus with simple partial and complex partial seizures by means of EEG, CT, MRI and ictal SPECT. All these examinations showed focal abnormalities with identical location due to oedema and hypervascularisation; these were, however, absent during examinations carried out before and after status epilepticus.
The contribution of MRI is reported in four adult patients with tuberculous meningoencephalitis (TbM) and with autopsy correlation in one. Contrast-enhanced T1-weighted MRI revealed the characteristic basal meningeal inflammation of TbM and its focal spreading into adjacent brain. Mixed and T2-weighted pulse sequences delineated a plethora of parenchymal abnormalities. Their relation to TbM was established by a close matching of the patient's neurological findings, contrast enhancement or a change in lesion size. The latter accurately reflected the clinical course in all patients. It remained difficult, however, to distinguish between ischaemic and inflammatory changes, which in some locations were intermixed even histologically. From our experience and that of other groups, MRI provides more diagnostic information in TbM than CT. Moreover, MRI promises to be a useful tool for monitoring treatment response.
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The CT scan's of 22 patients with lissencephaly type I, a severe developmental disorder of the cerebral cortex, were studied. In 6 patients a magnetic resonance (MR), scan was also performed. The CT and MR scans of the lissencephaly patients were compared to a control group consisting of 49 patients with a normal CT or MR scan. In lissencephaly the cortical thickness was always larger than 10 mm, as compared to less than 7 mm in the normal situation. In lissencephaly the WSF/DSF index (with/depth of the sylvian fissure) was always larger than 0.29, while in the normal situation less than 0.25.