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ROC analysis of statistical methods used in functional MRI: individual subjects.

The complicated structure of fMRI signals and associated noise sources make it difficult to assess the validity of various steps involved in the statistical analysis of brain activation. Most methods used for fMRI analysis assume that observations are independent and that the noise can be treated as white gaussian noise. These assumptions are usually not true but it is difficult to assess how severely these assumptions are violated and what are their practical consequences. In this study a direct comparison is made between the power of various analytical methods used to detect activations, without reference to estimates of statistical significance. The statistics used in fMRI are treated as metrics designed to detect activations and are not interpreted probabilistically. The receiver operator characteristic (ROC) method is used to compare the efficacy of various steps in calculating an activation map in the study of a single subject based on optimizing the ratio of the number of detected activations to the number of false-positive findings. The main findings are as follows: Preprocessing. The removal of intensity drifts and high-pass filtering applied on the voxel time-course level is beneficial to the efficacy of analysis. Temporal normalization of the global image intensity, smoothing in the temporal domain, and low-pass filtering do not improve power of analysis. Choices of statistics. the cross-correlation coefficient and t-statistic, as well as nonparametric Mann-Whitney statistics, prove to be the most effective and are similar in performance, by our criterion. Task design. the proper design of task protocols is shown to be crucial. In an alternating block design the optimal block length is be approximately 18 s. Spatial clustering. an initial spatial smoothing of images is more efficient than cluster filtering of the statistical parametric activation maps.

Brain↗

A method for removing imaging artifact from continuous EEG recorded during functional MRI.

Combined EEG/fMRI recording has been used to localize the generators of EEG events and to identify subject state in cognitive studies and is of increasing interest. However, the large EEG artifacts induced during fMRI have precluded simultaneous EEG and fMRI recording, restricting study design. Removing this artifact is difficult, as it normally exceeds EEG significantly and contains components in the EEG frequency range. We have developed a recording system and an artifact reduction method that reduce this artifact effectively. The recording system has large dynamic range to capture both low-amplitude EEG and large imaging artifact without distortion (resolution 2 microV, range 33.3 mV), 5-kHz sampling, and low-pass filtering prior to the main gain stage. Imaging artifact is reduced by subtracting an averaged artifact waveform, followed by adaptive noise cancellation to reduce any residual artifact. This method was validated in recordings from five subjects using periodic and continuous fMRI sequences. Spectral analysis revealed differences of only 10 to 18% between EEG recorded in the scanner without fMRI and the corrected EEG. Ninety-nine percent of spike waves (median 74 microV) added to the recordings were identified in the corrected EEG compared to 12% in the uncorrected EEG. The median noise after artifact reduction was 8 microV. All these measures indicate that most of the artifact was removed, with minimal EEG distortion. Using this recording system and artifact reduction method, we have demonstrated that simultaneous EEG/fMRI studies are for the first time possible, extending the scope of EEG/fMRI studies considerably.

Adult↗

The effects of aging upon the hemodynamic response measured by functional MRI.

We comparedthe characteristics of the visually evoked hemodynamic response (HDR) in groups of young and elderly adults. Checkerboard stimuli were presented for 500 ms either singly or in pairs separated by a 2-s intrapair interval while gradient-echo echoplanar fMRI images were acquired concurrently every 1 s. Activated voxels, identified by correlation with an empirically derived reference waveform, were found for both groups in cortex along the calcarine sulcus and in the fusiform gyrus, with the mean HDR latency in calcarine cortex peaking approximately 300 ms earlier than the HDR evoked in the fusiform gyrus. On average, younger subjects had twice as many activated voxels as older subjects. The mean HDR had a similar onset time, rate of rise, and peak amplitude in both groups. However, the HDRs of older subjects reached their peak earlier and were more variable across subjects. Despite having average HDR amplitudes similar to those of younger subjects, older subjects had higher noise levels in activated voxels, resulting in lower signal-to-noise ratios. Distribution analyses of voxel statistics (t value, peak amplitude, peak latency) revealed that older subjects had proportionally fewer small-effect-size voxels, due to their increased voxelwise noise. This finding was consistent with the smaller spatial extent of activation in older subjects. To investigate age differences in the refractory period of the visual HDR, the HDR evoked by the second stimulus of each pair was isolated by subtracting the HDR evoked by a single stimulus from the composite HDR evoked by a pair. Recovery measures were similar across the age groups.

Adolescent↗

Removal of confounding effects of global signal in functional MRI analyses.

Local signals obtained from BOLD fMRI are generally confounded by global effects. In this paper, we make an essential distinction between global effects and the global signal. Global effects have a similar influence on local signals from a large proportion of cerebral voxels. They may reflect diffuse physiological processes or variations in scanner sensitivity and are difficult to measure directly. Global effects are often estimated from the global signal, which is the spatial average of local signals from all cerebral voxels. If the global signal is strongly correlated with experimental manipulations, meaningfully different results may be obtained whether or not global effects are modeled (G. K. Aguirre et al., 1998, NeuroImage, 8, 302-306). In particular, if local BOLD signals make a significant contribution to the global signal, analyses using ANCOVAor proportional scaling models may yield artifactual deactivations. In this paper, we present a modification to the proportional scaling model that accounts for the contribution of local BOLD signals to the global signal. An event-related oddball stimulus paradigm and a block design working memory task were used to illustrate the efficacy of our model.

Acoustic Stimulation↗

Locally regularized spatiotemporal modeling and model comparison for functional MRI.

In this work we treat fMRI data analysis as a spatiotemporal system identification problem and address issues of model formulation, estimation, and model comparison. We present a new model that includes a physiologically based hemodynamic response and an empirically derived low-frequency noise model. We introduce an estimation method employing spatial regularization that improves the precision of spatially varying noise estimates. We call the algorithm locally regularized spatiotemporal (LRST) modeling. We develop a new model selection criterion and compare our model to the SPM-GLM method. Our findings suggest that our method offers a better approach to identifying appropriate statistical models for fMRI studies.

Arousal↗

Right-hemispheric organization of language following early left-sided brain lesions: functional MRI topography.

Left-hemispheric (LH) brain lesions acquired early in life can induce language organization in the undamaged right hemisphere (RH). This study addresses the anatomical correlates of language processing in the RH of such individuals. Five hemiparetic patients with left periventricular brain lesions of pre- and perinatal origin were included, in whom fMRI during a word generation task had yielded predominantly RH activation; five age- and sex-matched healthy right-handers served as controls. The patterns of activation in the RH of patients showed a striking similarity with the LH patterns of the normal controls, and voxel-wise comparison failed to detect significant differences. This demonstrates that in patients with early LH damage, RH recruitment for language occurs in brain areas homotopic to the LH regions involved in language processing under normal circumstances.

Adult↗

Modulation of the lexical-semantic network by auditory semantic priming: an event-related functional MRI study.

The current event-related fMRI study specifies the neuroanatomical correlates of semantic priming and differences in semantic relation types using an auditory primed lexical decision task (LDT). Word pairs consisted of different relation types, associations (key-chain), pure categorical relations (cow-dog), and unrelated words (table-window), as well as word-pseudoword (way-tinne) and pseudoword-pseudoword (ahurn-döva) pairs. The factor lexical status, i.e., the processing of words compared to pseudowords, was associated with activation in the middle temporal gyri and the left striatum. The factor relatedness, i.e., the contrast between unrelated and related target words, was associated with increased activation of the left inferior frontal gyrus, the deep frontal operculum bilaterally, and the middle frontal gyri. A direct contrast between the two semantic relation types indicated that the processing of purely categorical compared to associative information recruits the right precuneus, the isthmus gyrus cinguli, and the cuneus, suggesting more effortful processing of the former information type. The present data show that the factors lexical status, semantic relatedness, and type of semantic relation in a primed LDT modulate the hemodynamic response in cerebral areas that subserve auditory word recognition and subsequent lexical-semantic processing.

Adult↗

A dual-route account for access to grammatical gender: evidence from functional MRI.

Research investigating the neural correlates of grammatical gender processing has provided contradictory evidence with respect to activation in the left inferior frontal gyrus (IFG). A possible account for these discrepancies is a dual-route model proposing explicit vs implicit access to the gender information. In this event-related fMRI experiment, we investigated this issue by taking into account different processing strategies reported by the subjects. The participants performed two tasks, a gender judgement of German nouns and a non-lexical baseline task (spacing of consonant letter strings). Depending on the reported strategy (silent production of the definite determiner or direct access to the gender information), different patterns of activation in the left IFG were observed. Direct access to gender information yielded activation in the inferior tip of BA 44, whereas the verbalisation strategy elicited activation in the superior portion of BA 44, BA 45/47, and the fronto-median wall. These results speak in favour of a dual-route account for modelling the access to grammatical gender information during language comprehension.

Adolescent↗

Relationship between tumour growth rate and carbogen-based functional MRI for a chemically induced HCC in mice.

We previously performed MRI studies of HCC (hepatocellular carcinomas) in mice showing the feasibility of measuring a carbogen effect. In the present study carbogen response of the whole tumour was compared with growth characteristics during longitudinal follow-up. HCC were chemically induced. The imaging protocol at 4.7 T comprised a fast spin-echo sequence for high-resolution screening and measurement of growth curves, and a fast gradient echo sequence allowing an entire T2*w image acquisition per respiratory cycle to perform fMRI under carbogen breathing. A new parameter, T+, the fraction of tumour voxels with increased intensity under carbogen was measured on manually defined ROIs. Twenty-two HCC were followed for 3-10 weeks. Tumours were divided into two groups, "regularly" and "irregularly" growing tumours. A linear correlation between T+ and tumour growth rate was observed only for "regularly" growing HCC. These results suggest a link between tumour growth rates and tumour fractions exhibiting signal increase upon carbogen breathing. They are compatible with observations by others that rapidly growing tumours are more hypoxic than slowly growing ones. Combined measurement of T+ and tumour growth may become a useful noninvasive follow-up approach for assessment and/or management of therapies involving vasculature-targeting and anti-proliferative drugs.

Animals↗

Functional MRI of brain during breath holding at 4 T.

Both theoretical considerations and animal experiments predict increased signal intensity in brain cortex on T2*-weighted images that develops over a breath hold period. This has not been observed in recent human studies performed at 1.0 and 1.5 T. To clarify this inconsistency, we undertook a study in normal volunteers at 4.0 T. Unlike the earlier studies, we observed a 3-10% signal intensity increase in the gray matter. Possible reasons for the discrepant results are discussed. We conclude that regional cerebral hemodynamics are observable by fMRI in man and this may have clinical applications.

Artifacts↗

Mapping drug-induced changes in cerebral R2* by Multiple Gradient Recalled Echo functional MRI.

A multiple Gradient Recalled Echo MRI sequence was used to map spatial and temporal changes in the rate of MR signal decay (R2*) in response to L-3,4-dihydroxyphenylalanine (levodopa) in the striatal dopaminergic system of a rhesus monkey unilaterally lesioned with 4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). R2* decreased significantly in the right (dopamine depleted) putamen and caudate following levodopa. More focal areas of smaller R2* decline were also observed in these structures in the left hemisphere. The observed spatial and temporal patterns of R2* change support the view that the method is monitoring changes in neural activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Noninvasive analysis of coronary artery disease with combination of MDCT and functional MRI.

RATIONALE AND OBJECTIVES: We evaluated the diagnostic accuracy of an eight-row multidetector computed tomography coronary angiography (MDCT-CA) in detecting high-grade (>50%) stenoses in the three main coronary arteries in patients with coronary artery disease (CAD). Side branches were excluded. We correlated magnetic resonance imaging (MRI) findings of the myocardium with MDCT-CA of the coronary arteries. MATERIALS AND METHODS: Fourteen CAD patients underwent conventional coronary angiography (CCA), MDCT-CA, and MRI. We determined the calcium burden with non-enhanced MDCT scan. Then MDCT-CA was performed after intravenous contrast injection during a single breathhold. The left ventricular (LV) MR cine imaging was assessed at rest and perfusion defects were observed during pharmacologic stress after contrast administration. Delayed contrast-enhanced MRI was performed to picture infarctions. RESULTS: MDCT-CA had sensitivity 82%, specificity 94%, positive predictive value 79%, and negative predictive value 95% of stenoses of more than 50% in the main coronary arteries when compared with CCA. LV wall dysfunction, perfusion defects, and infarctions were detected in 50%-78% of sectors assigned to calcifications or stenoses, but also in sectors supplied by normally perfused coronary arteries. CONCLUSIONS: CCA and MDCT-CA revealed comparable results in evaluating stenotic lesions above 50% in the main subepicardial coronary branches. There were no significant correlations between the degree of stenosis or calcification at MDCT-CA and the MR findings, but the combined information of MDCT-CA and MRI showed the variability of myocardial changes in regions perfused by significantly stenosed, calcified, and normal main coronary arteries.

Adult↗

Functional MRI of conventional and anomalous metaphors in Mandarin Chinese.

This study looks at whether conventional and anomalous metaphors are processed in different locations in the brain while being read when compared with a literal condition in Mandarin Chinese. We find that conventional metaphors differ from the literal condition with a slight amount of increased activation in the right inferior temporal gyrus. In addition, when the anomalous metaphor condition is compared with the literal condition, increased activation occurs bilaterally in the frontal and temporal gyri. Lastly, the comparison between the anomalous and conventional metaphor conditions shows bilateral activation in the middle frontal gyrus and the precentral gyrus, and right-hemisphere activation in the superior frontal gyrus. Left hemisphere activation is found in the inferior frontal gyrus and fusiform gyrus. The left hemisphere activation in the frontal and temporal gyri point to the recruitment of traditional language-based areas for anomalous metaphor sentences, while the right-hemisphere activation found suggests that remote associations are being formed. In short, our study supports the idea that metaphors are not a homogenous type of figurative language and that distinguishing between different types of metaphors will advance theories of language comprehension.

Adult↗

Age-related differences in response regulation as revealed by functional MRI.

This fMRI study studied age-related differences in neural activities during response regulation. Twenty-one male participants from two age groups, a younger group and an older group (mean ages: 29.9 and 65.2 years, respectively), were scanned while performing a task with response compatibility manipulation. They were presented with a sequence of arrowheads that pointed either upward or downward. In the "Response Compatible" condition, they were required to press an up or a down button consistent with the direction of the arrowhead. In the "Response Incompatible" condition, they were required to press the button opposite to the arrowhead direction so that an upward arrow should elicit a down response, and vice versa. Findings showed age-related differences in response regulation in several brain regions, including the right frontal, the right cingulate, and the left inferior parietal cortexes. The findings suggested a higher level of neural activity in the right prefrontal and left inferior parietal regions during response regulation for the older adults than for the younger adults.

Adult↗

Polysyllabic pseudo-word processing in reading and lexical decision: converging evidence from behavioral data, connectionist simulations and functional MRI.

The cognitive mechanisms involved in polysyllabic pseudo-word processing -- and their neurobiological correlates -- were studied through the analysis of length effects on French words and pseudo-words in reading and lexical decision. Connectionist simulations conducted on the ACV98 network paralleled the behavioral data in showing a strong length effect on naming latencies for pseudo-words only and the absence of length effect for both words and pseudo-words in lexical decision. Length effects in reading were characterized at the neurobiological level by a significant and specific activity increase for pseudo-words as compared to words in the right lingual gyrus (BA 19), the left superior parietal lobule and precuneus (BA7), the left middle temporal gyrus (BA21) and the left cerebellum. The behavioral results suggest that polysyllabic pseudo-word reading mainly relies on an analytic procedure. At the biological level, additional activations in visual and visual attentional brain areas during long pseudo-word reading emphasize the role of visual and visual attentional processes in pseudo-word reading. The present findings place important constraints on theories of reading in suggesting the involvement of a serial mechanism based on visual attentional processing in pseudo-word reading.

Adult↗