FMRI group analysis combining effect estimates and their variances.

Conventional functional magnetic resonance imaging (FMRI) group analysis makes two key assumptions that are not always justified. First, the data from each subject is condensed into a single number per voxel, under the assumption that within-subject variance for the effect of interest is the same across all subjects or is negligible relative to the cross-subject variance. Second, it is assumed that all data values are drawn from the same Gaussian distribution with no outliers. We propose an approach that does not make such strong assumptions, and present a computationally efficient frequentist approach to FMRI group analysis, which we term mixed-effects multilevel analysis (MEMA), that incorporates both the variability across subjects and the precision estimate of each effect of interest from individual subject analyses. On average, the more accurate tests result in higher statistical power, especially when conventional variance assumptions do not hold, or in the presence of outliers. In addition, various heterogeneity measures are available with MEMA that may assist the investigator in further improving the modeling. Our method allows group effect t-tests and comparisons among conditions and among groups. In addition, it has the capability to incorporate subject-specific covariates such as age, IQ, or behavioral data. Simulations were performed to illustrate power comparisons and the capability of controlling type I errors among various significance testing methods, and the results indicated that the testing statistic we adopted struck a good balance between power gain and type I error control. Our approach is instantiated in an open-source, freely distributed program that may be used on any dataset stored in the universal neuroimaging file transfer (NIfTI) format. To date, the main impediment for more accurate testing that incorporates both within- and cross-subject variability has been the high computational cost. Our efficient implementation makes this approach practical. We recommend its use in lieu of the less accurate approach in the conventional group analysis.

A neural basis for interindividual differences in the McGurk effect, a multisensory speech illusion.

The McGurk effect is a compelling illusion in which humans perceive mismatched audiovisual speech as a completely different syllable. However, some normal individuals do not experience the illusion, reporting that the stimulus sounds the same with or without visual input. Converging evidence suggests that the left superior temporal sulcus (STS) is critical for audiovisual integration during speech perception. We used blood-oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) to measure brain activity as McGurk perceivers and non-perceivers were presented with congruent audiovisual syllables, McGurk audiovisual syllables, and non-McGurk incongruent syllables. The inferior frontal gyrus showed an effect of stimulus condition (greater responses for incongruent stimuli) but not susceptibility group, while the left auditory cortex showed an effect of susceptibility group (greater response in susceptible individuals) but not stimulus condition. Only one brain region, the left STS, showed a significant effect of both susceptibility and stimulus condition. The amplitude of the response in the left STS was significantly correlated with the likelihood of perceiving the McGurk effect: a weak STS response meant that a subject was less likely to perceive the McGurk effect, while a strong response meant that a subject was more likely to perceive it. These results suggest that the left STS is a key locus for interindividual differences in speech perception.

Neural correlates of interindividual differences in children's audiovisual speech perception.

Children use information from both the auditory and visual modalities to aid in understanding speech. A dramatic illustration of this multisensory integration is the McGurk effect, an illusion in which an auditory syllable is perceived differently when it is paired with an incongruent mouth movement. However, there are significant interindividual differences in McGurk perception: some children never perceive the illusion, while others always do. Because converging evidence suggests that the posterior superior temporal sulcus (STS) is a critical site for multisensory integration, we hypothesized that activity within the STS would predict susceptibility to the McGurk effect. To test this idea, we used BOLD fMRI in 17 children aged 6-12 years to measure brain responses to the following three audiovisual stimulus categories: McGurk incongruent, non-McGurk incongruent, and congruent syllables. Two separate analysis approaches, one using independent functional localizers and another using whole-brain voxel-based regression, showed differences in the left STS between perceivers and nonperceivers. The STS of McGurk perceivers responded significantly more than that of nonperceivers to McGurk syllables, but not to other stimuli, and perceivers' hemodynamic responses in the STS were significantly prolonged. In addition to the STS, weaker differences between perceivers and nonperceivers were observed in the fusiform face area and extrastriate visual cortex. These results suggest that the STS is an important source of interindividual variability in children's audiovisual speech perception.

The developmental trajectory of brain-scalp distance from birth through childhood: implications for functional neuroimaging.

Measurements of human brain function in children are of increasing interest in cognitive neuroscience. Many techniques for brain mapping used in children, including functional near-infrared spectroscopy (fNIRS), electroencephalography (EEG), magnetoencephalography (MEG) and transcranial magnetic stimulation (TMS), use probes placed on or near the scalp. The distance between the scalp and the brain is a key variable for these techniques because optical, electrical and magnetic signals are attenuated by distance. However, little is known about how scalp-brain distance differs between different cortical regions in children or how it changes with development. We investigated scalp-brain distance in 71 children, from newborn to age 12 years, using structural T1-weighted MRI scans of the whole head. Three-dimensional reconstructions were created from the scalp surface to allow for accurate calculation of brain-scalp distance. Nine brain landmarks in different cortical regions were manually selected in each subject based on the published fNIRS literature. Significant effects were found for age, cortical region and hemisphere. Brain-scalp distances were lowest in young children, and increased with age to up to double the newborn distance. There were also dramatic differences between brain regions, with up to 50% differences between landmarks. In frontal and temporal regions, scalp-brain distances were significantly greater in the right hemisphere than in the left hemisphere. The largest contributors to developmental changes in brain-scalp distance were increases in the corticospinal fluid (CSF) and inner table of the cranium. These results have important implications for functional imaging studies of children: age and brain-region related differences in fNIRS signals could be due to the confounding factor of brain-scalp distance and not true differences in brain activity.

Dynamic changes in superior temporal sulcus connectivity during perception of noisy audiovisual speech.

Humans are remarkably adept at understanding speech, even when it is contaminated by noise. Multisensory integration may explain some of this ability: combining independent information from the auditory modality (vocalizations) and the visual modality (mouth movements) reduces noise and increases accuracy. Converging evidence suggests that the superior temporal sulcus (STS) is a critical brain area for multisensory integration, but little is known about its role in the perception of noisy speech. Behavioral studies have shown that perceptual judgments are weighted by the reliability of the sensory modality: more reliable modalities are weighted more strongly, even if the reliability changes rapidly. We hypothesized that changes in the functional connectivity of STS with auditory and visual cortex could provide a neural mechanism for perceptual reliability weighting. To test this idea, we performed five blood oxygenation level-dependent functional magnetic resonance imaging and behavioral experiments in 34 healthy subjects. We found increased functional connectivity between the STS and auditory cortex when the auditory modality was more reliable (less noisy) and increased functional connectivity between the STS and visual cortex when the visual modality was more reliable, even when the reliability changed rapidly during presentation of successive words. This finding matched the results of a behavioral experiment in which the perception of incongruent audiovisual syllables was biased toward the more reliable modality, even with rapidly changing reliability. Changes in STS functional connectivity may be an important neural mechanism underlying the perception of noisy speech.

fMRI-Guided transcranial magnetic stimulation reveals that the superior temporal sulcus is a cortical locus of the McGurk effect.

A compelling example of auditory-visual multisensory integration is the McGurk effect, in which an auditory syllable is perceived very differently depending on whether it is accompanied by a visual movie of a speaker pronouncing the same syllable or a different, incongruent syllable. Anatomical and physiological studies in human and nonhuman primates have suggested that the superior temporal sulcus (STS) is involved in auditory-visual integration for both speech and nonspeech stimuli. We hypothesized that the STS plays a critical role in the creation of the McGurk percept. Because the location of multisensory integration in the STS varies from subject to subject, the location of auditory-visual speech processing in the STS was first identified in each subject with fMRI. Then, activity in this region of the STS was disrupted with single-pulse transcranial magnetic stimulation (TMS) as subjects rated their percept of McGurk and non-McGurk stimuli. Across three experiments, TMS of the STS significantly reduced the likelihood of the McGurk percept but did not interfere with perception of non-McGurk stimuli. TMS of the STS was effective at disrupting the McGurk effect only in a narrow temporal window from 100 ms before auditory syllable onset to 100 ms after onset, and TMS of a control location did not influence perception of McGurk or control stimuli. These results demonstrate that the STS plays a critical role in the McGurk effect and auditory-visual integration of speech.

Relationship between collagen autofluorescence of the human cervix and menopausal status.

The goal of this study was to evaluate the effect of different menopausal states (pre- and post-) on the endogenous fluorescence of normal cervical tissues. In particular, the average fluorescence as well as the interpatient and intrasample variability in the average fluorescence of the epithelium and stroma were evaluated as a function of pre- and postmenopausal states. High-resolution fluorescence images at excitation-emission wavelengths of 440, 520 nm and 365, 465 nm were obtained from epithelia and stroma of freeze-trapped cervical tissue blocks maintained at -196 degrees C. The fluorescence images were recorded using a low temperature optical scanner. Fluorescence images from a normal sample population (n = 27) were quantitatively analyzed, and the average epithelial and stromal fluorescence intensities were obtained. Data grouped according to menopausal status (pre- vs post-) showed statistically significant differences (P < 0.002) in stromal fluorescence. In particular, the cervical stroma of postmenopausal women showed (1) significantly greater average fluorescence and (2) greater interpatient and intrasample variability in the fluorescence, relative to that of premenopausal women. These results provide evidence for changes in collagen cross-linking with menopause.