As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting-state networks (RSNs) of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12–71 years). Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. RSNs were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functional network connectivity. Results revealed robust effects of age on all three outcome measures, largely indicating decreases in network coherence and connectivity with increasing age. Gender effects were of smaller magnitude but suggested stronger intra-network connectivity in females and more inter-network connectivity in males, particularly with regard to sensorimotor networks. These findings, along with the analysis approach and statistical framework described here, provide a useful baseline for future investigations of brain networks in health and disease.

4AbstrackThis study investigated the cortical sources of the early (5&250 ms) components of the pattern-onset visual evoked potential (VEP). VEPs were recorded in response to a small circular checkerboard stimulus that was flashed over a range of visual field positions. Temporally and spatially overlapping VEP components were distinguished by differences in retinotopic sensitivity and scalp topography, and by inverse dipole modeling. The C1 component (5Cr80 ms) was found to change its polarity and topography systematically as a function of stimulus position in a manner consistent with the retinotopic organization of the striate cortex. The P1 component (comprised of the P75 and PlO0 subcomponents) had a time course that overlapped the C1 but could be distinguished from the C1 by its differing topography and reduced sensitivity to stimulus position. The P1 generators were localized to the lateral extrastriate cortex. Inverse dipole models were consistent with these striate and extrastriate source locations for the C1 and P1, respectively. The N1 component (120-180 ms) was found to originate from several spatially distinct generators that differed in their retinotopic organization.

Three experiments were conducted to determine whether attention-related changes in luminance detectability reflect a modulation of early sensory processing. Experiments 1 and 2 used peripheral cues to direct attention and found substantial effects of cue validity on target detectability; these effects were consistent with a sensory-level locus of selection but not with certain memory- or decision-level mechanisms. In Experiment 3, event-related brain potentials were recorded in a similar paradigm using central cues, and attention was found to produce changes in sensory-evoked brain activity beginning within the 1st 100 ms of stimulus processing. These changes included both an enhancement of sensory responses to attended stimuli and a suppression of sensory responses to unattended stimuli; the enhancement and suppression effects were isolated to different neural responses, indicating that they may arise from independent attentional mechanisms.

The differential effect of stimulus inversion on face and object recognition suggests that inverted faces are processed by mechanisms for the perception of other objects rather than by face perception mechanisms. We investigated the face inversion using functional magnetic resonance imaging (fMRI). The principal effect of face inversion on was an increased response in ventral extrastriate regions that respond preferentially to another class of objects (houses). In contrast, house inversion did not produce a similar change in face-selective regions. Moreover, stimulus inversion had equivalent, minimal effects for faces in in face-selective regions and for houses in house-selective regions. The results suggest that the failure of face perception systems with inverted faces leads to the recruitment of processing resources in object perception systems, but this failure is not reflected by altered activity in face perception systems.

The effects of spatial selective attention on sensory processing in visual cortical areas were investigated by means of visual evoked potential (VEP) recordings and source localization techniques. Patterned stimuli were rapidly presented in random order to the left and right visual fields while subjects maintained central fixation and attended to one visual field at a time. Attended stimuli evoked enhanced P1 (100-130 msec) and N1 (120-200 msec) components of the VEP, whereas no effects of attention were observed on the C1 (50-100 msec) or P2 (200-240 msec) components. Spatiotemporal dipole modeling of the early VEP sources was carried out in relation to MRI-defined cortical anatomy. The dipolar generator of the C1 component was found to lie in calcarine cortex, the human homologue of area V1, whereas the attention-sensitive P1 generator was localized to ventral-lateral occipital cortex, within extrastriate area 19. These results support the hypothesis that spatial attention does not affect the initial activity evoked in area V1 but rather produces an enhancement within extrastriate visual areas of sensory signals arising from stimuli at attended locations.

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.Significance StatementLeft-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.

Previous studies have found that the P300 or P3 event-related potential (ERP) component is useful in the diagnosis and treatment of many disorders that influence CNS function. However, the anatomic locations of brain regions involved in this response are not precisely known. In the present event-related functional magnetic resonance imaging (fMRI) study, methods of stimulus presentation, data acquisition, and data analysis were optimized for the detection of brain activity in response to stimuli presented in the three-stimulus oddball task. This paradigm involves the interleaved, pseudorandom presentation of single block-letter target and distractor stimuli that previously were found to generate the P3b and P3a ERP subcomponents, respectively, and frequent standard stimuli. Target stimuli evoked fMRI signal increases in multiple brain regions including the thalamus, the bilateral cerebellum, and the occipital-temporal cortex as well as bilateral superior, medial, inferior frontal, inferior parietal, superior temporal, precentral, postcentral, cingulate, insular, left middle temporal, and right middle frontal gyri. Distractor stimuli evoked an fMRI signal change bilaterally in inferior anterior cingulate, medial frontal, inferior frontal, and right superior frontal gyri, with additional activity in bilateral inferior parietal lobules, lateral cerebellar hemispheres and vermis, and left fusiform, middle occipital, and superior temporal gyri. Significant variation in the amplitude and polarity of distractor-evoked activity was observed across stimulus repetitions. No overlap was observed between target- and distractor-evoked activity. These event-related fMRI results shed light on the anatomy of responses to target and distractor stimuli that have proven useful in many ERP studies of healthy and clinically impaired populations.

In a study of the neural processes that mediate visual attention in humans, 32-channel recordings of event-related potentials were obtained from 14 normal subjects while they performed a spatial attention task. The generator locations of the early C1, P1, and N1 components of the visual evoked response were estimated by means of topographic maps of voltage and current source density in conjunction with dipole modelling. The topography of the C1 component (ca. 85 ms post-stimulus) was consistent with a generator in striate cortex, and this component was unaffected by attention. In contrast, the P1 and N1 components (ca. 95 and 170 ms) exhibited current density foci at scalp sites overlying lateral extrastriate cortex and were larger for attended stimuli than for unattended stimuli. The voltage topographies in the 75-175 ms latency range were modeled with a 5-dipole configuration consisting of a single striate dipole and left-right pairs of dipoles located in lateral extrastriate and inferior occipito-temporal areas. This model was found to account for the voltage topographies produced by both attended and unattended stimuli with low residual variance. These results support the proposal that visual-spatial attention modulates neural activity in extrastriate visual cortex but does not affect the initial evoked response in striate cortex.