A.M. Dale

Stochastic designs in event-related fMRI.

This article considers the efficiency of event-related fMRI designs in terms of the optimum temporal pattern of stimulus or trial presentations. The distinction between stochastic and deterministic is used to distinguish between designs that are specified in terms of the probability that an event will occur at a series of time points (stochastic) and those in which events always occur at prespecified time (deterministic). Stochastic designs may be stationary, in which the probability is constant, or nonstationary, in which the probabilities change with time. All these designs can be parameterized in terms of a vector of occurrence probabilities and a prototypic design matrix that embodies constraints (such as the minimum stimulus onset asynchrony) and the model of hemodynamic responses. A simple function of these parameters is presented and used to compare the relative efficiency of different designs. Designs with slow modulation of occurrence probabilities are generally more efficient than stationary designs. Interestingly the most efficient design is a conventional block design. A critical point, made in this article, is that the most efficient design for one effect may not be the most efficient for another. This is particularly important when considering evoked responses and the differences among responses. The most efficient designs for evoked responses, as opposed to differential responses, require trial-free periods during which baseline levels can be attained. In the context of stochastic, rapid-presentation designs this is equivalent to the inclusion of null events.

Age-Related Changes in Prefrontal White Matter Measured by Diffusion Tensor Imaging

Age‐related degeneration of brain white matter (WM) has received a great deal of attention, with recent studies demonstrating that such changes are correlated with cognitive decline and increased risk for the development of age‐related neurodegenerative disease. Past studies have used magnetic resonance imaging (MRI) to measure the volume of normal and abnormal tissue signal as an index of tissue pathology. More recently, diffusion tensor MRI (DTI) has been employed to obtain regional measures of tissue microstructure, such as fractional anisotropy (FA), providing better spatial resolution and potentially more sensitive metrics of tissue damage than traditional volumetric measures. We used DTI to examine the regional basis of age‐related alterations in prefrontal WM. As expected from prior volumetric and DTI studies, prefrontal FA was reduced in older adults (OA) compared to young adults (YA). Although WM volume has been reported to be relatively preserved until late aging, FA was significantly reduced by middle age. Much of prefrontal WM showed reduced FA with increasing age. Ventromedial and deep prefrontal regions showed a somewhat greater reduction compared to other prefrontal areas. Prefrontal WM anisotropy correlated with prefrontal WM volume, but the correlation was significant only when the analysis was limited to participants over age 40. This evidence of widespread and regionally accelerated alterations in prefrontal WM with aging illustrates FAs potential as a microstructural index of volumetric measures.

Regional rates of neocortical atrophy from normal aging to early Alzheimer disease

Objective: To evaluate the spatial pattern and regional rates of neocortical atrophy from normal aging to early Alzheimer disease (AD). Methods: Longitudinal MRI data were analyzed using high-throughput image analysis procedures for 472 individuals diagnosed as normal, mild cognitive impairment (MCI), or AD. Participants were divided into 4 groups based on Clinical Dementia Rating Sum of Boxes score (CDR-SB). Annual atrophy rates were derived by calculating percent cortical volume loss between baseline and 12-month scans. Repeated-measures analyses of covariance were used to evaluate group differences in atrophy rates across regions as a function of impairment. Planned comparisons were used to evaluate the change in atrophy rates across levels of disease severity. Results: In patients with MCI–CDR-SB 0.5–1, annual atrophy rates were greatest in medial temporal, middle and inferior lateral temporal, inferior parietal, and posterior cingulate. With increased impairment (MCI–CDR-SB 1.5–2.5), atrophy spread to parietal, frontal, and lateral occipital cortex, followed by anterior cingulate cortex. Analysis of regional trajectories revealed increasing rates of atrophy across all neocortical regions with clinical impairment. However, increases in atrophy rates were greater in early disease within medial temporal cortex, whereas increases in atrophy rates were greater at later stages in prefrontal, parietal, posterior temporal, parietal, and cingulate cortex. Conclusions: Atrophy is not uniform across regions, nor does it follow a linear trajectory. Knowledge of the spatial pattern and rate of decline across the spectrum from normal aging to Alzheimer disease can provide valuable information for detecting early disease and monitoring treatment effects at different stages of disease progression.

Diffusion tensor imaging correlates of memory and language impairments in temporal lobe epilepsy

Objective: To investigate the relationship between white matter tract integrity and language and memory performances in patients with temporal lobe epilepsy (TLE). Methods: Diffusion tensor imaging (DTI) was performed in 17 patients with TLE and 17 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated for six fiber tracts (uncinate fasciculus [UF], arcuate fasciculus [AF], fornix [FORX], parahippocampal cingulum [PHC], inferior fronto-occipital fasciculus [IFOF], and corticospinal tract [CST]). Neuropsychological measures of memory and language were obtained and correlations were performed to evaluate the relationship between DTI and neuropsychological measures. Hierarchical regression was performed to determine unique contributions of each fiber tract to cognitive performances after controlling for age and hippocampal volume (HV). Results: Increases in MD of the left UF, PHC, and IFOF were associated with poorer verbal memory in TLE, as were bilateral increases in MD of the AF, and decreases in FA of the right AF. Increased MD of the AF and UF, and decreased FA of the AF, UF, and left IFOF were related to naming performances. No correlations were found between DTI measures and nonverbal memory or fluency in TLE. Regression analyses revealed that several fibers, including the AF, UF, and IFOF, independently predicted cognitive performances after controlling for HV. Conclusions: The results suggest that structural compromise to multiple fiber tracts is associated with memory and language impairments in patients with temporal lobe epilepsy. Furthermore, we provide initial evidence that diffusion tensor imaging tractography may provide clinically unique information for predicting neuropsychological status in patients with epilepsy. GLOSSARY: AF = arcuate fasciculus; BNT = Boston Naming Test; CST = corticospinal tract; DTI = diffusion tensor imaging; FA = fractional anisotropy; FORX = fornix; HV = hippocampal volume; ICHV = intracranial-adjusted HV; IFOF = inferior fronto-occipital fasciculus; LM = Logical Memory; MD = mean diffusivity; MTS = mesial temporal sclerosis; PHC = parahippocampal cingulum; TLE = temporal lobe epilepsy; UF = uncinate fasciculus; WMS-III = Wechsler Memory Scale–Third Edition.

Spatiotemporal brain imaging of visual-evoked activity using interleaved EEG and fMRI recordings.

Combined analysis of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has the potential to provide higher spatiotemporal resolution than either method alone. In some situations, in which the activity of interest cannot be reliably reproduced (e.g., epilepsy, learning, sleep states), accurate combined analysis requires simultaneous acquisition of EEG and fMRI. Simultaneous measurements ensure that the EEG and fMRI recordings reflect the exact same brain activity state. We took advantage of the spatial filtering properties of the bipolar montage to allow recording of very short (125--250 ms) visual-evoked potentials (VEPs) during fMRI. These EEG and fMRI measurements are of sufficient quality to allow source localization of the cortical generators. In addition, our source localization approach provides a combined EEG/fMRI analysis that does not require any manual selection of fMRI activations or placement of source dipoles. The source of the VEP was found to be located in the occipital cortex. Separate analysis of EEG and fMRI data demonstrated good spatial overlap of the observed activated sites. As expected, the combined EEG/fMRI analysis provided better spatiotemporal resolution than either approach alone. The resulting spatiotemporal movie allows for the millisecond-to-millisecond display of changes in cortical activity caused by visual stimulation. These data reveal two peaks in activity corresponding to the N75 and the P100 components. This type of simultaneous acquisition and analysis allows for the accurate characterization of the location and timing of neurophysiological activity in the human brain.

Global clinical dementia rating of 0.5 in MCI masks variability related to level of function

Objective: To evaluate whether ratings on Clinical Dementia Rating (CDR) items related to instrumental activities of daily living (IADL) are associated with cognitive or brain morphometric characteristics of participants with mild cognitive impairment (MCI) and global CDR scores of 0.5. Methods: Baseline cognitive and morphometric data were analyzed for 283 individuals with MCI who were divided into 2 groups (impaired and intact) based on their scores on the 3 CDR categories assessing IADL. Rates of progression to Alzheimer disease (AD) over 2 years were also compared in the 2 groups. Results: The impaired IADL MCI group showed a more widespread pattern of gray matter loss involving frontal and parietal regions, worse episodic memory and executive functions, and a higher percentage of individuals progressing to AD than the relatively intact IADL MCI group. Conclusions: The results demonstrate the importance of considering functional information captured by the CDR when evaluating individuals with MCI, even though it is not given equal weight in the assignment of the global CDR score. Worse impairment on IADL items was associated with greater involvement of brain regions beyond the mesial temporal lobe. The conventional practice of relying on the global CDR score as currently computed underutilizes valuable IADL information available in the scale, and may delay identification of an important subset of individuals with MCI who are at higher risk of clinical decline.

A surface-based coordinate system for a canonical cortex

Automatic Reconstruction of the Cortical Surface To apply surface-based techniques routinely, the cortical surface reconstruction process must be automated. Several years ago, a method was devised for recovering the complete cortical surface of each hemisphere from high resolution MRI images in the context of improved solutions to the inverse problem for EEG and MEG (2). Since then, these programs have been improved and extended to incorporate functional MRI imaging data (3) (see also http://cogsci.ucsd.edu/~sereno).

Topography of the ipsilateral representation in human visual cortex revealed by fMRI

Purpose. Previously, retinotopic studies of human visual cortex have analyzed input from the contralateral field, because most input to visual cortex is crossed. Here we study the ipsilateral representation in human visual cortex. Methods. We used functional magnetic resonance imaging techniques to image activity in visual cortex while subjects fixated wedge-shaped stimuli containing visual motion. A series of such stimuli, extending 40, 20, 10, 5, and 0 degrees from the vertical meridian, was used to measure the extent of ipsilateral influence in each cortical area. Flattened views of visual cortex were reconstructed. Results. In flattened format, two distinct bands of activation were produced by stimuli 20 degrees from the vertical meridan. Consistent with physiological evidence, human ipsilateral activity was concentrated in nonretinotopic, higher-tier areas, and along the vertical meridian in retinotopic areas. One band lies immediately anterior to human V3A, extending towards inferior parietal cortex. The other band runs antero-posteriorly along the lateral surface, overlying human MT/MSTd. Presumptive human area LIP showed unusually discrete ipsilateral activation, compared to neighboring areas, and area MSTd showed distinctively greater ipsilateral influence compared with immediately adjacent area MT; this is consistent with evidence from macaque monkeys. Additional experiments using non-motion, pictorial stimuli confirm and extend these findings by demonstrating activation that ovelaps highly with that produced by motion, but is shifted ventrally. Conclusions. The ipsilateral visual field representation is thus a highly organized system, topographically well integrated with other landmarks in human visual cortex. The observed transfer of information across the interhemispheric seam may coincide with locations of preferential callosal connections, and is presumably related to the construction of a unitary percept of the visual world.

Event-related FMRI of tactile stimulus detection

Introduction A variety of studies have investigated the effect of vibrotactile frequency, amplitude, and probability of detection on single-unit activity in the primate cortex (e.g., Mountcastle et al., 1969). In this study, we examined the effect of these variables on activation across human cortical regions using event-related fMRI. The event-related fMR1 approach facilitated evaluation of the response to relatively brief stimuli (1-set duration), the derivation of hemodynamic gain functions, and the correlation of correct and incorrect psychophysical responses with the pattern and amplitude of cortical activity.

Regional cortical thinning of the aging brain

Brain atrophy has been reported in a number of MR studies of aging leg ‘) *’ Importantly, age-related alterations in regional volumes . have been correlated with performance on neuropsychological and experimental cognitive tasks ‘3, 41. Thus, changes in cortical morphology may have clinical significance. Similarly, understanding patterns of regional degeneration in the brain may aid in distinguishing between normal aging and preclinical dementia. Volumetric studies have provided valuable information on changes in the brain associated with aging “I. Still, few studies have examined changes over the entire cortex due to the labor-intensive nature of such measurements. We employed measurements of cortical thickness “’ based on accurate, automated reconstmctions of the brain from MR scans 16. ‘I allowing visualization of change across the complete cortical surface. Methods Structural MR scans were obtained from younger (YP; n = 19; mean age = 23.6, 18-31; 9MllOF) and older participants (OP; n = 10; mean age = 75.9.66-89; 3M/7F). All participants were nondemented (CDR = 0). YP were recruited from the Washington University community. OP were recruited through the Washington University Alzheimer’s Disease Center. OP were excluded if they had a history of neurologic, psychiatric, or medical illness that could contribute to dementia. Two to four MP-RAGE scans were averaged per participant (Siemens 1.5-T Vision System, resolution 1 X 1 X 1.25 mm, TR = 9.7ms, TE = 4ms, FA = lo”, TI = 20ms, TD = 500ms). Thickness measurements were obtained by reconstructing representations of the gray/white matter boundary and the cortical surface and then calculating the minimal distance between those two surfaces for each point on the gray/white matter boundary “I. Thickness maps were averaged across participants using a spherical morph to align cortical folding “I. ReSUltS Preliminary results suggested OP had significantly thinner cortex bilaterally in regions including the prefrontal cortex (near Brodmann Area [BA] 44), pre/postcentral regions (near BA 4/6), parietal (near BA 40/39), and occipital cortex (near BA 17/18) with a relative sparing of superior prefrontal cortex (e.g. near BA 8/9) and temporal lobes. The figure shows regions of statistically thinner cortex in OP with red to yellow indicating less to greater significance, respectively). Differences were preliminarily estimated between -0.25 to 0.50 mm. Aging is accompanied by thickness changes in prefrontal, somatosensory and occipital cortex. These conclusions must be considered with caution as there are potential confounds. Importantly, changes in tissue signal properties in aging and disease may contaminate measures of thickness. Additionally, larger groups of matched subjects should be examined. Nonetheless, these preliminary results suggest great promise for using cortical thickness measures to detect preclinical dementia and anatomic changes associated with cognitive decline [91.