Biomedical subjects

A M Dale

Publications and source records attributed to A M Dale.

At least 19 recordsLinked to original sources

PubMed2026

Early-childhood temperament trajectories map onto transdiagnostic psychiatric risk.

Early-childhood temperament is associated with later mental health. Temperament continues to develop throughout the first years of life, and a single assessment cannot capture its trajectory. Whether departures from an individual's developmental trajectory carry psychiatric risk remains unknown. Using data from more than 50,000 children in the Norwegian Mother, Father and Child Cohort Study, we modeled longitudinal temperament at 1.5, 3, and 5 years of age with the FEMA-Long mixed-effects framework. We then quantified each child's departures from their predicted trajectories. Multivariate analysis revealed two transdiagnostic dimensions linking trajectory departures to psychiatric diagnoses across childhood and adolescence. Higher scores on the first dimension were associated with an increased hazard of subsequent ADHD diagnosis (hazard ratio = 1.54), and higher scores on the second with an increased hazard of Asperger syndrome (hazard ratio = 1.64). To examine the genetic basis of these associations, we performed longitudinal GWAS of temperament and conjunctional FDR analysis to detect loci shared with the associated diagnoses. The effects of these loci changed across early childhood, with some strengthening and others attenuating with age. These findings show that departures from predicted temperament trajectories reflect transdiagnostic psychiatric risk with a shared genetic basis. Longitudinal, trajectory-based monitoring could help identify children at elevated psychiatric risk.

Journal Article↗

PubMed1999

The representation of illusory and real contours in human cortical visual areas revealed by functional magnetic resonance imaging.

Illusory contours (perceived edges that exist in the absence of local stimulus borders) demonstrate that perception is an active process, creating features not present in the light patterns striking the retina. Illusory contours are thought to be processed using mechanisms that partially overlap with those of "real" contours, but questions about the neural substrate of these percepts remain. Here, we employed functional magnetic resonance imaging to obtain physiological signals from human visual cortex while subjects viewed different types of contours, both real and illusory. We sampled these signals independently from nine visual areas, each defined by retinotopic or other independent criteria. Using both within- and across-subject analysis, we found evidence for overlapping sites of processing; most areas responded to most types of contours. However, there were distinctive differences in the strength of activity across areas and contour types. Two types of illusory contours differed in the strength of activation of the retinotopic areas, but both types activated crudely retinotopic visual areas, including V3A, V4v, V7, and V8, bilaterally. The extent of activation was largely invariant across a range of stimulus sizes that produce illusory contours perceptually, but it was related to the spatial frequency of displaced-grating stimuli. Finally, there was a striking similarity in the pattern of results for the illusory contour-defined shape and a similar shape defined by stereoscopic depth. These and other results suggest a role in surface perception for this lateral occipital region that includes V3A, V4v, V7, and V8.

Brain Mapping↗

PubMed1999

Functional MRI reveals spatially specific attentional modulation in human primary visual cortex.

Selective visual attention can strongly influence perceptual processing, even for apparently low-level visual stimuli. Although it is largely accepted that attention modulates neural activity in extrastriate visual cortex, the extent to which attention operates in the first cortical stage, striate visual cortex (area V1), remains controversial. Here, functional MRI was used at high field strength (3 T) to study humans during attentionally demanding visual discriminations. Similar, robust attentional modulations were observed in both striate and extrastriate cortical areas. Functional mapping of cortical retinotopy demonstrates that attentional modulations were spatially specific, enhancing responses to attended stimuli and suppressing responses when attention was directed elsewhere. The spatial pattern of modulation reveals a complex attentional window that is consistent with object-based attention but is inconsistent with a simple attentional spotlight. These data suggest that neural processing in V1 is not governed simply by sensory stimulation, but, like extrastriate regions, V1 can be strongly and specifically influenced by attention.

Attention↗

PubMed1999

Cortical surface-based analysis. I. Segmentation and surface reconstruction.

Several properties of the cerebral cortex, including its columnar and laminar organization, as well as the topographic organization of cortical areas, can only be properly understood in the context of the intrinsic two-dimensional structure of the cortical surface. In order to study such cortical properties in humans, it is necessary to obtain an accurate and explicit representation of the cortical surface in individual subjects. Here we describe a set of automated procedures for obtaining accurate reconstructions of the cortical surface, which have been applied to data from more than 100 subjects, requiring little or no manual intervention. Automated routines for unfolding and flattening the cortical surface are described in a companion paper. These procedures allow for the routine use of cortical surface-based analysis and visualization methods in functional brain imaging.

Brain Mapping↗

PubMed1999

Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system.

The surface of the human cerebral cortex is a highly folded sheet with the majority of its surface area buried within folds. As such, it is a difficult domain for computational as well as visualization purposes. We have therefore designed a set of procedures for modifying the representation of the cortical surface to (i) inflate it so that activity buried inside sulci may be visualized, (ii) cut and flatten an entire hemisphere, and (iii) transform a hemisphere into a simple parameterizable surface such as a sphere for the purpose of establishing a surface-based coordinate system.

Artifacts↗

PubMed1999

Utility of vibration thresholds in patients with brachial plexus nerve compression.

The diagnosis of brachial plexus nerve compression is controversial due to the subjective nature of patient symptoms and the lack of objective, quantifiable tests. It has been hypothesized that quantitative sensory evaluation of sensory threshold is the most sensitive method of evaluating nerve compression, particularly in the early stages. This study evaluated the sensitivity and specificity of vibration thresholds for detection of brachial plexus nerve compression. A multiple-frequency vibrometer was used to evaluate 40 control subjects and 35 patients with brachial plexus nerve compression. Calculated sensitivity values were modest (0.49 at 63, 250, and 500 cps) with high specificity values (0.98 at 8 cps) for individual frequencies using a fifth percentile criterion. The low sensitivity values indicate that this instrument is not adequate as a screening device.

Adult↗

PubMed1999

Location of human face-selective cortex with respect to retinotopic areas.

Functional Magnetic Resonance Imaging (fMRI) was used to identify a small area in the human posterior fusiform gyrus that responds selectively to faces (PF). In the same subjects, phase-encoded rotating and expanding checkerboards were used with fMRI to identify the retinotopic visual areas V1, V2, V3, V3A, VP and V4v. PF was found to lie anterior to area V4v, with a small gap present between them. Further recordings in some of the same subjects used moving low-contrast rings to identify the visual motion area MT. PF was found to lie ventral to MT. In addition, preliminary evidence was found using fMRI for a small area that responded to inanimate objects but not to faces in the collateral sulcus medial to PF. The retinotopic visual areas and MT responded equally to faces, control randomized stimuli, and objects. Weakly face-selective responses were also found in ventrolateral occipitotemporal cortex anterior to V4v, as well as in the middle temporal gyrus anterior to MT. We conclude that the fusiform face area in humans lies in non-retinotopic visual association cortex of the ventral form-processing stream, in an area that may be roughly homologous in location to area TF or CITv in monkeys.

Adult↗

PubMed1998

Randomized event-related experimental designs allow for extremely rapid presentation rates using functional MRI.

Previous studies have shown that hemodynamic response overlap severely limits the maximum presentation rate with event-related functional MRI (fMRI) using fixed intertrial experimental designs. Here we demonstrate that the use of randomized experimental designs can largely overcome this limitation, thereby allowing for event-related fMRI experiments with extremely rapid presentation rates. In the first experiment, fMRI time courses were simulated using a fixed intertrial interval design with intervals of 16, 3, and 1 s, and using a randomized design having the same mean intertrial intervals. We found that using fixed intertrial interval designs the transient information decreased with decreasing intertrial intervals, whereas using randomized designs the transient information increased with decreasing mean intertrial intervals. In a second experiment, fMRI data were collected from two subjects using a randomized paradigm with visual hemifield stimuli presented randomly every 500 ms. Robust event-related activation maps and hemodynamic response estimates were obtained. These results demonstrate the feasibility of performing event-related fMRI experiments with rapid, randomized paradigms identical to those used in electrophysiological and behavioral studies, thereby expanding the applicability of event-related fMRI to a whole new range of cognitive neurosciences questions and paradigms.

Cerebrovascular Circulation↗

PubMed1998

Building memories: remembering and forgetting of verbal experiences as predicted by brain activity.

A fundamental question about human memory is why some experiences are remembered whereas others are forgotten. Brain activation during word encoding was measured using blocked and event-related functional magnetic resonance imaging to examine how neural activation differs for subsequently remembered and subsequently forgotten experiences. Results revealed that the ability to later remember a verbal experience is predicted by the magnitude of activation in left prefrontal and temporal cortices during that experience. These findings provide direct evidence that left prefrontal and temporal regions jointly promote memory formation for verbalizable events.

Adolescent↗

PubMed1998

Spatiotemporal imaging of human brain activity using functional MRI constrained magnetoencephalography data: Monte Carlo simulations.

The goal of our research is to develop an experimental and analytical framework for spatiotemporal imaging of human brain function. Preliminary studies suggest that noninvasive spatiotemporal maps of cerebral activity can be produced by combining the high spatial resolution (millimeters) of functional MRI (fMRI) with the high temporal resolution (milliseconds) of electroencephalography (EEG) and magnetoencephalography (MEG). Although MEG and EEG are sensitive to millisecond changes in mental activity, the ability to resolve source localization and timing is limited by the ill-posed "inverse" problem. We conducted Monte Carlo simulations to evaluate the use of MRI constraints in a linear estimation inverse procedure, where fMRI weighting, cortical location and orientation, and sensor noise statistics were realistically incorporated. An error metric was computed to quantify the effects of fMRI invisible ("missing") sources, "extra" fMRI sources, and cortical orientation errors. Our simulation results demonstrate that prior anatomical and functional information from MRI can be used to regularize the EEG/MEG inverse problem, giving an improved solution with high spatial and temporal resolution. An fMRI weighting of approximately 90% was determined to provide the best compromise between separation of activity from correctly localized sources and minimization of error caused by missing sources. The accuracy of the estimate was relatively independent of the number and extent of the sources, allowing for incorporation of physiologically realistic multiple distributed sources. This linear estimation method provides an operator-independent approach for combining information from fMRI, MEG, and EEG and represents a significant advance over traditional dipole modeling.

Brain↗

PubMed1998

Event-related functional MRI: past, present, and future.

The past two decades have seen an enormous growth in the field of human brain mapping. Investigators have extensively exploited techniques such as positron emission tomography and MRI to map patterns of brain activity based on changes in cerebral hemodynamics. However, until recently, most studies have investigated equilibrium changes in blood flow measured over time periods upward of 1 min. The advent of high-speed MRI methods, capable of imaging the entire brain with a temporal resolution of a few seconds, allows for brain mapping based on more transient aspects of the hemodynamic response. Today it is now possible to map changes in cerebrovascular parameters essentially in real time, conferring the ability to observe changes in brain state that occur over time periods of seconds. Furthermore, because robust hemodynamic alterations are detectable after neuronal stimuli lasting only a few tens of milliseconds, a new class of task paradigms designed to measure regional responses to single sensory or cognitive events can now be studied. Such "event related" functional MRI should provide for fundamentally new ways to interrogate brain function, and allow for the direct comparison and ultimately integration of data acquired by using more traditional behavioral and electrophysiological methods.

Brain↗

PubMed1998

Functional analysis of primary visual cortex (V1) in humans.

Human area V1 offers an excellent opportunity to study, using functional MRI, a range of properties in a specific cortical visual area, whose borders are defined objectively and convergently by retinotopic criteria. The retinotopy in V1 (also known as primary visual cortex, striate cortex, or Brodmann's area 17) was defined in each subject by using both stationary and phase-encoded polar coordinate stimuli. Data from V1 and neighboring retinotopic areas were displayed on flattened cortical maps. In additional tests we revealed the paired cortical representations of the monocular "blind spot." We also activated area V1 preferentially (relative to other extrastriate areas) by presenting radial gratings alternating between 6% and 100% contrast. Finally, we showed evidence for orientation selectivity in V1 by measuring transient functional MRI increases produced at the change in response to gratings of differing orientations. By systematically varying the orientations presented, we were able to measure the bandwidth of the orientation "transients" (45 degrees).

Brain Mapping↗

PubMed1998

The representation of the ipsilateral visual field in human cerebral cortex.

Previous studies of cortical retinotopy focused on influences from the contralateral visual field, because ascending inputs to cortex are known to be crossed. Here, functional magnetic resonance imaging was used to demonstrate and analyze an ipsilateral representation in human visual cortex. Moving stimuli, in a range of ipsilateral visual field locations, revealed activity: (i) along the vertical meridian in retinotopic (presumably lower-tier) areas; and (ii) in two large branches anterior to that, in presumptive higher-tier areas. One branch shares the anterior vertical meridian representation in human V3A, extending superiorly toward parietal cortex. The second branch runs antero-posteriorly along lateral visual cortex, overlying motion-selective area MT. Ipsilateral stimuli sparing the region around the vertical meridian representation also produced signal reductions (perhaps reflecting neural inhibition) in areas showing contralaterally driven retinotopy. Systematic sampling across a range of ipsilateral visual field extents revealed significant increases in ipsilateral activation in V3A and V4v, compared with immediately posterior areas V3 and VP. Finally, comparisons between ipsilateral stimuli of different types but equal retinotopic extent showed clear stimulus specificity, consistent with earlier suggestions of a functional segregation of motion vs. form processing in parietal vs. temporal cortex, respectively.

Brain Mapping↗

PubMed1998

Functional-anatomic study of episodic retrieval. II. Selective averaging of event-related fMRI trials to test the retrieval success hypothesis.

In a companion paper (R. L. Buckner et al., 1998, NeuroImage 7, 151-162) we used fMRI to identify brain areas activated by episodic memory retrieval. Prefrontal areas were shown to differentiate component processes related to retrieval success and retrieval effort in block-designed paradigms. Importantly, a right anterior prefrontal area was most active during task blocks involving greatest retrieval success, consistent with an earlier PET study by M. D. Rugg et al. (1996, Brain 119, 2073-2083). However, manipulation of these variables within the context of blocked trials confounds differences related to varying levels of retrieval success with potential shifts in subjects' strategies due to changes in the probability of target events across blocks. To test more rigorously the hypothesis that certain areas are directly related to retrieval success, we adopted recently developed procedures for event-related fMRI. Fourteen subjects studied words under deep encoding and were then tested in a mixed trial paradigm where old and new words were randomly presented. This recognition testing procedure activated similar areas to the blocked trial paradigm, with all areas showing similar levels of activation across old and new items. Of critical importance, significant activation was detected in right anterior prefrontal cortex for new items when subjects correctly indicated they were new (correct rejections). These findings go against the retrieval success hypothesis as formally proposed and provide an important constraint for interpretation of this region's role in episodic retrieval. Furthermore, anterior prefrontal activation was found to occur late, relative to other brain areas, suggesting that it may be involved in retrieval verification or monitoring processes or perhaps even in anticipation of subsequent trial events (although an alternative possibility, that the late onset is mediated by a late vascular response, cannot be ruled out). These findings and their relation to the results obtained in the companion blocked-trial paradigm are discussed.

Adolescent↗

PubMed1998

Functional-anatomic correlates of object priming in humans revealed by rapid presentation event-related fMRI.

Human functional-anatomic correlates of object repetition were explored in a cohort of 20 subjects using fMRI. Subjects performed an object classification task where the target objects were either novel or repeated. Objects appeared rapidly, one every 2 s, in a randomly intermixed task design similar to traditional behavioral, event-related potential (ERP), and single-unit physiological studies. Recently developed event-related fMRI methods were used to analyze the data. Clear effects of repetition were observed. Brain areas in midlevels of the processing hierarchy, including extrastriate visual cortex extending into inferotemporal cortex and left dorsal prefrontal cortex, showed reductions in the amount of activation after repetition. By contrast, early visual areas and output motor areas were activated equally by both novel and repeated objects and did not show effects of repetition, suggesting that the observed correlates of repetition were anatomically selective. We discuss these findings in relation to previous positron emission tomography (PET) and fMRI studies of item repetition and single-unit physiological studies; we also address the broad impact that rapid event-related fMRI is likely to have on functional neuroimaging.

Adolescent↗

PubMed1998

The retinotopy of visual spatial attention.

We used high-field (3T) functional magnetic resonance imaging (fMRI) to label cortical activity due to visual spatial attention, relative to flattened cortical maps of the retinotopy and visual areas from the same human subjects. In the main task, the visual stimulus remained constant, but covert visual spatial attention was varied in both location and load. In each of the extrastriate retinotopic areas, we found MR increases at the representations of the attended target. Similar but smaller increases were found in V1. Decreased MR levels were found in the same cortical locations when attention was directed at retinotopically different locations. In and surrounding area MT+, MR increases were lateralized but not otherwise retinotopic. At the representation of eccentricities central to that of the attended targets, prominent MR decreases occurred during spatial attention.

Attention↗

PubMed1998

Retinotopy and color sensitivity in human visual cortical area V8.

Prior studies suggest the presence of a color-selective area in the inferior occipital-temporal region of human visual cortex. It has been proposed that this human area is homologous to macaque area V4, which is arguably color selective, but this has never been tested directly. To test this model, we compared the location of the human color-selective region to the retinotopic area boundaries in the same subjects, using functional magnetic resonance imaging (fMRI), cortical flattening and retinotopic mapping techniques. The human color-selective region did not match the location of area V4 (neither its dorsal nor ventral subdivisions), as extrapolated from macaque maps. Instead this region coincides with a new retinotopic area that we call 'V8', which includes a distinct representation of the fovea and both upper and lower visual fields. We also tested the response to stimuli that produce color afterimages and found that these stimuli, like real colors, caused preferential activation of V8 but not V4.

Afterimage↗

PubMed1998

Cortical fMRI activation produced by attentive tracking of moving targets.

Attention can be used to keep track of moving items, particularly when there are multiple targets of interest that cannot all be followed with eye movements. Functional magnetic resonance imaging (fMRI) was used to investigate cortical regions involved in attentive tracking. Cortical flattening techniques facilitated within-subject comparisons of activation produced by attentive tracking, visual motion, discrete attention shifts, and eye movements. In the main task, subjects viewed a display of nine green "bouncing balls" and used attention to mentally track a subset of them while fixating. At the start of each attentive-tracking condition, several target balls (e.g., 3/9) turned red for 2 s and then reverted to green. Subjects then used attention to keep track of the previously indicated targets, which were otherwise indistinguishable from the nontargets. Attentive-tracking conditions alternated with passive viewing of the same display when no targets had been indicated. Subjects were pretested with an eye-movement monitor to ensure they could perform the task accurately while fixating. For seven subjects, functional activation was superimposed on each individual's cortically unfolded surface. Comparisons between attentive tracking and passive viewing revealed bilateral activation in parietal cortex (intraparietal sulcus, postcentral sulcus, superior parietal lobule, and precuneus), frontal cortex (frontal eye fields and precentral sulcus), and the MT complex (including motion-selective areas MT and MST). Attentional enhancement was absent in early visual areas and weak in the MT complex. However, in parietal and frontal areas, the signal change produced by the moving stimuli was more than doubled when items were tracked attentively. Comparisons between attentive tracking and attention shifting revealed essentially identical activation patterns that differed only in the magnitude of activation. This suggests that parietal cortex is involved not only in discrete shifts of attention between objects at different spatial locations but also in continuous "attentional pursuit" of moving objects. Attentive-tracking activation patterns were also similar, though not identical, to those produced by eye movements. Taken together, these results suggest that attentive tracking is mediated by a network of areas that includes parietal and frontal regions responsible for attention shifts and eye movements and the MT complex, thought to be responsible for motion perception. These results are consistent with theoretical models of attentive tracking as an attentional process that assigns spatial tags to targets and registers changes in their position, generating a high-level percept of apparent motion.

Adult↗