Biomedical subjects

G L Shulman

Publications and source records attributed to G L Shulman.

At least 19 recordsLinked to original sources

PubMed2001

Blood flow and oxygen delivery to human brain during functional activity: theoretical modeling and experimental data.

Coupling of cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO(2)) in physiologically activated brain states remains the subject of debates. Recently it was suggested that CBF is tightly coupled to oxidative metabolism in a nonlinear fashion. As part of this hypothesis, mathematical models of oxygen delivery to the brain have been described in which disproportionately large increases in CBF are necessary to sustain even small increases in CMRO(2) during activation. We have explored the coupling of CBF and oxygen delivery by using two complementary methods. First, a more complex mathematical model was tested that differs from those recently described in that no assumptions were made regarding tissue oxygen level. Second, [(15)O] water CBF positron emission tomography (PET) studies in nine healthy subjects were conducted during states of visual activation and hypoxia to examine the relationship of CBF and oxygen delivery. In contrast to previous reports, our model showed adequate tissue levels of oxygen could be maintained without the need for increased CBF or oxygen delivery. Similarly, the PET studies demonstrated that the regional increase in CBF during visual activation was not affected by hypoxia. These findings strongly indicate that the increase in CBF associated with physiological activation is regulated by factors other than local requirements in oxygen.

Adult↗

PubMed2001

Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function.

Medial prefrontal cortex (MPFC) is among those brain regions having the highest baseline metabolic activity at rest and one that exhibits decreases from this baseline across a wide variety of goal-directed behaviors in functional imaging studies. This high metabolic rate and this behavior suggest the existence of an organized mode of default brain function, elements of which may be either attenuated or enhanced. Extant data suggest that these MPFC regions may contribute to the neural instantiation of aspects of the multifaceted "self." We explore this important concept by targeting and manipulating elements of MPFC default state activity. In this functional magnetic resonance imaging (fMRI) study, subjects made two judgments, one self-referential, the other not, in response to affectively normed pictures: pleasant vs. unpleasant (an internally cued condition, ICC) and indoors vs. outdoors (an externally cued condition, ECC). The ICC was preferentially associated with activity increases along the dorsal MPFC. These increases were accompanied by decreases in both active task conditions in ventral MPFC. These results support the view that dorsal and ventral MPFC are differentially influenced by attentiondemanding tasks and explicitly self-referential tasks. The presence of self-referential mental activity appears to be associated with increases from the baseline in dorsal MPFC. Reductions in ventral MPFC occurred consistent with the fact that attention-demanding tasks attenuate emotional processing. We posit that both self-referential mental activity and emotional processing represent elements of the default state as represented by activity in MPFC. We suggest that a useful way to explore the neurobiology of the self is to explore the nature of default state activity.

Adult↗

PubMed2001

A default mode of brain function.

A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.

Adult↗

PubMed2001

Multiple neural correlates of detection in the human brain.

We used event-related functional MRI to examine the neural consequences of detecting the presence or absence of a stimulus. Subjects detected a brief interval of coherent motion embedded in dynamic noise that was presented throughout a test period. Several brain regions, including V1/V2, middle temporal complex (MT+), left intraparietal cortex, and the frontal eye field, were activated at the onset of the dynamic noise, irrespective of whether a coherent motion target was presented early or late in the test period, or not at all. These regions, many of which were motion sensitive, were likely involved in searching for and detecting the target. The blood oxygenation level-dependent signal in these regions was higher in trials in which a target was detected than in trials in which it was missed or not presented, indicating that these regions were modulated by detection. Moreover, the blood oxygenation leveldependent signal in these regions decayed quickly once a target was detected, even though the dynamic noise continued to be displayed, indicating that they were shut down after detection. Therefore, detection-related modulations occurred in the same regions that accumulate target information over time, in agreement with current psychological and neural models of detection. Many other regions, however, including areas in prefrontal cortex and anterior cingulate, were not involved in searching for a target. In these regions, activation began early in the test period when an early target was detected but began late in the test period when a late target was detected or when a response was correctly withheld in the absence of a motion target. The signal in these regions was therefore triggered by a discrete event during the test interval that was related to presence-absence detection.

Acoustic Stimulation↗

PubMed2001

Separating processes within a trial in event-related functional MRI I. The Method.

Many behavioral paradigms involve temporally overlapping sensory, cognitive, and motor components within a single trial. The complex interplay among these factors makes it desirable to separate the components of the total response without assumptions about shape of the underlying hemodynamic response. We present a method that does this. Four conditions were studied in four subjects to validate the method. Two conditions involved rapid event-related studies, one with a low-contrast (5%) flickering checkerboard and another with a high-contrast (95%) checkerboard. In the third condition, the same high-contrast checkerboard was presented with widely spaced trials. Finally, multicomponent trials were formed from temporally adjacent low-contrast and high-contrast stimuli. These trials were presented as a rapid event-related study. Low-contrast stimuli presented in isolation (partial trials) made it possible to uniquely estimate both the low-contrast and high-contrast responses. These estimated responses matched those measured in the first three conditions, thereby validating the method. Nonlinear interactions between adjacent low-contrast and high-contrast responses were shown to be significant but weak in two of the four subjects.

Algorithms↗

PubMed2001

Separating processes within a trial in event-related functional MRI II. Analysis.

Many cognitive processes occur on time scales that can significantly affect the shape of the blood oxygenation level-dependent (BOLD) response in event-related functional MRI. This shape can be estimated from event related designs, even if these processes occur in a fixed temporal sequence (J. M. Ollinger, G. L. Shulman, and M. Corbetta. 2001. NeuroImage 13: 210-217). Several important considerations come into play when interpreting these time courses. First, in single subjects, correlations among neighboring time points give the noise a smooth appearance that can be confused with changes in the BOLD response. Second, the variance and degree of correlation among estimated time courses are strongly influenced by the timing of the experimental design. Simulations show that optimal results are obtained if the intertrial intervals are as short as possible, if they follow an exponential distribution with at least three distinct values, and if 40% of the trials are partial trials. These results are not particularly sensitive to the fraction of partial trials, so accurate estimation of time courses can be obtained with lower percentages of partial trials (20-25%). Third, statistical maps can be formed from F statistics computed with the extra sum of square principle or by t statistics computed from the cross-correlation of the time courses with a model for the hemodynamic response. The latter method relies on an accurate model for the hemodynamic response. The most robust model among those tested was a single gamma function. Finally, the power spectrum of the measured BOLD signal in rapid event-related paradigms is similar to that of the noise. Nevertheless, high-pass filtering is desirable if the appropriate model for the hemodynamic response is used.

Algorithms↗

PubMed2000

Voluntary orienting is dissociated from target detection in human posterior parietal cortex.

Human ability to attend to visual stimuli based on their spatial locations requires the parietal cortex. One hypothesis maintains that parietal cortex controls the voluntary orienting of attention toward a location of interest. Another hypothesis emphasizes its role in reorienting attention toward visual targets appearing at unattended locations. Here, using event-related functional magnetic resonance (ER-fMRI), we show that distinct parietal regions mediated these different attentional processes. Cortical activation occurred primarily in the intraparietal sulcus when a location was attended before visual-target presentation, but in the right temporoparietal junction when the target was detected, particularly at an unattended location.

Adolescent↗

PubMed1999

Areas involved in encoding and applying directional expectations to moving objects.

Two experiments used functional magnetic resonance imaging (fMRI) to examine the cortical areas involved in establishing an expectation about the direction of motion of an upcoming object and applying that expectation to the analysis of the object. In Experiment 1, subjects saw a stationary cue that either indicated the direction of motion of a subsequent test stimulus (directional cue) or provided no directional information (neutral cue). Their task was to detect the presence of coherent motion in the test stimulus. The stationary directional cue produced larger modulations than the neutral cue, with respect to a passive viewing baseline, both in motion-sensitive areas such as left MT+ and the anterior intraparietal sulcus, as well as motion-insensitive areas such as the posterior intraparietal sulcus and the junction of the left medial precentral sulcus and superior frontal sulcus. Experiment 2 used an event-related fMRI technique to separate signals during the cue period, in which the expectation was encoded and maintained, from signals during the subsequent test period, in which the expectation was applied to the test object. Cue period activations from a stationary, directional cue included many of the same motion-sensitive and -insensitive areas from Experiment 1 that produced directionally specific modulations. Prefrontal activations were not observed during the cue period, even though the stationary cue information had to be translated into a format appropriate for influencing motion detection, and this format was maintained for the duration of the cue period (approximately 5 sec).

Analysis of Variance↗

PubMed1998

Human cortical mechanisms of visual attention during orienting and search.

Functional anatomical studies indicate that a set of neural signals in parietal and frontal cortex mediates the covert allocation of attention to visual locations across a wide variety of visual tasks. This frontoparietal network includes areas, such as the frontal eye field and supplementary eye field. This anatomical overlap suggests that shifts of attention to visual locations of objects recruit areas involved in oculomotor programming and execution. Finally, the fronto-parietal network may be the source of spatial attentional modulations in the ventral visual system during object recognition or discrimination.

Attention↗

PubMed1998

A common network of functional areas for attention and eye movements.

Functional magnetic resonance imaging (fMRI) and surface-based representations of brain activity were used to compare the functional anatomy of two tasks, one involving covert shifts of attention to peripheral visual stimuli, the other involving both attentional and saccadic shifts to the same stimuli. Overlapping regional networks in parietal, frontal, and temporal lobes were active in both tasks. This anatomical overlap is consistent with the hypothesis that attentional and oculomotor processes are tightly integrated at the neural level.

Adolescent↗

PubMed1998

Effect of motion contrast on human cortical responses to moving stimuli.

The cortical areas activated by motion-defined contours were studied in humans using positron emission tomography (PET). Subjects observed four types of random dot fields, displayed through a 21 degrees diam aperture: unidirectional motion of a translating dot field, motion in opposing directions of two superimposed translating fields, motion in opposing directions of dots in contiguous spatial regions (motion contrast), producing a square wave grating defined by motion, and luminance variation of stationary dots in contiguous spatial regions, producing a square wave grating defined by luminance. Relative to a static dot field, the unidirectional motion condition activated areas previously described, including areas 17/18, lateral temporal-occipital-parietal cortex (MT/MST), and the superior temporal sulcus. Motion-defined gratings increased the activation of areas 17/18 and MT/MST, but not the superior temporal sulcus, and added more dorsal areas in the cuneus, roughly corresponding to V3/V3a, and ventral areas in the lingual gyrus/collateral sulcus, roughly corresponding to V2/VP. Luminance defined gratings, relative to a static dot field, activated areas 17/18, regions in the dorsal cuneus similar to those activated by motion defined gratings, and a region near the left collateral sulcus, slightly lateral to the motion grating activation. They also activated a region in the right fusiform gyrus that was more weakly activated by the motion grating. These results indicate that adding motion contrast to large moving fields increases activity in areas 17/18 and MT/MST and adds both dorsal and ventral regions that are similar for motion and luminance defined contours.

Adult↗

PubMed1995

Superior parietal cortex activation during spatial attention shifts and visual feature conjunction.

Positron emission tomography was used to measure changes in the regional cerebral blood flow of normal people while they searched visual displays for targets defined by color, by motion, or by a conjunction of color and motion. A region in the superior parietal cortex was activated only during the conjunction task, at a location that had previously been shown to be engaged by successive shifts of spatial attention. Correspondingly, the time needed to detect a conjunction target increased with the number of items in the display, which is consistent with the use of a mechanism that successively analyzes each item in the visual field.

Attention↗

PubMed1994

PET studies of parietal involvement in spatial attention: comparison of different task types.

Five experiments are described that concern the mechanisms that direct attention to spatial and non-spatial features of a stimulus and the effects that attention has on the visual system's analysis of that stimulus. Shifts of attention from one spatial location to another activated the superior parietal lobe and this activation was fairly independent of the task performed on the attended object, the response made to the attended object, and whether the shift of attention was controlled endogenously or exogenously. Maintaining attention tonically on a location or a particular visual feature such as shape, colour or motion did not produce a superior parietal response. Tonic attention to a feature (colour, shape, motion) or location, however, did produce enhancements in the response of various regions that are probably specialized for processing the attended visual feature. The activation of superior parietal cortex during shifts of spatial attention as well as the activation of parietal-occipital cortex when attention is tonically maintained on a location suggest that the parietal cortex plays an important role in spatial computations.

Animals↗

PubMed1993

Attentional effects of adaptation of rotary motion in the plane.

The effect of attention on the adaptation effects produced by stimuli rotating in the picture plane was examined in five experiments. In experiment 1, subjects performed a task either on a rotating adapting stimulus or on an irrelevant distractor stimulus. Adaptation of a subsequent ambiguous test stimulus was greater when the adapting stimulus was attended than when the irrelevant stimulus was attended. In experiments 2, 3, and 5, two adapting stimuli were presented, rotating in opposite directions, and subjects attended to one or the other. The direction of rotation of the ambiguous test stimulus depended on which adapting stimulus was attended. In experiment 4, the influence of eye movements in producing adaptation in ambiguous motion displays was determined by contrasting the effects of adaptation produced by dual adaptation stimuli rotating in the same or opposite direction. Adaptation effects were not predicted by eye movement hypotheses.

Attention↗

PubMed1993

A PET study of visuospatial attention.

Positron emission tomography (PET) was used to identify the neural systems involved in shifting spatial attention to visual stimuli in the left or right visual field along foveofugal or foveocentric directions. Psychophysical evidence indicated that stimuli at validly cued locations were responded to faster than stimuli at invalidly cued locations. Reaction times to invalid probes were faster when they were presented in the same than in the opposite direction of an ongoing attention movement. PET evidence indicated that superior parietal and superior frontal cortex were more active when attention was shifted to peripheral locations than when maintained at the center of gaze. Both regions encoded the visual field and not the direction of an attention shift. In the right superior parietal lobe, two distinct responses were localized for attention to left and right visual field. Finally, the superior parietal region was active when peripheral locations were selected on the basis of cognitive or sensory cues independent of the execution of an overt response. The frontal region was active only when responses were made to stimuli at selected peripheral locations. These findings indicate that parietal and frontal regions control different aspects of spatial selection. The functional asymmetry in superior parietal cortex may be relevant for the pathophysiology of unilateral neglect.

Adult↗

PubMed1992

Attentional modulation of a figural aftereffect.

Evidence is reported that indicates that adaptation of the Schroder staircase is affected by attention. In previous work it has been shown that if subjects adapt to an unambiguous staircase, responses to an ambiguous test figure are biased towards the opposing perspective. In the current work, subjects adapted to superimposed upright and inverted Schroder staircases. Both staircases were centered on a common fixation point and were of different sizes and colors. Attention to each staircase was controlled by asking subjects to detect color changes in the line segments that defined one or the other staircase. Responses to an ambiguous test figure depended on which of the adapting staircases was attended.

Adaptation, Ocular↗

PubMed1992

Attentional modulation of size contrast.

A test circle surrounded by smaller context circles appears larger if presented in isolation, whereas a test circle surrounded by large context circles is seen as smaller than in isolation. Two experiments are reported indicating that this phenomenon, the Ebbinghaus illusion, depends on whether subjects are attending to the context circles. Subjects first saw a reference circle and then a briefly presented (150 msec) test circle. Their task was to determine whether the test circle was larger or smaller than the reference. The test circle was surrounded by smaller context circles of one colour arrayed along a horizontal axis centred on the test, and larger context circles of a different colour arrayed along a vertical axis centred on the test. Subjects judged both the size of the test and the colours of either the small or large context circles. Perceived test size changed systematically, depending on which context circles were task-relevant.

Attention↗

PubMed1991

Selective attention modulates extrastriate visual regions in humans during visual feature discrimination and recognition.

Positron emission tomography (PET) was used to identify regions of the human visual system which were selectively modulated by attention during feature discrimination and recognition tasks. In a first experiment, subjects were cued to the shape, colour or speed of visual stimulus arrays during a same-different match-to-sample paradigm. The psychophysical sensitivity for discriminating subtle attribute variations was enhanced by selective attention. Correspondingly, the neural activity (as measured by blood flow changes) in different visual associative regions was enhanced when subjects attended to different attributes of the same stimulus (intraparietal sulcus for speed; collateral sulcus and dorsolateral occipital cortex for colour; collateral sulcus, fusiform and parahippocampal gyri, superior temporal sulcus for shape). These regions appeared to be specialized for processing the selected attribute. Attention to a visual feature, therefore, enhances the psychophysical sensitivity as well as the neural activity of specialized processing regions of the human visual system. In a second experiment the effect of target probability (which biases attentional selection) was studied during visual search tasks involving the recognition of a single-feature (i.e. colour) or a feature-conjunction (i.e. colour x orientation) target. Target probability positively modulated neural activity of extrastriate visual regions, which were related to the single-feature or feature-conjunction processing level. These results suggest that selective attention can influence different processing levels in the visual system, possibly reflecting a facilitatory effect on different visual computations or task components.

Attention↗