Positive BOLD Responses Research Articles

Negative BOLD in the visual cortex: evidence against blood stealing.

The positive BOLD (blood oxygen level-dependent) response elicited in human visual cortex by a localized visual stimulus is accompanied by a reduction in the BOLD response in regions of the visual cortex that represent unstimulated locations in the visual field. We have suggested previously that this negative BOLD reflects attention-related suppression of neural activity, but it might also be explained in terms of "blood stealing," i.e., hemodynamic changes that have no neural correlate. We distinguish two possible hemodynamic effects of this type: (1). blood flow reduction caused by locally reduced pressure in vessels that share their blood supply with nearby dilated vessels; and (2). blood flow reduction caused by active constriction of vessels under neural control. The first is ruled out as an explanation of negative BOLD by showing that a visual stimulus that stimulates primary visual cortex in one hemisphere can cause extensive suppression in the other hemisphere i.e., it is not a local phenomenon. Negative BOLD most likely reflects suppression of neural activity, but could also reflect an active blood flow control system.

Combination of event-related fMRI and diffusion tensor imaging in an infant with perinatal stroke

Focal ischemic brain injury, or stroke, is an important cause of later handicap in children. Early assessment of structure–function relationships after such injury will provide insight into clinico-anatomic correlation and potentially guide early intervention strategies. We used combined functional MRI (fMRI) with diffusion tensor imaging (DTI) in a 3-month-old infant to explore the structure–function relationship after unilateral perinatal stroke that involved the visual pathways. With visual stimuli, fMRI showed a negative BOLD activation in the visual cortex of the intact right hemisphere, principally in the anterior part, and no activation in the injured hemisphere. The functional activation in the intact hemisphere correlated clearly with the fiber tract of the optic radiation visualized with DTI. DTI confirmed the absence of the optic radiation in the damaged left hemisphere. In addition, event-related fMRI (ER-fMRI) experiments were performed to define the characteristics of the BOLD response. The shape is that of an inverted gamma function (similar to a negative mirror image of the known positive adult BOLD response). The maximum decrease was reached at 5–7 s with signal changes of −1.7 ± 0.4%. Thus, this report describes for the first time the combined use of DTI and event-related fMRI in an infant and provides insight into the localization of the fMRI visual response in the young infant and the characteristics of the BOLD response.

Abnormal brain activation to visual stimulation in cocaine abusers

Chronic cocaine abuse has been associated with cerebrovascular pathology. This is likely to reflect its vasoactive effects; cocaine produces vasoconstriction and reduces cerebral blood flow. We propose that cerebrovascular pathology in chronic cocaine abusers would result in abnormal BOLD [blood oxygenation level dependent] responses to activation stimuli. Here, we used fMRI to compared the BOLD response to photic visual stimulation in neurologically intact active cocaine abusers to that in non-drug-using healthy controls. Cocaine abusers showed a significantly enhanced positive BOLD response to photic stimulation when compared to control subjects. The enhanced activation in the cocaine abusers could result from low resting cerebral blood flow secondary to increased vasoconstriction and/or from low oxidative metabolism during activation. Alternatively, the larger signal intensity in the cocaine abusers could result from inefficient neuronal processing as has been shown to occur in other conditions of cerebral pathology. These findings provide evidence of cerebral dysfunction with chronic cocaine abuse, which could reflect cerebral blood flow or neuronal changes. Further studies are required to determine if the cerebrovascular changes we observed in the cocaine abusers recover with detoxification and to assess their functional consequences.

Sustained Negative BOLD, Blood Flow and Oxygen Consumption Response and Its Coupling to the Positive Response in the Human Brain

Most fMRI studies are based on the detection of a positive BOLD response (PBR). Here, we demonstrate and characterize a robust sustained negative BOLD response (NBR) in the human occipital cortex, triggered by stimulating part of the visual field. The NBR was spatially adjacent to but segregated from the PBR. It depended on the stimulus and thus on the pattern of neuronal activity. The time courses of the NBR and PBR were similar, and their amplitudes covaried both with increasing stimulus duration and increasing stimulus contrast. The NBR was associated with reductions in blood flow and with decreases in oxygen consumption. Our findings support the contribution to the NBR of (1) a significant component of reduction in neuronal activity and (2) possibly a component of hemodynamic changes independent of the local changes in neuronal activity.

MRI of Functional Deactivation: Temporal and Spatial Characteristics of Oxygenation-Sensitive Responses in Human Visual Cortex

Magnetic resonance imaging (MRI) of neuronal “activation” relies on the elevation of blood flow and oxygenation and a related increase of the blood oxygenation level-dependent (BOLD) MRI signal. Because most cognitive paradigms involve both switches from a low degree of activity to a high degree of activity and vice versa, we have undertaken a baseline study of the temporal and spatial characteristics of positive and negative BOLD MRI responses in human visual cortex. Experiments were performed at 2.0 T using a multislice gradient-echo EPI sequence (TR=1 s, mean TE=54 ms, flip angle 50°) at 2 × 2-mm2spatial resolution. Activation and “deactivation” processes were accomplished by reversing the order of stimulus presentations in paradigms using homogeneous gray light and an alternating checkerboard as distinct functional states. For sustained stimulation (≥60 s) the two conditions resulted in markedly different steady-state BOLD MRI signal strengths. The transient responses to brief stimulation (≤18 s) differed insofar as activation processes temporally separate positive BOLD and negative undershoot effects by about 10 s, whereas negative BOLD effects and undershoot contributions overlap for deactivation processes. Apart from differences in stimulus features (e.g., motion) the used activation and deactivation protocols revealed similar maps of neuronal activity changes.