Conscious perception and the modulatory role of dopamine: no effect of the dopamine D2 agonist cabergoline on visual masking, the attentional blink, and probabilistic discrimination.

RATIONALE: Conscious perception is thought to depend on global amplification of sensory input. In recent years, striatal dopamine has been proposed to be involved in gating information and conscious access, due to its modulatory influence on thalamocortical connectivity. OBJECTIVES: Since much of the evidence that implicates striatal dopamine is correlational, we conducted a double-blind crossover pharmacological study in which we administered cabergoline-a dopamine D2 agonist-and placebo to 30 healthy participants. Under both conditions, we subjected participants to several well-established experimental conscious-perception paradigms, such as backward masking and the attentional blink task. RESULTS: We found no evidence in support of an effect of cabergoline on conscious perception: key behavioral and event-related potential (ERP) findings associated with each of these tasks were unaffected by cabergoline. CONCLUSIONS: Our results cast doubt on a causal role for dopamine in visual perception. It remains an open possibility that dopamine has causal effects in other tasks, perhaps where perceptual uncertainty is more prominent.

Dopamine and temporal attention: An attentional blink study in Parkinson's disease patients on and off medication.

The current study aimed to shed more light on the role of dopamine in temporal attention. To this end, we pharmacologically manipulated dopamine levels in a large sample of Parkinson's disease patients (n=63) while they performed an attentional blink (AB) task in which they had to identify two targets (T1 and T2) presented in close temporal proximity among distractors. We specifically examined 1) differences in the magnitude of the AB between unmedicated Parkinson patients, who have depleted levels of striatal dopamine, and healthy controls, and 2) effects of two dopaminergic medications (l-DOPA and dopamine agonists) on the AB in the Parkinson patients at the group level and as a function of individual baseline performance. In line with the notion that relatively low levels of striatal dopamine may impair target detection in general, Parkinson patients OFF medications displayed overall poor target perception compared to healthy controls. Moreover, as predicted, effects of dopaminergic medication on AB performance critically depended on individual baseline AB size, although this effect was only observed for l-DOPA. l-DOPA generally decreased the size of the AB in patients with a large baseline AB (i.e., OFF medications), while l-DOPA generally increased the AB in patients with a small baseline AB. These findings may support a role for dopamine in the AB and temporal attention, more generally and corroborate the notion that there is an optimum dopamine level for cognitive function. They also emphasize the need for more studies that examine the separate effects of DA agonists and l-DOPA on cognitive functioning.

Facilitation and inhibition in attention: Functional dissociation of pre-stimulus alpha activity, P1, and N1 components.

Attention--the ability to attend to some things while ignoring others - can be best described as an emergent property of many neural mechanisms, facilitatory and inhibitory, working together to resolve competition for processing resources and control of behavior. Previous EEG and MEG studies examining the neural mechanisms underlying facilitation and inhibition of stimulus processing typically used paradigms requiring alternating shifts of attention in the spatial domain, with stimuli occurring at both attended and unattended locations. These studies generally observed greater pre-stimulus alpha oscillations over task-irrelevant vs. relevant posterior regions and bilateral attentional modulations of early sensory processing. In contrast, in the current series of experiments, participants continuously attended to only one hemifield and stimuli were only presented at the attended location, affording us an opportunity to elucidate the inhibitory and facilitatory effects of attention in the brain in a context in which spatial relevance was fixed. We found that continuous attention to one hemifield did not modulate prestimulus alpha activity in ipsilateral regions but did result in a perfectly lateralized P1 attention effect to ipsilateral posterior regions. Moreover, we found a bilateral N1 effect. These findings suggest that pre-stimulus alpha activity, the P1 and the N1 reflect qualitatively different aspects of attention; While pre-stimulus alpha-band activity may reflect a top-down inhibitory mechanism that critically depends on functional competition between task-relevant and irrelevant sensory regions, the ipsilateral P1 effect may reflect stimulus-triggered blocking of sensory processing in irrelevant networks, and the N1 effect facilitation of task-relevant processing.

Subcortical, modality-specific pathways contribute to multisensory processing in humans.

Oftentimes, we perceive our environment by integrating information across multiple senses. Recent studies suggest that such integration occurs at much earlier processing stages than once thought possible, including in thalamic nuclei and putatively unisensory cortical brain regions. Here, we used diffusion tensor imaging (DTI) and an audiovisual integration task to test the hypothesis that anatomical connections between sensory-related subcortical structures and sensory cortical areas govern multisensory processing in humans. Twenty-five subjects (mean age 22 years, 22 females) participated in the study. In line with our hypothesis, we show that estimated strength of white-matter connections between the first relay station in the auditory processing stream (the cochlear nucleus), the auditory thalamus, and primary auditory cortex predicted one's ability to combine auditory and visual information in a visual search task. This finding supports a growing body of work that indicates that subcortical sensory pathways do not only feed forward unisensory information to the cortex, and suggests that anatomical brain connectivity contributes to multisensory processing ability in humans.

fMRI evidence for both generalized and specialized components of attentional control.

A central question in the study of selective attention is whether top-down attentional control mechanisms are generalized or specialized for the type of information that is to be attended. The current study examined this question using a voluntary orienting task that cued observers to attend to either one of two locations or to one of two colors. Location (spatial) and color (nonspatial) conditions were presented either randomly intermixed within the same block of trials or in separate blocks. Functional magnetic resonance imaging revealed that directing attention to a location or to a color activated a network of overlapping dorsal frontal and parietal areas, previously implicated in attentional control. The pattern of observed overlap was not affected by the intermixed versus blocked presentation of location and color conditions. Although portions of the frontal-parietal network were more active in response to location cues than to color cues, a secondary analysis also revealed that medial dorsal frontal and parietal cortex were specifically engaged in shifting visual attention regardless of the cued dimension (location or color). Together, the present results support the conclusion that attentional control is the combination of a generalized network that works in concert with subregions of the frontoparietal network that are highly specialized for directing attention based on the content of the to-be-attended information.

Brain regions activated by endogenous preparatory set shifting as revealed by fMRI.

An ongoing controversy concerns whether executive control mechanisms can actively reconfigure the cognitive system in preparation for switching to a new task set. To address this question, we recorded brain activity from 14 healthy participants, using event-related functional magnetic resonance imaging, while they performed a cued attention task. Critically, in any particular trial, the cued task set was either the same as that in the previous trial or switched. As was hypothesized, cue-related, switch-specific preparatory activity was observed in a network of dorsal frontal and parietal brain areas that are typically associated with cognitive control processes. Moreover, the magnitude of switch-specific preparatory activity varied with the number of possible task sets that could be presented in a given trial block. These findings provide compelling support for the existence of top-down, preparatory control processes that enable set switching. Furthermore, they demonstrate that global task structure is a critical determinant of whether switch-specific preparatory activity is observed.

Functional anatomical correlates of controlled and automatic processing.

Behavioral studies have shown that consistent practice of a cognitive task can increase the speed of performance and reduce variability of responses and error rate, reflecting a shift from controlled to automatic processing. This study examines how the shift from controlled to automatic processing changes brain activity. A verbal Sternberg task was used with continuously changing targets (novel task, NT) and with constant, practiced targets (practiced task, PT). NT and PT were presented in a blocked design and contrasted to a choice reaction time (RT) control task (CT) to isolate working memory (WM)-related activity. The three-dimensional (3-D) PRESTO functional magnetic resonance imaging (fMRI) sequence was used to measure hemodynamic responses. Behavioral data revealed that task processing became automated after practice, as responses were faster, less variable, and more accurate. This was accompanied specifically by a decrease in activation in regions related to WM (bilateral but predominantly left dorsolateral prefrontal cortex (DLPFC), right superior frontal cortex (SFC), and right frontopolar area) and the supplementary motor area. Results showed no evidence for a shift of foci of activity within or across regions of the brain. The findings have theoretical implications for understanding the functional anatomical substrates of automatic and controlled processing, indicating that these types of information processing have the same functional anatomical substrate, but differ in efficiency. In addition, there are practical implications for interpreting activity as a measure for task performance, such as in patient studies. Whereas reduced activity can reflect poor performance if a task is not sensitive to practice effects, it can reflect good performance if a task is sensitive to practice effects.

Probing emotion in the developing brain: functional neuroimaging in the assessment of the neural substrates of emotion in normal and disordered children and adolescents.

Virtually all developmental neuropsychiatric disorders involve some dysfunction or dysregulation of emotion. Moreover, many psychiatric disorders with adult onset have early subclinical manifestations in children. This essay selectively reviews the literature on the neuroimaging of affect and disorders of affect in children. Some critical definitional and conceptual issues are first addressed, including the distinctions between the perception and production of emotion and between emotional states and traits. Developmental changes in morphometric measures of brain structure are then discussed and the implications of such findings for studies of functional brain activity are considered. Data on functional neuroimaging and childhood depression are then reviewed. While the extant data in this area are meager, they are consistent with studies in adults that have observed decreased left-sided anterolateral prefrontal cortex activation in depression. Studies in children on the recognition of emotion and affective intent in faces using functional magnetic resonance imaging are then reviewed. These findings indicate that the amygdala plays an important role in such affective face processing in children, similar to the patterns of activation observed in adults. Moreover, one study has reported abnormalities in amygdala activation during a task requiring the judgment of affective intent from the eye region of the face in subjects with autism. Some of the methodological complexities of developmental research in this area are discussed, and directions for future research are suggested.