Although attention is distributed across time as well as space, the temporal allocation of attention has been less well researched than its spatial counterpart. A temporal analog of the covert spatial orientation task [Posner MI, Snyder CRR, Davidson BJ (1980) Attention and the detection of signals. J Exp Psychol Gen 109:160-174] was developed to compare the neural systems involved in directing attention to spatial locations versus time intervals. We asked whether there exists a general system for allocating attentional resources, independent of stimulus dimension, or whether functionally specialized brain regions are recruited for directing attention toward spatial versus temporal aspects of the environment. We measured brain activity in seven healthy volunteers by using positron emission tomography (PET) and in eight healthy volunteers by using functional magnetic resonance imaging (fMRI). The task manipulated cued attention to spatial locations (S) and temporal intervals (T) in a factorial design. Symbolic central cues oriented subjects toward S only (left or right), toward T only (300 msec or 1500 msec), toward both S and T simultaneously, or provided no information regarding S or T. Subjects also were scanned during a resting baseline condition. Behavioral data showed benefits and costs for performance during temporal attention similar to those established for spatial attention. Brain-imaging data revealed a partial overlap between neural systems involved in the performance of spatial versus temporal orientation of attention tasks. Additionally, hemispheric asymmetries revealed preferential right and left parietal activation for spatial and temporal attention, respectively. Parietal cortex was activated bilaterally by attending to both dimensions simultaneously. This is the first direct comparison of the neural correlates of attending to spatial versus temporal cues. Key words: attention; space; time; orienting; parietal; lateralization; imagingImagine waiting at traffic lights in L ondon that have just turned from red to amber. With this cue, anticipation of the moment when the lights turn green begins. Common experience tells us that focusing attention on the anticipated moment will lead to quicker responses than if our mind is occupied elsewhere. Similarly, within the spatial domain, attention must be directed toward the light to respond efficiently. Focusing of attention within the spatial domain has been well investigated. The brain is capable of directing attention dynamically across extrapersonal space on the basis of expectations of where relevant events are likely to appear. Stimuli appearing in predicted locations are detected more rapidly and accurately than those that are not (Posner et al., 1980). Convergent findings from neuropsychological (for review, see Mesulam, 1990) and brain-imaging studies (Corbetta et al., 1993;Nobre et al., 1997) have defined the neural network for spatial attention, the core elements of which are posterior parietal cortex around intraparietal sulcus, frontal eye fie...

We examined whether the known noradrenergic attenuation of the alerting effect (the beneficial effect of a warning cue) results from an underlying effect of noradrenaline on temporal orienting (orienting toward a particular moment in time). Following a within-subjects, counterbalanced design, 10 healthy human volunteers received placebo, 200 microg clonidine or 1 mg guanfacine (alpha2 agonists) in three separate testing sessions. Subjects were scanned by fMRI while performing attentional orienting tasks containing spatially informative, temporally informative, non-informative or no cues. The alerting effect primarily activated left-lateralized prefrontal, premotor and parietal regions. Clonidine, but not guanfacine, impaired behavioural measures of the alerting effect while attenuating activity in the left temporo-parietal junction. Replicating previous results, the temporal orienting task activated left parietal and frontal cortex, while parietal cortex was activated bilaterally during spatial orienting. Of these networks, clonidine, but not guanfacine, attenuated left prefrontal cortex and insula activity during temporal orienting and attenuated right superior parietal cortex activity during spatial orienting,. To complement these neuroanatomical changes, clonidine produced selective behavioural effects on both temporal and spatial orienting. The anatomical dissociation between the effects of clonidine during temporal orienting versus alerting suggests that noradrenergic modulation of the alerting effect does not result only from an underlying effect on temporal orienting. Furthermore, we have demonstrated lateralized neuroanatomical substrates for the noradrenergic modulation of human attentional orienting in the spatial and temporal domains.

Clinical Development Phases 1 4 1 Postmarketing Regulatory, Quality, Phase IV Manufacturing

A placebo‐controlled cross‐over trial (n=89) investigated the use of a chronic dose of the cholinesterase inhibitor THA, as a treatment for dementia of the Alzheimer type (DAT). Effects on both subjective clinical rating scales and objective computerised tests were assessed. In regard to the former, analysis of the three main clinical outcome measures showed statistically significant effects of the drug on the Mini‐Mental State Examination (MMSE) and the Abbreviated Mental Test Score (AMTS), but not on the Activities of Daily Living scale (ADL). Using the objective computerised CANTAB tests, sensitive to specific aspects of memory and attention, evidence was found for improvements in attentional function rather than memory, in patients with mild to moderate DAT. Although these improvement: were significant, they were small and restricted to certain tests of attentional function. Nevertheless, they add to the growing body of evidence that the cholinergic system is involved in the control of attentional processes: and are substantiated by the findings of a second study examining the effects of an acute dose of nicotine on attentional and mnemonic performance in patients with DAT. This study found significant improvements in cognitive performance in patients receiving nicotine, in objective tests of attention but not of short‐term memory. These data will clearly provide important comparative data for future investigations of putative cognitive enhancing drugs in DAT sufferers.

Dopaminergic projections are hypothesized to stabilize neural signaling and neural representations, but how they shape local information processing and large-scale network interactions remains unclear. Here we investigated the effects of lowered dopamine levels on functional connectivity and signal variability in the healthy brain at rest. The acute phenylalanine and tyrosine depletion (APTD) method was used to decrease dopamine synthesis in 51 healthy participants who underwent high-resolution resting-state functional MRI (fMRI). Functional connectivity and regional signal variability were estimated for each participant. Multivariate partial least squares (PLS) analysis was used to statistically assess changes in signal variability following APTD as compared to the balanced control treatment. The analysis captured a pattern of increased signal variability following dopamine depletion. Changes in signal variability were concomitant with changes in functional connectivity, such that nodes with the greatest increase in signal variability following dopamine depletion also experienced the greatest decrease in functional connectivity. Our results suggest that dopamine may act to stabilize neural signaling, particularly in networks related to motor function and orienting attention towards behaviorally-relevant stimuli. Moreover, dopamine-dependent signal variability is critically associated with the functional embedding of individual areas in large-scale networks.