Pupillary dilations in a Target/Distractor visual task paradigm and attention deficit hyperactivity disorder (ADHD).

ADHD is a neurocognitive disorder characterized by attention difficulties, hyperactivity, and impulsivity, often persisting into adulthood with substantial personal and societal consequences. Despite the importance of neurophysiological assessment and treatment monitoring tests, their availability outside of research settings remains limited. Cognitive neuroscience investigations have identified distinct components associated with ADHD, including deficits in sustained attention, inefficient enhancement of attended Targets, and altered suppression of ignored Distractors. In this study, we examined pupil activity in control and ADHD subjects during a sustained visual attention task specifically designed to evaluate the mechanisms underlying Target enhancement and Distractor suppression. Our findings revealed some distinguishing factors between the two groups which we discuss in light of their neurobiological implications.

Targeting alertness to improve cognition in older adults: A preliminary report of benefits in executive function and skill acquisition.

Efficient self-regulation of alertness declines with age exacerbating normal declines in performance across multiple cognitive domains, including learning and skill acquisition. Previous cognitive intervention studies have shown that it is possible to enhance alertness in patients with acquired brain injury and marked attention impairments, and that this benefit generalizes to improvements in more global cognitive functions. In the current preliminary studies, we sought to test whether this approach, that targets both tonic (over a period of minutes) and phasic (moment-to-moment) alertness, can improve key executive functioning declines in older adults, and enhance the rate of skill acquisition. The results of both Experiments 1 and 2 demonstrate that, compared to active control (AC) training, alertness training significantly enhanced performance in several validated executive function measures. In Experiment 2, alertness training significantly improved skill acquisition compared to AC training in a well-characterized speed of processing (SOP) task, with the largest benefits shown in the most challenging SOP blocks. The results of the current study suggest that targeting intrinsic alertness through cognitive training provides a novel approach to improve executive functions in older adults and may be a useful adjunct treatment to enhance benefits gained in other clinically validated treatments.

Measurement of Neurophysiological Signals of Ignoring and Attending Processes in Attention Control.

Attention control is the ability to selectively attend to some sensory signals while ignoring others. This ability is thought to involve two processes: enhancement of sensory signals that are to be attended and the attenuation of sensory signals that are to be ignored. The overall strength of attentional modulation is often measured by comparing the amplitude of a sensory neural response to an external input when attended versus when ignored. This method is robust for detecting attentional modulation, but precludes the ability to assess the separate dynamics of attending and ignoring processes. Here, we describe methodology to measure independently the neurophysiological signals of attending and ignoring using the intermodal attention task (IMAT). This task, when combined with electroencephalography, isolates neurophysiological sensory responses in auditory and visual modalities, when either attending or ignoring, with respect to a passive control. As a result, independent dynamics of attending and of a ignoring can be assessed in either modality. Our results using this task indicate that the timing and cortical sources of attending and ignoring effects differ, as do their contributions to the attention modulation effect, pointing to unique neural trajectories and demonstrating sample utility of measuring them separately.

Neurophysiological signals of ignoring and attending are separable and related to performance during sustained intersensory attention.

The ability to attend to an input selectively while ignoring distracting sensations is thought to depend on the coordination of two processes: enhancement of target signals and attenuation of distractor signals. This implies that attending and ignoring may be dissociable neural processes and that they make separable contributions to behavioral outcomes of attention. In this study, we tested these hypotheses in the context of sustained attention by measuring neurophysiological responses to attended and ignored stimuli in a noncued, continuous, audiovisual selective attention task. We compared these against responses during a passive control to quantify effects of attending and ignoring separately. In both sensory modalities, responses to ignored stimuli were attenuated relative to a passive control, whereas responses to attended stimuli were enhanced. The scalp topographies and brain activations of these modulatory effects were consistent with the sensory regions that process each modality. They also included parietal and prefrontal activations that suggest these effects arise from interactions between top-down and sensory cortices. Most importantly, we found that both attending and ignoring processes contributed to task accuracy and that these effects were not correlated--suggesting unique neural trajectories. This conclusion was supported by the novel observation that attending and ignoring differed in timing and in active cortical regions. The data provide direct evidence for the separable contributions of attending and ignoring to behavioral outcomes of attention control during sustained intersensory attention.

Perspective: causes and functional significance of temporal variations in attention control.

Attention control describes the human ability to selectively modulate the plethora of sensory signals and internal thoughts. The neural systems of attention control have been studied extensively, warranted by the importance of this ability to daily functioning. Here, we consider an emerging theme in the study of attention control-slow temporal fluctuations. We posit that these fluctuations are functionally significant, and may reflect underlying interactions between the neural systems related to attention control. We explore thought experiments to generate different perspectives on landscapes created by the interactions between attention control networks and the sources of input to these control systems. We examine interactions of the fronto-parietal and the default mode networks in the context of internal cognition, and the noradrenergic modulatory projections in the context of arousal, and we consider the implications of these inter-network dynamics on attention states and attention disorders. Through these thought experiments we highlight the breadth of potential knowledge to be gained from the study of slow fluctuations in attention control.

Computerized cognitive training restores neural activity within the reality monitoring network in schizophrenia.

Schizophrenia patients suffer from severe cognitive deficits, such as impaired reality monitoring. Reality monitoring is the ability to distinguish the source of internal experiences from outside reality. During reality monitoring tasks, schizophrenia patients make errors identifying "I made it up" items, and even during accurate performance, they show abnormally low activation of the medial prefrontal cortex (mPFC), a region that supports self-referential cognition. We administered 80 hr of computerized training of cognitive processes to schizophrenia patients and found improvement in reality monitoring that correlated with increased mPFC activity. In contrast, patients in a computer games control condition did not show any behavioral or neural improvements. Notably, recovery in mPFC activity after training was associated with improved social functioning 6 months later. These findings demonstrate that a serious behavioral deficit in schizophrenia, and its underlying neural dysfunction, can be improved by well-designed computerized cognitive training, resulting in better quality of life.

Dynamic activation of frontal, parietal, and sensory regions underlying anticipatory visual spatial attention.

Although it is well established that multiple frontal, parietal, and occipital regions in humans are involved in anticipatory deployment of visual spatial attention, less is known about the electrophysiological signals in each region across multiple subsecond periods of attentional deployment. We used MEG measures of cortical stimulus-locked, signal-averaged (event-related field) activity during a task in which a symbolic cue directed covert attention to the relevant location on each trial. Direction-specific attention effects occurred in different cortical regions for each of multiple time periods during the delay between the cue and imperative stimulus. A sequence of activation from V1/V2 to extrastriate, parietal, and frontal regions occurred within 110 ms after cue, possibly related to extraction of cue meaning. Direction-specific activations ∼300 ms after cue in frontal eye field (FEF), lateral intraparietal area (LIP), and cuneus support early covert targeting of the cued location. This was followed by coactivation of a frontal-parietal system [superior frontal gyrus (SFG), middle frontal gyrus (MFG), LIP, anterior intraparietal sulcus (IPSa)] that may coordinate the transition from targeting the cued location to sustained deployment of attention to both space and feature in the last period. The last period involved direction-specific activity in parietal regions and both dorsal and ventral sensory regions [LIP, IPSa, ventral IPS, lateral occipital region, and fusiform gyrus], which was accompanied by activation that was not direction specific in right hemisphere frontal regions (FEF, SFG, MFG). Behavioral performance corresponded with the magnitude of attention-related activity in different brain regions at each time period during deployment. The results add to the emerging electrophysiological characterization of different cortical networks that operate during anticipatory deployment of visual spatial attention.

Adolescent smokers show decreased brain responses to pleasurable food images compared with nonsmokers.

INTRODUCTION: Nicotine acts on the mesocorticolimbic circuits of the brain leading to the release of dopamine. Repeated elevations of dopamine in the brain may cause smokers to become less sensitive to "natural reinforcers." To test the theory that adolescents with low nicotine exposure may already have decreased activation when exposed to a natural reinforcer, we looked at the effect of visual cues representing "pleasurable" food on light adolescent smokers compared with nonsmokers. METHODS: Twelve adolescent light smokers (aged 13-17 years, smoked 1-5 cigarettes/day) and 12 nonsmokers (aged 13-17 years, never smoked a cigarette) from the San Francisco Bay Area underwent functional magnetic resonance imaging scanning. During scanning, they viewed blocks of photographic images representing pleasurable foods (sweet, high fat, and salty foods) and control cues. RESULTS: Smokers reported smoking a mean of 3.6 cigarettes/day. There was no difference in body mass index between groups (24.1 vs. 24.0, respectively, p = .99). Food images elicited greater activations in nonsmokers in multiple areas including the insula (T = 4.38, p < .001), inferior frontal region (T = 5.12, p < .001), and rolandic operculum (T = 6.18, p < .001). There were no regions where smokers demonstrated greater blood oxygenation level-dependent activations compared with nonsmokers when viewing food versus neutral images. CONCLUSIONS: The finding of decreased activation to pleasurable food among adolescent light smokers supports the theory that these adolescents are displaying decreased sensitivity to at least one natural reinforcer. This also supports the theory that nicotine may affect the brain early in the trajectory of smoking, thus underscoring the need for early intervention among adolescent smokers.

Smoking-related cue-induced brain activation in adolescent light smokers.

PURPOSE: To examine using functional magnetic resonance imaging whether adolescents with low levels of nicotine exposure (light smokers) display neural activation in areas shown to be involved with addiction in response to smoking-related stimuli. DESIGN/SETTING/PARTICIPANTS: A total of 12 adolescent light smokers (aged 13-17, who smoked 1-5 cigarettes per day) and 12 nonsmokers (ages 13-17, never smoked a cigarette) from the San Francisco Bay Area underwent functional magnetic resonance imaging scanning. During scanning, the adolescents were shown photographic blocks of smoking and control cues. Smoking cues comprised pictures of individuals smoking cigarettes and smoking-related objects such as lighters and ashtrays. Neutral cues comprised images of everyday objects and individuals engaged in daily activities. FINDINGS: For smokers, smoking cues elicited greater activation than neutral cues in the mesolimbic reward circuit (left anterior cingulate: t = 7.04, p < .001; right hippocampus: t = 6.37, p < .001). We found activation from smoking cues versus neutral cues within both the left and right frontal medial orbital regions (t = 5.09, p < .001 and t = 3.94, p = .001, respectively). Nonsmokers showed no significant difference in activation between smoking-related cues and neutral cues. CONCLUSION: Our finding that smoking cues produced activation in adolescent light smokers in brain regions, similar to that seen in adult and teenage heavy smokers, suggests that adolescents exhibit heightened reactivity to smoking cues even at low levels of smoking. This article adds to the existing published data by suggesting that nicotine dependence may begin with exposure to low levels of nicotine, thus underscoring the need for early intervention among adolescent smokers.

Timing is everything: neural response dynamics during syllable processing and its relation to higher-order cognition in schizophrenia and healthy comparison subjects.

Successful linguistic processing requires efficient encoding of successively-occurring auditory input in a time-constrained manner, especially under noisy conditions. In this study we examined the early neural response dynamics to rapidly-presented successive syllables in schizophrenia participants and healthy comparison subjects, and investigated the effects of noise on these responses. We used magnetoencephalography (MEG) to reveal the time-course of stimulus-locked activity over bilateral auditory cortices during discrimination of syllable pairs that differed either in voice onset time (VOT) or place of articulation (POA), in the presence or absence of noise. We also examined the association of these early neural response patterns to higher-order cognitive functions. The M100 response, arising from auditory cortex and its immediate environs, showed less attenuation to the second syllable in patients with schizophrenia than healthy comparison subjects during VOT-based discrimination in noise. M100 response amplitudes were similar between groups for the first syllable during all three discrimination conditions, and for the second syllable during VOT-based discrimination in quiet and POA-based discrimination in noise. Across subjects, the lack of M100 attenuation to the second syllable during VOT-based discrimination in noise was associated with poorer task accuracy, lower education and IQ, and lower scores on measures of Verbal Learning and Memory and Global Cognition. Because the neural response to the first syllable was not significantly different between groups, nor was a schizophrenia-related difference obtained in all discrimination tasks, early linguistic processing dysfunction in schizophrenia does not appear to be due to general sensory input problems. Rather, data suggest that faulty temporal integration occurs during successive syllable processing when the signal-to-noise ratio is low. Further, the neural mechanism by which the second syllable is suppressed during noise-challenged VOT discrimination appears to be important for higher-order cognition and provides a promising target for neuroscience-guided cognitive training approaches to schizophrenia.

When top-down meets bottom-up: auditory training enhances verbal memory in schizophrenia.

A critical research priority for our field is to develop treatments that enhance cognitive functioning in schizophrenia and thereby attenuate the functional losses associated with the illness. In this article, we describe such a treatment method that is grounded in emerging research on the widespread sensory processing impairments of schizophrenia, as described elsewhere in this special issue. We first present the rationale for this treatment approach, which consists of cognitive training exercises that make use of principles derived from the past 2 decades of basic science research in learning-induced neuroplasticity; these exercises explicitly target not only the higher order or "top-down" processes of cognition but also the content building blocks of accurate and efficient sensory representations to simultaneously achieve "bottom-up" remediation. We then summarize our experience to date and briefly review our behavioral and serum biomarker findings from a randomized controlled trial of this method in outpatients with long-term symptoms of schizophrenia. Finally, we present promising early psychophysiological evidence that supports the hypothesis that this cognitive training method induces changes in aspects of impaired bottom-up sensory processing in schizophrenia. We conclude with the observation that neuroplasticity-based cognitive training brings patients closer to physiological patterns seen in healthy participants, suggesting that it changes the brain in an adaptive manner in schizophrenia.

A novel ANCOVA design for analysis of MEG data with application to a visual attention study.

Statistical inference from MEG-based distributed activation maps is well suited to the general linear modeling framework, a standard approach to the analysis of fMRI and PET neuroimaging studies. However, there are important differences from the other neuroimaging modalities related to how observations are created and fitted in GLM models, as well as how subsequent statistical inference is performed. In this paper, we demonstrate how MEG oscillatory components can be analyzed in this framework based on a custom ANCOVA model that takes into account baseline and inter-hemispheric effects, rather than a simpler ANOVA design. We present the methodology using as an example an MEG study of visual spatial attention, since the model design depends on the specific experiment and neuroscience hypotheses being tested. However, the techniques presented here can be readily adapted to accommodate other experimental paradigms. We create statistics that estimate the temporal evolution of attention effects on alpha power in several cortical regions. We present evidence for direction-specific attention effects on alpha activity in occipital and parietal regions and demonstrate the sub-second timing of these effects in each region. The results support a mechanism for anticipatory attentional deployment that dynamically modulates the local alpha synchrony in a network of parietal control and occipital sensory regions.

ERP correlates of anticipatory attention: spatial and non-spatial specificity and relation to subsequent selective attention.

Brain-based models of visual attention hypothesize that attention-related benefits afforded to imperative stimuli occur via enhancement of neural activity associated with relevant spatial and non-spatial features. When relevant information is available in advance of a stimulus, anticipatory deployment processes are likely to facilitate allocation of attention to stimulus properties prior to its arrival. The current study recorded EEG from humans during a centrally-cued covert attention task. Cues indicated relevance of left or right visual field locations for an upcoming motion or orientation discrimination. During a 1 s delay between cue and S2, multiple attention-related events occurred at frontal, parietal and occipital electrode sites. Differences in anticipatory activity associated with the non-spatial task properties were found late in the delay, while spatially-specific modulation of activity occurred during both early and late periods and continued during S2 processing. The magnitude of anticipatory activity preceding the S2 at frontal scalp sites (and not occipital) was predictive of the magnitude of subsequent selective attention effects on the S2 event-related potentials observed at occipital electrodes. Results support the existence of multiple anticipatory attention-related processes, some with differing specificity for spatial and non-spatial task properties, and the hypothesis that levels of activity in anterior areas are important for effective control of subsequent S2 selective attention.

Deficit in a neural correlate of reality monitoring in schizophrenia patients.

Patients who suffer from the devastating psychiatric illness schizophrenia are plagued by hallucinations, bizarre behavior, and delusional ideas, such as believing that they are controlled by malevolent outside forces. A fundamental human cognitive operation that may contribute to these hallmark symptoms is the ability to maintain accurate and coherent self-referential processing over time, such as occurs during reality monitoring (distinguishing self-generated from externally perceived information). However, the neural bases for a disturbance in this operation in schizophrenia have not been fully explored. Using functional magnetic resonance imaging, we asked clinically stable schizophrenia patients to remember whether or not they had generated a target word during an earlier sentence completion task. We found that, during accurate performance of this self-referential source memory task, the schizophrenia subjects manifest a deficit in rostral medial prefrontal cortex (mPFC) activity--a brain region critically implicated in both the instantiation and the retrieval of self-referential information in healthy subjects. Impairment in rostral mPFC function likely plays a key role in the profound subjective disturbances that characterize schizophrenia and that are the aspect of the disorder most troubling to patients and to society at large.

Transient and sustained brain activity during anticipatory visuospatial attention.

In this study, we determined whether the visuospatial attention network of frontal, parietal, and occipital cortex can be parsed into two different subsets of active regions associated with transient and sustained processes within the same cue-to-target delay period of an endogenously cued visuospatial attention task. We identified regions with early transient activity and regions with later sustained activity during the same trials using a general linear model analysis of event-related BOLD functional MRI data with two timecourse covariates for the same cue-to-target delay period. During the delay between the cue and target, we observed significant transient activity in right frontal eye field and right occipital-parietal junction, and significant sustained activity in right ventral intraparietal sulcus and right dorsolateral and anterior prefrontal cortex.

Preparatory allocation of attention and adjustments in conflict processing.

Attentional control involves the ability to allocate preparatory attention to improve subsequent stimulus processing and response selection. There is behavioral evidence to support the hypothesis that increased expectancy of stimulus and response conflict may decrease the subsequent experience of conflict during task performance. We used a cued flanker and event-related fMRI design to separate processes involved in preparation from those involved in resolving conflict and to identify the brain systems involved in these processes as well as the association between preparatory activity levels and activity related to subsequent conflict processing. Our results demonstrate that preparatory attentional allocation following a cue to the upcoming level of conflict is mediated by a network involving Dorsolateral Prefrontal Cortex (DLPFC) and the Intraparietal Sulcus (IPS). Informed preparation for conflict processing was associated with decreased Anterior Cingulate Cortex/pre-Supplementary Motor Area (ACC/pre-SMA) and IPS activity during the flanker target presentation, supporting their roles in conflict processing and visuospatial attention during the flanker task. Ventrolateral Prefrontal Cortex/Orbitofrontal Cortex (VLPFC/OFC) was active when specific strategic task rule and outcome information was available.

Rapid targeting followed by sustained deployment of visual spatial attention.

We investigated preparatory attention processes when a spatial discrimination was required at a cued location, by measuring electroencephalography following a central symbolic cue to deploy spatial attention. Electroencephalography activity in response to the cue revealed three cue-related activations: an early-onset positivity following the P1 at posterior scalp sites contralateral to the cued location, followed by cue-related frontal scalp activity and later-onset sustained activity at posterior scalp sites contralateral to the cued location. The early contralateral positivity may reflect rapid targeting of the cued location. Our results also extend the findings of cue-related frontal activity followed by posterior activity contralateral to the cued location, found with nonspatial feature discriminations, to a task requiring a spatial discrimination.

Brain activation patterns during memory of cognitive agency.

Agency is the awareness that one's own self is the agent or author of an action, a thought, or a feeling. The implicit memory that one's self was the originator of a cognitive event - the sense of cognitive agency - has not yet been fully explored in terms of relevant neural systems. In this functional magnetic resonance imaging (fMRI) study, we examined brain activation patterns differentiating memory for the source of previously self-generated vs. experimenter-presented word items from a sentence completion paradigm designed to be emotionally neutral and semantically constrained in content. Accurate memory for the source of self-generated vs. externally-presented word items resulted in activation of dorsal medial prefrontal cortex (mPFC) bilaterally, supporting an emerging body of work that indicates a key role for this region in self-referential processing. Our data extend the function of mPFC into the domain of memory and the accurate retrieval of the sense of cognitive agency under conditions where agency was encoded implicitly.

Parallel networks operating across attentional deployment and motion processing: a multi-seed partial least squares fMRI study.

Anticipatory deployment of attention may operate through networks of brain areas that modulate the representations of to-be-attended items in advance of their occurrence through top-down control. Luks and Simpson (2004) (Luks, T.L., Simpson, G.V., 2004. Preparatory deployment of attention to motion activates higher order motion-processing brain regions. NeuroImage 22, 1515-1522) found activations in both control areas and sensory areas during anticipatory deployment of attention to visual motion in the absence of stimuli. In the present follow-up analysis, we tested which network activity during anticipatory deployment of attention is functionally connected with task-related network activity during subsequent selective processing of motion stimuli. Following a cue (anticipatory phase), participants monitored a sequence of complex motion stimuli for a target motion pattern (task phase). We analyzed fMR signal using a partial least squares analysis with previously identified cue- and motion-related voxels as seed regions. The method identified two networks that covaried with the activity of seed regions during the cue and motion-stimulus-processing phases of the task. We suggest that the first network, involving ventral intraparietal sulcus, superior parietal lobule and motor areas, is related to anticipatory and sustained visuomotor attention. Operating in parallel to this visuomotor attention network, there is a second network, involving visual occipital areas, frontal areas as well as angular and supramarginal gyri, that may underlie anticipatory and sustained visual attention processes.

Biasing the brain's attentional set: II. effects of selective intersensory attentional deployments on subsequent sensory processing.

This study used high-density mapping of human event-related potentials to examine the brain activity associated with selective information processing when subjects were cued on a trial-by-trial basis to perform a discrimination in either the visual or auditory modality. On each trial, word-cues (S1) instructed subjects to attend to features within one sensory-modality of an impending compound auditory-visual stimulus (S2) that arrived approximately 1-second following the cue. Subjects made a discrimination within the cued modality of the S2 stimulus. The spatio-temporal patterns of activity in response to the compound S2 stimulus were examined as a function of the sensory modality being attended. The earliest effects of intersensory attention on visual processing were seen subsequent to the initial activation of visual cortex, beginning at 80 ms and continuing into the P1 and N1 components of the visual ERP. The scalp-topography of this earliest modulation was consistent with modulation of activity in ventral visual stream areas. Thus, the locus of effects on visual S2 processing differed from the anticipatory parieto-occipital biasing activity that preceded S2 presentation. This pattern of effects strongly suggests that the anticipatory activity (following the cue) associated with sustaining the focus of attention during intersensory attention, at least in the context of this paradigm, does not operate as a simple gain mechanism in early visual sensory areas. Rather, attentional biasing can operate through a higher-order process whereby parieto-occipital cortices influence the subsequent flow of visual processing in the ventral stream.