Impact of a Clinical Decision Support System on Inappropriate Prescription of Glucose-lowering Agents for Patients With Renal Insufficiency in an Ambulatory Care Setting.

PURPOSE: Inappropriate dosing of glucose-lowering drugs in patients with renal insufficiency can cause severe harm. This study evaluated the short- and long-term effects of clinical decision support systems (CDSS) on inappropriate prescriptions of glucose-lowering agents for patients with renal insufficiency in an ambulatory care setting. METHODS: This retrospective longitudinal observational study was conducted by using an electronic medical record database and the CDSS log data at Taipei Veterans General Hospital between January 1, 2015, and December 31, 2018. Outpatients who received 7 target glucose-lowering medications and had an estimated glomerular filtration rate <50 mL/min/1.73 m2 were included. Inappropriate prescriptions were defined as a dose, frequency, or daily dose of target drugs that exceeded the dosing recommendations based on renal function. Inappropriate monthly rates were calculated, and the interrupted time series analysis method was used to explore the 1- and 3-year post-implementation effects of CDSS. The major outcome measurements were the level changes and the inappropriate prescription rate trend changes after renal CDSS implementation. The acceptance rates of alerts were also analyzed. FINDINGS: A total of 141,037 drug prescriptions were obtained during the study period. In the short-term analysis, the baseline inappropriate rate for overall medications was estimated to range from 30.54% in the first month to 27.06% in month 12. The predicted inappropriate rate 12 months after implementation was 19.35%, corresponding to an estimated 28.49% [(27.06 - 19.35)/27.06] decrease in inappropriate rate. However, after long-term analysis, the predicted inappropriate rate at the end of the study (36 months after implementation) was 18.02%. A total of 27,189 alerts were generated and 628 were accepted during the study period. Thus, after short- and long-term analysis, the overall acceptance rate was 3.06% and 2.31%, respectively. IMPLICATIONS: Implementing a CDSS for renal dosing adjustment could significantly decrease the inappropriate prescription rate of glucose-lowing agents among patients with renal insufficiency in an ambulatory setting in the short term, while the long-term effect of a CDSS is limited.

Independent subsequent memory effects of conflict resolution and response inhibition.

Learning and memory are an integral part of life, yet we often take them for granted. We remember what we have learned. However, the relationship between learning and memory may not be as simple as it seems. This is especially true when the learning is incidental as we go about fulfilling other behavioral goals and using various cognitive control functions. Cognitive control, which is required to produce goal-directed behavior, includes several component functions that may modulate incidental learning in various ways. Some cognitive control components (e.g., conflict resolution) appear to help, while others (e.g., response inhibition) appear to hurt memory encoding, resulting in opposite subsequent memory effects (SMEs). Better subsequent memory performance for target stimuli requiring control to resolve semantic conflicts between targets and distractors, and poorer subsequent memory for those requiring response withholding or cancellation. Here, we asked the question of how different components of cognitive control (i.e., response inhibition, conflict resolution) relate to one another in memory encoding. If their joint SEMs reflect the same mechanism whereby cognitive control determines how information is encoded, we would find a significant interaction in their joint SMEs. We report results from three experiments using a single task paradigm that requires both response inhibition and conflict resolution, and a surprise memory task to assess their joint SMEs. Across three experiments, we found that while conflict resolution enhances memory encoding, response inhibition impairs it. Importantly, their joint SMEs were robustly additive. This finding suggests that while response inhibition and conflict resolution commonly guide processing to select goal-directed actions, they seem to act on information encoding orthogonally with each other. This finding also highlights the diversity of cognitive control functions in terms of their mnemonic consequences.

Hemisphere-specific Parietal Contributions to the Interplay between Working Memory and Attention.

To achieve our moment-to-moment goals, we must often keep information temporarily in mind. Yet, this working memory (WM) may compete with demands for our attention in the environment. Attentional and WM functions are thought to operate by similar underlying principles, and they often engage overlapping fronto-parietal brain regions. In a recent fMRI study, bilateral parietal cortex BOLD activity displayed an interaction between WM and visual attention dual-task demands. However, prior studies also suggest that left and right parietal cortices make unique contributions to WM and attentional functions. Moreover, behavioral performance often shows no interaction between concurrent WM and attentional demands. Thus, the scope of reciprocity between WM and attentional functions, as well as the specific contribution that parietal cortex makes to these functions, remain unresolved. Here, we took a causal approach, targeting brain regions that are implicated in shared processing between WM and visual attention, to better characterize how those regions contribute to behavior. We first examined whether behavioral indices of WM and visual search differentially correlate with left and right parietal dual-task BOLD responses. Then, we delivered TMS over fMRI-guided left and right parietal sites during dual-task WM-visual search performance. Only right-parietal TMS influenced visual search behavior, but the stimulation either helped or harmed search depending on the current WM load. Therefore, whereas the left and right parietal contributions were distinct here, attentional and WM functions were codependent. Right parietal cortex seems to hold a privileged role in visual search behavior, consistent with prior findings, but the current results reveal that behavior may be sensitive to the interaction between visual search and WM load only when normal parietal activity is perturbed. The parietal response to heightened WM and attentional demands may therefore serve to protect against dual-task interference.

Voices from the COVID-19 frontline: Nurses' trauma and coping.

AIM: To describe the experiences of frontline nurses who are working in critical care areas during the COVID-19 pandemic with a focus on trauma and the use of substances as a coping mechanism. DESIGN: A qualitative study based on content analysis. METHODS: Data were collected from mid-June 2020 to early September 2020 via an online survey. Nurses were recruited through the research webpage of the American Association of Critical Care Nurses as well as an alumni list from a large, public Midwest university. Responses to two open-ended items were analysed: (1) personal or professional trauma the nurse had experienced; and (2) substance or alcohol use, or other mental health issues the nurse had experienced or witnessed in other nurses. RESULTS: For the item related to psychological trauma five themes were identified from 70 nurses' comments: (1) Psychological distress in multiple forms; (2) Tsunami of death; (3) Torn between two masters; (4) Betrayal; and (5) Resiliency/posttraumatic growth through self and others. Sixty-five nurses responded to the second item related to substance use and other mental health issues. Data supported three themes: (1) Mental health crisis NOW!!: 'more stressed than ever and stretched thinner than ever'; (2) Nurses are turning to a variety of substances to cope; and (3) Weakened supports for coping and increased maladaptive coping due to ongoing pandemic. CONCLUSIONS: This study brings novel findings to understand the experiences of nurses who care for patients with COVID-19, including trauma experienced during disasters, the use of substances to cope and the weakening of existing support systems. Findings also reveal nurses in crisis who are in need of mental health services. IMPACT: Support for nurses' well-being and mental health should include current and ongoing services offered by the organization and include screening for substance use issues.

Proactive and reactive metacontrol in task switching.

While cognitive control enables the selection of goal-relevant responses, metacontrol enables the selection of context-appropriate control operations. In task switching, metacontrol modulates task-switching efficiency by retrieving the associations between a contextual cue and a particular cognitive control demand. While the automatic retrieval of cognitive control is appealing due to its time and energy efficiency, the effects of different contextual cues have been shown in separate studies and appear to have different characteristics. Here, we devised a single task-switching paradigm to test whether we can observe both list-wide and item-specific metacontrol within subjects. In two experiments, we demonstrated reduced switch costs in lists associated with a high probability of switching as compared with lists with a low probability of switching (i.e., a list-wide switch probability [LWSP] effect). Similarly, we observed an analogous item-specific switch probability (ISSP) effect such that items associated with a high probability of switching incurred smaller switch costs as compared with items associated with a low probability of switching. We also confirmed that both list-wide and item-specific switch probability effects were not dependent on lower-level stimulus-response associations. However, the LWSP and the ISSP effects were uncorrelated, suggesting a lack of dependence. Together, these findings suggest that there are two distinct modes of metacontrol that are deployed in a context-sensitive manner in order to adapt to specific cognitive demands.

Item-specific priming of voluntary task switches.

The ability to switch efficiently between different tasks underpins cognitive flexibility and is impaired in various psychiatric disorders. Recent research has suggested that the control processes mediating switching can be subject to learning, because "switch readiness" can become associated with, and primed by, specific stimuli. In cued task switching, items that are frequently associated with the need to switch incur a smaller behavioral switch cost than do items associated with a low probability of switching, known as the item-specific switch probability (ISSP) effect (Chiu & Egner, 2017). However, it remains unknown whether ISSP associations modulate the efficiency of only cued switching or also impact people's voluntary choice to switch tasks. Here, we addressed this question by combining an ISSP manipulation with a protocol that mixed 75% standard cued task trials with 25% free choice trials, allowing us to measure the effect of ISSP on voluntary switch rate (VSR). We observed robust ISSP effects on cued trials, replicating previous findings. Crucially, we also found that the VSR was greater for items associated with a high than with a low switch likelihood. We thus demonstrate that associating specific stimuli with frequent switch requirements not only reduces switch costs but also enhances participants' tendency to switch voluntarily. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Cortical and subcortical contributions to context-control learning.

"Cognitive control" describes our ability to strategically bias information processing in line with internal goals. Traditionally, research has focused on delineating the sources of top-down biasing, implicating the lateral prefrontal cortex. The past two decades, however, have seen increasing interest in the regulation of control, that is, how learning processes guide the context-sensitive application of top-down biasing. Here, we review and synthesize recent research into the cognitive and neural mechanisms of this type of "context-control learning". We first discuss a fast-growing cognitive psychology literature documenting how specific cognitive control states can become associated with, and subsequently triggered by, contextual cues. We then review neuroimaging studies that speak to the neural substrates of contextual adjustments in control, with a particular focus on recent work that explicitly modeled context-control learning processes. We conclude that these studies suggest an important subcortical extension of the traditional frontal control network, as they indicate a key role for the caudate nucleus in forming associations between contextual cues and appropriate control settings.

Automatic Prioritization of Self-Referential Stimuli in Working Memory.

People preferentially attend to external stimuli that are related to themselves compared with others. Whether a similar self-reference bias applies to internal representations, such as those maintained in working memory (WM), is presently unknown. We tested this possibility in four experiments, in which participants were first trained to associate social labels (self, friend, stranger) with arbitrary colors and then performed a delayed match-to-sample spatial WM task on color locations. Participants consistently responded fastest to WM probes at locations of self-associated colors (Experiments 1-4). This self-bias was driven not by differential exogenous attention during encoding or retrieval (Experiments 1 and 2) but by internal attentional prioritization of self-related representations during WM maintenance (Experiment 3). Moreover, self-prioritization in WM was nonstrategic, as this bias persisted even under conditions in which it hurt WM performance. These findings document an automatic prioritization of self-referential items in WM, which may form the basis of some egocentric biases in decision making.

Cueing cognitive flexibility: Item-specific learning of switch readiness.

The rich behavioral repertoire of the human species derives from our ability to flexibly reconfigure processing strategies (task sets) in response to changing requirements. This updating of task sets is effortful, as reflected by longer response times when switching a task than repeating it (switch costs). However, some recent data suggest that switch costs can be reduced by cueing switch readiness bottom-up, by associating particular stimuli with frequent switch requirements. This type of "stimulus-control (S-C) learning" would be highly adaptive, as it combines the speed of automatic (bottom-up) processing with the flexibility and generalizability of controlled (top-down) processing. However, it is unclear whether S-C learning of switch readiness is truly possible, and what the underlying mechanisms are. Here we address these questions by pairing specific stimuli with a need to update task-sets either frequently or rarely. In all 3 experiments, we observe robust item-specific switch probability (ISSP) effects as revealed by smaller switch costs for frequent switch items than for rare switch items. By including a neutral condition, we also show that the ISSP effect is primarily driven by S-C learning reducing switch costs in frequent switch items. Furthermore, by employing 3 tasks in Experiment 3, we establish that the ISSP effect reflects an enhancement of general switch readiness, rather than of the readiness to switch to a specific alternate task. These results firmly establish that switch readiness is malleable by item-specific S-C learning processes, documenting that a generalizable state of cognitive flexibility can be primed by a bottom-up stimulus. (PsycINFO Database Record

The Caudate Nucleus Mediates Learning of Stimulus-Control State Associations.

A longstanding dichotomy in cognitive psychology and neuroscience pits controlled, top-down driven behavior against associative, bottom-up driven behavior, where cognitive control processes allow us to override well-learned stimulus-response (S-R) associations. By contrast, some previous studies have raised the intriguing possibility of an integration between associative and controlled processing in the form of stimulus-control state (S-C) associations, the learned linkage of specific stimuli to particular control states, such as high attentional selectivity. The neural machinery mediating S-C learning remains poorly understood, however. Here, we combined human functional magnetic resonance imaging (fMRI) with a previously developed Stroop protocol that allowed us to dissociate reductions in Stroop interference based on S-R learning from those based on S-C learning. We modeled subjects' acquisition of S-C and S-R associations using an associative learning model and then used trial-by-trial S-C and S-R prediction error (PE) estimates in model-based behavioral and fMRI analyses. We found that PE estimates derived from S-C and S-R associations accounted for the reductions in behavioral Stroop interference effects in the S-C and S-R learning conditions, respectively. Moreover, model-based fMRI analyses identified the caudate nucleus as the key structure involved in selectively updating stimulus-control state associations. Complementary analyses also revealed a greater reliance on parietal cortex when using the learned S-R versus S-C associations to minimize Stroop interference. These results support the emerging view that generalizable control states can become associated with specific bottom-up cues, and they place the caudate nucleus of the dorsal striatum at the center of the neural stimulus-control learning machinery. SIGNIFICANCE STATEMENT: Previous behavioral studies have demonstrated that control states, for instance, heightened attentional selectivity, can become directly associated with, and subsequently retrieved by, particular stimuli, thus breaking down the traditional dichotomy between top-down and bottom-up driven behavior. However, the neural mechanisms underlying this type of stimulus-control learning remain poorly understood. We therefore combined noninvasive human neuroimaging with a task that allowed us to dissociate the acquisition of stimulus-control associations from that of stimulus-response associations. The results revealed the caudate nucleus as the key brain structure involved in selectively driving stimulus-control learning. These data represent the first identification of the neural mechanisms of stimulus-specific control associations, and they significantly extend current conceptions of the type of learning processes mediated by the caudate.

Tracking the will to attend: Cortical activity indexes self-generated, voluntary shifts of attention.

The neural substrates of volition have long tantalized philosophers and scientists. Over the past few decades, researchers have employed increasingly sophisticated technology to investigate this issue, but many studies have been limited considerably by their reliance on intrusive experimental procedures (e.g., abrupt instructional cues), measures of brain activity contaminated by overt behavior, or introspective self-report techniques of questionable validity. Here, we used multivoxel pattern time-course analysis of functional magnetic resonance imaging data to index voluntary, covert perceptual acts-shifts of visuospatial attention-in the absence of instructional cues, overt behavioral indices, and self-report. We found that these self-generated, voluntary attention shifts were time-locked to activity in the medial superior parietal lobule, supporting the hypothesis that this brain region is engaged in voluntary attentional reconfiguration. Self-generated attention shifts were also time-locked to activity in the basal ganglia, a novel finding that motivates further research into the role of the basal ganglia in acts of volition. Remarkably, prior to self-generated shifts of attention, we observed early and selective increases in the activation of medial frontal (dorsal anterior cingulate) and lateral prefrontal (right middle frontal gyrus) cortex-activity that likely reflects processing related to the intention or preparation to reorient attention. These findings, which extend recent evidence on freely chosen motor movements, suggest that dorsal anterior cingulate and lateral prefrontal cortices play key roles in both overt and covert acts of volition, and may constitute core components of a brain network underlying the will to attend.

Distractor-relevance determines whether task-switching enhances or impairs distractor memory.

Richter and Yeung (2012) recently documented a novel task-switching effect, a switch-induced reduction in "memory selectivity," characterized by relatively enhanced memory for distractor stimuli and impaired memory for target stimuli encountered on switch trials compared with repeat trials. One interpretation of this finding argues that task-switching involves opening a "gate" to working memory, which promotes updating of the task-set, but at the same time allows for increased distraction from task-irrelevant information. However, in that study, the distractor category on a switch trial also represented the task-relevant target category from the previous trial. Thus, distractors were only intermittently task-irrelevant, such that switch-enhanced distractor memory could alternatively be because of remnant attention to the previously relevant stimuli, or "task-set inertia." Here we adjudicated between the open-gate and the task-set inertia accounts of switch-enhanced distractor memory by assessing incidental memory for distractors that were either intermittently or always task-irrelevant. While we replicated switch-enhanced distractor memory in the intermittently irrelevant distractor condition, this effect was reversed in the always-irrelevant distractor condition. These results speak against the open-gate account, and instead indicate that switch-enhanced distractor memory arises from task-set inertia, and will not be observed for truly task-irrelevant stimuli presented during switching.

Inhibition-Induced Forgetting Results from Resource Competition between Response Inhibition and Memory Encoding Processes.

Response inhibition is a key component of executive control, but its relation to other cognitive processes is not well understood. We recently documented the "inhibition-induced forgetting effect": no-go cues are remembered more poorly than go cues. We attributed this effect to central-resource competition, whereby response inhibition saps attention away from memory encoding. However, this proposal is difficult to test with behavioral means alone. We therefore used fMRI in humans to test two neural predictions of the "common resource hypothesis": (1) brain regions associated with response inhibition should exhibit greater resource demands during encoding of subsequently forgotten than remembered no-go cues; and (2) this higher inhibitory resource demand should lead to memory encoding regions having less resources available during encoding of subsequently forgotten no-go cues. Participants categorized face stimuli by gender in a go/no-go task and, following a delay, performed a surprise recognition memory test for those faces. Replicating previous findings, memory was worse for no-go than for go stimuli. Crucially, forgetting of no-go cues was predicted by high inhibitory resource demand, as quantified by the trial-by-trial ratio of activity in neural "no-go" versus "go" networks. Moreover, this index of inhibitory demand exhibited an inverse trial-by-trial relationship with activity in brain regions responsible for the encoding of no-go cues into memory, notably the ventrolateral prefrontal cortex. This seesaw pattern between the neural resource demand of response inhibition and activity related to memory encoding directly supports the hypothesis that response inhibition temporarily saps attentional resources away from stimulus processing. SIGNIFICANCE STATEMENT: Recent behavioral experiments showed that inhibiting a motor response to a stimulus (a "no-go cue") impairs subsequent memory for that cue. Here, we used fMRI to test whether this "inhibition-induced forgetting effect" is caused by competition for neural resources between the processes of response inhibition and memory encoding. We found that trial-by-trial variations in neural inhibitory resource demand predicted subsequent forgetting of no-go cues and that higher inhibitory demand was furthermore associated with lower concurrent activation in brain regions responsible for successful memory encoding of no-go cues. Thus, motor inhibition and stimulus encoding appear to compete with each other: when more resources have to be devoted to inhibiting action, less are available for encoding sensory stimuli.

Inhibition-induced forgetting: when more control leads to less memory.

The ability to inhibit prepotent responses is a core executive function, but the relation of response inhibition to other cognitive operations is poorly understood. In the study reported here, we examined inhibitory control through the lens of incidental memory. Participants categorized face stimuli by gender in a go/no-go task (Experiments 1 and 2) or a stop-signal task (Experiment 3) and, after a short delay, performed a surprise recognition memory task for those faces. Memory was impaired for stimuli presented during no-go and stop trials compared with those presented during go trials. Experiment 4 showed that this inhibition-induced forgetting was not attributable to event congruency. In Experiment 5, we combined a go/no-go task with a dot-probe test and found that probe detection during no-go trials was inferior to that on go trials. This result supports the hypothesis that inhibition-induced forgetting occurs when response inhibition shunts attentional resources from perceptual stimulus encoding to action control.

Intracellular delivery of recombinant arginine deiminase (rADI) by heparin-binding hemagglutinin adhesion peptide restores sensitivity in rADI-resistant cancer cells.

Recombinant arginine deiminase (rADI) has been used in clinical trials for arginine-auxotrophic cancers. However, the emergence of rADI resistance, due to the overexpression of argininosuccinate synthetase (AS), has introduced an obstacle in its clinical application. Here, we have proposed a strategy for the intracellular delivery of rADI, which depletes both extracellular and intracellular arginine, to restore the sensitivity of rADI-resistant cancer cells. In this study, the C terminus of heparin-binding hemagglutinin adhesion protein from Mycobacterium tuberculosis (HBHAc), which contains 23 amino acids, was used to deliver rADI into rADI-resistant human breast adenocarcinoma cells (MCF-7). Chemical conjugates (l- and d-HBHAc-SPDP-rADI) and a recombinant fusion protein (rHBHAc-ADI) were produced. l- and d-HBHAc-SPDP-rADI showed a significantly higher cellular uptake of rADI by MCF-7 cells compared to that of rADI alone. Cell viability was significantly decreased in a dose-dependent manner in response to l- and d-HBHAc-SPDP-rADI treatments. In addition, the ratio of intracellular concentration of citrulline to arginine in cells treated with l- and d-HBHAc-SPDP-rADI was significantly increased by 1.4- and 1.7-fold, respectively, compared with that obtained in cells treated with rADI alone (p < 0.001). Similar results were obtained with the recombinant fusion protein rHBHAc-ADI. Our study demonstrates that the increased cellular uptake of rADI by HBHAc modification can restore the sensitivity of rADI treatment in MCF-7 cells. rHBHAc-ADI may represent a novel class of antitumor enzyme with an intracellular mechanism that is independent of AS expression.

Opposing effects of appetitive and aversive cues on go/no-go behavior and motor excitability.

Everyday life, as well as psychiatric illness, is replete with examples where appetitive and aversive stimuli hijack the will, leading to maladaptive behavior. Yet the mechanisms underlying this phenomenon are not well understood. Here we investigate how motivational cues influence action tendencies in healthy individuals with a novel paradigm. Behaviorally, we observed that an appetitive cue biased go behavior (making a response), whereas an aversive cue biased no-go behavior (withholding a response). We hypothesized that the origin of this behavioral go/no-go bias occurs at the motor system level. To test this, we used single-pulse TMS as a motor system probe (rather than a disruptive tool) to index motivational biasing. We found that the appetitive cue biased the participants to go more by relatively increasing motor system excitability, and that the aversive cue biased participants to no-go more by relatively decreasing motor system excitability. These results show, first, that maladaptive behaviors arise from motivational cues quickly spilling over into the motor system and biasing behavior even before action selection and, second, that this occurs in opposing directions for appetitive and aversive cues.

Unconsciously triggered response inhibition requires an executive setting.

Much research on response inhibition has focused on a consciously triggered variety (i.e., outright stopping of action). However, recent studies have shown that response inhibition can also be triggered unconsciously. For example, van Gaal, Ridderinkhof, Scholte, and Lamme (2010) showed that an unconscious no-go prime slowed down ongoing behavior, at least when outright stopping was sometimes required (i.e., in an executive setting). Here we replicated that result but also went further by including a condition with no executive setting. Then there was no slowing following a no-go prime. These results support the hypothesis that an executive setting is necessary for unconsciously triggered inhibition. We speculate that this arises from the fact that when the context includes outright stopping, the brain network for response inhibition is primed, and it can be triggered by the unconscious prime. The result has theoretical implications for the distinction between conscious and unconscious response inhibition and also clinical implications for how to train response inhibition so that it is instantiated automatically.

Response suppression by automatic retrieval of stimulus-stop association: evidence from transcranial magnetic stimulation.

Behavioral studies show that subjects respond more slowly to stimuli to which they previously stopped. This response slowing could be explained by "automatic inhibition" (i.e., the reinstantiation of motor suppression when a stimulus retrieves a stop association). Here we tested this using TMS. In Experiment 1, participants were trained to go or no-go to stimuli. Then, in a test phase, we compared the corticospinal excitability for go stimuli that were previously associated with stopping (no-go_then_go) with go stimuli that were previously associated with going (go_then_go). Corticospinal excitability was reduced for no-go_then_go compared with go_then_go stimuli at a mere 100 msec poststimulus. Although these results fit with automatic inhibition, there was, surprisingly, no suppression for no-go_then_no-go stimuli, although this should occur. We speculated that automatic inhibition lies within a continuum between effortful top-down response inhibition and no inhibition at all. When the need for executive control and active response suppression disappears, so does the manifestation of automatic inhibition. Therefore, it should emerge during go/no-go learning and disappear as performance asymptotes. Consistent with this idea, in Experiment 2, we demonstrated reduced corticospinal excitability for no-go versus go trials most prominently in the midphase of training but it wears off as performance asymptotes. We thus provide neurophysiological evidence for an inhibition mechanism that is automatically reinstantiated when a stimulus retrieves a learned stopping episode, but only in an executive context in which active suppression is required. This demonstrates that automatic and top-down inhibition jointly contribute to goal-directed behavior.

Visuotopic cortical connectivity underlying attention revealed with white-matter tractography.

Visual attention selects behaviorally relevant information for detailed processing by resolving competition for representation among stimuli in retinotopically organized visual cortex. The signals that control this attentional biasing are thought to arise in a frontoparietal network of several brain regions, including posterior parietal cortex. Recent studies have revealed a topographic organization in the intraparietal sulcus (IPS) that mirrors the retinotopic organization in visual cortex, suggesting that connectivity between these regions might provide the mechanism by which attention acts on early cortical representations. Using white-matter imaging and functional MRI, we examined the connectivity between two topographic regions of IPS and six retinotopically defined areas in visual cortex. We observed a strong positive correlation between attention modulations in visual cortex and connectivity of posterior IPS, suggesting that these white-matter connections mediate the attention signals that resolve competition among stimuli for representation in visual cortex. Furthermore, we found that connectivity between IPS and V1 consistently respects visuotopic boundaries, whereas connections to V2 and V3/VP disperse by 60%. This pattern is consistent with changes in receptive field size across regions and suggests that a primary role of posterior IPS is to code spatially specific visual information. In summary, we have identified white-matter pathways that are ideally suited to carry attentional biasing signals in visuotopic coordinates from parietal control regions to sensory regions in humans. These results provide critical evidence for the biased competition theory of attention and specify neurobiological constraints on the functional brain organization of visual attention.

Tracking cognitive fluctuations with multivoxel pattern time course (MVPTC) analysis.

The posterior parietal cortex, including the medial superior parietal lobule (mSPL), becomes transiently more active during acts of cognitive control in a wide range of domains, including shifts of spatial and nonspatial visual attention, shifts between working memory representations, and shifts between categorization rules. Furthermore, spatial patterns of activity within mSPL, identified using multivoxel pattern analysis (MVPA), reliably distinguish between different acts of control. Here we describe a novel multivoxel pattern-based analysis that uses fluctuations in cognitive state over time to reveal inter-regional functional connectivity. First, we used MVPA to model patterns of activity in mSPL associated with shifting or maintaining spatial attention. We then computed a multivoxel pattern time course (MVPTC) that reflects, moment-by-moment, the degree to which the pattern of activity in mSPL more closely matches an attention-shift pattern or a sustained-attention pattern. We then entered the MVPTC as a regressor in a univariate (i.e., voxelwise) general linear model (GLM) to identify voxels whose BOLD activity covaried with the MVPTC. This analysis revealed several regions, including the striatum of the basal ganglia and bilateral middle frontal gyrus, whose activity was significantly correlated with the MVPTC in mSPL. For comparison, we also conducted a conventional functional connectivity analysis, entering the mean BOLD time course in mSPL as a regressor in a univariate GLM. The latter analysis revealed correlations in extensive regions of the frontal lobes but not in any subcortical area. The MVPTC analysis provides greater sensitivity (e.g., revealing the striatal-mSPL connectivity) and greater specificity (i.e., revealing more-focal clusters) than a conventional functional connectivity analysis. We discuss the broad applicability of MVPTC analysis to a variety of neuroimaging contexts.