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People respond more slowly in two-choice tasks when either a previous stimulus feature or the previous response repeats in partial repetition trials than when (a) both repeat in complete repetition trials or (b) both alternate in complete alternation trials. The binding account posits that such partial repetition costs index a memory-retrieval conflict, which occurs because partial repetition trials trigger the retrieval of a previous stimulus feature or response that conflicts with a current stimulus feature or response. However, such costs may additionally reflect a simple decision-making heuristic that uses the repetition or alternation of a previous stimulus feature as a “signal” to bias response selection toward a repetition or an alternation of the previous response. To determine whether signaling contributes to partial repetition costs, we employed a four-choice task. Here, a stimulus feature repetition still signals a response repetition, but a stimulus feature alternation does not signal which of the three remaining responses to make. Consistent with an influence of signaling, we sometimes observed complete repetition advantages without complete alternation advantages. Exploratory analyses further revealed that partial repetition costs measured more broadly were smaller in the four-choice task than in a matched two-choice task. These findings suggest that partial repetition costs index a mixture of binding and signaling.

Adaptive control processes that minimise distraction often operate in a context-specific manner. For example, they may minimise distraction from irrelevant conversations during a lecture but not in the hallway afterwards. It remains unclear, however, whether (a) salient perceptual features or (b) task sets based on such features serve as contextual boundaries for adaptive control in standard distractor-interference tasks. To distinguish between these possibilities, we manipulated whether the structure of a standard, visual distractor-interference task allowed (Experiment 1) or did not allow (Experiment 2) participants to associate salient visual features (i.e., colour patches and colour words) with different task sets. We found that changing salient visual features across consecutive trials reduced a popular measure of adaptive control in distractor-interference tasks—the congruency sequence effect (CSE)—only when the task structure allowed participants to associate these visual features with different task sets. These findings extend prior support for the task set hypothesis from somewhat atypical cross-modal tasks to a standard unimodal task. In contrast, they pose a challenge to an alternative “attentional reset” hypothesis, and related views, wherein changing salient perceptual features always results in a contextual boundary for the CSE.

Current views posit that forming and retrieving memories of ongoing events influences action control. However, the organizational structure of these memories, or event files, remains unclear. The hierarchical coding view posits a hierarchical structure, wherein task sets occupy a high level of the hierarchy. Here, the contents of an event file can be retrieved only if the task set repeats. In contrast, the binary coding view posits a nonhierarchical structure, which consists of a collection of independent, binary bindings between different feature pairs. In this view, repeating an abstract feature from a previous event (e.g., the previous trial's S-R mapping) triggers the retrieval of the associated feature from the same binding (e.g., the previous trial's congruency) even if the task set changes. To distinguish between these views, we investigated the nature of task set boundaries for the congruency sequence effect (CSE), an index of adaptive control that reflects event file formation and retrieval. Specifically, we investigated whether or not a CSE appears when the task set changes but the previous trial's S-R mapping repeats. Three experiments involving a cross-modal prime-probe task yielded a CSE under these conditions and ruled out alternative explanations. These findings show that the typical binary structure of event files generalizes from concrete features (e.g., colors and locations) to abstract features (e.g., S-R mappings and task sets). Therefore, contrary to the hierarchical coding view, they provide a nonhierarchical explanation of task set boundaries for the CSE. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The ability to remain flexible while engaging in goal-directed behavior is a critical aspect of cognitive control. A classic example of such flexibility is the congruency sequence effect (CSE) in distractor-interference tasks. In such tasks, participants respond more slowly when a distractor cues a different response than a target (incongruent trials) than when it cues the same response (congruent trials). However, this congruency effect is smaller after incongruent trials than after congruent trials. Interestingly, recent data from the prime-probe task indicate that this CSE is largest when participants treat the distractor, or prime, as the first of two temporally separated targets. It remains unclear, however, whether the CSE in this task indexes (1) control processes that modulate response activation before the second target (i.e., probe) appears or (2) congruency switch costs that delay responses after the probe appears. To distinguish between these accounts, participants' responses were recorded with force-sensitive keys. After responding to the prime, but before the probe appeared, participants exerted greater force on (1) the key cued by the prime after congruent trials, but on (2) the opposite key after incongruent trials. These findings indicate that the ability to remain flexible while engaging in goal-directed behavior relies on control processes that modulate response activation prior to the appearance of a goal-relevant stimulus.

For monitoring of concussion, brain function, organ condition and other medical applications, what is needed is a non-invasive method of monitoring tissue metabolism. MRI-based functional imaging technology detects changes in blood oxygenation, a correlate of neural activity, and thus may offer a prediction of prognosis in cases of concussion and other cerebral traumas. Yet, potential relationships between perturbations to cerebral metabolism and patient outcomes cannot be effectively exploited clinically because we lack a practical, low-cost, non-invasive means to monitor cerebral oxygenation and metabolism in the emergency department, operating room, or medical facilities. We have developed a device to optically assay the redox state of Cytochrome-C-Oxidase (CCO), the mitochondrial enzyme responsible for the last step of the electron transport chain. Changes in CCO redox reflect changes in respiratory flux, and thus changes in the rate of oxidative adenosine triphosphate (ATP) synthesis. In other words, changes in CCO reflect brain cell’s metabolic activity more directly than the traditional blood oxygenation measurement methods. To non-invasively measure changes in CCO as well as blood oxygenation, we have developed a Super-Continuum Infrared Spectroscopy of Cytochrome-C-Oxidase (SCISCCO) system that uses an all-fiber integrated, super-continuum light source to simultaneously measure both of the new (CCO) and the traditional (blood oxygenation) markers of neural metabolism. The SCISCCO system is validated by confirming the near-infrared spectrum of CCO in vitro. To demonstrate in vivo feasibility, the measured responses of oxygenation and CCO responses to acute ischemia (e.g., blood pressure tests) in human participants are compared to data from the literature. Furthermore, we show that the new device’s measurements of oxygenated (HbO) and deoxygenated (HbR) hemoglobin in response to breath hold challenges are principled and consistent with previously reported findings. The validated SCISCCO system is finally applied to measure cerebral oxygenation and the redox state of CCO in participants during an attention test protocol. Twenty-five healthy adults completed an attention task that included nine 60-second periods of attention task, interleaved with 60-s periods of resting baseline. It has been well established that the frontal lobe of the human brain is active during tasks of attention. We therefore predicted that attention task should elicit an increase in HbO concentration accompanied by a decrease in redox state of CCO (e.g., ratio of oxidized CCO to reduced CCO) in frontal lobe brain regions as measured with the SCISCCO system. Our findings are consistent with our predictions: HbO concentration increases while CCO concentration decreases during the attention blocks relative to the resting baseline, thereby indicating an increase in oxidative metabolism of the frontal lobe brain regions of interest. Our systematic, multi-method approach thus validates the new device as well as the validity of the metabolic biomarkers that it measures. The SCISCCO system could be a new tool for monitoring brain and organ metabolism, which could be invaluable for screening concussion patients or use in an operating or emergency room to gauge patient’s organ response to treatments.

Lexical retrieval requires selecting and retrieving the most appropriate word from the lexicon to express a desired concept. Prior studies investigating the neuroanatomic underpinnings of lexical retrieval used lesion models that rely on stereotyped vascular distributions, functional neuroimaging methods that lack causal certainty, or awake brain mapping that is typically limited to narrow cortical exposures. Further, few studies have probed lexical retrieval with tasks other than picture naming and when non-picture naming lexical retrieval tasks have been applied, both convergent and divergent models emerged. Because of this existing controversy, we set out to test the hypothesis that cortical and subcortical brain regions specifically involved in lexical retrieval in response to visual and auditory stimuli represent overlapping neural systems. Fifty-three patients with dysnomic aphasia due to dominant-hemisphere brain tumors performed four language tasks: picture naming, auditory naming, text reading, and describing line drawings with correct syntax. A subset of participants also underwent the Quick Aphasia Battery which provides a validated measure of lexical retrieval via the word finding subtest. Generalized linear modeling and principal components analysis revealed multicollinearity between picture naming, auditory naming, and word finding, implying redundancies between the linguistic measures. Support vector regression lesion-symptom mapping across participants was used to model accuracies on each of the four language tasks. Picture naming and auditory naming survived cluster-level corrections. Specifically, lesions within overlapping clusters of 8,333 voxels and 21,512 voxels in the left lateral PFC were predictive of impaired picture naming and auditory naming, respectively. These data indicate a convergence of heteromodal lexical retrieval within the PFC.Importance of the StudyLexical retrieval (i.e., selecting and retrieving words to convey desired concepts) is a crucial component of language processing. However, existing studies of the neuroanatomic underpinnings of lexical retrieval lack causal relationships and have provided conflicting evidence, suggesting both convergent and divergent models. In order to resolve these conflicting models, we used lesion-symptom mapping to investigate lexical retrieval in 53 patients with dominant-hemisphere brain tumors. We observed significant associations between performance on visual and auditory naming tasks. Further, performance on these tasks predicted performance on a validated neuropsychological measure of lexical retrieval. Critically, multivariate, nonparametric lesion-symptom mapping within a brain tumor framework revealed that lesions in overlapping regions of the left lateral prefrontal cortex (PFC) predict impaired visual and auditory naming. In a clinical context, this approach to identifying causal brain-behavior relationships could help to guide brain tumor therapies such as cytoreductive surgery and supportive rehabilitation services.

Adapting flexibly to recent events is essential in everyday life. A robust measure of such adaptive behavior is the congruency sequence effect (CSE) in the prime-probe task, which refers to a smaller congruency effect after incongruent trials than after congruent trials. Prior findings indicate that the CSE in the prime-probe task reflects control processes that modulate response activation after the prime onsets but before the probe appears. They also suggest that similar control processes operate even in a modified prime-probe task wherein the initial prime is a relevant target, rather than merely a distractor. Because adaptive behavior frequently occurs in the absence of irrelevant stimuli, the present study investigates the nature of the control processes that operate in this modified prime-probe task. Specifically, it investigates whether these control processes modulate only the response cued by the prime (response-specific control) or also other responses (response-general control). To make this distinction, we employed a novel variant of the modified prime-probe task wherein primes and probes are mapped to different responses (i.e., effectors), such that only response-general control processes can engender a CSE. Critically, we observed a robust CSE in each of 2 experiments. This outcome supports the response-general control hypothesis. More broadly, it suggests that the control processes underlying the CSE overlap with general mechanisms for adapting to sequential dependencies in the environment. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Age-related neural dedifferentiation – a decline in the distinctiveness of neural representations in the aging brain– has been associated with age-related declines in cognitive abilities. But why does neural distinctiveness decline with age? Based on prior work in non-human primates and more recent work in humans, we hypothesized that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) declines with age and is associated with neural dedifferentiation in older adults. To test this hypothesis, we used magnetic resonance spectroscopy (MRS) to measure GABA and functional MRI (fMRI) to measure neural distinctiveness in the ventral visual cortex in a set of older and younger participants. Relative to younger adults, older adults exhibited lower GABA levels and less distinct activation patterns for faces and houses in the ventral visual cortex. Furthermore, individual differences in GABA within older adults positively predicted individual differences in neural distinctiveness. These results provide novel support for the view that age-related reductions of GABA contribute to age-related reductions in neural distinctiveness (i.e., neural dedifferentiation) in the human ventral visual cortex.

Normal aging is associated with declines in sensorimotor function. Previous studies have linked age-related behavioral declines to decreases in neural differentiation (i.e., dedifferentiation), including decreases in the distinctiveness of neural activation patterns and in the segregation of large-scale neural networks at rest. However, no studies to date have explored the relationship between these two neural measures and whether they explain the same aspects of behavior. To investigate these issues, we collected a battery of sensorimotor behavioral measures in older and younger adults and estimated (a) the distinctiveness of neural representations in sensorimotor cortex and (b) sensorimotor network segregation in the same participants. Consistent with prior findings, sensorimotor representations were less distinct and sensorimotor resting state networks were less segregated in older compared to younger adults. We also found that participants with the most distinct sensorimotor representations exhibited the most segregated sensorimotor networks. However, only sensorimotor network segregation was associated with individual differences in sensorimotor performance, particularly in older adults. These novel findings link network segregation to neural distinctiveness, but also suggest that network segregation may play a larger role in maintaining sensorimotor performance with age.

The congruency effect in distractor-interference tasks is typically smaller after incongruent trials than after congruent trials. Current views posit that this congruency sequence effect (CSE) reflects control processes that come into play when an irrelevant distractor cues a different response than a relevant target. However, the CSE is counterintuitively larger in the prime-probe task when the prime is occasionally a second target than when the prime is more frequently a distractor. In the present study, we investigated whether this effect occurs because the appearance of an occasional prime target (a) constitutes a rare, unexpected event that triggers heightened control or (b) allows participants to use the same task set (i.e., stimulus-response mapping) for the prime and probe in each trial. Consistent with the latter hypothesis, we observed this effect in Experiment 1 even when the critical trial types appeared equally often. Further, in Experiment 2, we extended this finding while ruling out perceptual differences between conditions as an alternative account. These findings provide novel support for the task set hypothesis and reveal that the CSE reflects control processes that do more than minimize distraction from irrelevant stimuli.

Cognitive control processes that enable purposeful behavior are often context-specific. A teenager, for example, may inhibit the tendency to daydream at work but not in the classroom. However, the nature of contextual boundaries for cognitive control processes remains unclear. Therefore, we revisited an ongoing controversy over whether such boundaries reflect (a) an attentional reset that occurs whenever a context-defining (e.g., sensory) feature changes or (b) a disruption of episodic memory retrieval that occurs only when the updated context-defining feature is linked to a different task set. To distinguish between these hypotheses, we used a cross-modal distractor-interference task to determine precisely when changing a salient context-defining feature-the sensory modality in which task stimuli appear-bounds control processes underlying the congruency sequence effect (CSE). Consistent with the task set hypothesis, but not with the attentional reset hypothesis, Experiments 1 and 2 revealed that changing the sensory modality in which task stimuli appear eliminates the CSE only when the task structure enables participants to form modality-specific task sets. Experiment 3 further revealed that such "modality-specific" CSEs are associated with orienting attention to the sensory modality in which task stimuli appear, which may facilitate the formation of a modality-specific task set. These findings support the view that task sets serve as boundaries for the CSE. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Resisting distraction and response inhibition are crucial aspects of cognitive control. Interestingly, each of these abilities transiently improves just after it is utilized. Competing views differ, however, as to whether utilizing either of these abilities (e.g., resisting distraction) enhances future performance involving the other ability (e.g., response inhibition). To distinguish between these views, we combined a Stroop-like task that requires resisting distraction with a restraint variant of the stop-signal task that requires response inhibition. We observed similar sequential-trial effects (i.e., performance enhancements) following trials in which participants (a) resisted distraction (i.e., incongruent go trials) and (b) inhibited a response (i.e., congruent stop trials). First, the congruency effect in go trials, which indexes overall distractibility, was smaller after both incongruent go trials and congruent stop trials than it was after congruent go trials. Second, stop failures were less frequent after both incongruent go trials and congruent stop trials than after congruent go trials. A control experiment ruled out the possibility that perceptual conflict or surprise engendered by occasional stop signals triggers sequential-trial effects independent of stopping. Thus, our findings support a novel, integrated view in which resisting distraction and response inhibition trigger similar sequential enhancements of future performance.

The past two decades have witnessed an explosion of interest in the cognitive and neural mechanisms of adaptive control processes that operate in selective attention tasks. This has spawned not only a large empirical literature and several theories but also the recurring identification of potential confounds and corresponding adjustments in task design to create confound-minimized metrics of adaptive control. The resulting complexity of this literature can be difficult to navigate for new researchers entering the field, leading to suboptimal study designs. To remediate this problem, we present here a consensus view among opposing theorists that specifies how researchers can measure four hallmark indices of adaptive control (the congruency sequence effect, and list-wide, context-specific, and item-specific proportion congruency effects) while minimizing easy-to-overlook confounds.

Age-related neural dedifferentiation – reduced distinctiveness of neural representations in the aging brain– has been associated with age-related declines in cognitive abilities. But why does neural distinctiveness decline with age? Based on prior work in non-human primates, we hypothesized that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) declines with age and is associated with neural dedifferentiation. To test this hypothesis, we used magnetic resonance spectroscopy (MRS) to measure GABA and functional MRI (fMRI) to measure neural distinctiveness in the ventral visual cortex in a set of older and younger participants. Relative to younger adults, older adults exhibited lower GABA levels and less distinct activation patterns for faces and houses in the ventral visual cortex. Furthermore, individual differences in GABA within older adults predicted individual differences in neural distinctiveness even after controlling for gray matter volume and age. These results provide novel support for the view that age-related reductions of GABA contribute to age-related reductions in neural distinctiveness (i.e., neural dedifferentiation) in the human ventral visual cortex. Significance Statement Neural representations in the ventral visual cortex are less distinguishable in older compared to younger humans, and this neural dedifferentiation is associated with age-related cognitive deficits. Animal models suggest that reductions in the inhibitory neurotransmitter gamma aminobutyric acid (GABA) may play a role. To investigate this hypothesis, we combined functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) in a study of the human ventral visual cortex. We observed reduced distinctiveness of neural patterns and reduced GABA levels in older compared to younger adults. Furthermore, older adults with higher GABA levels tended to have more distinctive neural representations. These findings suggest that reduced GABA levels contribute to age-related declines in neural distinctiveness in the human ventral visual cortex.

Neural activation patterns in the ventral visual cortex in response to different categories of visual stimuli (e.g., faces vs. houses) are less selective, or distinctive, in older adults than in younger adults, a phenomenon known as age-related neural dedifferentiation. Previous work in animals suggests that age-related reductions of the inhibitory neurotransmitter, gamma aminobutyric acid (GABA), may play a role in this age-related decline in neural distinctiveness. In this study, we investigated whether neural dedifferentiation extends to auditory cortex and whether individual differences in GABA are associated with individual differences in neural distinctiveness in humans. 20 healthy young adults (ages 18-29) and 23 healthy older adults (over 65) completed a functional magnetic resonance imaging (fMRI) scan, during which neural activity was estimated while they listened to foreign speech and music. GABA levels in the auditory, ventrovisual and sensorimotor cortex were estimated in the same individuals in a separate magnetic resonance spectroscopy (MRS) scan. Relative to the younger adults, the older adults exhibited both (1) less distinct activation patterns for music vs. speech stimuli and (2) lower GABA levels in the auditory cortex. Also, individual differences in auditory GABA levels (but not ventrovisual or sensorimotor GABA levels) predicted individual differences in neural distinctiveness in the auditory cortex in the older adults. These results demonstrate that age-related neural dedifferentiation extends to the auditory cortex and suggest that declining GABA levels may play a role in neural dedifferentiation in older adults.Significance StatementPrior work has revealed age-related neural dedifferentiation in the visual cortex. GABA levels also decline with age in several parts of the human cortex. Here, we report that these two age-related changes are linked; neural dedifferentiation is associated with lower GABA levels in older adults. We also show that age-related neural dedifferentiation extends to auditory cortex, suggesting that it may be a general feature of the aging brain. These findings provide novel insights into the neurochemical basis of age-related neural dedifferentiation in humans and also offer a potential new avenue for investigating age-related declines in central auditory processing.

Intra-subject variation in reaction time (ISVRT) is a developmentally-important phenomenon that decreases from childhood through young adulthood in parallel with the development of executive functions and networks. Prior work has shown a significant association between trial-by-trial variations in reaction time (RT) and trial-by-trial variations in brain activity as measured by the blood-oxygenated level-dependent (BOLD) response in functional magnetic resonance imaging (fMRI) studies. It remains unclear, however, whether such “RT-BOLD” relationships vary with age. Here, we determined whether such trial-by-trial relationships vary with age in a cross-sectional design. We observed an association between age and RT-BOLD relationships in 11 clusters located in visual/occipital regions, frontal and parietal association cortex, precentral/postcentral gyrus, and thalamus. Some of these relationships were negative, reflecting increased BOLD associated with decreased RT, manifesting around the time of stimulus presentation and positive several seconds later. Critically for present purposes, all RT-BOLD relationships increased with age. Thus, RT-BOLD relationships may reflect robust, measurable changes in the brain-behavior relationship across development.

OBJECTIVEMaximal safe tumor resection in language areas of the brain relies on a patient’s ability to perform intraoperative language tasks. Assessing the performance of these tasks during awake craniotomies allows the neurosurgeon to identify and preserve brain regions that are critical for language processing. However, receiving sedation and analgesia just prior to experiencing an awake craniotomy may reduce a patient’s wakefulness, leading to transient language and/or cognitive impairments that do not completely subside before language testing begins. At present, the degree to which wakefulness influences intraoperative language task performance is unclear. Therefore, the authors sought to determine whether any of 5 brief measures of wakefulness predicts such performance during awake craniotomies for glioma resection.METHODSThe authors recruited 21 patients with dominant hemisphere low- and high-grade gliomas. Each patient performed baseline wakefulness measures in addition to picture-naming and text-reading language tasks 24 hours before undergoing an awake craniotomy. The patients performed these same tasks again in the operating room following the cessation of anesthesia medications. The authors then conducted statistical analyses to investigate potential relationships between wakefulness measures and language task performance.RESULTSRelative to baseline, performance on 3 of the 4 objective wakefulness measures (rapid counting, button pressing, and vigilance) declined in the operating room. Moreover, these declines appeared in the complete absence of self-reported changes in arousal. Performance on language tasks similarly declined in the intraoperative setting, with patients experiencing greater declines in picture naming than in text reading. Finally, performance declines on rapid counting and vigilance wakefulness tasks predicted performance declines on the picture-naming task.CONCLUSIONSCurrent subjective methods for assessing wakefulness during awake craniotomies may be insufficient. The administration of objective measures of wakefulness just prior to language task administration may help to ensure that patients are ready for testing. It may also allow neurosurgeons to identify patients who are at risk for poor intraoperative performance.

Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .

BackgroundAging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway).Methods/DesignThe MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy (MRS), and diffusion weighted imaging (DWI) sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take (1) a benzodiazepine (lorazepam) that should increase GABA activity or (2) a placebo.DiscussionBy collecting multimodal imaging measures (fMRI, MRS, DWI) along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines.

Rationale and Objectives Healthy aging is associated with pervasive declines in cognitive, motor, and sensory functioning. There are, however, substantial individual differences in behavioral performance among older adults. Several lines of animal research link age-related reductions of gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter, to age-related cognitive, motor, and sensory decline. Our study used proton magnetic resonance spectroscopy (MRS) at 3T to explore whether occipital GABA declines with age in humans and whether individual differences in occipital GABA are linked to individual differences in fluid processing ability. Materials and Methods We used a MEGA-PRESS sequence that combines frequency spectral editing with a point-resolved spectroscopy sequence to quantify GABA. Spectra were obtained from a 30 × 30 × 25 mm voxel placed in the occipital cortex of 20 young adults (mean age 20.7 years) and 18 older adults (mean age 76.5 years). Participants also performed 11 fluid processing tasks outside the scanner, the results of which were z-scored and averaged to calculate a summary measure of fluid processing ability. Regression analysis was employed to determine the relationship between GABA concentrations in the occipital cortex and a summary measure of fluid processing ability. Results Occipital GABA was significantly lower in older participants compared to the younger participants. We also observed a significant positive relationship between occipital GABA and fluid processing ability. In fact, higher GABA was associated with better task performance in 10 of the 11 tasks. Conclusion These findings suggest that GABA levels decline with age in humans and are associated with declines in fluid processing ability.

Aging is typically associated with declines in sensorimotor performance. Previous studies have linked some age-related behavioral declines to reductions in network segregation. For example, compared to young adults, older adults typically exhibit weaker functional connectivity within the same functional network but stronger functional connectivity between different networks. Based on previous animal studies, we hypothesized that such reductions of network segregation are linked to age-related reductions in the brain's major inhibitory transmitter, gamma aminobutyric acid (GABA). To investigate this hypothesis, we conducted graph theoretical analyses of resting state functional MRI data to measure sensorimotor network segregation in both young and old adults. We also used magnetic resonance spectroscopy to measure GABA levels in the sensorimotor cortex and collected a battery of sensorimotor behavioral measures. We report four main findings. First, relative to young adults, old adults exhibit both less segregated sensorimotor brain networks and reduced sensorimotor GABA levels. Second, less segregated networks are associated with lower GABA levels. Third, less segregated networks and lower GABA levels are associated with worse sensorimotor performance. Fourth, network segregation mediates the relationship between GABA and performance. These findings link age-related differences in network segregation to age-related differences in GABA levels and sensorimotor performance. More broadly, they suggest a neurochemical substrate of age-related dedifferentiation at the level of large-scale brain networks.

The congruency effect observed in distracter interference tasks is usually smaller after incongruent relative to congruent trials. However, the nature of control processes underlying this congruency sequence effect (CSE) remains a topic of active debate. For example, while some researchers have suggested that these processes are recruited only when participants utilize the same response mode (e.g., the same hand) to respond in consecutive trials, others have argued that these processes can operate independently of response mode. To distinguish between these views, we investigated whether changes of response mode across consecutive trials influence the CSE in a prime-probe task (Experiment 1) or a flanker task (Experiment 2). Such changes did not influence the CSE in either task. Further, the CSE was significant even when participants utilized different response modes (i.e., different hands) to respond in consecutive trials. These findings indicate that control processes underlying the CSE can operate independently of response mode and thereby clarify the nature of control processes that minimize distraction from irrelevant stimuli.

The congruency effect in distracter interference tasks is typically smaller when the previous trial was incongruent as compared to congruent, suggesting the operation of a control process that minimizes the influence of irrelevant stimuli on behavior. However, both the conditions under which this congruency sequence effect (CSE) can be most easily observed without the typical learning and memory confounds, and the control process underlying it, remain controversial. We therefore tested a recent hypothesis that the CSE is most easily observed without the typical confounds when the distracter is processed before the target. In line with this "distracter head start" hypothesis, in Experiments 1 and 2 the CSE was larger when the distracter appeared before, relative to with, the target. Further, in Experiment 3, we observed a negative congruency effect after incongruent trials when a long interval separated the distracter from the target, consistent with a modulation of the response engendered by the distracter but not with a shift of attention toward the target. These findings reveal an important determinant of CSE magnitude when the typical learning and memory confounds are absent and new insights into the nature of control processes that contribute to this phenomenon.

The perceptual load hypothesis posits that early and late selection occurs under conditions of high and low perceptual load, respectively. Recent work, however, suggests that the absence of a congruency effect in high-load trials - the behavioral signature of early selection in studies of perceptual load - may not provide an exhaustive index of failing to identify task-irrelevant distractors. Prior research also suggests that the congruency sequence effect (CSE) - a modulation of the congruency effect after incongruent relative to congruent trials - provides complementary information about whether participants identify distractors. We therefore conducted a novel test of the perceptual load hypothesis that employed both the congruency effect and the CSE as measures of distractor identification. Experiment 1 revealed that distractors were identified not only in low-load trials but also in high-load trials wherein there was no overall congruency effect. Experiment 2 further revealed which task parameters allowed us to observe such "hidden" distractor identification. These findings suggest that perceptual load is not always a crucial determinant of early versus late selection.

The ability to adaptively increase cognitive control in response to cognitive challenges is crucial for goal-directed behavior. Recent findings suggest that aversive arousal triggers adaptive increases of control, but the neurochemical mechanisms underlying these effects remain unclear. Given the known contributions of the opioid system to hedonic states, we investigated whether blocking this system increases adaptive control modulations. To do so, we conducted a double-blind, placebo-controlled psychopharmacological study (n=52 females) involving a Stroop-like task. Specifically, we assessed the effect of naltrexone, an opioid blocker most selective to the mu-opioid system, on two measures of adaptive control that are thought to depend differentially on aversive arousal: post-error slowing and conflict adaptation. Consistent with our hypothesis, relative to placebo, naltrexone increased post-error slowing without influencing conflict adaptation. This finding not only supports the view that aversive arousal triggers adaptive control but also reveals a novel role for the opioid system in modulating such effects.

Prior work has revealed that posttraumatic stress disorder (PTSD) is associated with altered (a) attentional performance and (b) resting-state functional connectivity (rsFC) in brain networks linked to attention. Here, we sought to characterize and link these behavioral and brain-based alterations in the context of Posner and Peterson's tripartite model of attention. Male military veterans with PTSD (N = 49; all deployed to Iraq or Afghanistan) and healthy age-and-gender-matched community controls (N = 26) completed the Attention Network Task. A subset of these individuals (36 PTSD and 21 controls) also underwent functional magnetic resonance imaging (fMRI) to assess rsFC. The behavioral measures revealed that the PTSD group was impaired at disengaging spatial attention, relative to the control group. FMRI measures further revealed that, relative to the control group, the PTSD group exhibited greater rsFC between the salience network and (a) the default mode network, (b) the dorsal attention network, and (c) the ventral attention network. Moreover, problems with disengaging spatial attention increased the rsFC between the networks above in the control group, but not in the PTSD group. The present findings link PTSD to both altered orienting of spatial attention and altered relationships between spatial orienting and functional connectivity involving the salience network. Interventions that target orienting and disengaging spatial attention may be a new avenue for PTSD research.

Prior findings suggest that coping with distraction relies on cognitive control processes that increase attention to task-relevant processing and/or decrease attention to task-irrelevant processing. In line with this view, the size of the congruency effect in unimodal Stroop-like tasks, a popular measure of distraction, is typically reduced after more distracting incongruent trials relative to after less distracting congruent trials. It remains unclear, however, whether, and under what conditions, the control processes underlying this congruency sequence effect (CSE) minimize cross-modal distraction. The contingent attentional capture hypothesis predicts a cross-modal CSE when a distracter possesses a target-defining feature. In contrast, the perceptual conflict hypothesis predicts a cross-modal CSE when there is perceptual conflict between a distracter and a target. To distinguish between these hypotheses, we conducted two experiments wherein an auditory distracter word preceded a visual target that appeared in one of two formats (i.e., word or arrow). We observed robust, cross-modal CSEs. Moreover, the pattern of CSEs that we observed was more consistent with the contingent attentional capture hypothesis than with the perceptual conflict hypothesis. These findings reveal a novel attentional mechanism for minimizing cross-modal distraction.

In functional magnetic resonance imaging (fMRI) studies, researchers often attempt to ensure that group differences in brain activity are not confounded with group differences in mean reaction time (RT). However, even when groups are matched for performance, they may differ in terms of the RT-BOLD relationship: the degree to which brain activity varies with RT on a trial-by-trial basis. Group activation differences might therefore be influenced by group differences in the relationship between brain activity and time on task. Here, we investigated whether correcting for this potential confound alters group differences in brain activity. Specifically, we reanalyzed data from a functional MRI study of response conflict in children and adults, in which conventional analyses indicated that conflict-related activity did not differ between groups. We found that the RT-BOLD relationship was weaker in children than in adults. Consequently, after removing the effect of RT on brain activity, children exhibited greater conflict-related activity than adults in both the posterior medial prefrontal cortex and the right dorsolateral prefrontal cortex. These results identify the RT-BOLD relationship as an important potential confound in fMRI studies of group differences. They also suggest that the magnitude of the RT-BOLD relationship may be a useful biomarker of brain maturity.

Functional neuroimaging studies of endogenous cued attention suggest that a fronto-parietal attentional network keeps track of current task objectives in working memory and enhances activity in posterior sensory regions that underlie the perceptual processing of behaviorally relevant stimuli. Relatively little is known, however, about whether consciously perceived, irrelevant instructional cues can hijack the attentional network, leading to an enhancement of the perceptual processing of irrelevant stimuli. Using a cross-modal attentional cueing task in combination with functional magnetic resonance imaging, we found that such irrelevant cues can indeed hijack the attentional network, as indexed by increased activity in (a) frontal regions that control attention and (b) sensory cortices that underlie the perceptual processing of task-irrelevant stimuli. Furthermore, we found that in left ventrolateral (but not dorsolateral) prefrontal regions, the magnitude of this increased activity varies with whether an irrelevant instructional cue is presented simultaneously with (versus after) a relevant instructional cue. These findings show that consciously perceived, irrelevant instructional cues can activate inappropriate task objectives in working memory, resulting in a hijacking of the attentional network. Moreover, they reveal different time courses of hijacking effects in ventrolateral and dorsolateral prefrontal regions, consistent with models in which these regions make distinct contributions to cognitive control.

Lapses of attention manifest as delayed behavioral responses to salient stimuli. Although they can occur even after a normal night's sleep, they are longer in duration and more frequent after sleep deprivation (SD). To identify changes in task-associated brain activation associated with lapses during SD, we performed functional magnetic resonance imaging during a visual, selective attention task and analyzed the correct responses in a trial-by-trial manner modeling the effects of response time. Separately, we compared the fastest 10% and slowest 10% of correct responses in each state. Both analyses concurred in finding that SD-related lapses differ from lapses of equivalent duration after a normal night's sleep by (1) reduced ability of frontal and parietal control regions to raise activation in response to lapses, (2) dramatically reduced visual sensory cortex activation, and (3) reduced thalamic activation during lapses that contrasted with elevated thalamic activation during nonlapse periods. Despite these differences, the fastest responses after normal sleep and after SD elicited comparable frontoparietal activation, suggesting that performing a task while sleep deprived involves periods of apparently normal neural activation interleaved with periods of depressed cognitive control, visual perceptual functions, and arousal. These findings reveal for the first time some of the neural consequences of the interaction between efforts to maintain wakefulness and processes that initiate involuntary sleep in sleep-deprived persons.

Brain activity can predict a person’s level of engagement in an attentional task. However, estimates of brain activity are often confounded by measurement artifacts and systemic physiological noise. The optimal method for filtering this noise – thereby increasing such state prediction accuracy – remains unclear. To investigate this, we asked study participants to perform an attentional task while we monitored their brain activity with functional near infrared spectroscopy (fNIRS). We observed higher state prediction accuracy when noise in the fNIRS hemoglobin [Hb] signals was filtered with a non-stationary (adaptive) model as compared to static regression (84% ± 6% versus 72% ± 15%).

In the present study, we followed up on a recent report of two experiments in which the congruency sequence effect-the reduction of the congruency effect after incongruent relative to congruent trials in Stroop-like tasks-was observed without feature repetition or contingency learning confounds. Specifically, we further scrutinized these data to determine the plausibility of a temporal learning account as an alternative to the popular conflict adaptation account. To this end, we employed a linear mixed effects model to investigate the role of previous response time in producing the congruency sequence effect, because previous response time is thought to influence temporal learning. Interestingly, slower previous response times were associated with a reduced current-trial congruency effect, but only when the previous trial was congruent. An adapted version of the parallel episodic processing (PEP) model was able to fit these data if it was additionally assumed that attention "wanders" during different parts of the experiment (e.g., due to fatigue or other factors). Consistent with this assumption, the magnitude of the congruency effect was correlated across small blocks of trials. These findings demonstrate that a temporal learning mechanism provides a plausible account of the congruency sequence effect.

Attending to a stimulus is known to enhance the neural responses to that stimulus. Recent experiments on visual attention have shown that this modulation can have object-based characteristics, such that, when certain parts of a visual object are attended, other parts automatically also receive enhanced processing. Here, we investigated whether visual attention can modulate neural responses to other components of a multisensory object defined by synchronous, but spatially disparate, auditory and visual stimuli. The audiovisual integration of such multisensory stimuli typically leads to mislocalization of the sound toward the visual stimulus (ventriloquism illusion). Using event-related potentials and functional MRI, we found that the brain's response to task-irrelevant sounds occurring synchronously with a visual stimulus from a different location was larger when that accompanying visual stimulus was attended versus unattended. The event-related potential effect consisted of sustained, frontally distributed, brain activity that emerged relatively late in processing, an effect resembling attention-related enhancements seen at earlier latencies during intramodal auditory attention. Moreover, the functional MRI data confirmed that the effect included specific enhancement of activity in auditory cortex. These findings indicate that attention to one sensory modality can spread to encompass simultaneous signals from another modality, even when they are task-irrelevant and from a different location. This cross-modal attentional spread appears to reflect an object-based, late selection process wherein spatially discrepant auditory stimulation is grouped with synchronous attended visual input into a multisensory object, resulting in the auditory information being pulled into the attentional spotlight and bestowed with enhanced processing.

Data from brain-damaged and neurologically intact populations indicate hemispheric asymmetries in the temporo-parietal cortex for discriminating an object's global form (e.g. the overall shape of a bicycle) versus its local parts (e.g. the spokes in a bicycle tire). However, it is not yet clear whether such asymmetries reflect processes that (i) bias attention toward upcoming global versus local stimuli and/or (ii) attend/identify global versus local stimuli after they are presented. To investigate these possibilities, we asked sixteen healthy participants to perform a cued global/local attention task while their brain activity was recorded using event-related functional magnetic resonance imaging (fMRI). The results indicated a novel double dissociation. Hemispheric asymmetries for deploying attention toward expected global versus local object features were specific to the intraparietal sulcus (iPs). However, hemispheric asymmetries for identifying global versus local features after they were presented were specific to the inferior parietal lobe/superior temporal gyrus (IPL/STG). This double dissociation provides the first direct evidence that hemispheric asymmetries associated with different components of global/local attention occur in distinct temporo-parietal loci. Furthermore, it parallels an analogous dissociation reported in a recent fMRI study of spatial orienting, suggesting that global/local attention and spatial attention might rely on similar cognitive/neural mechanisms.

In everyday life, we often focus greater attention on behaviorally relevant stimuli to limit the processing of distracting events. For example, when distracting voices intrude upon a conversation at a noisy social gathering, we concentrate more attention on the speaker of interest to better comprehend his or her speech. In the present study, we investigated whether dorsal/caudal regions of the anterior cingulate cortex (dACC), thought to make a major contribution to cognitive control, boost attentional resources toward behaviorally relevant stimuli as a means for limiting the processing of distracting events. Sixteen healthy participants performed a cued global/local selective attention task while brain activity was recorded with event-related functional magnetic resonance imaging. Consistent with our hypotheses, greater dACC activity during distracting events predicted reduced behavioral measures of interference from those same events. dACC activity also differed for cues to attend to global versus local features of upcoming visual objects, further indicating a role in directing attention toward task-relevant stimuli. Our findings indicate a role for dACC in focusing attention on behaviorally relevant stimuli, especially when the achievement of our behavioral goals is threatened by distracting events.

Recently, a number of investigators have examined the neural loci of psychological processes enabling the control of visual spatial attention using cued-attention paradigms in combination with event-related functional magnetic resonance imaging. Findings from these studies have provided strong evidence for the involvement of a fronto-parietal network in attentional control. In the present study, we build upon this previous work to further investigate these attentional control systems. In particular, we employed additional controls for nonattentional sensory and interpretative aspects of cue processing to determine whether distinct regions in the fronto-parietal network are involved in different aspects of cue processing, such as cue-symbol interpretation and attentional orienting. In addition, we used shorter cue-target intervals that were closer to those used in the behavioral and event-related potential cueing literatures. Twenty participants performed a cued spatial attention task while brain activity was recorded with functional magnetic resonance imaging. We found functional specialization for different aspects of cue processing in the lateral and medial subregions of the frontal and parietal cortex. In particular, the medial subregions were more specific to the orienting of visual spatial attention, while the lateral subregions were associated with more general aspects of cue processing, such as cue-symbol interpretation. Additional cue-related effects included differential activations in midline frontal regions and pretarget enhancements in the thalamus and early visual cortical areas.

The congruency effect in distracter interference tasks is often reduced after incongruent as compared to congruent trials. Here, we investigated whether this congruency sequence effect (CSE) is triggered by (a) attentional adaptation resulting from perceptual conflict or (b) contingent attentional capture arising from distracters that possess target-defining perceptual features. To distinguish between these hypotheses, we varied the perceptual format in which a distracter (word or arrow) and a subsequent target (word or arrow) appeared in a prime-probe task. In Experiment 1, we varied these formats across four blocks of a factorial design, such that targets always appeared in a single perceptual format. Consistent with both hypotheses, we observed a CSE only when the distracter appeared in the same perceptual format as the target. In Experiment 2, we varied these formats randomly across trials within each block, such that targets appeared randomly in either format. Consistent with the attentional capture account but inconsistent with the perceptual conflict account, we observed equivalent CSEs in the same and different perceptual format conditions. These findings show for the first time that contingent attentional capture plays an important role in triggering the CSE.

Set-specific contingent attentional capture is a particularly strong form of capture that occurs when multiple attentional sets guide visual search (e.g., "search for green letters" and "search for orange letters"). In this type of capture, a potential target that matches one attentional set (e.g. a green stimulus) impairs the ability to identify a temporally proximal target that matches another attentional set (e.g. an orange stimulus). In the present study, we investigated whether set-specific capture stems from a bottleneck in working memory or from a depletion of limited resources that are distributed across multiple attentional sets. In each trial, participants searched a rapid serial visual presentation (RSVP) stream for up to three target letters (T1-T3) that could appear in any of three target colors (orange, green, or lavender). The most revealing findings came from trials in which T1 and T2 matched different attentional sets and were both identified. In these trials, T3 accuracy was lower when it did not match T1's set than when it did match, but only when participants failed to identify T2. These findings support a bottleneck model of set-specific capture in which a limited-capacity mechanism in working memory enhances only one attentional set at a time, rather than a resource model in which processing capacity is simultaneously distributed across multiple attentional sets.

This article illustrates a shortcoming of using regression to control for confounds in nested designs. As an example, we consider the congruency sequence effect, which is the observation that the congruency effect in distractor interference (e.g., Stroop) tasks is smaller following incongruent as compared with congruent trials. The congruency sequence effect is often interpreted as indexing conflict adaptation: a relative increase of attention to the target following incongruent trials. However, feature repetitions across consecutive trials can complicate this interpretation. To control for this confound, the standard procedure is to delete all trials with a stimulus or response repetition and analyze the remaining trials. Notebaert and Verguts (2007) present an alternative method that allows researchers to use all trials. Specifically, they employ multiple regression to model conflict adaptation independent of feature repetitions. We show here that this approach fails to account for certain feature repetition effects. Furthermore, modeling these additional effects is typically not possible because of an upper bound on the number of degrees of freedom in the experiment. These findings have important implications for future investigations of conflict adaptation and, more broadly, for all researchers who attempt to regress out confounds in nested designs.

The ability to distinguish between high and low levels of task engagement in the real world is important for detecting and preventing performance decrements during safety-critical operational tasks. We therefore investigated whether functional Near Infrared Spectroscopy (fNIRS), a portable brain neuroimaging technique, can be used to distinguish between high and low levels of task engagement during the performance of a selective attention task. A group of participants performed the multi-source interference task (MSIT) while we recorded brain activity with fNIRS from two brain regions. One was a key region of the “task-positive” network, which is associated with relatively high levels of task engagement. The second was a key region of the “task-negative” network, which is associated with relatively low levels of task engagement (e.g., resting and not performing a task). Using activity in these regions as inputs to a multivariate pattern classifier, we were able to predict above chance levels whether participants were engaged in performing the MSIT or resting. We were also able to replicate prior findings from functional magnetic resonance imaging (fMRI) indicating that activity in task-positive and task-negative regions is negatively correlated during task performance. Finally, data from a companion fMRI study verified our assumptions about the sources of brain activity in the fNIRS experiment and established an upper bound on classification accuracy in our task. Together, our findings suggest that fNIRS could prove quite useful for monitoring cognitive state in real-world settings.

Congruency effects in distracter interference tasks are often smaller after incongruent trials than after congruent trials. However, the sources of such congruency sequence effects (CSEs) are controversial. The conflict monitoring model of cognitive control links CSEs to the detection and resolution of response conflict. In contrast, competing theories attribute CSEs to attentional or affective processes that vary with previous-trial congruency (incongruent vs. congruent). The present study sought to distinguish between conflict monitoring and congruency-based accounts of CSEs. To this end, we determined whether CSEs are driven by previous-trial reaction time (RT)—a putative measure of response conflict—or by previous-trial congruency. In two experiments using a face-word Stroop task (n = 49), we found that current-trial congruency effects did not vary with previous-trial RT independent of previous-trial congruency. In contrast, current-trial congruency effects were influenced by previous-trial congruency independent of previous-trial RT. These findings appear more consistent with theories that attribute CSEs to non-conflict processes whose recruitment varies with previous-trial congruency than with theories that link CSEs to previous-trial response conflict.