Anatomical Connectivity Constrains Dynamic Functional Connectivity among Neural Systems: Implications for Cognition and Behavior.

Leslie Ungerleider had a tremendous impact across many different areas of cognitive neuroscience. Her ideas and her approach, as well as her findings, will continue to impact the field for generations to come. One of the most impactful aspects of her approach was her focus on the ways that anatomical connections constrain functional communications among brain regions. Furthermore, she emphasized that changes in these functional communications, whether from lesions to the anatomical connections or temporary modulations of the efficacy of information transmission resulting from selective attention, have consequences for cognition and behavior. By necessity, this short review cannot cover the vast amount of research that contributed to or benefited from Leslie's work. Rather, we focus on one line of research that grew directly from some of Leslie's early work and her mentoring on these important concepts. This research and the many other lines of research that arose from these same origins has helped develop our understanding of the visual system, and cognitive systems more generally, as collections of highly organized, specialized, dynamic, and interacting subsystems.

A qualitative exploration of 40 Hz sound and music for older adults with mild cognitive impairment.

Emerging evidence suggests that 40 Hz auditory stimulation may benefit cognition. Nested within a randomized crossover trial, this qualitative study evaluates the acceptability and experience of three auditory interventions-self-selected music, 40 Hz sound, and a novel combination, termed 40 Hz music-in individuals with Mild Cognitive Impairment (MCI). Semi-structured interviews were conducted with individuals with MCI post-intervention exposure. Findings indicated a preference for self-selected music due to its memory-boosting and emotional benefits, while responses to 40 Hz sound were mixed, with several participants reporting discomfort. The composite 40 Hz music intervention showed promise, striking a balance by enhancing user experience and mitigating the 40 Hz sound's negative aspects. Engagement was influenced by personal music interests, listening routines, and support networks. This study highlights the potential of integrating 40 Hz sound with personalized music to offer a more acceptable 40 Hz auditory intervention for cognition in older adults with MCI.

'Working memory is a distributed dynamic process'.

I propose working memory be considered, not as a process for static maintenance in a particular set of brain regions, but rather as a dynamic process unfolding to serve future needs. Brain regions such as the hippocampus, or sensory and motor regions, may be necessarily recruited during this process, depending on task demands. Information stored in working memory is thus a distributed representation reflected in the structural and functional state of multiple brain areas and the trajectory of that state over time. Recent research is discussed in support of this view.

Modulation of Peak Alpha Frequency Oscillations During Working Memory Is Greater in Females Than Males.

Peak alpha frequency is known to vary not just between individuals, but also within an individual over time. While variance in this metric between individuals has been tied to working memory performance, less understood are how short timescale modulations of peak alpha frequency during task performance may facilitate behavior. This gap in understanding may be bridged by consideration of a key difference between individuals: sex. Inconsistent findings in the literature regarding the relationship between peak alpha frequency and cognitive performance, as well as known sex-related-differences in peak alpha frequency and its modulation motivated our hypothesis that cognitive and neural processes underlying working memory-modulation of peak alpha frequency in particular-may differ based upon sex. Targeting sex as a predictive factor, we analyzed the EEG data of participants recorded while they performed four versions of a visual spatial working memory task. A significant difference between groups was present: females modulated peak alpha frequency more than males. Task performance did not differ by sex, yet a relationship between accuracy and peak alpha frequency was present in males, but not in females. These findings highlight the importance of considering sex as a factor in the study of oscillatory activity, particularly to further understanding of the neural mechanisms that underlie working memory.

Knowledge of objects' physical properties implicitly guides attention during visual search.

Our interactions with the world are guided by our understanding of objects' physical properties. When packing groceries, we place fragile items on top of more durable ones and position sharp corners so they will not puncture the bags. However, physical properties are not always readily observable, and we often must rely on our knowledge of attributes such as weight, hardness, and slipperiness to guide our actions on familiar objects. Here, we asked whether our knowledge of physical properties not only shapes our actions but also guides our attention to the visual world. In a series of four visual search experiments, participants viewed arrays of everyday objects and were tasked with locating a specified object. The target was sometimes differentiated from the distractors based on its hardness, while a host of other visual and semantic attributes were controlled. We found that observers implicitly used the hardness distinction to locate the target more quickly, even though none reported being aware that hardness was relevant. This benefit arose from fixating fewer distractors overall and spending less time interrogating each distractor when the target was distinguished by hardness. Progressively more stringent stimulus controls showed that surface properties and curvature cues to hardness were not necessary for the benefit. Our findings show that observers implicitly recruit their knowledge of objects' physical properties to guide how they attend to and engage with visual scenes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Age-related differences in the structural and effective connectivity of cognitive control: a combined fMRI and DTI study of mental arithmetic.

Cognitive changes with aging are highly variable across individuals. This study investigated whether cognitive control performance might depend on preservation of structural and effective connectivity in older individuals. Specifically, we tested inhibition following working memory (WM) updating and maintenance. We analyzed diffusion tensor imaging and functional magnetic resonance imaging data in thirty-four young adults and thirty-four older adults, who performed an arithmetic verification task during functional magnetic resonance imaging. Results revealed larger arithmetic interference in older adults relative to young adults after WM updating, whereas both groups showed similar interference after WM maintenance. In both groups, arithmetic interference was associated with larger activations and stronger effective connectivity among bilateral anterior cingulate, bilateral inferior frontal gyrus, and left angular gyrus, with larger activations of frontal regions in older adults than in younger adults. In older adults, preservation of frontoparietal structural microstructure, especially involving the inferior frontaloccipital fasciculus, was associated with reduced interference, and stronger task-related effective connectivity. These results highlight how both structural and functional changes in the cognitive control network contribute to individual variability in performance during aging.

Evidence for selective adjustments of inhibitory control in a variant of the stop signal task.

The ability to inhibit actions inappropriate for the context is essential for meeting the shifting demands of complex environments. The stop signal task (SST) has been used in many previous studies to examine the interactions between go and stop responses in a cognitively demanding task involving attention, conflict resolution, and motor plan selection. The current study uses a variant of the SST, in which the continue signal instructs participants to proceed with the go response they were preparing. Reaction times (RTs) on continue trials were bimodally distributed, suggesting that an aspect of inhibition was involved in at least some of the trials. We investigated whether the cognitive processes delaying the generation of a behavioural response on continue trials are the same as for stop trials. We found improvement of stop signal reaction times (SSRTs) following stop trials, but the decrease in continue signal reaction times (CSRTs) was not significant. No improvement in either SSRT or CSRT was found following continue trials, suggesting that activation of the processes delaying the response on continue trials is insufficient to drive subsequent adjustments in SSRT or CSRT. In addition, go RTs only slowed following stop trials. These effects may suggest the presence of a selective learning process, which requires that the initial inhibition captured by SSRT and CSRT be combined with recognition of the stop signal specifically to affect subsequent performance.

Information processing biases in the brain: Implications for decision-making and self-governance.

To make behavioral choices that are in line with our goals and our moral beliefs, we need to gather and consider information about our current situation. Most information present in our environment is not relevant to the choices we need or would want to make and thus could interfere with our ability to behave in ways that reflect our underlying values. Certain sources of information could even lead us to make choices we later regret, and thus it would be beneficial to be able to ignore that information. Our ability to exert successful self-governance depends on our ability to attend to sources of information that we deem important to our decision-making processes. We generally assume that, at any moment, we have the ability to choose what we pay attention to. However, recent research indicates that what we pay attention to is influenced by our prior experiences, including reward history and past successes and failures, even when we are not aware of this history. Even momentary distractions can cause us to miss or discount information that should have a greater influence on our decisions given our values. Such biases in attention thus raise questions about the degree to which the choices that we make may be poorly informed and not truly reflect our ability to otherwise exert self-governance.

Neural Basis of Cognitive Control over Movement Inhibition: Human fMRI and Primate Electrophysiology Evidence.

Executive control involves the ability to flexibly inhibit or change an action when it is contextually inappropriate. Using the complimentary techniques of human fMRI and monkey electrophysiology in a context-dependent stop signal task, we found a functional double dissociation between the right ventrolateral prefrontal cortex (rVLPFC) and the bi-lateral frontal eye field (FEF). Different regions of rVLPFC were associated with context-based signal meaning versus intention to inhibit a response, while FEF activity corresponded to success or failure of the response inhibition regardless of the stimulus response mapping or the context. These results were validated by electrophysiological recordings in rVLPFC and FEF from one monkey. Inhibition of a planned behavior is therefore likely not governed by a single brain system as had been previously proposed, but instead depends on two distinct neural processes involving different sub-regions of the rVLPFC and their interactions with other motor-related brain regions.

Probabilistic White Matter Atlases of Human Auditory, Basal Ganglia, Language, Precuneus, Sensorimotor, Visual and Visuospatial Networks.

Background: Despite the popularity of functional connectivity analyses and the well-known topology of several intrinsic cortical networks, relatively little is known about the white matter regions (i.e., structural connectivity) underlying these networks. In the current study, we have therefore performed fMRI-guided diffusion tensor imaging (DTI) tractography to create probabilistic white matter atlases for eight previously identified functional brain networks, including the Auditory, Basal Ganglia, Language, Precuneus, Sensorimotor, Primary Visual, Higher Visual and Visuospatial Networks. Methods: Whole-brain diffusion imaging data were acquired from a cohort of 32 healthy volunteers, and were warped to the ICBM template using a two-stage, high-dimensional, non-linear spatial normalization procedure. Deterministic tractography, with fractional anisotropy (FA) ≥0.15 and deviation angle <50°, was then performed using the Fiber Association by Continuous Tracking (FACT) algorithm, and a multi-ROI approach to identify tracts of interest. Regions-of-interest (ROIs) for each of the eight networks were taken from a pre-existing atlas of functionally defined regions to explore all ROI-to-ROI connections within each network, and all resulting streamlines were saved as binary masks to create probabilistic atlases (across participants) for tracts between each ROI-to-ROI pair. Results: The resulting functionally-defined white matter atlases (i.e., for each tract and each network as a whole) were saved as NIFTI images in stereotaxic ICBM coordinates, and have been added to the UManitoba-JHU Functionally-Defined Human White Matter Atlas (http://www.nitrc.org/projects/uofm_jhu_atlas/). Conclusion: To the best of our knowledge, this work represents the first attempt to comprehensively identify and map white matter connectomes for the Auditory, Basal Ganglia, Language, Precuneus, Sensorimotor, Primary Visual, Higher Visual and Visuospatial Networks. Therefore, the resulting probabilistic atlases represent a unique tool for future neuroimaging studies wishing to ascribe voxel-wise or ROI-based changes (i.e., in DTI or other quantitative white matter imaging signals) to these functional brain networks.

Linking dopaminergic reward signals to the development of attentional bias: A positron emission tomographic study.

The attention system is shaped by reward history, such that learned reward cues involuntarily draw attention. Recent research has begun to uncover the neural mechanisms by which learned reward cues compete for attention, implicating dopamine (DA) signaling within the dorsal striatum. How these elevated priority signals develop in the brain during the course of learning is less well understood, as is the relationship between value-based attention and the experience of reward during learning. We hypothesized that the magnitude of the striatal DA response to reward during learning contributes to the development of a learned attentional bias towards the cue that predicted it, and examined this hypothesis using positron emission tomography with [11C]raclopride. We measured changes in dopamine release for rewarded versus unrewarded visual search for color-defined targets as indicated by the density and distribution of the available D2/D3 receptors. We then tested for correlations of individual differences in this measure of reward-related DA release to individual differences in the degree to which previously reward-associated but currently task-irrelevant stimuli impair performance in an attention task (i.e., value-driven attentional bias), revealing a significant relationship in the right anterior caudate. The degree to which reward-related DA release was right hemisphere lateralized was also predictive of later attentional bias. Our findings provide support for the hypothesis that value-driven attentional bias can be predicted from reward-related DA release during learning.

Density of available striatal dopamine receptors predicts trait impulsiveness during performance of an attention-demanding task.

The density (measured at binding potential) of available striatal D2/D3 receptors has been shown to predict trait impulsiveness. This relationship is highly robust and well replicated. In each case, however, the availability of dopamine receptors was measured at rest. More broadly, the extent to which relationships between dopamine receptor availability and behavioral traits hold when participants perform a cognitive task is unclear. Furthermore, the performance of a cognitive task engages fundamentally different neural networks than are maximally engaged during the resting state. This complicates interpretation of previously observed correlations, which could be influenced by two distinct factors. The first is variation in available receptor density, which reflects a stable trait of the individual. The second is variation in context-specific dopamine release, which differentially displaces some dopamine radiotracers (such as raclopride) across individuals. Using an existing data set, we related trait impulsiveness, as measured using the Barratt Impulsiveness Scale (BIS-11), to the density (binding potential) of available striatal D2/D3 receptors as measured using positron emission tomography (PET) with [11C]raclopride. Importantly, the PET scan was completed while participants performed an attention-demanding visual search task. We replicate robust correlations between this measure of receptor availability and trait impulsiveness previously demonstrated during the resting state, extending this relationship to periods of active task engagement. Our results support the idea that this relationship depends on striatal D2/D3 receptor density and not on context-dependent dopamine release.NEW & NOTEWORTHY Several studies have demonstrated a relationship between the density of available striatal D2/D3 receptors and trait impulsiveness. However, in each case, the availability of dopamine receptors was measured during the resting state. This complicates interpretation of previously observed correlations, which could be influenced by either stable variation in receptor density or context-dependent dopamine release. We present evidence uniquely consistent with the former interpretation, providing clarity to the nature of this brain-behavior relationship.

Keeping Track of Where We Are: Spatial Working Memory in Navigation.

Spatial working memory (WM) seems to include two types of spatial information, locations and relations. However, this distinction has been based on small-scale tasks. Here, we used a virtual navigation paradigm to examine whether WM for locations and relations applies to the large-scale spatial world. We found that navigators who successfully learned two routes and also integrated them were superior at maintaining multiple locations and multiple relations in WM. However, over the entire spectrum of navigators, WM for spatial relations, but not locations, was specifically predictive of route integration performance. These results lend further support to the distinction between these two forms of spatial WM and point to their critical role in individual differences in navigation proficiency.

N-back versus Complex Span Working Memory Training.

Working memory (WM) is the ability to maintain and manipulate task-relevant information in the absence of sensory input. While its improvement through training is of great interest, the degree to which WM training transfers to untrained WM tasks (near transfer) and other untrained cognitive skills (far transfer) remains debated and the mechanism(s) underlying transfer are unclear. Here we hypothesized that a critical feature of dual n-back training is its reliance on maintaining relational information in WM. In Experiment 1, using an individual differences approach, we found evidence that performance on an n-back task was predicted by performance on a measure of relational WM (i.e., WM for vertical spatial relationships independent of absolute spatial locations); whereas the same was not true for a complex span WM task. In Experiment 2, we tested the idea that reliance on relational WM is critical to produce transfer from n-back but not complex span task training. Participants completed adaptive training on either a dual n-back task, a symmetry span task, or on a non-WM active control task. We found evidence of near transfer for the dual n-back group; however, far transfer to a measure of fluid intelligence did not emerge. Recording EEG during a separate WM transfer task, we examined group-specific, training-related changes in alpha power, which are proposed to be sensitive to WM demands and top-down modulation of WM. Results indicated that the dual n-back group showed significantly greater frontal alpha power after training compared to before training, more so than both other groups. However, we found no evidence of improvement on measures of relational WM for the dual n-back group, suggesting that near transfer may not be dependent on relational WM. These results suggest that dual n-back and complex span task training may differ in their effectiveness to elicit near transfer as well as in the underlying neural changes they facilitate.

Distinct Neural Substrates for Maintaining Locations and Spatial Relations in Working Memory.

Previous work has demonstrated a distinction between maintenance of two types of spatial information in working memory (WM): spatial locations and spatial relations. While a body of work has investigated the neural mechanisms of sensory-based information like spatial locations, little is known about how spatial relations are maintained in WM. In two experiments, we used fMRI to investigate the involvement of early visual cortex in the maintenance of spatial relations in WM. In both experiments, we found less quadrant-specific BOLD activity in visual cortex when a single spatial relation, compared to a single spatial location, was held in WM. Also across both experiments, we found a consistent set of brain regions that were differentially activated during maintenance of locations vs. relations. Maintaining a location, compared to a relation, was associated with greater activity in typical spatial WM regions like posterior parietal cortex and prefrontal regions. Whereas maintaining a relation, compared to a location, was associated with greater activity in the parahippocampal gyrus and precuneus/retrosplenial cortex. Further, in Experiment 2 we manipulated WM load and included trials where participants had to maintain three spatial locations or relations. Under this high load condition, the regions sensitive to locations vs. relations were somewhat different than under low load. We also identified regions that were sensitive to load specifically for location or relation maintenance, as well as overlapping regions sensitive to load more generally. These results suggest that the neural substrates underlying WM maintenance of spatial locations and relations are distinct from one another and that the neural representations of these distinct types of spatial information change with load.

A neural mechanism of cognitive control for resolving conflict between abstract task rules.

Conflict between multiple sensory stimuli or potential motor responses is thought to be resolved via bias signals from prefrontal cortex (PFC). However, population codes in the PFC also represent abstract information, such as task rules. How is conflict between active abstract representations resolved? We used functional neuroimaging to investigate the mechanism responsible for resolving conflict between abstract representations of task rules. Participants performed two different tasks based on a cue. We manipulated the degree of conflict at the task-rule level by training participants to associate the color and shape dimensions of the cue with either the same task rule (congruent cues) or different ones (incongruent cues). Phonological and semantic tasks were used in which performance depended on learned, abstract representations of information, rather than sensory features of the target stimulus or on any habituated stimulus-response associations. In addition, these tasks activate distinct regions that allowed us to measure magnitude of conflict between tasks. We found that incongruent cues were associated with increased activity in several cognitive control areas, including the inferior frontal gyrus, inferior parietal lobule, insula, and subcortical regions. Conflict between abstract representations appears to be resolved by rule-specific activity in the inferior frontal gyrus that is correlated with enhanced activity related to the relevant information. Furthermore, multi-voxel pattern analysis of the activity in the inferior frontal gyrus was shown to carry information about both the currently relevant rule (semantic/phonological) and the currently relevant cue context (color/shape). Similar to models of attentional selection of conflicting sensory or motor representations, the current findings indicate part of the frontal cortex provides a bias signal, representing task rules, that enhances task-relevant information. However, the frontal cortex can also be the target of these bias signals in order to enhance abstract representations that are independent of particular stimuli or motor responses.

Effects of Body Mass Index and Body Fat Percent on Default Mode, Executive Control, and Salience Network Structure and Function.

It is well established that obesity decreases overall life expectancy and increases the risk of several adverse health conditions. Mounting evidence indicates that body fat is likely also associated with structural and functional brain changes, reduced cognitive function, and greater impulsivity. However, previously reported differences in brain structure and function have been variable across studies and difficult to reconcile due to sample population and methodological differences. To clarify these issues, we correlated two independent measures of body composition-i.e., body mass index (BMI) and body fat percent (BFP)-with structural and functional neuroimaging data obtained from a cohort of 32 neurologically healthy adults. Whole-brain voxel-wise analyses indicated that higher BMI and BFP were associated with widespread decreases in gray matter volume, white matter volume, and white matter microstructure (including several regions, such as the striatum and orbitofrontal cortex, which may influence value assessment, habit formation, and decision-making). Moreover, closer examination of resting state functional connectivity, white matter volume, and white matter microstructure throughout the default mode network (DMN), executive control network (ECN), and salience network (SN) revealed that higher BMI and BFP were associated with increased SN functional connectivity and decreased white matter volumes throughout all three networks (i.e., the DMN, ECN, and SN). Taken together, these findings: (1) offer a biologically plausible explanation for reduced cognitive performance, greater impulsivity, and altered reward processing among overweight individuals, and (2) suggest neurobiological mechanisms (i.e., altered functional and structural brain connectivity) that may affect overweight individuals' ability to establish and maintain healthy lifestyle choices.

The role of alpha oscillations in deriving and maintaining spatial relations in working memory.

Previous research has demonstrated distinct neural correlates for maintenance of abstract, relational versus concrete, sensory information in working memory (WM). Storage of spatial relations in WM results in suppression of posterior sensory regions, which suggests that sensory information is task-irrelevant when relational representations are maintained in WM. However, the neural mechanisms by which abstract representations are derived from sensory information remain unclear. Here, using electroencephalography, we investigated the role of alpha oscillations in deriving spatial relations from a sensory stimulus and maintaining them in WM. Participants encoded two locations into WM, then after an initial maintenance period, a cue indicated whether to convert the spatial information to another sensory representation or to a relational representation. Results revealed that alpha power increased over posterior electrodes when sensory information was converted to a relational representation, but not when the information was converted to another sensory representation. Further, alpha phase synchrony between posterior and frontal regions increased for relational compared to sensory trials during the maintenance period. These results demonstrate that maintaining spatial relations and locations in WM rely on distinct neural oscillatory patterns.

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.