Association of disruption of the right posterior arcuate fasciculus with spatial neglect.

OBJECTIVE: Spatial neglect is a debilitating condition observed in patients with right-sided brain injuries in whom there is defective awareness of the contralesional space. Although classically considered a right parietal lobe deficit, there has been increasing interest in the specific white matter (WM) architecture subserving spatial neglect. Patients who have lesions associated with chronic disruptions in visuospatial networks are of significant relevance in elucidating the WM tracts associated with spatial attention. In this study, the authors used two independent analytical methods to examine the relationship between WM connectivity changes and spatial attention. METHODS: Thirty patients with right-sided glioma underwent diffusion tensor imaging (DTI) tractography and neuropsychological testing prior to tumor resection. Spatial neglect was assessed using the Bells Test. Diffusion connectometry analysis was performed to calculate the probability of injury to 55 WM tracts. Next, quantitative DTI tractography was used to reconstruct 9 major WM tracts and obtain fractional anisotropy (FA) and streamline number values as indices of connectivity. Differences in connectivity were assessed between patients with neglect and controls. RESULTS: Of the WM tracts analyzed by diffusion connectometry, only the right posterior segment of the arcuate fasciculus (psAF) showed a higher probability of disconnection in patients with evidence of hemispatial neglect compared to tract reconstructions of previously published healthy controls (hemineglect: 42% ± 12.5%, vs control: 6.3% ± 4.8% [mean ± SEM]; p < 0.05). Of the WM tracts reconstructed by DTI tractography, only the right psAF demonstrated consistently lower indices of connectivity based on the mean streamline number (hemineglect: 550.35 ± 183.41, vs control: 1407.01 ± 319.93; p < 0.05) and FA value (hemineglect: 0.40 ± 0.013, vs control: 0.44 ± 0.0063; p < 0.05) in patients who demonstrated neglect compared to controls. The right long segment of the arcuate fasciculus, inferior frontooccipital fasciculus, and inferior longitudinal fasciculus also demonstrated a lower streamline number, but not a lower FA value, in patients with evidence of hemineglect. CONCLUSIONS: These findings suggest that parietotemporal networks mediated by the right psAF may play a critical role in visuospatial attention. This analysis may help to disentangle the organization of the visuospatial attention networks, predict deficits in patients with glioma, and optimize surgical planning.

White matter tracts contribute selectively to cognitive functioning in patients with glioma.

Objective: The functional organization of white matter (WM) tracts is not well characterized, especially in patients with intrinsic brain tumors where complex patterns of tissue injury, compression, and neuroplasticity may be present. This study uses diffusion tensor imaging (DTI) to investigate the relationships between WM tract disruption and cognitive deficits in glioma patients. Methods: Seventy-nine patients with glioma underwent preoperative DTI and neuropsychological testing. Thirteen WM tracts were reconstructed bilaterally. Fractional anisotropy and streamline number were obtained for each tract as indices of connectivity. Univariate regression models were used to model the association between WM tract connectivity and neuropsychological outcomes. Results: Glioma patients exhibited variable injury to WM tracts and variable cognitive deficits on validated neuropsychological tests. We identified 16 age-adjusted associations between WM tract integrity and neuropsychological function. The left inferior frontal-occipital fasciculus (IFOF) predicted list learning and dominant-hand fine motor dexterity. The right IFOF predicted non-dominant-hand fine motor dexterity and visuospatial index scores. The left inferior longitudinal fasciculus (ILF) predicted immediate memory list learning and index scores. The right ILF predicted non-dominant-hand fine motor dexterity and backward digit span scores. The left superior longitudinal fasciculus (SLF) I predicted processing speed. The left SLF III predicted list learning, immediate memory index scores, phonemic fluency, and verbal abstract reasoning. The left cingulum predicted processing speed. The right anterior AF predicted verbal abstract reasoning. Conclusion: WM tract disruption predicts cognitive dysfunction in glioma patients. By improving knowledge of WM tract organization, this analysis may guide maximum surgical resection and functional preservation in glioma patients.

Resource sharing in cognitive control: Behavioral evidence and neural substrates.

Cognitive control is a capacity-limited function responsible for the resolution of conflict among competing cognitive processes. However, whether cognitive control handles multiple concurrent requests through a single bottleneck or a resource sharing mechanism remains elusive. In this functional magnetic resonance imaging study, we examined the effect of dual flanker conflict processing on behavioral performance and on activation in regions of the cognitive control network (CCN). In each trial, participants completed two flanker conflict tasks (T1 and T2) sequentially, with the stimulus onset asynchrony (SOA) varied as short (100 ms) and long (1000 ms). We found a significant conflict effect (indexed by the difference between incongruent and congruent flanker conditions) in reaction time (RT) for both T1 and T2, together with a significant interaction between SOA and T1-conflict on RT for T2 with an additive effect. Importantly, there was a small but significant SOA effect on T1 with a prolonged RT under the short SOA compared to the long SOA. Increased activation in the CCN was associated with conflict processing and the main effect of SOA. The anterior cingulate cortex and anterior insular cortex showed a significant interaction effect between SOA and T1-conflict in activation parallel with the behavioral results. The behavioral and brain activation patterns support a central resource sharing model, in which the core resources for cognitive control are shared when multiple simultaneous conflicting processes are required.

Same, Same but Different? A Multi-Method Review of the Processes Underlying Executive Control.

Attention, working memory, and executive control are commonly considered distinct cognitive functions with important reciprocal interactions. Yet, longstanding evidence from lesion studies has demonstrated both overlap and dissociation in their behavioural expression and anatomical underpinnings, suggesting that a lower dimensional framework could be employed to further identify processes supporting goal-directed behaviour. Here, we describe the anatomical and functional correspondence between attention, working memory, and executive control by providing an overview of cognitive models, as well as recent data from lesion studies, invasive and non-invasive multimodal neuroimaging and brain stimulation. We emphasize the benefits of considering converging evidence from multiple methodologies centred on the identification of brain mechanisms supporting goal-driven behaviour. We propose that expanding on this approach should enable the construction of a comprehensive anatomo-functional framework with testable new hypotheses, and aid clinical neuroscience to intervene on impairments of executive functions.

Representational coding of overt and covert orienting of visuospatial attention in the frontoparietal network.

Orienting of visuospatial attention refers to reallocation of attentional focus from one target or location to another and can occur either with (overt) or without (covert) eye movement. Although it has been demonstrated that both types of orienting commonly involve frontal and parietal brain regions as the frontoparietal network (FPN), the underlying representational coding of these two types of orienting remains unclear. In this functional magnetic resonance imaging study, participants performed a task that elicited overt and covert orienting to endogenously or exogenously cued targets with eye-tracking to monitor eye movement. Although the FPN was commonly activated for both overt and covert orienting, multivariate patterns of the activation of voxels in the FPN accurately predicted whether eye movements were involved or not during orienting. These overt- and covert-preferred voxels were topologically distributed as distinct and interlaced clusters in a millimeter scale. Inclusion of the two types of clusters predicted orienting type more accurately than one type of clusters alone. These findings suggest that overt and covert orienting are represented by interdependent functional clusters of neuronal populations in regions of the FPN, which might reflect a generalizable principle in the nervous system for functional organization of closely associated processes.

The functional anatomy of cognitive control: A domain-general brain network for uncertainty processing.

Cognitive control is the coordination of mental operations under conditions of uncertainty in accordance with goal-directed behaviors, and plays a key role in the domains of executive control, working memory, and decision-making. Although there is emerging evidence of common involvement of the cognitive control network (CCN) of the brain in these domains, this network has mostly been linked to the processing of conflict, which is just one case of an increase in uncertainty. Here, we conducted an activation-likelihood-estimation-based large-scale meta-analysis of 289 functional magnetic resonance imaging studies in the three domains to examine the common involvement of the CCN in uncertainty processing by contrasting the high-uncertainty versus low-uncertainty conditions. We found a general association between increase in uncertainty and an activation increase in regions of the CCN, including the frontoparietal network (comprising the frontal eye fields, the areas near and along the intraparietal sulcus, and the dorsolateral prefrontal cortex), the cingulo-opercular network (including the anterior cingulate cortex extending to the supplementary motor area, and the anterior insular cortex), and a subcortical structure (the striatum). These results demonstrate that the CCN is a domain-general construct underlying uncertainty processing to support goal-directed behaviors.

Deficit of supramodal executive control of attention in schizophrenia.

Although a deficit in executive control of attention is one of the hallmarks in schizophrenia that has significant impact on everyday functioning due to its relationship with thought processing, whether this deficit occurs across modalities, i.e., is supramodal, remains unclear. To investigate the supramodal mechanism in SZ, we examined cross-modal correlations between visual and auditory executive control of attention in a group of patients with schizophrenia (SZ, n = 55) compared to neurotypical controls (NC, n = 55). While the executive control effects were significantly correlated between the two modalities in the NC group, these effects were not correlated in the SZ group, with a significant group difference in the correlation. Further, the inconsistency and magnitude of the cross-modal executive control effects were significantly larger in the SZ group compared to the NC group. Together, these results suggest that there is a disruption of a common supramodal executive control mechanism in patients with schizophrenia, which may be related to the thought processing disorder characterizing the disorder.

Hick-Hyman Law is Mediated by the Cognitive Control Network in the Brain.

The Hick-Hyman law describes a linear increase in reaction time (RT) as a function of the information entropy of response selection, which is computed as the binary logarithm of the number of response alternatives. While numerous behavioral studies have provided evidence for the Hick-Hyman law, its neural underpinnings have rarely been examined and are still unclear. In this functional magnetic resonance imaging study, by utilizing a choice reaction time task to manipulate the entropy of response selection, we examined brain activity mediating the input and the output, as well as the connectivity between corresponding regions in human participants. Beyond confirming the Hick-Hyman law in RT performance, we found that activation of the cognitive control network (CCN) increased and activation of the default mode network (DMN) decreased, both as a function of entropy. However, only the CCN, but not the DMN, was involved in mediating the relationship between entropy and RT. The CCN was involved in both stages of uncertainty representation and response generation, while the DMN was mainly involved at the stage of uncertainty representation. These findings indicate that the CCN serves as a core entity underlying the Hick-Hyman law by coordinating uncertainty representation and response generation in the brain.

The Capacity of Cognitive Control Estimated from a Perceptual Decision Making Task.

Cognitive control refers to the processes that permit selection and prioritization of information processing in different cognitive domains to reach the capacity-limited conscious mind. Although previous studies have suggested that the capacity of cognitive control itself is limited, a direct quantification of this capacity has not been attempted. In this behavioral study, we manipulated the information rate of cognitive control by parametrically varying both the uncertainty of stimul measured as information entropy and the exposure time of the stimuli. We used the relationship between the participants' response accuracy and the information rate of cognitive control (in bits per second, bps) in the model fitting to estimate the capacity of cognitive control. We found that the capacity of cognitive control was approximately 3 to 4 bps, demonstrating that cognitive control as a higher-level function has a remarkably low capacity. This quantification of the capacity of cognitive control may have significant theoretical and clinical implications.

Venlafaxine treatment reduces the deficit of executive control of attention in patients with major depressive disorder.

Attention plays an essential role in supporting other cognitive functions and behavior, and disturbance of attention is one of the most common symptoms in major depressive disorder (MDD). Although treatment with venlafaxine for MDD symptoms has been shown to reduce deficits in cognition and emotion regulation, it remains unclear whether venlafaxine improves specific attentional functions. We used the Attention Network Test to measure the attentional functions of alerting, orienting, and executive control before and after treatment with venlafaxine in patients with MDD compared to untreated healthy controls. Before treatment, the MDD group showed a selective impairment in alerting and executive control of attention, while there were no significant group differences in the orienting function. The interaction between group and session was significant for executive control, and after treatment with venlafaxine, the performance of the MDD group on executive control of attention was not significantly different from that of controls. Reported symptoms of MDD were also significantly reduced after treatment with venlafaxine. These results demonstrate that treatment with venlafaxine selectively normalizes the executive control function of attention in addition to improving clinical symptoms in MDD.

The activation of interactive attentional networks.

Attention can be conceptualized as comprising the functions of alerting, orienting, and executive control. Although the independence of these functions has been demonstrated, the neural mechanisms underlying their interactions remain unclear. Using the revised attention network test and functional magnetic resonance imaging, we examined cortical and subcortical activity related to these attentional functions and their interactions. Results showed that areas in the extended frontoparietal network (FPN), including dorsolateral prefrontal cortex, frontal eye fields (FEF), areas near and along the intraparietal sulcus, anterior cingulate and anterior insular cortices, basal ganglia, and thalamus were activated across multiple attentional functions. Specifically, the alerting function was associated with activation in the locus coeruleus (LC) in addition to regions in the FPN. The orienting functions were associated with activation in the superior colliculus (SC) and the FEF. The executive control function was mainly associated with activation of the FPN and cerebellum. The interaction effect of alerting by executive control was also associated with activation of the FPN, while the interaction effect of orienting validity by executive control was mainly associated with the activation in the pulvinar. The current findings demonstrate that cortical and specific subcortical areas play a pivotal role in the implementation of attentional functions and underlie their dynamic interactions.

Reduced Efficiency and Capacity of Cognitive Control in Autism Spectrum Disorder.

Cognitive control constrains mental operations to prioritize information that reaches conscious awareness and is essential to flexible, adaptive behavior under conditions of uncertainty. Cognitive control can be compromised by neurodevelopmental disorders such as autism spectrum disorder (ASD), which is characterized by the presence of social and communicative deficits, and restricted interests/repetitive behaviors. Although prior investigations have attempted to elucidate the nature of cognitive control in ASD, whether there is an underlying information processing deficit associated with cognitive control remains unclear. This study challenged cognitive control in 15 high-functioning adults with ASD and 15 typically developing (TD) controls using three novel tasks designed to systematically manipulate uncertainty. We aimed to investigate the efficiency of cognitive control in sequential information processing, cognitive control of nonsequential information processing across a range of cognitive loads and cognitive control capacity under time constraint. Results demonstrated that the ASD group performed less efficiently on sequential and nonsequential information processing, and had reduced cognitive control capacity under time constraint relative to the TD group. These findings suggest that inefficient cognitive control of information processing may be a fundamental deficit in ASD.

Interocular suppression prevents interference in a flanker task.

Executive control of attention refers to processes that detect and resolve conflict among competing thoughts and actions. Despite the high-level nature of this faculty, the role of awareness in executive control of attention is not well understood. In this study, we used interocular suppression to mask the flankers in an arrow flanker task, in which the flankers and the target arrow were presented simultaneously in order to elicit executive control of attention. Participants were unable to detect the flanker arrows or to reliably identify their direction when masked. There was a typical conflict effect (prolonged reaction time and increased error rate under flanker-target incongruent condition compared to congruent condition) when the flanker arrows were unmasked, while the conflict effect was absent when the flanker arrows were masked with interocular suppression. These results suggest that blocking awareness of competing stimuli with interocular suppression prevents the involvement of executive control of attention.

Clozapine improves the orienting of attention in schizophrenia.

Attentional deficits are prominent in the cognitive profile of patients with schizophrenia. However, it remains unclear whether treatment with clozapine, an atypical antipsychotic and first-line intervention used to reduce positive and negative symptoms of psychosis, improves the attentional functions. We used the revised attention network test to measure alerting, orienting, and executive control of attention both pre- and post-treatment with clozapine in patients with schizophrenia (n=32) and compared performance to healthy controls (n=32). Results revealed that there were deficits in all three attentional functions pre-treatment, and while clozapine improved the orienting function in patients with schizophrenia, there was no evidence for improvement in the alerting and executive control of attention. The enhancement of the orienting function by clozapine may increase the ability of patients with schizophrenia to orient towards objects and thoughts of interest.

Supramodal executive control of attention.

The human attentional system can be subdivided into three functional networks of alerting, orienting, and executive control. Although these networks have been extensively studied in the visuospatial modality, whether the same mechanisms are deployed across different sensory modalities remains unclear. In this study we used the attention network test for the visuospatial modality, in addition to two auditory variants with spatial and frequency manipulations to examine cross-modal correlations between network functions. Results showed that among the visual and auditory tasks, the effects of executive control, but not effects of alerting and orienting, were significantly correlated. These findings suggest that while alerting and orienting functions rely more upon modality-specific processes, the executive control of attention coordinates complex behavior via supramodal mechanisms.

Cognitive control and attentional functions.

Cognitive control is essential to flexible, goal-directed behavior under uncertainty, yet its underlying mechanisms are not clearly understood. Because attentional functions are known to allocate mental resources and prioritize the information to be processed, we propose that the attentional functions of alerting, orienting, and executive control and the interactions among them contribute to cognitive control in the service of uncertainty reduction. To test this hypothesis, we examined the relationship between cognitive control and attentional functions. We used the Majority Function Task (MFT) to manipulate uncertainty in order to evoke cognitive control along with the Revised Attention Network Test (ANT-R) to measure the efficiency and the interactions of attentional functions. A backwards, stepwise regression model revealed that performance on the MFT could be significantly predicted by attentional functions and their interactions as measured by the ANT-R. These results provide preliminary support for our theory that the attentional functions are involved in the implementation of cognitive control as required to reduce uncertainty, though further investigation is needed.