Episodic memory retrieval, parietal cortex, and the default mode network: Functional and topographic analyses

The default mode network (DMN) is often considered a functionally homogeneous system that is broadly associated with internally directed cognition (e.g., episodic memory, theory of mind, self-evaluation). However, few studies have examined how this network interacts with other networks during putative default processes such as episodic memory retrieval. Using functional magnetic resonance imaging, we investigated the topography and response profile of human parietal regions inside and outside the DMN, independently defined using task-evoked deactivations and resting-state functional connectivity, during episodic memory retrieval. Memory retrieval activated posterior nodes of the DMN, particularly the angular gyrus, but also more anterior and dorsal parietal regions that were anatomically separate from the DMN. The two sets of parietal regions showed different resting-state functional connectivity and response profiles. During memory retrieval, responses in DMN regions peaked sooner than non-DMN regions, which in turn showed responses that were sustained until a final memory judgment was reached. Moreover, a parahippocampal region that showed strong resting-state connectivity with parietal DMN regions also exhibited a pattern of task-evoked activity similar to that exhibited by DMN regions. These results suggest that DMN parietal regions directly supported memory retrieval, whereas non-DMN parietal regions were more involved in postretrieval processes such as memory-based decision making. Finally, a robust functional dissociation within the DMN was observed. Whereas angular gyrus and posterior cingulate/precuneus were significantly activated during memory retrieval, an anterior DMN node in medial prefrontal cortex was strongly deactivated. This latter finding demonstrates functional heterogeneity rather than homogeneity within the DMN during episodic memory retrieval

Dorsal and ventral attention systems underlie social and symbolic cueing

none3siEye gaze is a powerful cue for orienting attention in space. Studies examining whether gaze and symbolic cues recruit the same neural mechanisms have found mixed results. We tested whether there is a specialized attentional mechanism for social cues. We separately measured BOLD activity during orienting and reorienting attention following predictive gaze and symbolic cues. Results showed that gaze and symbolic cues exerted their influence through the same neural networks but also produced some differential modulations. Dorsal frontoparietal regions in left intraparietal sulcus (IPS) and bilateral MT+/lateral occipital cortex only showed orienting effects for symbolic cues, whereas right posterior IPS showed larger validity effects following gaze cues. Both exceptions may reflect the greater automaticity of gaze cues: Symbolic orienting may require more effort, while disengaging attention during reorienting may be more difficult following gaze cues. Face-selective regions, identified with a face localizer, showed selective activations for gaze cues reflecting sensory processing but no attentional modulations. Therefore, no evidence was found linking face-selective regions to a hypothetical, specialized mechanism for orienting attention to gaze cues. However, a functional connectivity analysis showed greater connectivity between face-selective regions and right posterior IPS, posterior STS, and inferior frontal gyrus during gaze cueing, consistent with proposals that face-selective regions may send gaze signals to parts of the dorsal and ventral frontoparietal attention networks. Finally, although the default-mode network is thought to be involved in social cognition, this role does not extend to gaze orienting as these regions were more deactivated following gaze cues and showed less functional connectivity with face-selective regions during gaze cues.mixedCallejas, Alicia; Shulman, Gordon L.; Corbetta, MaurizioCallejas, Alicia; Shulman, Gordon L.; Corbetta, Maurizi

The effects of hemodynamic lag on functional connectivity and behavior after stroke

Stroke disrupts the brain's vascular supply, not only within but also outside areas of infarction. We investigated temporal delays (lag) in resting state functional magnetic resonance imaging signals in 130 stroke patients scanned two weeks, three months and 12 months post stroke onset. Thirty controls were scanned twice at an interval of three months. Hemodynamic lag was determined using cross-correlation with the global gray matter signal. Behavioral performance in multiple domains was assessed in all patients. Regional cerebral blood flow and carotid patency were assessed in subsets of the cohort using arterial spin labeling and carotid Doppler ultrasonography. Significant hemodynamic lag was observed in 30% of stroke patients sub-acutely. Approximately 10% of patients showed lag at one-year post-stroke. Hemodynamic lag corresponded to gross aberrancy in functional connectivity measures, performance deficits in multiple domains and local and global perfusion deficits. Correcting for lag partially normalized abnormalities in measured functional connectivity. Yet post-stroke FC-behavior relationships in the motor and attention systems persisted even after hemodynamic delays were corrected. Resting state fMRI can reliably identify areas of hemodynamic delay following stroke. Our data reveal that hemodynamic delay is common sub-acutely, alters functional connectivity, and may be of clinical importance

Attention to memory and the environment: functional specialization and dynamic competition in human posterior parietal cortex

none3siPosterior parietal cortex has been traditionally associated with perceptual attention and sensory-motor processing, but recent studies also indicate a potential role in episodic memory retrieval. Here, we developed a new paradigm to isolate top-down attention-related activity directed to either memory or perceptual information. We demonstrated a robust topographic separation in human posterior parietal cortex associated with searching for task-relevant information in episodic memory or in the environment. Control analyses confirmed that this difference was not dependent on differences in sensory stimulation or eye movements across tasks. Notably, we observed in memory-and perception-related regions a mechanism of reciprocal dynamic competition that was related to behavioral performance. These results provide the first evidence for a double dissociation between parietal networks involved in top-down attention to memory and the environment and support the idea of neural competition between perception and memory.openSestieri, Carlo; Shulman, Gordon L.; Corbetta, MaurizioSestieri, Carlo; Shulman, Gordon L.; Corbetta, Maurizi

Early diffusion evidence of retrograde transsynaptic degeneration in the human visual system

We investigated whether diffusion tensor imaging (DTI) indices of white matter integrity would offer early markers of retrograde transsynaptic degeneration (RTD) in the visual system after stroke Objective: We investigated whether diffusion tensor imaging (DTI) indices of white matter integrity would offer early markers of retrograde transsynaptic degeneration (RTD) in the visual system after stroke. Methods: We performed a prospective longitudinal analysis of the sensitivity of DTI markers of optic tract health in 12 patients with postsynaptic visual pathway stroke, 12 stroke controls, and 28 healthy controls. We examined group differences in (1) optic tract fractional anisotropy (FA-asymmetry), (2) perimetric measures of visual impairment, and (3) the relationship between FA-asymmetry and perimetric assessment. Results: FA-asymmetry was higher in patients with visual pathway lesions than in control groups. These differences were evident 3 months from the time of injury and did not change significantly at 12 months. Perimetric measures showed evidence of impairment in participants with visual pathway stroke but not in control groups. A significant association was observed between FA-asymmetry and perimetric measures at 3 months, which persisted at 12 months. Conclusions: DTI markers of RTD are apparent 3 months from the time of injury. This represents the earliest noninvasive evidence of RTD in any species. Furthermore, these measures associate with measures of visual impairment. DTI measures offer a reproducible, noninvasive, and sensitive method of investigating RTD and its role in visual impairment

Why use a connectivity-based approach to study stroke and recovery of function?

The brain is organized into a set of widely distributed networks. Therefore, although structural damage from stroke is focal, remote dysfunction can occur in regions connected to the area of lesion. Historically, neuroscience has focused on local processing due in part to the absence of tools to study the function of distributed networks. In this article we discuss how a more comprehensive understanding of the effects of stroke can be attained using resting state functional connectivity BOLD magnetic resonance imaging (resting state fcMRI). Resting state fcMRI has a number of advantages over task-evoked fMRI for studying brain network reorganization in response to stroke, including the ability to image subjects with a broad range of impairments and the ability to study multiple networks simultaneously. We describe our rationale for using resting state connectivity as a tool for investigating the neural substrates of stroke recovery in a heterogeneous population of stroke patients and discuss the main questions we hope to answer, in particular whether resting state fcMRI measures in the acute phase of stroke can predict subsequent recovery. Early results suggest that disruption of inter-hemispheric connectivity in the somatomotor network and the dorsal attention network is more strongly associated with behavioral impairment in those domains than is intra-hemispheric connectivity within either the lesioned or unaffected hemisphere. We also observe in the somatomotor network an interesting interaction between corticospinal tract damage and decreased interhemispheric connectivity that suggests that both processes combine to contribute to neuromotor impairment after stroke. A connectivity-based approach will provide greater insight into network reorganization in the acute and chronic phases after stroke and will contribute to improving prognostic ability and the development of therapeutic interventions. (C) 2012 Elsevier Inc. All rights reserved

Exploring the physiological correlates of chronic mild traumatic brain injury symptoms

We report on the results of a multimodal imaging study involving behavioral assessments, evoked and resting-state BOLD fMRI, and DTI in chronic mTBI subjects. We found that larger task-evoked BOLD activity in the MT+/LO region in extra-striate visual cortex correlated with mTBI and PTSD symptoms, especially light sensitivity. Moreover, higher FA values near the left optic radiation (OR) were associated with both light sensitivity and higher BOLD activity in the MT+/LO region. The MT+/LO region was localized as a region of abnormal functional connectivity with central white matter regions previously found to have abnormal physiological signals during visual eye movement tracking (Astafiev et al., 2015). We conclude that mTBI symptoms and light sensitivity may be related to excessive responsiveness of visual cortex to sensory stimuli. This abnormal sensitivity may be related to chronic remodeling of white matter visual pathways acutely injured

Stronger prediction of motor recovery and outcome post-stroke by cortico-spinal tract integrity than functional connectivity

<div><p>Objectives</p><p>To examine longitudinal changes in structural and functional connectivity post-stroke in patients with motor impairment, and define their importance for recovery and outcome at 12 months.</p><p>Methods</p><p>First-time stroke patients (N = 31) were studied at 1–2 weeks, 3 months, and 12 months post-injury with a validated motor battery and resting-state fMRI to measure inter-hemispheric functional connectivity (FC). Fractional anisotropy (FA) of the cortico-spinal tract (CST) was derived from diffusion tensor imaging as a measure of white matter organization. ANOVAs were used to test for changes in FC, FA, and motor performance scores over time, and regression analysis related motor outcome to clinical and neuroimaging variables.</p><p>Results</p><p>FA of the ipsilesional CST improved significantly from 3 to 12 months and was strongly correlated with motor performance. FA improved even in the absence of direct damage to the CST. Inter-hemispheric FC also improved over time, but did not correlate with motor performance at 12 months. Clinical variables (early motor score, education level, and age) predicted 80.4% of the variation of motor outcome, and FA increased the predictability to 84.6%. FC did not contribute to the prediction of motor outcome.</p><p>Conclusions</p><p>Stroke causes changes to the CST microstructure that can account for behavioral variability even in the absence of demonstrable lesion. Ipsilesional CST undergoes remodeling post-stroke, even past the three-month window when most of the motor recovery happens. FA of the CST, but not inter-hemispheric FC, can improve to the prediction of motor outcome based on early motor scores.</p></div

Distinct phase-amplitude couplings distinguish cognitive processes in human attention

Abstract Spatial attention is the cognitive function that coordinates the selection of visual stimuli with appropriate behavioral responses. Recent studies have reported that phase-amplitude coupling (PAC) of low and high frequencies covaries with spatial attention, but differ on the direction of covariation and the frequency ranges involved. We hypothesized that distinct phase-amplitude frequency pairs have differentiable contributions during tasks that manipulate spatial attention. We investigated this hypothesis with electrocorticography (ECoG) recordings from participants who engaged in a cued spatial attention task. To understand the contribution of PAC to spatial attention we classified cortical sites by their relationship to spatial variables or behavioral performance. Local neural activity in spatial sites was sensitive to spatial variables in the task, while local neural activity in behavioral sites correlated with reaction time. We found two PAC frequency clusters that covaried with different aspects of the task. During a period of cued attention, delta-phase/high-gamma (DH) PAC was sensitive to cue direction in spatial sites. In contrast, theta-alpha-phase/beta-low-gamma-amplitude (TABL) PAC robustly correlated with future reaction times in behavioral sites. Finally, we investigated the origins of TABL PAC and found it corresponded to behaviorally relevant, sharp waveforms, which were also coupled to a low frequency rhythm. We conclude that TABL and DH PAC correspond to distinct mechanisms during spatial attention tasks and that sharp waveforms are elements of a coupled dynamical process