Susan M. Courtney

Transient neural activity in human parietal cortex during spatial attention shifts

Observers viewing a complex visual scene selectively attend to relevant locations or objects and ignore irrelevant ones. Selective attention to an object enhances its neural representation in extrastriate cortex, compared with those of unattended objects, via top-down attentional control signals. The posterior parietal cortex is centrally involved in this control of spatial attention. We examined brain activity during attention shifts using rapid, event-related fMRI of human observers as they covertly shifted attention between two peripheral spatial locations. Activation in extrastriate cortex increased after a shift of attention to the contralateral visual field and remained high during sustained contralateral attention. The time course of activity was substantially different in posterior parietal cortex, where transient increases in activation accompanied shifts of attention in either direction. This result suggests that activation of the parietal cortex is associated with a discrete signal to shift spatial attention, and is not the source of a signal to continuously maintain the current attentive state.

Distinguishing the Functional Roles of Multiple Regions in Distributed Neural Systems for Visual Working Memory

We have investigated the human neural systems for visual working memory using functional magnetic resonance imaging to distinguish sustained activity during memory delays from transient responses related to perceptual and motor operations. These studies have identified six distinct frontal regions that demonstrate sustained activity during memory delays. These regions could be distinguished from brain regions in extrastriate cortex that participate more in perception and from brain regions in medial and lateral frontal cortex that participate more in motor control. Moreover, the working memory regions could be distinguished from each other based on the relative strength of their participation in spatial and face working memory and on the relative strength of sustained activity during memory delays versus transient activity related to stimulus presentation. These results demonstrate that visual working memory performance involves the concerted activity of multiple regions in a widely distributed system. Distinctions between functions, such as perception versus memory maintenance, or spatial versus face working memory, are a matter of the degree of participation of different regions, not the discrete parcellation of different functions to different modules.

Functional Magnetic Resonance Imaging of Human Visual Cortex during Face Matching: A Comparison with Positron Emission Tomography

Cortical areas associated with the perception of faces were identified using functional magnetic resonance imaging (fMRI). T2*-weighted gradient echo, echo-planar MR images were obtained using a modified 1.5-T GE Signa MRI. In all nine subjects studied, performance of a face-matching task was associated with a region of significantly increased MR signal in the ventral occipitotemporal cortex, extending from the inferior occipital sulcus to the lateral occipitotemporal sulcus and fusiform gyrus. Smaller and more variable signal increases were found in dorsolateral occipitoparietal cortex near the intraparietal sulcus. Signal decreases were found in the angular gyrus and posterior cingulate cortex. Single-subject fMRI analyses revealed discrete areas of activation with well-defined borders. Group analyses of spatially smoothed fMRI data produced results that replicated most aspects of previous studies of face processing using positron emission tomography (PET). These results show that PET and fMRI identify functional areas with similar anatomical locations. In addition, fMRI reveals interindividual variation in the anatomical location of higher-level processing areas with greater anatomical precision.

Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing–remitting MS

Cognitive deficits affecting memory, attention and speed of information processing are common in multiple sclerosis (MS). The mechanisms of cognitive impairment remain unclear. Here, we examined the association between neuropsychological test performance and brain atrophy in a group of mildly disabled patients with relapsing-remitting MS. We applied voxel-based morphometry (SPM2) to investigate the distribution of brain atrophy in relation to cognitive performance. Patients had lower scores than control subjects on tests of memory and executive function, including the PASAT, Digit Span Backward and a test of short-term verbal memory (Memo). Among patients, but not healthy controls, performance on the PASAT, a comprehensive measure of cognitive function and reference task for the cognitive evaluation of MS-patients, correlated with global grey matter volume as well as with grey matter volume in regions associated with working memory and executive function, including bilateral prefrontal cortex, precentral gyrus and superior parietal cortex as well as right cerebellum. Compared to healthy subjects, patients showed a volume reduction in left temporal and prefrontal cortex, recently identified as areas predominantly affected by diffuse brain atrophy in MS. A comparison of low performers in the patient group with their matched control subjects showed more extensive and bilateral temporal and frontal volume reductions as well as bilateral parietal volume loss, compatible with the progression of atrophy found in more advanced MS-patients. These findings indicate that MS-related deficits in cognition are closely associated with cortical atrophy.

Attention and cognitive control as emergent properties of information representation in working memory

A hallmark of primate, and particularly human, behavior is cognitive control, the ability to integrate information from a multitude of sources and use that information to flexibly guide behavior in order to achieve an infinite number of goals. The neural mechanisms of cognitive control have yet to be fully elucidated, although the prefrontal cortex is known to play a critical role. Here, I review evidence suggesting that a unifying principle regarding the role of various portions of the prefrontal cortex in a wide range of cognitive tasks is the active maintenance in working memory of different types of currently relevant information—from specific stimulus features, to instructional cues, to motivational goals and contexts. I argue that the key to demonstrating the existence of this domain-dependent organization lies in a better understanding of the nature of the representation of this information and the ways in which this information itself controls cognition and behavior.

What fMRI has taught us about human vision.

The recent application of functional magnetic resonance imaging (fMRI) to visual studies has begun to elucidate how the human visual system is anatomically and functionally organized. Bottom-up hierarchical processing among visual cortical areas has been revealed in experiments that have correlated brain activations with human perceptual experience. Top-down modulation of activity within visual cortical areas has been demonstrated through studies of higher cognitive processes such as attention and memory.

Functional topography of working memory for face or voice identity

We used functional magnetic resonance imaging (fMRI) to investigate whether the neural systems for nonspatial visual and auditory working memory exhibits a functional dissociation. The subjects performed a delayed recognition task for previously unfamiliar faces and voices and an audiovisual sensorimotor control task. During the initial sample and subsequent test stimulus presentations, activation was greater for the face than for the voice identity task bilaterally in the occipitotemporal cortex and, conversely, greater for voices than for faces bilaterally in the superior temporal sulcus/gyrus (STS/STG). Ventral prefrontal regions were activated by both memory delays in comparison with the control delays, and there was no significant difference in direct voxelwise comparisons between the tasks. However, further analyses showed that there was a subtle difference in the functional topography for two delay types within the ventral prefrontal cortex. Face delays preferentially activate the dorsal part of the ventral prefrontal cortex (BA 44/45) while voice delays preferentially activate the inferior part (BA 45/47), indicating a ventral/dorsal auditory/visual topography within the ventral prefrontal cortex. The results confirm that there is a modality-specific attentional modulation of activity in visual and auditory sensory areas during stimulus presentation. Moreover, within the nonspatial information-type domain, there is a subtle across-modality dissociation within the ventral prefrontal cortex during working memory maintenance of faces and voices.

Dissociation of the neural systems for working memory maintenance of verbal and nonspatial visual information

Working memory for names and faces was investigated to ascertain whether verbal and nonspatial visual information is maintained in working memory by separate neural systems. The subjects performed a delayed match-to-sample task for famous or unfamous faces and names and a sensorimotor control task. Several occipital, temporal, parietal, and prefrontal areas were activated during all memory delays, in comparison with the control delays. Greater delay activity for unfamous faces than for names was obtained in the right fusiform gyrus, right inferior frontal gyrus (IFG), right IFG/ precentral gyrus, and right medial superior frontal gyrus, whereas greater delay activity for unfamous names than for faces was observed in the precuneus, left insula/postcentral gyrus, and left IFG/ precentral gyrus. There was no significant difference in the prefrontal activity in the comparison between famous faces and names. Greater delay activity for famous names than for faces was obtained in visual association and parietal areas. The results indicate that there is a functional dissociation based on information type within the neural system that is responsible for working memory maintenance of verbal and nonspatial visual information.

Functional MRI of Sentence Comprehension in Children with Dyslexia: Beyond Word Recognition

Sentence comprehension (SC) studies in typical and impaired readers suggest that reading for meaning involves more extensive brain activation than reading isolated words. Thus far, no reading disability/dyslexia (RD) studies have directly controlled for the word recognition (WR) components of SC tasks, which is central for understanding comprehension processes beyond WR. This experiment compared SC to WR in 29, 9-14 year olds (15 typical and 14 impaired readers). The SC-WR contrast for each group showed activation in left inferior frontal and extrastriate regions, but the RD group showed significantly more activation than Controls in areas associated with linguistic processing (left middle/superior temporal gyri), and attention and response selection (bilateral insula, right cingulate gyrus, right superior frontal gyrus, and right parietal lobe). Further analyses revealed this overactivation was driven by the RD groups response to incongruous sentences. Correlations with out-of-scanner measures showed that better word- and text-level reading fluency was associated with greater left occipitotemporal activation, whereas worse performance on WR, fluency, and comprehension (reading and oral) were associated with greater right hemisphere activation in a variety of areas, including supramarginal and superior temporal gyri. Results provide initial foundations for understanding the neurobiological correlates of higher-level processes associated with reading comprehension.

Association of Cortical Lesion Burden on 7-T Magnetic Resonance Imaging With Cognition and Disability in Multiple Sclerosis

IMPORTANCE Cortical lesions (CLs) contribute to physical and cognitive disability in multiple sclerosis (MS). Accurate methods for visualization of CLs are necessary for future clinical studies and therapeutic trials in MS. OBJECTIVE To evaluate the clinical relevance of measures of CL burden derived from high-field magnetic resonance imaging (MRI) in MS. DESIGN, SETTING, AND PARTICIPANTS An observational clinical imaging study was conducted at an academic MS center. Participants included 36 individuals with MS (30 relapsing-remitting, 6 secondary or primary progressive) and 15 healthy individuals serving as controls. The study was conducted from March 10, 2010, to November 23, 2012, and analysis was performed from June 1, 2011, to September 30, 2014. Seven-Tesla MRI of the brain was performed with 0.5-mm isotropic resolution magnetization-prepared rapid acquisition gradient echo (MPRAGE) and whole-brain, 3-dimensional, 1.0-mm isotropic resolution magnetization-prepared, fluid-attenuated inversion recovery (MPFLAIR). Cortical lesions, seen as hypointensities on MPRAGE, were manually segmented. Lesions were classified as leukocortical, intracortical, or subpial. Images were segmented using the Lesion-TOADS (Topology-Preserving Anatomical Segmentation) algorithm, and brain structure volumes and white matter (WM) lesion volume were reported. Volumes were normalized to intracranial volume. MAIN OUTCOMES AND MEASURES Physical disability was measured by the Expanded Disability Status Scale (EDSS). Cognitive disability was measured with the Minimal Assessment of Cognitive Function in MS battery. RESULTS Cortical lesions were noted in 35 of 36 participants (97%), with a median of 16 lesions per participant (range, 0-99). Leukocortical lesion volume correlated with WM lesion volume (ρ = 0.50; P = .003) but not with cortical volume; subpial lesion volume inversely correlated with cortical volume (ρ = -0.36; P = .04) but not with WM lesion volume. Total CL count and volume, measured as median (range), were significantly increased in participants with EDSS scores of 5.0 or more vs those with scores less than 5.0 (count: 29 [11-99] vs 13 [0-51]; volume: 2.81 × 10-4 [1.30 × 10-4 to 7.90 × 10-4] vs 1.50 × 10-4 [0 to 1.01 × 10-3]) and in cognitively impaired vs unimpaired individuals (count: 21 [0-99] vs 13 [1-54]; volume: 3.51 × 10-4 [0 to 1.01 × 10-4] vs 1.19 × 10-4 [0 to 7.17 × 10-4]). Cortical lesion volume correlated with EDSS scores more robustly than did WM lesion volume (ρ = 0.59 vs 0.36). Increasing log[CL volume] conferred a 3-fold increase in the odds of cognitive impairment (odds ratio [OR], 3.36; 95% CI, 1.07-10.59; P = .04) after adjustment for age and sex and a 14-fold increase in odds after adjustment for WM lesion volume and atrophy (OR, 14.26; 95% CI, 1.06-192.37; P = .045). Leukocortical lesions had the greatest effect on cognition (OR for log [leukocortical lesion volume], 9.65; 95% CI, 1.70-54.59, P = .01). CONCLUSIONS AND RELEVANCE This study provides in vivo evidence that CLs are associated with cognitive and physical disability in MS and that leukocortical and subpial lesion subtypes have differing clinical relevance. Quantitative assessments of CL burden on high-field MRI may further our understanding of the development of disability and progression in MS and lead to more effective treatments.