Mark P. McAvoy

Functional deactivations: Change with age and dementia of the Alzheimer type

Young adults typically deactivate specific brain regions during active task performance. Deactivated regions overlap with those that show reduced resting metabolic activity in aging and dementia, raising the possibility of a relation. Here, the magnitude and dynamic temporal properties of these typically deactivated regions were explored in aging by using functional MRI in 82 participants. Young adults (n = 32), older adults without dementia (n = 27), and older adults with early-stage dementia of the Alzheimer type (DAT) (n = 23) were imaged while alternating between blocks of an active semantic classification task and a passive fixation baseline. Deactivation in lateral parietal regions was equivalent across groups; in medial frontal regions, it was reduced by aging but was not reduced further by DAT. Of greatest interest, a medial parietal/ posterior cingulate region showed differences between young adults and older adults without dementia and an even more marked difference with DAT. The temporal profile of the medial parietal/posterior cingulate response suggested that it was initially activated by all three groups, but the response in young adults quickly reversed sign, whereas DAT individuals maintained activation throughout the task block. Exploratory whole-brain analyses confirmed the importance of medial parietal/posterior cingulate cortex differences in aging and DAT. These results introduce important opportunities to explore the functional properties of regions showing deactivations, how their dynamic functional properties relate to their baseline metabolic rates, and how they change with age and dementia.

Right Hemisphere Dominance during Spatial Selective Attention and Target Detection Occurs Outside the Dorsal Frontoparietal Network

Spatial selective attention is widely considered to be right hemisphere dominant. Previous functional magnetic resonance imaging studies, however, have reported bilateral blood-oxygenation-level-dependent responses in dorsal frontoparietal regions during anticipatory shifts of attention to a location (Kastner et al., 1999; Corbetta et al., 2000; Hopfinger et al., 2000). Right-lateralized activity has mainly been reported in ventral frontoparietal regions for shifts of attention to an unattended target stimulus (Arrington et al., 2000; Corbetta et al., 2000). However, clear conclusions cannot be drawn from these studies because hemispheric asymmetries were not assessed using direct voxelwise comparisons of activity in left and right hemispheres. Here, we used this technique to measure hemispheric asymmetries during shifts of spatial attention evoked by a peripheral cue stimulus and during target detection at the cued location. Stimulus-driven shifts of spatial attention in both visual fields evoked right-hemisphere dominant activity in temporoparietal junction (TPJ). Target detection at the attended location produced a more widespread right hemisphere dominance in frontal, parietal, and temporal cortex, including the TPJ region asymmetrically activated during shifts of spatial attention. However, hemispheric asymmetries were not observed during either shifts of attention or target detection in the dorsal frontoparietal regions (anterior precuneus, medial intraparietal sulcus, frontal eye fields) that showed the most robust activations for shifts of attention. Therefore, right hemisphere dominance during stimulus-driven shifts of spatial attention and target detection reflects asymmetries in cortical regions that are largely distinct from the dorsal frontoparietal network involved in the control of selective attention.

Interaction of Stimulus-Driven Reorienting and Expectation in Ventral and Dorsal Frontoparietal and Basal Ganglia-Cortical Networks

Shifts of attention to unattended stimuli (stimulus-driven reorienting) are often studied by measuring responses to unexpected stimuli, confounding reorienting and expectation. We separately measured the blood-oxygenation-level-dependent signal for both factors by manipulating the probability of salient visual cues that either shifted attention away from or maintained attention on a stream of visual stimuli. The results distinguished three networks recruited by reorienting. Right temporoparietal junction (TPJ), the posterior core of a ventral frontoparietal network, was activated more by cues for shifting than maintaining attention independently of cue location and probability, acting as a switch. TPJ was separately modulated by low probability cues, which signaled a breach of spatial expectation, independently of whether they shifted attention. Under resting conditions, TPJ activity was correlated [resting-state functional connectivity magnetic resonance imaging, (rs-fcMRI)] with right inferior frontal gyrus (IFG), an anterior component of the ventral network. Nevertheless, IFG was activated only by unexpected shifts of attention, dissociating its function from TPJ. Basal ganglia and frontal/insula regions also were activated only when reorienting was unexpected but showed strong rs-fcMRI among themselves, not with TPJ/IFG, defining a distinct network that may retrieve/activate commands for shifting attention. Within dorsal frontoparietal regions, shifting attention produced sustained spatially selective modulations in intraparietal sulcus (IPS) and frontal-eye field (FEF), and transient less selective modulations in precuneus and FEF. Modulations were observed even when reorienting was likely, but increased when reorienting was unexpected. The latter result may partly reflect interactions with lateral prefrontal components of the basal-ganglia/frontal/insula network that showed significant rs-fcMRI with the dorsal network.

Mixed blocked/event-related designs separate transient and sustained activity in fMRI.

Recent functional magnetic resonance imaging (fMRI) studies using mixed blocked/event-related designs have shown activity consistent with separable sustained task-related processes and transient trial-related processes. In the mixed design, control blocks are intermixed with task blocks, during which trials are presented at varying intervals. Two studies were conducted to assess the ability of this design to detect and dissociate sustained task-related from transient trial-related activity. Analyses on both simulated and empirical data were performed by using the general linear model with a shape assumed for sustained effects, but not transient effects. In the first study, simulated data were produced with sustained time courses, transient time courses, and the sum of both together. Analyses of these data showed appropriate parsing of sustained and transient activity in all three cases. For the empirical fMRI experiment, counterphase-flickering checkerboard stimuli were constructed to produce sustained, transient, and combined sustained and transient responses in visual cortex. As with the simulation, appropriate parsing of sustained and transient activity was seen in all three cases; i.e., sustained stimuli produced sustained time courses and transient stimuli produced transient time courses. Combined stimuli produced both transient and sustained time courses. Critically, transient stimuli alone did not produce spurious positive sustained responses; sustained stimuli alone produced negligible spurious transient time courses. The results of these two studies along with supplemental simulations provide strong evidence that mixed designs are an effective tool for separating transient, trial-related activity from sustained activity in fMRI experiments. Mixed designs can allow researchers a means to examine brain activity associated with sustained processes, potentially related to task-level control signals.

Separate Modulations of Human V1 Associated with Spatial Attention and Task Structure

Functional magnetic resonance imaging (fMRI) was used while normal human volunteers engaged in simple detection and discrimination tasks, revealing separable modulations of early visual cortex associated with spatial attention and task structure. Both modulations occur even when there is no change in sensory stimulation. The modulation due to spatial attention is present throughout the early visual areas V1, V2, V3, and VP, and varies with the attended location. The task structure activations are strongest in V1 and are greater in regions that represent more peripheral parts of the visual field. Control experiments demonstrate that the task structure activations cannot be attributed to visual, auditory, or somatosensory processing, the motor response for the detection/discrimination judgment, or oculomotor responses such as blinks or saccades. These findings demonstrate that early visual areas are modulated by at least two types of endogenous signals, each with distinct cortical distributions.

Neural correlates of incongruous visual information An event-related fMRI study

Incongruous information is better remembered than ordinary information. This result has been attributed both to semantic incongruity and surprise. To determine the contribution of each factor, we performed a functional magnetic resonance imaging study in which participants viewed pictures depicting ordinary and incongruous objects (e.g., head of a wrench fused onto a sheep body). To maximize surprise we administered novel incongruent pictures infrequently in an initial scan. (This scan also included infrequent color-inverted pictures as a control for frequency.) To obtain a pure measure of the effect of incongruity we conducted a second scan in which participants viewed equal numbers of ordinary and incongruous pictures. Signal increases were greater for incongruous versus ordinary and oddball stimuli throughout the ventral and dorsal visual pathways, and in prefrontal cortex bilaterally. Signal decreases were larger for incongruous than for ordinary stimuli bilaterally in lateral parietal regions. A subset of regions near the right frontal operculum and extending laterally responded only to, or more strongly to, infrequent incongruous pictures. A second, purely behavioral, experiment involving a separate group of participants demonstrated that incongruous pictures were better recognized than ordinary pictures. We interpret our results as suggesting that, although correlates of a surprise response can be observed, better memory for incongruous visual information is attributable mainly to more processing and, consequently, better encoding.

Resting states affect spontaneous BOLD oscillations in sensory and paralimbic cortex.

The brain exhibits spontaneous neural activity that depends on the behavioral state of the organism. We asked whether the blood oxygenation level-dependent (BOLD) signal reflects these modulations. BOLD was measured under three steady-state conditions: while subjects kept their eyes closed, kept their eyes open, or while fixating. The BOLD spectral density was calculated across brain voxels and subjects. Visual, sensory-motor, auditory, and retrosplenial cortex showed modulations of the BOLD spectral density by resting state type. All modulated regions showed greater spontaneous BOLD oscillations in the eyes closed than the eyes open or fixation conditions, suggesting that the differences were endogenously driven. Next, we examined the pattern of correlations between regions whose ongoing BOLD signal was modulated by resting state type. Regional neuronal correlations were estimated using an analytic procedure from the comparison of BOLD-BOLD covariances in the fixation and eyes closed conditions. Most regions were highly correlated with one another, with the exception of the primary visual cortices, which showed low correlations with the other regions. In conclusion, changes in resting state were associated with synchronous modulations of spontaneous BOLD oscillations in cortical sensory areas driven by two spatially overlapping, but temporally uncorrelated signals.

Pictures of a thousand words: Investigating the neural mechanisms of reading with extremely rapid event-related fMRI

Reading is one of the most important skills human beings can acquire, but has proven difficult to study naturalistically using functional magnetic resonance imaging (fMRI). We introduce a novel Event-Related Reading (ERR) fMRI approach that enables reliable estimation of the neural correlates of single-word processing during reading of rapidly presented narrative text (200-300 ms/word). Application to an fMRI experiment in which subjects read coherent narratives and made no overt responses revealed widespread effects of orthographic, phonological, contextual, and semantic variables on brain activation. Word-level variables predicted activity in classical language areas as well as the inferotemporal visual word form area, specifically supporting a role for the latter in mapping visual forms onto articulatory or acoustic representations. Additional analyses demonstrated that ERR results replicate across experiments and predict reading comprehension. The ERR approach represents a powerful and extremely flexible new approach for studying reading and language behavior with fMRI.

The BOLD onset transient: identification of novel functional differences in schizophrenia

Blood oxygen level dependent (BOLD) signals characteristically exhibit an overshoot (transient signal increase) at the beginning of fMRI task blocks. This onset transient has often been overlooked as an independent measure of neuronal activity, but it may represent unique functional processes. We examined onset transient responses in normal subjects and individuals with schizophrenia performing three cognitive tasks. These analyses revealed a regionally specific and task specific attenuation of the onset transient in individuals with schizophrenia during performance of a working memory task. Furthermore, this attenuation was often not accompanied by a corresponding population difference in the sustained response, and is missed through conventional fMRI analysis techniques. Relevance of these findings to both an interpretation of the onset transient and the pathology of schizophrenia are discussed.

Classification of temporal sequences via prediction using the simple recurrent neural network

Abstract An approach to classify temporal sequences using the simple recurrent neural network (SRNN) is developed in this paper. A classification problem is formulated as a component prediction problem and two training methods are described to train a single SRNN to predict the components of temporal sequences belonging to multiple classes. Issues related to the selection of the dimension of the context vector and the influence of the context vector on classification are identified and investigated. The use of a different initial context vector for each class is proposed as a means to improve classification and a classification rule which incorporates the different initial context vectors is formulated. A systematic method in which the SRNN is trained with noisy exemplars is developed to enhance the classification performance of the network. A 4-class localized object classification problem is selected to demonstrate that (a) a single SRNN can be trained to classify real multi-class sequences via component prediction, (b) the classification accuracy can be improved by using a distinguishing initial context vector for each class, and (c) the classification accuracy of the SRNN can be improved significantly by using the distinguishing initial context vector in conjunction with the systematic re-training method. It is concluded that, through the approach developed in this paper, the SRNN can robustly classify temporal sequences which may have an unequal number of components.