R. Todd Constable

Disruption of posterior brain systems for reading in children with developmental dyslexia.

BACKGROUND Converging evidence indicates a functional disruption in the neural systems for reading in adults with dyslexia. We examined brain activation patterns in dyslexic and nonimpaired children during pseudoword and real-word reading tasks that required phonologic analysis (i.e., tapped the problems experienced by dyslexic children in sounding out words). METHODS We used functional magnetic resonance imaging (fMRI) to study 144 right-handed children, 70 dyslexic readers, and 74 nonimpaired readers as they read pseudowords and real words. RESULTS Children with dyslexia demonstrated a disruption in neural systems for reading involving posterior brain regions, including parietotemporal sites and sites in the occipitotemporal area. Reading skill was positively correlated with the magnitude of activation in the left occipitotemporal region. Activation in the left and right inferior frontal gyri was greater in older compared with younger dyslexic children. CONCLUSIONS These findings provide neurobiological evidence of an underlying disruption in the neural systems for reading in children with dyslexia and indicate that it is evident at a young age. The locus of the disruption places childhood dyslexia within the same neurobiological framework as dyslexia, and acquired alexia, occurring in adults.

Brain Connectivity Related to Working Memory Performance

Several brain areas show signal decreases during many different cognitive tasks in functional imaging studies, including the posterior cingulate cortex (PCC) and a medial frontal region incorporating portions of the medial frontal gyrus and ventral anterior cingulate cortex (MFG/vACC). It has been suggested that these areas are components in a default mode network that is engaged during rest and disengaged during cognitive tasks. This study investigated the functional connectivity between the PCC and MFG/vACC during a working memory task and at rest by examining temporal correlations in magnetic resonance signal levels between the regions. The two regions were functionally connected in both conditions. In addition, performance on the working memory task was positively correlated with the strength of this functional connection not only during the working memory task, but also at rest. Thus, it appears these regions are components of a network that may facilitate or monitor cognitive performance, rather than becoming disengaged during cognitive tasks. In addition, these data raise the possibility that the individual differences in coupling strength between these two regions at rest predict differences in cognitive abilities important for this working memory task.

Development of left occipitotemporal systems for skilled reading in children after a phonologically- based intervention

BACKGROUND A range of neurobiological investigations shows a failure of left hemisphere posterior brain systems to function properly during reading in children and adults with reading disabilities. Such evidence of a disruption in the normal reading pathways provides a neurobiological target for reading interventions. In this study, we hypothesized that the provision of an evidence-based, phonologically mediated reading intervention would improve reading fluency and the development of the fast-paced occipitotemporal systems serving skilled reading. METHODS Functional magnetic resonance imaging was used to study the effects of a phonologically based reading intervention on brain organization and reading fluency in 77 children aged 6.1-9.4 years (49 with reading disability and 28 control subjects). Children comprised three experimental groups: experimental intervention (n = 37), community intervention (n = 12), and community control subjects (n = 28). RESULTS Immediately after the year-long intervention, children taught with the experimental intervention had made significant gains in reading fluency and demonstrated increased activation in left hemisphere regions, including the inferior frontal gyrus and the middle temporal gyrus; 1 year after the experimental intervention had ended these children were activating bilateral inferior frontal gyri and left superior temporal and occipitotemporal regions. CONCLUSIONS These data indicate that the nature of the remedial educational intervention is critical to successful outcomes in children with reading disabilities and that the use of an evidence-based phonologic reading intervention facilitates the development of those fast-paced neural systems that underlie skilled reading.

Imaging Response Inhibition in a Stop-Signal Task: Neural Correlates Independent of Signal Monitoring and Post-Response Processing

Execution of higher cortical functions requires inhibitory control to restrain habitual responses and meet changing task demands. We used functional magnetic resonance imaging to show the neural correlates of response inhibition during a stop-signal task. The task has a frequent “go” stimulus to set up a pre-potent response tendency and a less frequent “stop” signal for subjects to withhold their response. We contrasted brain activation between successful and failed inhibition for individual subjects and compared groups of subjects with short and long stop-signal reaction times. The two groups of subjects did not differ in their inhibition failure rates or the extent of signal monitoring, error monitoring, or task-associated frustration ratings. The results showed that short stop-signal reaction time or more efficient response inhibition was associated with greater activation in the superior medial and precentral frontal cortices. Moreover, activation of these inhibitory motor areas correlated negatively with stop-signal reaction time. These brain regions may represent the neural substrata of response inhibition independent of other cognitive and affective functions.

Neural systems for compensation and persistence: Young adult outcome of childhood reading disability

BACKGROUND This study examined whether and how two groups of young adults who were poor readers as children (a relatively compensated group and a group with persistent reading difficulties) differed from nonimpaired readers and if there were any factors distinguishing the compensated from persistently poor readers that might account for their different outcomes. METHODS Using functional magnetic resonance imaging, we studied three groups of young adults, ages 18.5-22.5 years, as they read pseudowords and real words: 1) persistently poor readers (PPR; n = 24); 2) accuracy improved (compensated) readers (AIR; n = 19); and 3) nonimpaired readers (NI, n = 27). RESULTS Compensated readers, who are accurate but not fluent, demonstrate a relative underactivation in posterior neural systems for reading located in left parietotemporal and occipitotemporal regions. Persistently poor readers, who are both not fluent and less accurate, activate posterior reading systems but engage them differently from nonimpaired readers, appearing to rely more on memory-based rather than analytic word identification strategies. CONCLUSIONS These findings of divergent neural outcomes as young adults are both new and unexpected and suggest a neural basis for reading outcomes of compensation and persistence in adults with childhood dyslexia.

The Angular Gyrus in Developmental Dyslexia: Task-Specific Differences in Functional Connectivity Within Posterior Cortex

Converging evidence from neuroimaging studies of developmental dyslexia reveals dysfunction at posterior brain regions centered in and around the angular gyrus in the left hemisphere. We examined functional connectivity (covariance) between the angular gyrus and related occipital and temporal lobe sites, across a series of print tasks that systematically varied demands on phonological assembly. Results indicate that for dyslexic readers a disruption in functional connectivity in the language-dominant left hemisphere is confined to those tasks that make explicit demands on assembly. In contrast, on print tasks that do not require phonological assembly, functional connectivity is strong for both dyslexic and nonimpaired readers. The findings support the view that neurobiological anomalies in developmental dyslexia are largely confined to the phonological-processing domain. In addition, the findings suggest that right-hemisphere posterior regions serve a compensatory role in mediating phonological performance in dyslexic readers.

Auditory Selective Attention: An fMRI Investigation

In the present experiment, 25 adult subjects discriminated speech tokens ([ba]/[da]) or made pitch judgments on tone stimuli (rising/falling) under both binaural and dichotic listening conditions. We observed that when listeners performed tasks under the dichotic conditions, during which greater demands are made on auditory selective attention, activation within the posterior (parietal) attention system and at primary processing sites in the superior temporal and inferior frontal regions was increased. The cingulate gyrus within the anterior attention system was not influenced by this manipulation. Hemispheric differences between speech and nonspeech tasks were also observed, both at Brocas Area within the inferior frontal gyrus and in the middle temporal gyrus.

Sex differences and correlations in a virtual Morris water task, a virtual radial arm maze, and mental rotation

Different tasks are often used to assess spatial memory in humans compared to nonhumans. In order to bridge this paradigmatic gap, we used a within-subject design to test 61 undergraduates on three spatial memory tasks. One of these tasks, the Vanderberg 3D mental rotation task, is classically used to assess spatial memory in humans. The other two tests are virtual analogues of two tasks used classically to assess spatial memory in rodents: the Morris water task and an eight-arm radial maze. We find that males perform significantly better than females on the mental rotation task and in finding a hidden platform in the virtual Morris water task. Moreover, during a probe trial, males spend significantly more distance of their swim in the training quadrant, but males and females do not differ in navigating to a visible platform. However, for the virtual eight-arm radial maze, there is no sex difference in working memory errors, reference memory errors, or distance to find the rewards. Surprisingly, an examination of the correlations among the three tasks indicates that only mental rotation ability and Morris water task probe trial performance correlate significantly among the three tasks (i.e. there are no significant correlations with traditional measures the tasks, e.g. time or distance to completion). Hence, the Morris water task and the eight-arm radial maze do not assess spatial memory in the same manner, and even after equating factors such as motivation, stress, and motor demands, there still are procedural demands of the tasks that reinforce differential strategy selection during spatial memory. This suggests that caution should be taken when utilizing these two tasks interchangeable as tests of spatial memory.

ROC Analysis of Statistical Methods Used in Functional MRI: Individual Subjects

The complicated structure of fMRI signals and associated noise sources make it difficult to assess the validity of various steps involved in the statistical analysis of brain activation. Most methods used for fMRI analysis assume that observations are independent and that the noise can be treated as white gaussian noise. These assumptions are usually not true but it is difficult to assess how severely these assumptions are violated and what are their practical consequences. In this study a direct comparison is made between the power of various analytical methods used to detect activations, without reference to estimates of statistical significance. The statistics used in fMRI are treated as metrics designed to detect activations and are not interpreted probabilistically. The receiver operator characteristic (ROC) method is used to compare the efficacy of various steps in calculating an activation map in the study of a single subject based on optimizing the ratio of the number of detected activations to the number of false-positive findings. The main findings are as follows: Preprocessing. The removal of intensity drifts and high-pass filtering applied on the voxel time-course level is beneficial to the efficacy of analysis. Temporal normalization of the global image intensity, smoothing in the temporal domain, and low-pass filtering do not improve power of analysis. Choices of statistics. the cross-correlation coefficient and t-statistic, as well as nonparametric Mann-Whitney statistics, prove to be the most effective and are similar in performance, by our criterion. Task design. the proper design of task protocols is shown to be crucial. In an alternating block design the optimal block length is be approximately 18 s. Spatial clustering. an initial spatial smoothing of images is more efficient than cluster filtering of the statistical parametric activation maps.

An fMRI study of the human cortical motor system response to increasing functional demands

Functional magnetic resonance imaging (fMRI) was used to study activation changes in the human primary motor-sensory areas (MAs), supplementary motor areas (SMAs), premotor areas (PMAs) and the superior and inferior parietal areas (SPAs, IPAs) during right hand finger movements as the rate, force and complexity of movement were varied. A preliminary reproducibility study of a single subject doing the same repetitive index finger movements in nine different sessions over a six week period demonstrated highly consistent and highly localized activation in the contralateral MA. ANOVAs demonstrated highly significant main effects of increasing the force and complexity of movement, thereby illustrating the distributed and integrated systemic character of the cortical motor system. Interactions between brain region and the rate and complexity of movements suggested functional specialization of some components of the system. Increasing the rate of movement led to increased activity only in the contralateral MA; increasing complexity led to greater increases in activity in the left and right SPAs and the left IPA than in other areas. Although activation was evident in varying degree throughout the multiple motor areas, only the MAs showed consistent lateralization of activation.