Biomedical subjects

Timothy A Keller

Publications and source records attributed to Timothy A Keller.

13 recordsLinked to original sources

PubMed2007

Volitional control of attention and brain activation in dual task performance.

This study used functional MRI (fMRI) to examine the neural effects of willfully allocating one's attention to one of two ongoing tasks. In a dual task paradigm, participants were instructed to focus either on auditory sentence comprehension, mental rotation, or both. One of the major findings is that the distribution of brain activation was amenable to strategic control, such that the amount of activation per task was systematically related to the attention-dividing instructions. The activation in language processing regions was lower when attending to mental rotation than when attending to the sentences, and the activation in visuospatial processing regions was lower when attending to sentences than when attending to mental rotations. Additionally, the activation was found to be underadditive, with the dual-task condition eliciting less activation than the sum of the attend sentence and attend rotation conditions. We also observed a laterality shift across conditions within language-processing regions, with the attend sentence condition showing bilateral activation, while the dual task condition showed a left hemispheric dominance. This shift suggests multiple language-processing modes and may explain the underadditivity in activation observed in the current and previous studies.

Acoustic Stimulation↗

PubMed2006

Inhibitory control in high-functioning autism: decreased activation and underconnectivity in inhibition networks.

BACKGROUND: Inhibiting prepotent responses is critical to optimal cognitive and behavioral function across many domains. Several behavioral studies have investigated response inhibition in autism, and the findings varied according to the components involved in inhibition. There has been only one published functional magnetic resonance imaging (fMRI) study so far on inhibition in autism, which found greater activation in participants with autism than control participants. METHODS: This study investigated the neural basis of response inhibition in 12 high-functioning adults with autism and 12 age- and intelligence quotient (IQ)-matched control participants during a simple response inhibition task and an inhibition task involving working memory. RESULTS: In both inhibition tasks, the participants with autism showed less brain activation than control participants in areas often found to be active in response inhibition tasks, namely the anterior cingulate cortex. In the more demanding inhibition condition, involving working memory, the participants with autism showed more activation than control participants in the premotor areas. In addition to the activation differences, the participants with autism showed lower levels of synchronization between the inhibition network (anterior cingulate gyrus, middle cingulate gyrus, and insula) and the right middle and inferior frontal and right inferior parietal regions. CONCLUSIONS: The results indicate that the inhibition circuitry in the autism group is activated atypically and is less synchronized, leaving inhibition to be accomplished by strategic control rather than automatically. At the behavioral level, there was no difference between the groups.

Adaptation, Psychological↗

PubMed2006

Functional connectivity in a baseline resting-state network in autism.

Brain activity in people with high-functioning autism has been shown to be atypical in a number of ways, including reduced synchronization across areas of activation measured by functional magnetic resonance imaging. This activation atypicality has been observed mostly during the performance of cognitive tasks. This study compares the resting-state network of 57 participants with autism and 57 control participants matched for age and intelligence quotient. The results indicate that both groups have a resting-state network that is very similar both in volume and in organization, but in autism this network is much more loosely connected. This functional underconnectivity was observed in the anterior-posterior connections. The results expand the theory of cortical underconnectivity in autism to the resting state of the brain.

Adult↗

PubMed2006

Neural basis of dyslexia: a comparison between dyslexic and nondyslexic children equated for reading ability.

Adults and children with developmental dyslexia exhibit reduced parietotemporal activation in functional neuroimaging studies of phonological processing. These studies used age-matched and/or intelligence quotient-matched control groups whose reading ability and scanner task performance were often superior to that of the dyslexic group. It is unknown, therefore, whether differences in activation reflect simply poorer performance in the scanner, the underlying level of reading ability, or more specific neural correlates of dyslexia. To resolve this uncertainty, we conducted a functional magnetic resonance imaging study, with a rhyme judgment task, in which we compared dyslexic children with two control groups: age-matched children and reading-matched children (younger normal readers equated for reading ability or scanner-performance to the dyslexic children). Dyslexic children exhibited reduced activation relative to both age-matched and reading-matched children in the left parietotemporal cortex and five other regions, including the right parietotemporal cortex. The dyslexic children also exhibited reduced activation bilaterally in the parietotemporal cortex when compared with children equated for task performance during scanning. Nine of the 10 dyslexic children exhibited reduced left parietotemporal activation compared with their individually selected age-matched or reading-matched control children. Additionally, normal reading fifth graders showed more activation in the same bilateral parietotemporal regions than normal-reading third graders. These findings indicate that the activation differences seen in the dyslexic children cannot be accounted for by either current reading level or scanner task performance, but instead represent a distinct developmental atypicality in the neural systems that support learning to read.

Brain Mapping↗

PubMed2006

Sentence comprehension in autism: thinking in pictures with decreased functional connectivity.

Comprehending high-imagery sentences like The number eight when rotated 90 degrees looks like a pair of eyeglasses involves the participation and integration of several cortical regions. The linguistic content must be processed to determine what is to be mentally imaged, and then the mental image must be evaluated and related to the sentence. A theory of cortical underconnectivity in autism predicts that the interregional collaboration required between linguistic and imaginal processing in this task would be underserved in autism. This functional MRI study examined brain activation in 12 participants with autism and 13 age- and IQ-matched control participants while they processed sentences with either high- or low-imagery content. The analysis of functional connectivity among cortical regions showed that the language and spatial centres in the participants with autism were not as well synchronized as in controls. In addition to the functional connectivity differences, there was also a group difference in activation. In the processing of low-imagery sentences (e.g. Addition, subtraction and multiplication are all math skills), the use of imagery is not essential to comprehension. Nevertheless, the autism group activated parietal and occipital brain regions associated with imagery for comprehending both the low and high-imagery sentences, suggesting that they were using mental imagery in both conditions. In contrast, the control group showed imagery-related activation primarily in the high-imagery condition. The findings provide further evidence of underintegration of language and imagery in autism (and hence expand the understanding of underconnectivity) but also show that people with autism are more reliant on visualization to support language comprehension.

Adult↗

PubMed2006

Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry.

The brain activation of a group of high-functioning autistic participants was measured using functional magnetic resonance imaging during the performance of a Tower of London task, in comparison with a control group matched with respect to intelligent quotient, age, and gender. The 2 groups generally activated the same cortical areas to similar degrees. However, there were 3 indications of underconnectivity in the group with autism. First, the degree of synchronization (i.e., the functional connectivity or the correlation of the time series of the activation) between the frontal and parietal areas of activation was lower for the autistic than the control participants. Second, relevant parts of the corpus callosum, through which many of the bilaterally activated cortical areas communicate, were smaller in cross-sectional area in the autistic participants. Third, within the autism group but not within the control group, the size of the genu of the corpus callosum was correlated with frontal-parietal functional connectivity. These findings suggest that the neural basis of altered cognition in autism entails a lower degree of integration of information across certain cortical areas resulting from reduced intracortical connectivity. The results add support to a new theory of cortical underconnectivity in autism, which posits a deficit in integration of information at the neural and cognitive levels.

Adult↗

PubMed2005

Interactions between the dorsal and the ventral pathways in mental rotation: an fMRI study.

In this fMRI study, we examined the relationship between activations in the inferotemporal region (ventral pathway) and the parietal region (dorsal pathway), as well as in the prefrontal cortex (associated with working memory), in a modified mental rotation task. We manipulated figural complexity (simple vs. complex) to affect the figure recognition process (associated with the ventral pathway) and the amount of rotation (0 degrees vs. 90 degrees), typically associated with the dorsal pathway. The pattern of activation not only showed that both streams are affected by both manipulations, but also showed an overadditive interaction. The effect of figural complexity was greater for 90 degrees rotation than for 0 degrees in multiple regions, including the ventral, dorsal, and prefrontal regions. In addition, functional connectivity analyses on the correlations across the time courses of activation between regions of interest showed increased synchronization among multiple brain areas as task demand increased. The results indicate that both the dorsal and the ventral pathways show interactive effects of object and spatial processing, and they suggest that multiple regions interact to perform mental rotation.

Adult↗

PubMed2004

Functional connectivity in an fMRI working memory task in high-functioning autism.

An fMRI study was used to measure the brain activation of a group of adults with high-functioning autism compared to a Full Scale and Verbal IQ and age-matched control group during an n-back working memory task with letters. The behavioral results showed comparable performance, but the fMRI results suggested that the normal controls might use verbal codes to perform the task, while the adults with autism might use visual codes. The control group demonstrated more activation in the left than the right parietal regions, whereas the autism group showed more right lateralized activation in the prefrontal and parietal regions. The autism group also had more activation than the control group in the posterior regions including inferior temporal and occipital regions. The analysis of functional connectivity yielded similar patterns for the two groups with different hemispheric correlations. The temporal profile of the activity in the prefrontal regions was more correlated with the left parietal regions for the control group, whereas it was more correlated with the right parietal regions for the autism group.

Adult↗

PubMed2004

Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity.

The brain activation of a group of high-functioning autistic participants was measured using functional MRI during sentence comprehension and the results compared with those of a Verbal IQ-matched control group. The groups differed in the distribution of activation in two of the key language areas. The autism group produced reliably more activation than the control group in Wernicke's (left laterosuperior temporal) area and reliably less activation than the control group in Broca's (left inferior frontal gyrus) area. Furthermore, the functional connectivity, i.e. the degree of synchronization or correlation of the time series of the activation, between the various participating cortical areas was consistently lower for the autistic than the control participants. These findings suggest that the neural basis of disordered language in autism entails a lower degree of information integration and synchronization across the large-scale cortical network for language processing. The article presents a theoretical account of the findings, related to neurobiological foundations of underconnectivity in autism.

Autistic Disorder↗

PubMed2004

Imagery in sentence comprehension: an fMRI study.

This study examined brain activation while participants read or listened to high-imagery sentences like The number eight when rotated 90 degrees looks like a pair of spectacles or low-imagery sentences, and judged them as true or false. The sentence imagery manipulation affected the activation in regions (particularly, the intraparietal sulcus) that activate in other mental imagery tasks, such as mental rotation. Both the auditory and visual presentation experiments indicated activation of the intraparietal sulcus area in the high-imagery condition, suggesting a common neural substrate for language-evoked imagery that is independent of the input modality. In addition to exhibiting greater activation levels during the processing of high-imagery sentences, the left intraparietal sulcus also showed greater functional connectivity in this condition with other cortical regions, particularly language processing regions, regardless of the input modality. The comprehension of abstract, nonimaginal information in low-imagery sentences was accompanied by additional activation in regions in the left superior and middle temporal areas associated with the retrieval and processing of semantic and world knowledge. In addition to exhibiting greater activation levels during the processing of low-imagery sentences, this left temporal region also revealed greater functional connectivity in this condition with other left hemisphere language processing regions and with prefrontal regions, regardless of the input modality. The findings indicate that sentence comprehension can activate additional cortical regions that process information that is not specifically linguistic but varies with the information content of the sentence (such as visual or abstract information). In particular, the left intraparietal sulcus area appears to be centrally involved in processing the visual imagery that a sentence can evoke, while activating in synchrony with some core language processing regions.

Adolescent↗

PubMed2003

Brain imaging of tongue-twister sentence comprehension: twisting the tongue and the brain.

This study used fMRI to investigate the neural basis of the tongue-twister effect in a sentence comprehension task. Participants silently read sentences equated for the syntactic structure and the lexical frequency of the constituent words, but differing in the proportion of words that shared similar initial phonemes. The manipulation affected not only the reading times and comprehension performance, but also the amount of activation seen in a number of language-related cortical areas. The effect was not restricted to cortical areas known to be involved in articulatory speech programming or rehearsal processes (the inferior frontal gyrus and anterior insula), but also extended to areas associated with other aspects of language processing (inferior parietal cortex) associated with phonological processing and storage.

Adult↗

PubMed2003

Differential effects of syntactic and semantic processing on the subregions of Broca's area.

This study attempts to specify the contribution of two subregions of Broca's area during syntactic and semantic processing of sentences by examining brain activation in a grammaticality judgment task. The processing of two types of ungrammatical sentences was examined. One type leaves the thematic interpretation generally unaffected, by violating the noun-verb agreement in number, while the other type introduces an extraneous verb, which cannot be incorporated into the developing thematic structure. Pars triangularis was more sensitive to the extra verb violation, whereas pars opercularis was more sensitive to the noun-verb agreement violation. The current study adds to the growing literature that suggests there are separable functional subregions of Broca's area, with pars triangularis more involved in thematic processing and pars opercularis more involved in syntactic processing. The posterior left temporal area was also involved in both types of processing.

Brain Mapping↗

PubMed2003

Ambiguity in the brain: what brain imaging reveals about the processing of syntactically ambiguous sentences.

Two fMRI studies investigated the time course and amplitude of brain activity in language-related areas during the processing of syntactically ambiguous sentences. In Experiment 1, higher levels of activation were found during the reading of unpreferred syntactic structures as well as more complex structures. In Experiments 2A and 2B higher levels of brain activation were found for ambiguous sentences compared with unambiguous sentences matched for syntactic complexity, even when the ambiguities were resolved in favor of the preferred syntactic construction (despite the absence of this difference in previous reading time results). Although results can be reconciled with either serial or parallel models of sentence parsing, they arguably fit better into the parallel framework. Serial models can admittedly be made consistent but only by including a parallel component. The fMRI data indicate the involvement of a parallel component in syntactic parsing that might be either a selection mechanism or a construction of multiple parses.

Adult↗