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Biomedical subjects

Kate E Watkins

Publications and source records attributed to Kate E Watkins.

6 recordsLinked to original sources

Stimulating language: insights from TMS.

Fifteen years ago, Pascual-Leone and colleagues used transcranial magnetic stimulation (TMS) to investigate speech production in pre-surgical epilepsy patients and in doing so, introduced a novel tool into language research. TMS can be used to non-invasively stimulate a specific cortical region and transiently disrupt information processing. These 'virtual lesion' studies offer not only the ability to explore causal relations between brain regions and language functions absent in functional neuroimaging, but also spatial and temporal precision not typically available in patient studies. For instance, TMS has been used to demonstrate functionally distinct sub-regions of the left inferior frontal gyrus; to clarify the relationship between pre-morbid language organization and susceptibility to unilateral lesions and to investigate the contribution of both left and right hemisphere language areas in recovery from aphasia. When TMS is used as a measure of functional connectivity, it demonstrates a close link between action words and motor programmes; it suggests a potential evolutionary link between hand gestures and language and it suggests a role in speech perception for the motor system underlying speech production. In combination with functional neuroimaging, it can elucidate the circuits responsible for this involvement. Finally, TMS may even be useful for enhancing recovery in aphasic patients. In other words, TMS has already become an important tool for studying language at both the cognitive and neural levels, and it is clear that further developments in TMS methodology are likely to result in even greater opportunities for language research.

Aphasia↗

Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data.

There has been much recent interest in using magnetic resonance diffusion imaging to provide information about anatomical connectivity in the brain, by measuring the anisotropic diffusion of water in white matter tracts. One of the measures most commonly derived from diffusion data is fractional anisotropy (FA), which quantifies how strongly directional the local tract structure is. Many imaging studies are starting to use FA images in voxelwise statistical analyses, in order to localise brain changes related to development, degeneration and disease. However, optimal analysis is compromised by the use of standard registration algorithms; there has not to date been a satisfactory solution to the question of how to align FA images from multiple subjects in a way that allows for valid conclusions to be drawn from the subsequent voxelwise analysis. Furthermore, the arbitrariness of the choice of spatial smoothing extent has not yet been resolved. In this paper, we present a new method that aims to solve these issues via (a) carefully tuned non-linear registration, followed by (b) projection onto an alignment-invariant tract representation (the "mean FA skeleton"). We refer to this new approach as Tract-Based Spatial Statistics (TBSS). TBSS aims to improve the sensitivity, objectivity and interpretability of analysis of multi-subject diffusion imaging studies. We describe TBSS in detail and present example TBSS results from several diffusion imaging studies.

Amyotrophic Lateral Sclerosis↗

Asymmetries of the planum temporale and Heschl's gyrus: relationship to language lateralization.

Morphological asymmetries favouring the left hemisphere in the planum temporale (PT) and Heschl's gyrus (HG) have both been presumed to relate to the typical left-hemisphere dominance for language functions. However, a direct link between structure and function has not been clearly established. The present study investigates this issue by measuring the volume of the PT and HG on the MRI scans of epilepsy patients classified into three groups: left speech group (LSG; n = 20), right speech group (RSG; n = 11) and bilateral speech group (BSG; n = 13), as assessed by the intracarotid Sodium Amytal procedure. Additionally, an automatic voxel-based morphometry (VBM) analysis was performed to explore collateral structural asymmetries. Although leftward structural asymmetries were found in the PT, consistent with the literature, they did not relate to language lateralization. For HG we also replicated asymmetries favouring the left side; interestingly, three of the individuals within the RSG showed a strongly reversed asymmetry, but as a whole the structure-function relationship for HG was not obligatory. The VBM analysis revealed a grey-matter concentration difference in the posterior part of the inferior frontal gyrus (pars opercularis, corresponding functionally to Broca's area), which favoured the left hemisphere in the LSG, and the right hemisphere in the RSG. The findings suggest that this frontal cortical region bears a direct relationship to language lateralization, which may be related to use-dependent plasticity in patients with language reorganization.

Adolescent↗

Word and nonword repetition in bilingual subjects: a PET study.

Learning a specific skill during childhood may partly determine the functional organization of the adult brain. This hypothesis led us to study brain activation patterns using positron emission tomography (PET), in which we compared word and nonword repetition in 10 right-handed native English-speakers (L1) who were proficient in their second language, French (L2), which was learned after the age of 5 years. Regional cerebral blood flow (rCBF) was measured by the H2 15O intravenous bolus method with intersubject averaging and coregistration of magnetic resonance and PET images. A comparison of CBF changes when repeating words in L2 with those seen when repeating words in (L1) demonstrated that the pattern of CBF was similar across the two conditions, with several significant CBF differences in the vicinity of the left insular cortex, ventral premotor region, and in the striatum. We hypothesize that these regions are activated when subjects are required to repeat known words, showing increased activity when there are increased articulatory demands imposed by speaking L2. Comparisons of nonword repetition in L1 and L2 revealed increased activity for L2 in the left ventral premotor region and in the cerebellum; rCBF increases were also observed in these regions in both L1 and L2 with increased number of syllables and increased articulatory complexity, suggesting a role for these regions in the complex motor control needed for the production of novel sequences.

Brain↗

Hemispheric specialization for processing auditory nonspeech stimuli.

The left hemisphere specialization for speech perception might arise from asymmetries at more basic levels of auditory processing. In particular, it has been suggested that differences in "temporal" and "spectral" processing exist between the hemispheres. Here we used functional magnetic resonance imaging to test this hypothesis further. Fourteen healthy volunteers listened to sequences of alternating pure tones that varied in the temporal and spectral domains. Increased temporal variation was associated with activation in Heschl's gyrus (HG) bilaterally, whereas increased spectral variation activated the superior temporal gyrus (STG) bilaterally and right posterior superior temporal sulcus (STS). Responses to increased temporal variation were lateralized to the left hemisphere; this left lateralization was greater in posteromedial HG, which is presumed to correspond to the primary auditory cortex. Responses to increased spectral variation were lateralized to the right hemisphere specifically in the anterior STG and posterior STS. These findings are consistent with the notion that the hemispheres are differentially specialized for processing auditory stimuli even in the absence of linguistic information.

Acoustic Stimulation↗

Bilateral brain abnormalities associated with dominantly inherited verbal and orofacial dyspraxia.

The KE family is a large three-generational pedigree in which half of the members suffer from a verbal and orofacial dyspraxia in association with a point mutation in the FOXP2 gene. This report extends previous voxel-based morphometric analyses of magnetic resonance imaging (MRI) scans (Watkins et al. [2002] Brain 125:465-478) using a bilateral conjunction analysis. This searches specifically for areas of grey matter density that differ bilaterally in the affected members compared with both matched controls and the unaffected family members. 3-D T1-weighted MRI datasets of 17 family members (10 affected, 7 unaffected) and matched controls were compared. The most significant findings were reduced grey matter density bilaterally in the caudate nucleus, the cerebellum, and the left and right inferior frontal gyrus in the affected members. In addition, increased grey matter density was found bilaterally in the planum temporale. These results confirm that a point mutation in FOXP2 is associated with several bilateral grey matter abnormalities in both motor and language related regions. The results also demonstrate the advantages of using a conjunction analysis when bilateral abnormalities are suspected.

Adolescent↗