BRFAA - Biomedical Research Foundation Academy Of Athens
Biomedical Research Foundation Academy Of AthensAcademy Of Athens

Research

Laterality

Morphological right-left asymmetry appears to be the rule, rather than the exception in nature, all the way from chiral molecules to the Baryon asymmetry in the universe. Asymmetry is the rule for biological systems as well, whereby even single-celled organisms are commonly asymmetric. 

Human beings are certainly structurally and functionally asymmetric, from the size of their feet and hands to the placement of their visceral organs and facial features. In fact, the two aspects of behavior specific to humans, the use of language and the strong population-level preference for hand use, are both asymmetric, lateralized traits. When it comes to language, the majority of humans are left-hemisphere dominant for language functions, while the right hand is the preferred hand for over 9 out of 10 individuals; a pattern far from negligible.

Laterality is the main focus of our work. We have been studying behavioral laterality (e.g., handedness, footedness, and cradling laterality) as well as brain laterality (also known as brain asymmetry, hemispheric dominance, or hemispheric specialization). We are using meta-analytic methods, as well as behavioral, hormonal, and brain imaging techniques to study questions such as sex differences in handedness and brain lateralization, handedness in populations with special education needs, and cerebral laterality during writing.

This endeavor, apart from its intrinsic interest, gains importance from the fact that the study of handedness and language lateralization contributes to the broader question of individual differences in brain organization and abilities. Such differences are of key importance to psychiatric, neurological, and neuropsychological research and practice as well as to the study of the genetics of asymmetry.


Neuroimaging: Functional transcranial Doppler ultrasonography

In our lab we use functional transcranial Doppler ultrasonography (fTCD) to assess cerebral laterality. FTCD involves placing probes on either side of the head and using ultrasound to measure blood flow in the middle cerebral arteries (MCAs). The cerebral blood flow velocity (CBFV) changes in the MCAs are taken to indicate the downstream increase of regional metabolic activity during a task. FTCD’s spatial resolution is low, restricted to the basal artery territories, but it has excellent temporal resolution and provides continuous measurement of blood flow changes, which are associated with functional cortical activation (Deppe, Flöel, et al., 2000). FTCD thus adds to the perfusion-sensitive techniques of functional imaging (fMRI, PET, etc.). These techniques are based on the close coupling of cerebral perfusion to cerebral metabolism and neural activation. In particular, changes in cerebral perfusion during cognitive tasks result in a more rapid CBFV in the feeding basal intracranial arteries compared with rest periods (Silvestrini, Letizia, Matteis, Troisi, & Caltagirone, 1994). In fMRI and PET studies, lateralization is usually determined by calculating the difference between the activated brain regions in the left and the right hemisphere relative to the sum of all activated regions in both hemispheres.

FTCD provides identical information in a more efficient way, by directly comparing the relative blood flow velocity changes in the two MCAs. The quantitative measurements obtained by fTCD are moreover not biased by defining variable statistical thresholds, as is often the case in the analysis of fMRI data. The typical sensitivity in fTCD studies for detecting perfusion asymmetries between two basal arteries is of the order of 1% (Deppe et al., 1997). FTCD is non-invasive and can be applied to individuals of all ages (Badcock et al., 2017), in large cohorts and in longitudinal studies, and it is also suitable for follow-up investigations (Lohmann, Ringelstein, & Knecht, 2006). It is completely safe, even for young children (Bishop et al., 2009) and six-month old babies (Badcock et al., 2018). Results obtained with fTCD are highly reproducible and have excellent agreement with those acquired using the intra-carotid amobarbital procedure (Wada test) and fMRI (Deppe, Knecht, et al., 2000; Deppe, Ringelstein, & Knecht, 2004). In addition, fTCD data are not affected by motor movements, which makes the method suitable for assessing language lateralization by employing tasks requiring writing. Furthermore, fTCD data processing has progressed significantly in recent years, owing to the development of an open-access, MATLAB-based toolbox (Badcock, Holt, Holden, & Bishop, 2012). This toolbox provides researchers with unprecedented control and therefore insights into their data, allowing them to establish gold-standard approaches to understanding lateralization assessed with fTCD. In addition, recent advancements in fTCD technology now allow for multi-depth readings during insonation of blood vessels, raw image functionality for retrospective adjustment of signal recordings, and the use of robotic ultrasound probes for greater precision and consistency of blood vessel insonation.

 

References

Badcock, N. A., Holt, G., Holden, A., & Bishop, D. V. (2012). dopOSCCI: A functional transcranial Doppler ultrasonography summary suite for the assessment of cerebral lateralization of cognitive function. Journal of Neuroscience Methods, 204(2), 383-388.

Badcock, N. A., Spooner, R., Hofmann, J., Flitton, A., Elliott, S., Kurylowicz, L., . . . Holden, A. (2018). What Box: A task for assessing language lateralization in young children. Laterality: Asymmetries of Body, Brain and Cognition, 23(4), 391-408.

Bishop, D. V., Watt, H., & Papadatou-Pastou, M. (2009). An efficient and reliable method for measuring cerebral lateralization during speech with functional transcranial Doppler ultrasound. Neuropsychologia, 47(2), 587-590.

Deppe, M., Flöel, A., Knecht, S., Lohmann, H., Konrad, C., Sommer, J., . . . Henningsen, H. (2000). Temporal characteristics of cerebral blood flow velocity changes evoked by short-term visual stimulation. NeuroImage, 11(5, Part 2), S790.

Deppe, M., Knecht, S., Ebner, A., Huber, T., Jokeit, H., Ringelstein, E.-B., & Henningsen, H. (1997). Determination of hemispheric language dominance: Reproducibility of assessment made by functional transcranial Doppler sonography. NeuroImage, 5(4), S587.

Deppe, M., Knecht, S., Papke, K., Lohmann, H., Fleischer, H., Heindel, W., . . . Henningsen, H. (2000). Assessment of hemispheric language lateralization: a comparison between fMRI and fTCD. Journal of Cerebral Blood Flow Metabolism, 20(2), 263-268.

Deppe, M., Ringelstein, E.-B., & Knecht, S. (2004). The investigation of functional brain lateralization by transcanial Doppler sonography. NeuroImage, 21(3), 1124-1146.

Lohmann, H., Ringelstein, E. B., & Knecht, S. (2006). Functional transcranial Doppler Sonography. Handbook on Neurovascular Ultrasound (Vol. 21, pp. 251-260): Karger Publishers.

Silvestrini, M., Letizia, M., Matteis, M., Troisi, E., & Caltagirone, C. (1994). Bilateral simultaneous assessment of cerebral flow velocity during mental activity. Journal of Cerebral Blood Flow Metabolism, 14, 643-648.