Elsevier

NeuroImage

Volume 21, Issue 3, March 2004, Pages 1124-1146
NeuroImage

The investigation of functional brain lateralization by transcranial Doppler sonography

https://doi.org/10.1016/j.neuroimage.2003.10.016Get rights and content

Abstract

Functional transcranial Doppler sonography (fTCD) adds to the techniques of functional imaging. fTCD measures cerebral perfusion changes related to neural activation in a way comparable to functional magnetic resonance tomography. fTCD contends itself with comparison of averaged, event-related blood flow velocity changes within the territories of two cerebral arteries, for example the left versus the right middle cerebral artery. It can thus serve to evaluate the functional lateralization of higher cognitive functions like hemispheric language dominance (HLD).

We present typical applications of fTCD by summarizing studies employing the technique. Then, the physical and physiological underpinnings of fTCD are reviewed. After a brief description of a prototype paradigm for assessing HLD, a detailed outline of the fTCD data analysis is presented. Caveats for fTCD, like other functional imaging techniques, are that the validity of results depends on adequate control of the task parameters, particularly cooperation and reference conditions. We complete the review with examinations of the reliability and validity of the fTCD technique. We conclude that fTCD can be employed to substitute the invasive amobarbital procedure to determine language lateralization in individual patients before undergoing brain surgery. Because of its easy applicability, robustness and mobility, fTCD can also be used to examine many subjects (including children) to obtain representative data on the variability of lateralization of higher cognitive functions, or to scan for atypical patterns of lateralization.

Introduction

Perfusion-sensitive techniques like functional magnetic resonance imaging (fMRI), positron emission tomography (PET), optical imaging and functional transcranial Doppler sonography (fTCD) have substantially contributed to the characterization of the neural systems underlying cognition in the human brain. These techniques are based on the fact that cerebral perfusion is closely coupled to cerebral metabolism and neural activation Fox and Raichle, 1986a, Kuschinsky, 1991, Lou et al., 1987.

The changes in cerebral perfusion during cognitive tasks, which underlie fMRI, result in corresponding alterations of blood flow velocities in the feeding basal arteries. These alterations can noninvasively and conveniently be assessed by fTCD. Early fTCD studies demonstrated increased blood flow velocities in the posterior cerebral arteries in response to visual stimulation (Aaslid, 1987) already years before similar studies with fMRI using the Blood Oxygenation Level Dependent (BOLD) contrast were published (Kwong et al., 1992). Since then, fTCD has been used in studies on vision Aaslid, 1987, Conrad and Klingelhofer, 1989, Deppe et al., 2000a, Njemanze et al., 1992, motor activation Bishop et al., 1986, Gomez et al., 1990, Kelley et al., 1992, Sitzer et al., 1994, epileptic discharges Diehl et al., 1998, Klingelhofer et al., 1991, migraine (Backer et al., 2001) transcranial magnetic stimulation Floel et al., 2000a, Knecht et al., 2002, Sander et al., 1996, electroconvulsive therapy (Vollmer-Haase et al., 1998b), acupuncture (Backer et al., 2002) music Evers et al., 1999, Matteis et al., 1997, Vollmer-Haase et al., 1998a, visuospatial tasks Backer et al., 1999, Bulla-Hellwig et al., 1996, Droste et al., 1996, Floel et al., 2001, Floel et al., 2002, Hartje et al., 1994, Vingerhoets and Stroobant, 1999b, attention (Knecht et al., 1997), habituation Lohmann et al., 1998, Vingerhoets and Stroobant, 1999a, Lohmann et al., 2004, memory (Cupini et al., 1996), language and language recovery Anneken et al., 2000, Buchinger et al., 2000, Deppe et al., 1997a, Drager and Knecht, 2002, Drager et al., 2001, Floel et al., 2000b, Hartje et al., 1994, Knake et al., 2003, Knecht et al., 1996, Knecht et al., 1998a, Knecht et al., 1998b, Knecht et al., 2000a, Knecht et al., 2000b, Rihs et al., 1995, Rihs et al., 1999, Silvestrini et al., 1995 genetics (Anneken et al., 2001), behaviour (Knecht et al., 2001) and other cognitive tasks (Stroobant and Vingerhoets, 2000).

While the principle of fTCD is simple, in the sense that cerebral blood flow velocities in the supplying arteries increase with neural activation in the corresponding brain region, a robust differentiation between the specific activation and other unrelated blood flow changes has been problematic (Deppe and Ringelstein, 2000). Task-related blood flow velocity changes (dV) in the basal intracranial arteries amount to only about 1–5% of the mean CBFV, while the spontaneous oscillations related to heart beat and breathing amount to 40%. In the past, the poor signal-to-noise ratio in fTCD studies has limited the technique to the examination of gross effects with rather heterogeneous results between subjects. One major and very successful step to circumvent the problem of large spontaneous oscillations has been the simultaneous measurement of CBFV in two basal arteries and the calculation of the relative regional perfusion increase. The middle cerebral arteries supply approximately three fourth of the cerebral hemispheres including the language-relevant areas van der Zwan and Hillen, 1991, van der Zwan et al., 1993. Therefore, comparison of the CBFV in the middle cerebral arteries provides a compound measure of functional brain lateralization. In effect, this measure corresponds to other indices of lateralization evaluated by various perfusion-sensitive imaging techniques including fMRI and PET Binder et al., 1996, Deppe et al., 2000b, Desmond et al., 1995, Detre et al., 1998, Knecht et al., 1999c, Lex et al., 1998, Loring et al., 1990, Pujol et al., 1999, Springer et al., 1997. In such studies, lateralization is usually determined by calculation of 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. Because fTCD provides identical information in a much more effective way, it has become one of the most potent tools for the investigation of functional lateralization in the brain.

Section snippets

Schematic of a TCD measurement

The blood flow velocity in the basal cerebral arteries can be measured by transcranial Doppler ultrasonography. Fig. 1 illustrates how an ultrasound probe is adjusted for the acquisition of the blood flow velocity in the middle cerebral artery. The velocity measurement is based on the Doppler effect.

Doppler effect

The frequency shift of light and sound waves caused by relative motion of transmitter and receiver has been first described 1842 by the Austrian physicist and mathematician Christian Doppler1

The three major cerebral arteries

The three major cerebral arteries, the anterior cerebral artery (ACA), the middle cerebral artery (MCA) and the posterior cerebral artery (PCA) originate from the Circle of Willis and supply the telencephalon (cerebrum) and parts of the diencephalon. Each of these arteries supplies, almost exclusively, a relatively well-defined territory. Only in case of a slow occlusion (due to atherosclerosis, for instance) will parts of these territories be supplied by collaterals derived from the adjacent

Demands on the TCD device

Clinical TCD examinations mainly address the perfusion characteristics of the basal cerebral arteries. Thus, usually the CBFV spectra (“The Doppler spectrum”) of different arteries will be recorded for this purpose. For lateralization studies by fTCD, we need continuous CBFV time series of at least two homolog cerebral arteries, acquired simultaneously during alternating rest and stimulation conditions. This operation mode, frequently named monitoring mode, is supported by the majority of

Overview

The off-line functional TCD analysis consists of a sequence of different steps. These steps fall into three main categories:

  • Editing the raw data: data import, data normalization, trigger signal modification, artifact detection, heart cycle detection and heart cycle integration.

  • Averaging: epoch definition, baseline correction, filtering and averaging process.

  • Statistical analysis and data reduction: event correlated hemispheric dominance, periods of interest and laterality index.

Analysis tool: AVERAGE 1.85

We implemented

Evaluation of fTCD

The sensitivity, reliability and validity of a research method are important for its evaluation. For the fTCD technique, these characteristics were analyzed by the prototype HLD paradigm described in “A prototype paradigm”. Investigations of the influence of habituation effects on the fTCD results should clarify whether the fTCD technique is suitable for longitudinal studies. The most important limitation of fTCD is its restriction in spatial resolution to the supply areas of the large cerebral

Investigation of reliability

We determined the reproducibility of fTCD from two consecutive examinations on 10 different subjects. The test–retest reproducibility was estimated by the Pearson product moment correlation coefficient and was r = 0.95, P > 0.0001. Fig. 20 illustrates the results. Details of the study are published elsewhere (Knecht et al., 1998b).

Habituation effects

Habituation and learning effects have been investigated as well Knecht et al., 1998b, Lohmann et al., 2004. Fig. 21 shows the results of 10 repetitive examinations on

Discussion

Until recently, an effective assessment of lateralization in large cohorts of healthy subjects had not been possible. The reason was that the available techniques were either not without risk, like the Wada test, or were too expensive and not easy to access, like fMRI. Even at present in case of resective neurosurgery, if reliable information on the side of hemispheric language dominance (HLD) is needed, the invasive Wada test represents the state-of-the-art technique. Sodium amytal is injected

Conclusion

At first sight it, may be surprising that cognitive functions based on extremely complex neural processes can be examined with a simple ultrasonic velocity measurement technique. On closer inspection, however, it turns out that its simple technical basis is the reason for the robustness and universal feasibility of fTCD. These characteristics make fTCD an ideal instrument for the investigation of functional hemispheric differences in all ages, in large cohorts and in longitudinal studies.

Acknowledgements

The authors thank Dr. Marcus Bäcker for his fruitful discussions about fTCD data analysis, Svea Polster for reviewing the manuscript and Dr. Katja Deppe, Dr. Bianca Dräger, Jens Sommer, Dr. Agnes Flöel and Andreas Jansen for their contributions to the present work.

This work was supported by the Nachwuchsgruppe Hemispheric Specialization of Nordrhein–Westfalen (Knecht 2000), the Innovative Medizinische Forschung (Kn-1-1-II/96-34), the Deutsche Forschungsgemeinschaft (Kn 285/6-1) and the

References (145)

  • R.R. Diehl et al.

    Spontaneous oscillations in cerebral blood flow velocity in normal humans and in patients with carotid artery disease

    Neurosci. Lett.

    (1991)
  • B. Drager et al.

    When finding words becomes difficult: is there activation of the subdominant hemisphere?

    NeuroImage

    (2002)
  • A. Floel et al.

    Combined assessment of language lateralization by activation and inactivation using functional Transcranial Doppler Ultrasonography (fTCD) and repetitive Transcranial Magnetic Stimulation (rTMS)

    NeuroImage

    (2000)
  • A. Floel et al.

    Reproducibility of hemispheric blood flow increases during line bisectioning

    Clin. Neurophysiol.

    (2002)
  • R.W. Gill

    Pulsed Doppler with B-mode imaging for quantitative blood flow measurement

    Ultrasound Med. Biol.

    (1979)
  • R.W. Gill

    Measurement of blood flow by ultrasound: accuracy and sources of error

    Ultrasound Med. Biol.

    (1985)
  • R. Grasso et al.

    Arterial baroreceptors are not essential for low frequency oscillation of arterial pressure

    J. Auton. Nerv. Syst.

    (1995)
  • W. Hartje et al.

    Transcranial Doppler ultrasonic assessment of middle cerebral artery blood flow velocity changes during verbal and visuospatial cognitive tasks

    Neuropsychologia

    (1994)
  • L. Jancke et al.

    Dichotic listening: what does it measure?

    Neuropsychologia

    (1992)
  • M. Jueptner et al.

    Review: does measurement of regional cerebral blood flow reflect synaptic activity? Implications for PET and fMRI

    NeuroImage

    (1995)
  • J. Klingelhofer et al.

    Do brief bursts of spike and wave activity cause a cerebral hyper- or hypoperfusion in man?

    Neurosci. Lett.

    (1991)
  • S. Knake et al.

    Language lateralization in patients with temporal lobe epilepsy: a comparison of functional transcranial Doppler sonography and the Wada test

    NeuroImage

    (2003)
  • R. Krapf et al.

    Failure to demonstrate a vasoconstrictive effect of vasopressin on the internal carotid and middle cerebral arteries: a transcranial ultrasound Doppler study

    Ultrasound Med. Biol.

    (1987)
  • U. Lex et al.

    Lateralization effects of language functions studied with fMRI

    NeuroImage

    (1998)
  • H. Lohmann et al.

    Habituation during generation in consecutive fMRI examinations

    NeuroImage

    (1998)
  • D.W. Loring et al.

    Cerebral language lateralization: evidence from intracarotid amobarbital testing

    Neuropsychologia

    (1990)
  • R. Aaslid

    Visually evoked dynamic blood flow response of the human cerebral circulation

    Stroke

    (1987)
  • R. Aaslid

    Developments and principles of transcranial Doppler

  • R. Aaslid et al.

    Cerebral autoregulation dynamics in humans

    Stroke

    (1989)
  • K. Anneken et al.

    Preliminary evidence for a genetic factor involved in determining the degree of hemispheric language lateralization

    NeuroImage

    (2001)
  • M.G. Arts et al.

    On the instantaneous measurement of blood flow by ultrasonic means

    Med. Biol. Eng.

    (1972)
  • M. Backer et al.

    Cortical tuning: a function of anticipated stimulus intensity

    NeuroReport

    (1999)
  • M. Backer et al.

    Altered cerebrovascular response pattern in interictal migraine during visual stimulation

    Cephalalgia

    (2001)
  • S. Baillet et al.

    Electromagnetic brain mapping

    IEEE Signal Proc. Mag.

    (2001)
  • B. Ballot

    Akustische Versuche auf der Niederländischen Eisenbahn nebst gelegentlichen Bemerkungen zur Theorie des Hrn

    Prof. Doppler Pog. Ann.

    (1845)
  • P.A. Bandettini et al.

    Time course EPI of human brain function during task activation

    Magn. Reson. Med.

    (1992)
  • E. Bartels et al.

    Quantitative measurements of blood flow velocity in basal cerebral arteries with transcranial duplex color-flow imaging. A comparative study with conventional transcranial Doppler sonography

    J. Neuroimaging

    (1994)
  • C. Baumgartner et al.

    Epileptic negative myoclonus: an EEG-single-photon emission CT study indicating involvement of premotor cortex

    Neurology

    (1996)
  • D. Bertram et al.

    The arterial baroreceptor reflex of the rat exhibits positive feedback properties at the frequency of Mayer waves

    J. Physiol. (London)

    (1998)
  • J.R. Binder et al.

    Determination of language dominance using functional MRI: a comparison with the Wada test

    Neurology

    (1996)
  • C.C.R. Bishop et al.

    Transcranial Doppler measurements of middle cerebral artery blood flow velocity: a validation study

    Stroke

    (1986)
  • J.E.J. Brian et al.

    Recent insights into the regulation of cerebral circulation

    Clin. Exp. Pharmacol. Physiol.

    (1996)
  • I.N. Bronstein et al.

    Taschenbuch der Mathematik

    (1987)
  • J.M. Clark et al.

    Relationship of 133Xe cerebral blood flow to middle cerebral arterial flow velocity in men at rest

    J. Cereb. Blood Flow Metab.

    (1996)
  • B. Conrad et al.

    Dynamics of regional cerebral blood flow for various visual stimuli

    Exp. Brain Res.

    (1989)
  • L.M. Cupini et al.

    Bilateral simultaneous transcranial Doppler monitoring of flow velocity changes during visuospatial and verbal working memory tasks

    Brain

    (1996)
  • P. Deetjen et al.

    Physiologie

    (1994)
  • A.F. de Molina et al.

    Sympathetic activity and the systemic circulation in the spinal cat

    J. Physiol. (London)

    (1965)
  • M. Deppe et al.

    From TCD to fTCD

    J. Int. Neuropsychol. Soc.

    (2000)
  • M. Deppe et al.

    Determination of hemispheric language dominance: reproducibility of assessment made by functional transcranial Doppler sonography

    NeuroImage

    (1997)
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