What can functional Transcranial Doppler Ultrasonography tell us about spoken language understanding?

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Language, Cognition and Neuroscience

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What can functional Transcranial Doppler

Ultrasonography tell us about spoken language

understanding?

N. A. Badcock & M. A. Groen

To cite this article: N. A. Badcock & M. A. Groen (2017): What can functional Transcranial

Doppler Ultrasonography tell us about spoken language understanding?, Language, Cognition

and Neuroscience, DOI: 10.1080/23273798.2016.1276608

To link to this article: http://dx.doi.org/10.1080/23273798.2016.1276608

Published online: 16 Jan 2017.

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What can functional Transcranial Doppler Ultrasonography tell us about spoken

language understanding?

N. A. Badcock

a,b

and M. A. Groen

ARC Centre of Excellence in Cognition and its Disorders, Department of Cognitive Science, Macquarie University, North Ryde, Australia;

Perception and Action Research Centre, Macquarie University, North Ryde, Australia;

Behavioural Science Institute, Radboud University,

Nijmegen, The Netherlands

ABSTRACT

This review describes language research conducted using the neurophysiological imaging

technique, functional Transcranial Doppler Ultrasound (fTCD). FTCD estimates the blood flow

velocity in the cerebral arteries from which, neural activity is inferred. The review provides a brief

history and introduction to fTCD, including data acquisition, task design, and data processing.

Challenges and solutions for the use of fTCD for language research are covered, reporting on

production and comprehension paradigms, task difficulty and behavioural performance during

covert and overt speech production, and participant characteristics (age and sex). We note the

limited application of fTCD to the topic of spoken language understanding, commenting on the

value of examining lateralisation in this endeavour, as well as the advantages of its use, namely

portability and low cost, to supplement other imaging techniques.

ARTICLE HISTORY

Received 15 February 2016

Accepted 16 December 2016

KEYWORDS

Speech; language;

lateralisation; Doppler;

functional Transcranial

Doppler ultrasound

1. Historical background

Following the first reports of extracranial blood flow vel-

ocity (BFV) record ings using Doppler ultrasound (Miya-

zaki & Kato, 1965; Satomura & Kaneko, 1960), Aaslid,

Markwalder, and Nornes et al. (1982) pioneered its use

for intracranial blood vessels. They overcame the

attenuative qualities of bone and soft tissues by using

lower frequency ultrasound (1–2 MHz) and focusing on

(or “insonating”) vessels through the temporal bone

windows – the thinnest skull region (see Figure 1(A)). In

this way, BFVs were measured non-invasively in the

middle, anterior, and posterior cerebral arteries (Aaslid

et al., 1982), leading to widespread medical applications.

More recently, researchers began to time-lock this

activity to cognitive tasks – known as functional Tran-

scranial Doppler Ultrasonography (fTCD) – taking unilat-

eral (Droste, Harders, & Rastogi, 1989) and bilateral

measurements (Hartje, Ringelstein, Kistinger, Fabianek,

& Willmes, 1994; Rihs et al., 1995; Silvestrini, Cupini,

Matteis, Troisi, & Caltagirone, 1994) with a goal of asses-

sing cerebral lateralisation of cognitive abilities – rela-

tively greater task-related activation of one

hemisphere, compared to the other hemisphere.

However, these early fTCD results with verbal and non-

verbal tasks were ambiguous and lacked sufficient

reliability to draw conclusions on an individual basis.

Subsequent developments in experimental design (e.g.

Knecht et al., 1996) and analysis (Deppe, Knecht, Hen-

ningsen, & Ringelstein, 1997), notably improved the sen-

sitivity of fTCD and facilitated its use as a clinical and

research tool for studying lateralisation.

Clinically, fTCD is used in pre-surgical evaluations of

epilepsy patients (e.g. Knake et al., 2003), and in follow-

up measurements with a range of patient populations

(Knake et al., 2006), but studying language lateralisation

is also of theoretical importance. A lateralised brain is

thought to process information more efficiently (Rogers

& Vallortigara, 2015; Vallortigara & Rogers, 2005), but

associations are unclear in humans: atypical language

lateralisation has not been associated with behavioural

impairments in adults (Knecht et al., 2001). However,

fTCD (Bishop, Holt, Whitehouse, & Groen, 2014;Illingworth

&Bishop,2009; Whitehouse & Bishop, 2009) and fMRI

(Badcock, Bishop, Hardiman, Barry, & Watkins, 2012;de

Guibert et al., 2011; Sun, Lee, & Kirby, 2010)researchhas

repeatedly reported weaker language lateralisation to be

more common in individuals with developmental

language and literacy impairments. Bishop (2013;Bishop

et al., 2014) discusses several possible explanations for

this conundrum, but currently, the evidence is indecisive.

sessing language lateralisation directly (rather than

relying on a behavioural proxy), in large samples of indi-

viduals varying in language proficiency and across devel-

opment is needed to shed light on this issue, and fTCD is a

fitting technique in this endeavour.

CONTACT N. A. Badcock [email protected]

LANGUAGE, COGNITION AND NEUROSCIENCE, 2017

http://dx.doi.org/10.1080/23273798.2016.1276608

2. Overview of the method

2.1. The neurophysiology of fTCD

Via insonating a blood vessel through the temporal bone

windows of the skull (i.e. transcranially; see Figure 1), BFV

(cm/s) can be determined be comparing frequency

changes of the transmitted and returned ultrasound

signals reflected against the moving blood cells (i.e. the

well-known Doppler effect). As cerebral BFV increases

in response to neural firing in order to maintain

resources to the cells (Escartin & Rouach, 2013;Li&

Freeman, 2015; Villringer & Dirnagl, 1995), neural activity

in the brain regions supplied by the insonated vessel can

be inferred. The middle cerebral artery (MCA) is the most

commonly insonated vessel in language research, sup-

plying blood to approximately 50% of the cortex (van

der Zwan, Hillen, Tulleken, & Dujovny, 1993), including

areas linked to language processing (see Table 1). There-

fore, when someone produces speech, there will be an

accompanying increase in BFV in the MCA which can

be measured using fTCD. See Bishop, Badcock, and

Holt (2010) for a video demonstration of the procedure

and Figure 2 for its relation to other neurophysiological

methods.

2.2. Data acquisition

An experienced user can insonate vessels in less than 5

minutes but the location is variable and, as a result,

setup time can be longer (for a setup guide, including

depth of insonation, see Badcock, Spooner, et al.,

2016). One caveat to the fTCD procedure is that

insonation of a vessel may fail in 5–10% of people (in

the authors’ experiences and given in Lohmann, Ringel-

stein, & Knecht, 2006), 9% of children (0–16 years, Iova

et al., 2004), and up to 25% in older adults (i.e. 55-years

and over: M = 71; Bakker et al., 2004 ). Failure is due to

the thickness and density of the temporal bone

window, which tends to affect women (i.e. thicker) and

older adults (i.e. less density leads to greater signal

refraction) with higher likelihood (Wijnhoud, Franckena,

van der Lugt, Koudstaal, & Dippel, 2008); medication

also affects bone thickness (Kattan, 1970; Lefebvre,

Haining, & Labbé, 1972). Once setup, session duration

is task dependent, typically requiring between 30 and

60 seconds per trial. Although not systematically investi-

gated (but see Badcock, Spooner, et al., 2016,for

reliability at varying numbers of trials), typical studies

include 20 or more trials, lasting between 10 and

20 minutes.

2.3. Task design

With regard to language research, fTCD has mainly been

used to study lateralisation. Bilateral monitoring makes it

particularly suited to this purpose. To illustrate the key

variables, we focus on the gold standard language later-

alisation task in fTCD research: word generation. For this

task, participants are asked to silently generate words

beginning with a visually presented letter (see

Figure 3). This is preceded by a 5-seconds preparatory

period with a “Clear Mind” instruction. Words are gener-

ated for 15 seconds, followed by a 5-second period of

overt report to ascertain task compliance. A 35-second

Figure 1. Panel A: A cartoon diagram of the left temporal window, underlying middle cerebral artery (MCA), and region supplied by

MCA. Panel B: Example insonation of the left and right middle cerebral arteries, including the headmount with the probes fitted. Please

note this is for illustration purposes only. For photographs and diagrams of the variability of temporal windows see Ringelstein,

Kahlscheuer, Niggemeyer, and Otis (1990 ). There is also a free interactive simulator that provides clear diagrams (available for

Windows operating systems from Haemodynamics AG, http://www.transcranial.com/edu/download.html).

2 N. A. BADCOCK AND M. A. GROEN

period of relaxation follows to return BFV to a resting

state (i.e. normalisation): a baseline against which acti-

vation can be compared. Each trial lasts for 60 seconds.

The task, pioneered by Knecht et al. (1996 ), is reliable

(Knecht, Deppe, Ringelstein, et al., 1998), and has been

validated against the Wada technique (Knecht, Deppe,

Ebner, et al., 1998) and fMRI (Deppe et al., 2000;

Somers et al., 2011). These comparisons, as well as its

extensive use in the literature, set word generation as a

standard paradigm for fTCD research.

The required elements of fTCD paradigms include nor-

malisation/baseline, preparation, and activation. Normal-

isation should be included before and after an event to

ensure that activity is sufficiently separated from adjacent

events. However, normalisation duration varies between

studies. Gutierrez-Sigut, Payne, and MacSweeney (2015)

used a 10-second normalisation, whereas Badcock, Nye,

and Bishop (2012) used 25 seconds. Despite Gutierrez-

Sigut et al. and Badcock et al. reporting typical distri-

butions of lateralisation, the task reliability was low

(split-half r = 0.61 and Cronbach’s α = 0.52, respectively)

compared with canonical replications of word generation

(e.g. r = 0.89; Bishop, Watt, & Papadatou-Pastou, 2009).

Although likely that some minimum is required, this has

not been investigated. Alternative strategies to the

“relax” normalisation have been implemented, for

example, watching a to-be-described video (i.e. anima-

tion description; Bishop et al., 2009) which is more

engaging for children and reported to result in non-later-

alised activity. This may be useful for lateralisation

research but for other applications, especially with

adults, less engaging normalisation may be best.

Task preparation is cued by a brief tone usually

accompanied by “Clear Mind” text presented for 5

seconds. The presence of the tone has been demon-

strated to increase the magnitude of the change in BFV

in the predicted direction; that is, greater left velocity

for word generation (Knecht et al., 1996); though again,

the text instruction has not been investigated.

Activation is cued by the presentation of a letter to

which participants are instructed to silently generate

words. Silent generation of words was originally encour-

aged to avoid movement artefacts, however, overt tasks

have been successfully employed without issue (e.g.

Gutierrez-Sigut, Payne, et al., 2015). The early work

encouraged the production of four words per letter

(Knecht et al., 1996), later adjusted to “as many as you

can” (Knecht, Deppe, Ebner et al., 1998). Presumably

this extension results in greater activation consistency

between trials and therefore internal reliability, although

this has not been tested.

The duration of normalisation and activation periods

allows time for change in BFV to plateau (i.e. approxi-

mately 10 seconds; Rosengarten, Osthaus, & Kaps,

2002); however, the required time is derived from a para-

digm without a preparation period. As noted by Knecht

Table 1. Description of the cortical coverage and relevance for language (from Price, 2010) of brain regions supplied by the left middle

cerebral artery. The coverage is based upon examination of 50 hemispheres from 25 post-mortem brains, and the description is

minimally adapted from Gibo, Carver, Rhoton, Lenkey, and Mitchell ( 1981).

Lobe Coverage Gyrus

Brodmann

area Relevance for language

Frontal Lateral half of the orbital surface and the area between the

Sylvian fissure below, the superior frontal sulcus with

frequent overlap onto the superior frontal gyrus above,

and the central sulcus posteriorly and near, but stopping

short of the frontal tip anteriorly. The branches of the MCA

did not reach the superior margin nor the medial surface

Pars orbitalis 47 Semantic retrieval processes

Pars triangularis 45 Word selection

(comprehension and

production)

Pars opercularis 44 Hierarchical sequencing and

articulatory planning

Middle frontal 46 Word retrieval (more in

production)

Precentral 6, 4 Initiation and execution of

movement Sensorimotor

interface

Parietal Bounded anteriorly by the central sulcus, inferiorly by the

Sylvian fissure, and superiorly by the inferior half of the

superior parietal lobule. Posteriorly, the area extended

backward onto the lateral surface of the occipital lobe

Postcentral 3, 1, 2 Phonological retrieval/covert

articulation Semantic

constraints

Inferior and superior parietal

lobules (including the

supramarginal and angular gyri)

40, 39

Temporal Entire lateral surface except for a small posteroinferior strip.

In addition, it supplied the lateral part of the inferior

surface of the temporal lobe, the temporal pole, the uncus,

and adjacent part of the parahippocampal gyrus. Branches

frequently extended onto the lateral surface of the

occipital lobe

Superior temporal (including

Heschl’s gyrus and the Planum

Temporale)

41, 42, 22 Auditory input Prelexical

auditory objects

Sensorimotor integration

Middle temporal 21 Semantic processing of single

words

Inferior temporal 20 Amodal semantic combinations

Temporal pole 38 Intelligible speech/amodal

semantic combinations

Occipital Branches supplying the parietal and temporal lobes

overlapped onto the lateral occipital gyri, but they did not

extend to the occipital pole

Lateral occipital gyri 19

LANGUAGE, COGNITION AN D NEUROSCIENCE 3

et al. (1996), peak change following cuing occurs at

around 4 seconds. Shorter activation periods have

been used; for example, single word report in less

than 5 seconds to brief (3 to 5 word) definitions

(Badcock, Nye, et al., 2012). Although the lateralisation

results were comparable to word generation, the

relationship between the two tasks was weak. Further

investigation to determine optimal task parameters is

warranted.

It is worth noting that fTCD language research uses

blocked designs, in contrast to rapid event-related

designs used with fMRI (D’Esposito, Zarahn, & Aguirre,

1999) or EEG (i.e. event-related potentials; Luck, 2014).

Theoretically, rapid event-related fTCD designs are poss-

ible, however, to our knowledge, this has not been

tested.

2.4. Data processing and analysis

FTCD data are processed in a number of steps to cal cu-

late event-related change in BFV (see Table 2 and

Deppe, Knecht, Lohmann, & Ringelstein, 2004; Deppe

et al., 1997, for further details). Example group data for

word generation are displayed in Figure 3. Critically,

the difference between the left and right velocities

shows an increase from 5 to 15 seconds, indicating left

lateralisation at the group level. Whilst the primary

purpose of the documented processing is for laterality

index calculation (see Table 2), the timing and amplitude

of left-right average, left and right independent (e.g. in a

vigilance experiment, Schultz, Matthews, Warm, & Wash-

burn, 2009), or single channel changes in velocity may

address new questions.

Figure 2. Schematic of the spatial resolution and temporal relationship between active (squares) and passive (ovals) neurophysiological

methods and physiological activity (Deppe, Ringelstein, & Knecht, 2004; Walsh & Cowey, 2000). Methods: transcranial direct current

stimulation (tDCS), transcranial magnetic stimulation (TMS), magnoencephalography (MEG), electroencephalography (EEG), positron

emission tomomography (PET), functional near infrared spectroscopy (fNIRS), fun ctional magnetic resonance imaging (fMRI), functional

Transcranial Doppler Ultrasound (fTCD).

Figure 3. Blood flow velocity (% change in cm/s) to silent word generation (a latency of 0 corresponds to letter presentation to cue

generation). Mean activity for a group (n = 17) are presented for the left and right middle cerebral arteries, and the left minus right

difference. Baseline and period of interest timings are marked, along with the peak difference (vertical bar within the period of interest).

A schematic of the task elements is displayed below the x-axis, including a period of relaxation to establish baseline blood flow velocity,

a preparatory cue to “Clear Mind”, a letter stimulus to cue silent word generation beginning with the presented letter, a period of silent

word generation, followed by overt report of the words (i.e. “Say”), and then relaxation to induce normalisation of blood flow velocity.

The laterality index is 2.07% change from baseline [95% confidence intervals: 1.99, 2.14].

4 N. A. BADCOCK AND M. A. GROEN

Deppe and colleagues developed the processing

steps, easily implemented with their software Average

(described in Deppe et al., 1997, 2004). Average is

Windows-based software, and a cross-platform

implementation of the methods is available with the

MATLAB toolbox, dopOSCCI (introduced in Badcock,

Holt, Holden, & Bishop, 2012). The toolbox allows for cus-

tomisation and extension to the steps, and introduced

activation correction for extreme values as well as rejec-

tion of extreme values based on the left minus right

difference (see Badcock, Spooner, et al., 2016).

At the individual level, changes in BFV have been ana-

lysed using comparison of indices to zero using 95% con-

fidence intervals (e.g. Groen, Whitehouse, Badcock, &

Bishop, 2013) and analyses of variance (e.g. Badcock,

Nye, et al., 2012).

3. Challenges and solutions for studying

spoken language

With the focus of fTCD language research on lateralisa-

tion and its potential use as a clinical tool in epilepsy

surgery, common language tasks for fTCD require the

production of words (e.g. word generation, naming) or

sentences (e.g. sentence construction, picture, or anima-

tion description). Although tasks vary in terms of the

amount of auditory input and comprehension

demands, few studies have investigated understanding

of spoken language per se. In the following sections,

we discuss existing use of receptive language tasks in

fTCD research, and how fTCD responses to language

tasks are associated with task difficulty and performance,

and participant characteristics.

3.1. Types of language tasks

Research has compared comprehension and language

production using listening to short stories (jokes,

poems, or everyday life events) versus producing short

stories from a picture cue (Stroobant, Van Boxstael, & Vin-

gerhoets, 2011), and sentence judgements versus word

generation (Buchinger et al., 2000). Consistent with

work using the Wada technique (e.g. Boatman et al.,

1998) and fMRI (e.g. Tzourio-Mazoyer, Josse, Crivello, &

Mazoyer, 2004), receptive tasks are less strongly latera-

lised than expressive tasks (Buchinger et al., 2000; Stroo-

bant et al., 2011). However, the expressive and receptive

tasks in this research were poorly matched for auditory

input or linguistic content, therefore lateralisation differ-

ences could be due to increased bilateral involvement in

multiple processes (e.g. phonological, syntactic, or

semantic knowledge). In a comparison of listening to

stories versus noise or melody, Carod Artal, Vazquez

Cabrera, and Horan (2004) reported a larger increase in

Table 2. Summary of processing and analysis steps for fTCD data (for further details see Deppe et al., 1997).

Step Description Comment

Downsampling Data are usually recorded at 100 Hz and downsampled to

25 Hz (1 sample every 40 ms)

Historically this step was required as computing power was limited,

in addition to the fact that the blood flow response is slow so

millisecond accuracy is overkill. Given the power of modern

computers, this step may be skipped, however, downsampling will

increase the speed of processing

Normalisation Data for each channel are transformed to have a mean of 100 The angle of the ultrasound probe will likely differ between left and

right channels, resulting in differences in overall velocity.

Normalisation corrects for this difference. This removes any intra-

individual differences as well resting state differences between

channels

Heart Cycle

Integration

Fluctuations in velocity due to the heart cycle (i.e. pulse) are

removed by averaging across individual cycles

This is a form a data cleaning that does not introduce artefacts

associated with bandpass filtering and improves the frequency

distribution of the data (from bimodal to unimodal), rendering it

suitable for traditional statistical interrogation. See Pinaya et al.

(2015) where this is not included and Badcock, Pascoe, and Groen

(2016) for a response to this

Epoching The continuous recording is divided into event-related time

periods

Data Screening Epochs with extreme values are excluded from further analysis Extreme data is considered a recording artefact, often due to probe

displacement caused by movement. This can be identified as a)

values beyond a certain range (e.g. ±50 cm/s beyond the mean of

the data) or b) a channel difference outside the expected range

(e.g. 20 cm/s where the average is usually less than 5 cm/s)

Baseline Correction Subtraction of average activity during a control period from all data

within an epoch, for the left and right channels separately

Requires the specification of a baseline time period within the epoch,

during which rest or control-task activity is assumed. The

percentage change in activation due to the task can be inferred.

Periods of 4 to 10 seconds have been used in the literature (10 in

Bishop et al., 2009; in Gutierrez-Sigut, Daws, et al., 2015) – the

effects have not been compared systematically

Laterality Index

Calculation

The peak left minus right channel activation difference within a

period of interest is determined. The average activation within a

2-second time-window around this peak is the laterality index

The period of interest is selected in relation to task-onset – typically

with a 5-second delay to allow velocity to peak. Left activation is

reflected by positive values, right is negative

LANGUAGE, COGNITION AN D NEUROSCIENCE 5

left lateralisation to stories. In this case, stimulus com-

plexity varied between conditions, complicating

interpretation of the results. Although most fTCD work

has investigated lateralisation for language as if

language were a unidimensional construct, Gutierrez-

Sigut, Daws, et al. (2015 , 2015) compared the traditional

word generation task (i.e. phonological fluency) with a

semantic fluency equivalent and did not find differences

in direction or degree in lateralisation indices. In contrast,

Stroobant, Buijs, and Vingerhoets (2009) compared tasks

tapping multiple linguistic processes and found stronger

left lateralisation for tasks involving word generation

(phonological fluency) or syntactic processes (sentence

construction) than one involving semantic (synonimity)

judgements.

To date, fTCD has been used for relatively crude categ-

orisation in tasks with high ecological validity, but poor

on experimental control, and which mostly conceptual-

ise language as a unidimensional construct. To increase

our understanding of lateralisation of language – and

the utility of fTCD to study it – it is important to

address the following issues. Firstly, experimental

control over a range of factors (e.g. task difficulty) that

influence lateralisation is poor. Secondly, lateralisation

for language is predominantly treated as a unidimen-

sional construct, however, as illustrated by Stroobant

et al. (2009), degree of la teralisation can vary between

language tasks. It remains an outstanding question

whether a single laterality measure is suitable to sum-

marise activity across tasks, or whether individual vari-

ation between language tasks is meaningful. Carefully

matching task properties tapping different linguistic

domains and processes in both production and compre-

hension, and recognising individual differences between

these domains are important next steps.

3.2. Associations with task difficulty and

performance

Task difficulty is one parameter that might influence

fTCD-estimated lateralisation, but results have been

inconsistent. Dräger and Knecht (2002) manipulated

the difficultly of word generation by providing partici-

pants with letters forming the beginnings of words, con-

trasting the frequency of available items (i.e. high = easy,

versus low = hard). Although behavioural accuracy

matched retrieval difficulty, fTCD outcomes did not: con-

sistent with other fTCD work with language (Badcock,

Nye, et al., 2012) and spatial ability (Rosch, Bishop, &

Badcock, 2012). In an fMRI follow-up, Dräger et al.

(2004) suggested that lack of suitable cerebral territory

supplied by the MCA rendered fTCD insensitive to their

difficulty manipulation: parietal regions outside this

territory were highlighted. However, recently, pace of

decision-making was evident using fTCD. Payne, Gutier-

rez-Sigut, Subik, Woll, and MacSweeney (2015) manipu-

lated the number of word-pair rhyme and line

orientation judgments required in a 17.5-second

period: 5 or 10. More judgments were associated with

stronger lateralisation for rhyme (greater left) and line

(greater right) tasks. Therefore, fTCD is sensitive to

some aspects of task difficulty.

The behaviour-lateralisation relationship is important

for interpreting silent word generation tasks comparing

groups that may differ in language abilities (e.g. dyslexia,

Illingworth & Bishop, 2009). In such studies, it is imposs-

ible to establish whether the behavioural differences

underpin neural differences – this concern is supported

by a lack of relationship between the number of words

reported and fTCD measureme nts in word generation

(Badcock, Nye, et al., 2012). However, Gutierrez-Sigut,

Payne, et al. (2015) have demonstrated similar activation

for covert and overt speech, observing a significant cor-

relation between behaviour and fTCD lateralisation for

overt speech. Therefore, overt speech paradigms are

recommended.

3.3. Associations with participant characteristics

Lateralisation is also influenced by participant character-

istics, such as age, sex or, relatedly, menstrual cycle.

Regarding age, one fTCD study in children (1–5 years)

reported greater left lateralisation at younger ages

(Kohler et al., 2015); however, the majority (ages

ranging from 2 to 16) report no association (Groen,

Whitehouse, Badcock, & Bishop, 2012; Haag et al., 2010;

Hodgson, Hirst, & Hudson, 2016; Lohmann, Dräger,

Müller-Ehrenberg, Deppe, & Knecht, 2005; Stroobant

et al., 2011) which is at odds with fMRI (Gaillard et al.,

2000; Holland et al., 2001, 2007; Szaflarski, Schmithorst,

et al., 2006; Szaflarski, Holland, Schmithorst, & Byars,

2006). This discrepancy could be explained by greater

sensitivity in fMRI to area-specific age-related changes

or by the fTCD tasks used. As Holland et al. (2007)

suggested, assessing late-acquired language skills may

result in age-related differences in lateralisation, but

the fTCD tasks typically require description of simple pic-

tures or animation, probing early-acquired skills. At the

other end of the spectrum, older participants showed

reduced left-lateralised activation during a word gener-

ation task (60–75 year-olds, Keage et al., 2015).

Concerning sex,

despite a long-standing debate on

male–female language lateralisation differences, empiri-

cal support for more bilateral language in women is

lacking (Sommer, Aleman, Bouma, & Kahn, 2004;

Sommer, Aleman, Somers, Boks, & Kahn, 2008), or

6 N. A. BADCOCK AND M. A. GROEN

effects are very small, and possi bly age-dependent (Hirn-

stein, Westerhausen, Korsnes, & Hugdahl, 2013). This is in

line with a lack of sex differences reported in fTCD

studies (e.g. Knecht et al., 2000; Whitehouse & Bishop,

2009). Interestingly, a recent study evaluating the test–

retest reliability of lateralisation using fTCD across

several weeks, found laterality indices were much more

variable in women (Helmstaedter, Jockwitz, & Witt,

2015); specifically, a relative shift towards bilateral acti-

vation in women at menstrual cycle onset. This finding

demands consideration of menstrual cycle when asses-

sing lateralisation and it may explain contrasting findings

on sex differences, and confound existing between

group research. Therefore, both age and sex are impor-

tant factors in lateralisation research and may be impor-

tant for fTCD research per se.

4. Advantages and future directions

Language research with fTCD is in its infancy, predomi-

nantly applied in clinical settings, using ecologically valid,

but poorly controlled paradigms, probing multiple

aspects of language simultaneously. As such, there are

no key empirical contributions to the understanding of

spoken language yet. Nevertheless, fTCD is worth consider-

ation as the field is ripe for paradigm development and

refinements in analysis, including considering measures

beyond laterality indices. These developments enable

the advancements of our understanding of language later-

alisation for production and comprehension.

4.1. Advantages of fTCD

Although its spatial resolution is limited (see Figure 2 and

Table 1), fTCD has several advantages, compared to other

techniques. It is highly portable and relatively inexpen-

sive (Pelletier, Sauerwein, Lepore, Saint-Amour, & Las-

sonde, 2007), making it a useful screening tool for

investigations requiring large sample-sizes, such as

genetic studies (e.g. Somers et al., 2015). Additionally,

its robustness to articulation and gross movements,

and participant friendly administration, make it well

suited for use with young children, older adults, and

patient groups. Indeed, adaptations of the gold standard

word generation t ask eliciting overt sentence production

in response to pictures (Haag et al., 2010; Lohmann et al.,

2005) or animations (Bishop et al., 2009) or picture

naming (Badcock et al., 2016; Kohler et al., 2015) have

resulted in reliable measurements of language lateralisa-

tion. Moreover, the nature of the ultrasound signal

makes it appropriate for research where other tech-

niques are not, such as in individuals with cochlear

implants (e.g. Chilosi et al., 2014). As fTCD is non-invasive

and can be administered repeatedly in the same partici-

pants, there are opportunities to examine and project

recovery from stroke (for e.g. in motor control see

Sarkar, Ghosh, Ghosh, & Collier, 2007). The advantages

of fTCD – low-cost, portability, robustness to articulation

and gross movements, and participant friendly adminis-

tration – support its use as an imaging technique for

language research in the foreseeable future, supple-

menting weaknesses of other techniques.

4.2. Future developments in task design and data

analysis

As mentioned, there are a number of task parameters yet

to be optimised for fTCD. This concerns all phases of a trial:

normalisation, preparation, and activation (see Section

2.3). There are outstanding questions regarding the influ-

ence of task instruction on preparation and behaviour.

Also, the number of required trials and the possibility of

adopting a rapid event-related (instead of a blocked)

design, merit investigation. Refining matching of stimulus

properties across conditions to equate demands between

production and comprehension tasks is needed to inves-

tigate whether a unidimensional view of language latera-

lisation is justified. Regarding analysis, we are yet to

optimise data cleaning techniques to maximise the

signal to noise ratio (Badcock, Spooner, et al., 2016)and

variables beyond the peak difference should be con-

sidered (e.g. trajectory of BFV increase to infer neural sub-

trates; Meyer, Spray, Fairlie, & Uomini, 2014). Following a

different approach, resting TCD can be used to investigate

cerebrovascular functioning (Keage et al., 2012). This

approach has associated poorer cerebrovascular function-

ing to decreased fluid, but not crystallised, intelligence in

aging populations (Keage et al., 2015). These develop-

ments offer exciting potential for the use of fTCD for the

investigation of spoken language.

Note

1. Here, we refer to the dichotomous variable sex. We note

that the continuous variable of hormones levels will

likely be the more accurate advancement for this

research (e.g. Hausmann, Slabbekoorn, Van Goozen,

Cohen-Kettenis, & Güntürkün, 2000).

Acknowledgements

Thanks to Heather Payne, Paul Sowman, and Alexandra

Woolgar for feedback on the work.

Disclosure statement

No potential conflict of interest was reported by the authors.

LANGUAGE, COGNITION AN D NEUROSCIENCE 7

ORCID

N. A. Badcock http://orcid.org/0000-0001-6862-4694

M. A. Groen

http://orcid.org/0000-0002-6178-2937

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