Repetitive transcranial magnetic stimulation over left angular gyrus modulates the predictability

41 Pages·2014·2.08 MB·English

by  Gesa Hartwigsen

Accepted Manuscript
Repetitive transcranial magnetic stimulation over left angular gyrus modulates the
predictability gain in degraded speech comprehension
Gesa Hartwigsen, Thomas Golombek, Jonas Obleser
PII: S0010-9452(14)00290-1
DOI: 10.1016/j.cortex.2014.08.027
Reference: CORTEX 1283
To appear in: Cortex
Received Date: 7 March 2014
Revised Date: 21 August 2014
Accepted Date: 26 August 2014
Please cite this article as: Hartwigsen G, Golombek T, Obleser J, Repetitive transcranial magnetic
stimulation over left angular gyrus modulates the predictability gain in degraded speech comprehension,
Cortex (2014), doi: 10.1016/j.cortex.2014.08.027.
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Repetitive transcranial magnetic stimulation over left angular gyrus modulates the
predictability gain in degraded speech comprehension
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Gesa Hartwigsen 1,2,3*+, Thomas Golombek 1,2+, Jonas ORbleser 2*
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1 Language & Aphasia Laboratory, Department of Neurology, University of Leipzig,
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04103 Leipzig, Germany
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2 Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany
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3 Department of Psychology, Christian-Albrechts-University, 24098 Kiel, Germany
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Running title: Angular Gyrus disruption modu lates speech comprehension
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Manuscript type: Research Article
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Number of text pages: 20, Number of Figures: 4
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Word count: Abstract: 214 words; Introduction: 765 words; Discussion: 1966 words
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Supplementary Information: 5 pages + 2 Figures
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Key words: language, transcranial magnetic stimulation, parietal cortex, virtual lesion, k-factor
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+ These authors contributed equally to the study
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*Corresponding authors:
Gesa Hartwigsen Jonas Obleser
Department of Psychology Max Planck Institute for Human
Christian-Albrechts-University Kiel Cognition and Brain Sciences
Olshausenstr. 62 Stephanstr. 1a
24098 Kiel, Germany 04103 Leipzig, Germany
phone: [phone] phone: [phone]
email: [email protected] email: [email protected]
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Abstract
Increased neural activity in left angular gyrus (AG) accompanies successful comprehension of
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acoustically degraded but highly predictable sentences, as previous functional imaging studies
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have shown. However, it remains unclear whether the left AG is causally relevant for the
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comprehension of degraded speech. Here, we applied transient virtual lesiRons to either the left
AG or superior parietal lobe (SPL, as a control area) with repetitivCe transcranial magnetic
stimulation (rTMS) while healthy volunteers listened to and repeated sentences with high- vs.
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low-predictable endings and different noise vocoding levels. UWe expected that rTMS of AG
should selectively modulate the predictability gain (i.eN., the comprehension benefit from
sentences with high-predictable endings) at a medium Adegradation level. We found that rTMS of
AG indeed reduced the predictability gain at a Mmedium degradation level of 4-band noise
vocoding (relative to control rTMS of SPL). In contrast, the behavioral perturbation induced by

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rTMS changed with increased signal quality. Hence, at 8-band noise vocoding, rTMS over AG
vs. SPL decreased the number of Ecorrectly repeated keywords for sentences with low-
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predictable endings. Together, these results show that the degree of the rTMS interference
depended jointly on signal qualiPty and predictability. Our results provide the first causal evidence
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that the left AG is a critical node for facilitating speech comprehension in challenging listening
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conditions.
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1. Introduction
Humans can comprehend speech very robustly, often despite severe degradation Tin adverse
listening situations or in chronically impaired hearing conditions (e.g., with cocPhlear implants;
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Pisoni, 2000). In recent years, much progress on the functional neuroanatomy of the networks
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involved in this feature has been made (e.g., Scott, 2000; Davis and Johnsrude, 2003; for review
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see Rauschecker and Scott, 2009), and the involvement of brain areas outside primary auditory
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cortex (e.g. superior temporal cortex), has been convincingly demonstrated (for review see
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Price, 2010; Peelle, 2012). In particular, a series of studies have implied the left angular gyrus
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(situated in inferior parietal cortex; for recent review see Seghier, 2013) to serve a critical, if ill-
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understood, function in achieving speech comprehension (Obleser et al., 2007; Obleser and
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Kotz, 2010; Bonner et al., 2012; Clos et al., 2012; Erb et al., 2013; Golestani et al., 2013).

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For instance, Obleser et al. (2007) demonstrated that semantic predictability of degraded
speech (e.g., “She cooked him a heartyE meal”) not only allowed for a substantial gain in speech
comprehension (i.e., a predictability Tgain), but also increased task-related activity in a network of
left-hemispheric, heteromodal bPrain areas. Within this network, the left angular gyrus exhibited
the maximal effect. AdditionEally, the effective connectivity of left angular gyrus with the other
areas appeared particuClarly increased when comprehension was likely to succeed (i.e., in
degraded but highlyC predictable speech). Moreover, patient studies implied a general relevance
of the angularA gyrus for sentence comprehension (Dronkers, 2004) and imaging data
demonstrated an engagement of the angular gyrus when healthy subjects had to recover
meaning in (pseudo-)word comprehension (Raettig and Kotz, 2008). Hence, it is not a question
of whether but rather of how the angular gyrus comes to support speech comprehension.
The above cited evidence supports a view where angular gyrus has access to higher-level
semantic and/or combinatorial knowledge (i.e., semantic memory) and is especially geared to
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draw on this knowledge when in need of enhancing or even superseding the degraded
perceptual evidence (Binder et al., 2009). In sum, the reported studies show that semantic
processing as the cognitive act of accessing stored knowledge about the world (Binder et al.,
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2009) engages, among others, the left angular gyrus.
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It is in line with such a framework that high semantic predictability most effectively improves
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speech comprehension at intermediate levels of degradation (e.g., Pichora-Fuller, 1995;
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Stickney and Assmann, 2001). If, on the one hand, the amount of acoustic–phonetic evidence is
too sparse (e.g., with 1-band vocoding, see Davis et al., 2011; StSrauss et al., 2013), semantic
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predictability cannot facilitate comprehension to substantial degrees, as no semantic cues can
be reliably extracted. If, on the other hand, speech compreNhension without context is already at
ceiling under ideal listening conditions, there is oAbviously nothing to gain in terms of
predictability. Most interestingly for the present studMy, angular gyrus activation has been found to
match this behavioral pattern well (Obleser et al., 2007). Thus, intermediate levels of

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degradation both yield most behavioral dynamic range for gains from semantic predictability, and
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most neural dynamic range for angular gyrus involvement (for review see Price, 2010, Obleser,
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2014).
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However, it remains unclear whether left angular gyrus involvement truly reflects a
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necessary neurocomputational stage that precedes comprehension, or whether its activation in
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functional imaging studies rather reflects an epiphenomenal outcome of successful
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comprehension. Therefore, the present study used repetitive transcranial magnetic stimulation
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(rTMS) to interrupt normal angular gyrus functioning while listeners tried to comprehend
degraded sentences (e.g. noise-vocoded speech; Shannon et al., 2005; Erb et al., 2013).
We employed the k-factor (Boothroyd & Nitrouer, 1988) as a measure that directly
expresses the predictability gain that results from context. To quote its inventors, the k-factor
“expresses the effect of context as the ratio of the logarithms of the error probabilities for the
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context and no-context situations” (p. 102). k is dimensionless and, critically, has the desirable
features of being independent of overall level of performance, the degree, or the type of
degradation (see below for details).
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Our main hypothesis was that the behavioral gain in comprehension that listeners draw
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from degraded, yet predictable speech (i.e., the predictability gain) necessitates angular gyrus
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involvement. Accordingly, an rTMS-induced interference should abolish or reduce the behavioral
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predictability gain (see Figure 1D). We here demonstrate that this is the case, and specifically
that rTMS reduces the predictability gain at a medium degradSation level of 4-band noise
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vocoded speech but rather disrupts sentences with low-predictable endings when the
intelligibility of the sentence increases. Together, our resultsN demonstrate a finely tuned interplay
of angular gyrus’ functional integrity, degradation severiAty, and the resulting predictability gain.
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2. Material and Methods
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2.1. Subjects
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Fifteen native German speakers (4 females, age range: 20-31 years, mean age: 24.8 years) with
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no history of psychiatric, neEurological or hearing disorders participated in the study. All subjects
were right-handed (meCan laterality index 0.97 ± 0.09 SD, according to the Edinburgh
Handedness Inventory; Oldfield, 1971) and experienced with TMS but naïve to noise vocoded
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speech. ParticipAants were paid 8 € per hour. Writte n informed consent was obtained before the
experiments. The study was performed according to the guidelines of the Declaration of Helsinki
and approved by the local Ethics Committee of the Medical Faculty of the University of Leipzig.
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2.2. Experimental procedures
This study used a 2 × 5 × 2 within-subject factorial design including the factors (1T) semantic
content (high- vs. low-predictability), (2) quality of the audio signal (noise vocodiPng level: 2-, 4-,
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8-, 16- and 32-band noise vocoded) and (3) rTMS site (angular gyrus (AG) vs. superior parietal
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lobule (SPL), with the latter serving as control site). Participants underwent two sessions during
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which rTMS was either applied to the angular gyrus or superior parietal lobule in
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counterbalanced order. Both sessions were performed at least 14 days apart to prevent carry-
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over effects from the rTMS procedures and avoid learning effects with the stimulus material. The
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same set of 200 sentences was presented auditorily in both sessions with a different
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randomization and vocoding level within each session.
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Prior to the experiment, subjects had a training of 10 trials that were not included in the

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main experiment (Figure 1A). Across the whole procedure, participants were seated comfortably
in an upright position facing a 15” LCD Emonitor at a distance of approximately 100 cm depicting
either a fixation cross or a green tTraffic light (Figure 1B). Neuronavigated TMS (Brainsight 2,
Rogue Research, Montreal) waPs used for stereotactical coil placement over the left AG or SPL
(Figure 1C). To prevent heEad movements, the subject’s head was fixated bilaterally with the
TMS coil (mounted on Can adjustable arm) on the left side and another arm with a head rest
(Manfrotto 244, CaCssola, Italy) on the right side. Note that after positioning, the coil remained
fixed across thAe whole procedure with its position being visualized on the screen of the
neuronavigation software. If necessary, the position of the coil was corrected by modifying the
adjustable arms’ alignment. Subsequently, the experiment started and subjects were asked to
listen to and repeat binaurally presented noise vocoded sentences. During each trial, a green
traffic light appeared on the screen at keyword onset (i.e., simultaneous with the acoustic onset
of the sentence-final word), indicating that the sentence should be repeated as quickly and as
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accurately as possible. At the same time, a short burst of 5 stimuli of 10 Hz rTMS was applied
over either the AG or SPL (Figure 1B), leading to a total of 1000 rTMS pulses in each session.
Given the variable sentence length and the randomized presentation of the stimuli, the inter-
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stimulus interval could not be anticipated. Applying online rTMS bursts with keyword onset was
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conceived to maximally interfere with the integration of the final keyword into the sentence
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context. It should thus selectively affect the behavioral predictability gain of high-predictability
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sentences, particularly so at a medium degradation level. Note that online rTMS is thought to
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acutely interfere with task processing for the duration of the stimulation period (i.e., 500 ms in
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our study; Hartwigsen & Siebner, 2012). Stimuli were applied via in-ear headphones (SE215,
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Shure, Niles, IL) providing approximately 30 db anti-noise shield against the rTMS evoked noise.
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A dynamic microphone (F-V220, Sony, Tokyo) inA combination with an internal PCI sound
card (SB X-Fi, Creative Technology Ltd., Jurong MEast) was used to record responses for 5
seconds during each trial. Stimulus presentation and response recording was controlled via

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presentation software (Neurobehavioral Systems; Albany, CA, version 16). After 100 trials, a
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short break of about 10 min was included. Participants did not receive any feedback about the
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accuracy of their responses. The whole experiment had a duration of about 90 minutes.
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2.3. Stimulus materCial
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The stimulus set consisted of 200 spoken sentences of the German SPIN (speech intelligibility in
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noise) set (Erb et al., 2012; Kalikow et al., 1977). Each sentence included 4–9 words (mean 6.3
± 0.95 SD) and 8–12 syllables (mean 10 ± 0.83 SD) and had a duration of 1574–2737 ms (mean
2109 ± 217.5 SD). The last word of each sentence served as keyword. Sentences were
structured such that it was either easy to predict the final word (high-predictability condition, e.g.
“The storm broke the sailboat’s mast.”) or unlikely to predict the final word (low-predictability
condition, e.g. “The old man thinks about the mast.”). Keywords comprised 1–2 syllables (mean
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1.55 ± 0.5 SD) and had a duration of 248–670 ms (mean 459 ± 81.9 SD). In total, this study
utilized 100 different keywords yielding 200 sentences (100 high-predictability vs. 100 low-
predictability sentences).
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Sentences were spoken by a professional female speaker and recorded in a soundproof
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chamber onto a PC using an A/D converter at 44.1 kHz and 16 bit resolution. Sentence audio
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files were cut at zero-crossings, down-sampled off-line to 22.05 kHz, and normalized with
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respect to average root-mean-squared amplitude. Each sentence was noise-vocoded (Shannon
et al., 1995) using Greenwood’s cochlear formula (Greenwood,S 1990) in Matlab 7.11 (The
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Mathworks, Inc., Natick, MA). For full details of the noise-vocoding algorithm see Erb et al.
(2012). In short, noise vocoding reduced the spectral inNformation in the signal to varying,
arbitrary degrees (depending on the number of bands uAsed) while the slow temporal cues of the
amplitude envelope remain intact (Rosen, 1992). TMhe intelligibility of the stimulus increases with
increasing numbers of bands, and this manipulation has been widely used in neuroimaging

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studies of speech comprehension (e.g., Davis et al., 2003; Scott, 2006; Obleser et al., 2007; Erb
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et al., 2013).
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Previous studies (e.g., Obleser et al., 2007; Obleser and Kotz, 2010; McGettigan et al.,
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2012) have demonstrated that the degradation levels where listeners would draw the most
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benefit from semantic cues (i.e., the most predictability gain) were in the range of 4- to 8-band
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noise vocoding. To cover these levels within our noise vocoded stimuli, we created 5 versions of
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each sentence (2-, 4-, 8-, 16- and 32-band noise vocoded).
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For each session, different trial sets were constructed via stratified block randomization
such that each noise vocoding band was represented by 40 sentences (20 high-predictability vs.
20 low-predictability sentences) in each session, leading to 200 sentences (or, trials per session)
for the whole study.
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2.4. Repetitive Transcranial Magnetic Stimulation (rTMS)
Neuronavigated rTMS was performed by using the mean Montreal Neurological InstTitute (MNI)
coordinates determined from two previous studies (i.e., angular gyrus: x, y, z= -4P6, -60, 34 mm
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(Obleser et al., 2007); superior parietal lobule: x, y, z= -34, -42, 70 mm (Blair et al., 2012); Figure
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1C). Before the experiment, a high-resolution MRI scan of the whole brain was acquired for each
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subject using an MPRAGE sequence in sagittal orientation (voxel size= 1x1x1.5 mm; TR=1.3 s,
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TE= 3.46 ms). Individual rTMS sites were determined by calculating the inverse of the
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normalisation transformation and transforming these coordinates from standard to individual
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space for each subject in Matlab 7.7 (for a similar procedure, see Hartwigsen et al., 2010a,
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Hartwigsen et al., 2010b; Hartwigsen et al., 2012). To this end, individual T1-weighted images
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were segmented using the standard tissue probability maps provided in the Statistical

Parametric Mapping software (SPM8; http://www.fil.ion.ucl.ac.uk/spm/) implemented in MATLAB
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7.7 (Mathworks) (Friston et al., 1995)). Afterward, the resulting image was normalized and
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resampled to 1 x 1 x 1 mm3 voxels.
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Note that MRI-guided, neuPro-navigated stimulation yields a high spatial accuracy in the
range of a few millimetres (ESparing et al., 2008) and represents the method of choice for exact
placement and monitorCing of the coil throughout the TMS experiment (see Hartwigsen et al.,
2010c). C
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We chose left superior parietal cortex as control site since it did not show any significant
upregulation whatsoever during fMRI in our previous studies that used comparable stimulus
material (Obleser et al., 2007; Obleser and Kotz, 2010). Previous neuroimaging studies
suggested that left superior parietal lobe is mainly involved in tasks that require visuo-spatial
processing and (visuo-) spatial attention (Bushara et al., 1999; Cai et al., 2013). Moreover,
Braun et al. (2001) demonstrated stronger activation of this area during signing than speaking.