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Cerebral Cortex
doi:10.1093/cercor/bht206
Address correspondence to Stéphane Perrey, Movement to Health (M2H), Montpellier-1 University, EuroMov, 700 Avenue du Pic Saint-Loup, 34090
Montpellier, France. Email: stephane.perrey@univ-montp1.fr
Sustained attention is fundamental for cognition and when impaired, (2005) stressed that the more cognitively demanding the task,
impacts negatively on important contemporary living skills. Degra- the higher the magnitude of these antagonistic patterns. In
dation in sustained attention is characterized by the time-on-task response to the TOT effect, marked increases (Paus et al. 1997;
(TOT) effect, which manifests as a gradual increase in reaction time Fairclough et al. 2005; Weissman et al. 2006; Yarkoni et al.
(RT). The TOT effect is accompanied by changes in relative brain 2009) and decreases (Paus et al. 1997; Coull et al. 1998; Lim
activity patterns in attention-related areas, most noticeably in the et al. 2010) in activity are evident in attention-related cortical
prefrontal cortex (PFC) and the right parietal areas. However, activity areas. In one particularly relevant study, Weissman et al.
changes in task-relevant motor structures have not been confirmed (2006) investigated the trial-by-trial relationship between fMRI-
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stimulus. Through such an approach, we were able to focus on
the neural correlates of motor preparation throughout the evol-
ution of the TOT effect. In the second experiment, functional
near-infrared spectroscopy (NIRS) was exploited to investigate
the time course of the changes in activity of the cortical motor
areas, PFC, and right parietal areas throughout the same sus-
tained attention RT task. NIRS facilitates the investigation of
cortical neural activity during hand movements in natural
environmental settings which are comfortable and natural for
subjects. This particular experiment allowed us to confirm pre-
vious results described in the literature regarding activity of
attention-related areas as well as capturing any changes in the
activity of relevant motor areas.
Figure 2. ( A) Neuromuscular tests (NMT). M and H represent the neural stimulation pulses performed at the intensity generating the M-wave and the superimposed H-reflex
responses, respectively. MVC, maximal voluntary contraction. (B) Time course of NIRS and TMS protocols. Protocol events are 1: Warming-up. 2: Resting period. 3: Familiarization
through 1 min of sustained attention. 4: pretask NMT. 5: NIRS experiment = pretask resting period; TMS experiment = pretask TMS. 6: Sustained attention task for 32 min. 7:
NIRS experiment = post-task resting period; TMS experiment = post-task TMS. 8: post-task NMT. The thin black arrows in NIRS experiments represent the NIRS events,
delineating the resting state periods and the task and each 5 min of the task. In TMS experiment, the thick gray arrows represent 4 TMS pulses without any contraction and the
thick white arrows represent 4 TMS superimposed pulses (with voluntary contractions at 10% MVC).
Cerebral Cortex 3
MRI, for example, in this case a sitting position, which is less suscep- Intensity was decreased by 5 mA, until the maximum amplitude of the
tible to drowsiness than supine (Kräuchi et al. 1997). Further, NIRS Hsup (IHsup) was obtained.
allows subjects to perform tasks free from disturbance from scanner
noise (in the case of MRI) and represents therefore a suitable technique Transcranial magnetic stimulation. Single TMS pulses of 1-ms
for the investigation of focused attention. Functional NIRS utilizes, as duration were delivered using a Magstim 200 (Magstim, Whitland, UK)
fMRI, the tight coupling between neuronal activity and regional cer- via a figure-of-eight coil (double 70 mm-diameter coil, maximum
ebral blood flow (Villringer and Dirnagl 1995) to measure regional output intensity 2.2 T). The coil was positioned over the right-hand
hemodynamic concentration changes in oxyhemoglobin (O2Hb) and cortical representation of left motor cortex according to the C3 point of
deoxyhemoglobin (HHb) in the brain. By placing a pair of probes— the 10-10 EEG system. The position was then adjusted in small
consisting of an emitter of near-infrared light and a receptor—the rela- amounts by moving the coil in the sagittal and coronal planes until the
tive local changes in the absorption and scattering of photons can be largest MEP was elicited in the right APB at 50% of the maximal
measured. These changes allow one to infer the relative local changes stimulator power output. The coil was held in position by straps
in hemoglobin state. Simulations have demonstrated (Hauessinger surrounding a metallic spindle mounted on a mechanical arm with 6
et al. 2011 that the mean penetration depth of the photons for an inter- degrees of freedom. Markers were positioned both on the subjects and
optode distance of 3.5 cm in adults is 23.6 ± 0.7 mm and it follows a the coil to precisely locate the position of the coil. An investigator
banana-shaped pathway. For more details about the basic principles of remained during the experiment behind the subject to ensure that the
NIRS, please refer to the recent review of Ferrari and Quaresima coil did not move (as could be assessed via relative movement between
(2012). the markers on the subject and the coil). To determine the TMS
NIRS measurements were performed using a continuous wave intensity of stimulation for each subject, individual recruitment curves
multichannel system (Oxymon Mk III, Artinis, The Netherlands). The were derived by gradually increasing the TMS intensity in steps of 10%
sampling rate was set to 10 samples per second. This particular device of the maximal stimulator power output. This process began at 50% of
measured changes in optical density at 2 different wavelengths in the the stimulator output and executed 4 stimulations per intensity with an
Statistical Analysis
Statistica software (version 7.0, Statsoft, Oklahoma, USA) was used for
all analyses. All data were examined for normality and homogeneity of
variance using Skewness, Kurtosis, and Brown–Forsythe tests. A 1-way
repeated-measure ANOVA was used to test for any significant effect of
time (1, 9, 14, 19, 24, and 29 min) on the changes in RT with a categori-
cal factor (experiment, NIRS vs. TMS) to test for any divergence
between the TOT effect on the RT during both experiments. Also, a
1-way repeated-measures ANOVA was used to test for any significant
effect of time (1, 5, 10, 15, 20, 25, and 30 min) on the changes in
Δ[O2Hb] over the lPFC, rPFC, mPFC, lPMC, lM1, and right parietal
areas. When appropriate, the Fisher’s LSD post hoc test was used to
detect paired differences. Due to multiple comparisons, we applied a
strict 0.008 alpha level of significance (after Bonferroni correction) in
the ANOVA performed on the NIRS data. Nonparametric Friedman
ANOVA was performed to test for the significant effect of time
( pretask, 1, 5, 10, 15, 20, 25, 30 min, and post-task) on the changes in
MEP amplitude during the TMS experiment. The same Friedman Figure 3. Evolution of reaction time over time during a sustained attention RT task of
ANOVA test was performed to test for the significant effect of time on 30 min. Significant increase in RT occurred after 9 min of task compared with RT
the changes in MEP amplitude during the control experiment as well. values of the first minute of task. ***P < .001; *P < 0.05. Vertical bars represent SD.
When appropriate, the Conover’s post hoc test was used to detect
paired differences. Student’s t-test was used for paired samples to test
for pretask to post-task differences in M, Hsup/M, MEPsup/M, MEP/M,
MEPsup/Hsup, SP duration, and MVC. Student’s t-test was also used Table 1
for groups to compare the RPE measured after the NIRS and TMS Comparison of pre- and post-task NMT and TMS variables
experiments. The significance level was set at P < 0.05. Data are pre-
sented mean ± standard deviation (SD). Variables Pretask Post-task P-value
MVC (N) (n = 27) 73.79 ± 44.9 62.4 ± 38.1 0.39
M amplitude (mV) (n = 22) 8.52 ± 3.29 8.49 ± 3.5 0.98
Hsup/M (mV) (n = 19) 0.19 ± 0.09 0.22 ± 0.1 0.43
Results MEPsup/M (mV) (n = 13) 0.65 ± 0.23 0.71 ± 0.29 0.57
MEPsup/Hsup (mV) (n = 12) 3.61 ± 2.19 3.67 ± 2.03 0.95
RT and RPE data MEP/M (mV) (n = 13) 0.20 ± 0.15 0.24 ± 0.18 0.53
SP duration (ms) (n = 13) 216.87 ± 41.29 218.3 ± 43.76 0.93
As expected, the results did not show any significant difference
between groups (i.e., from NIRS and TMS experiments) with Results represent mean±SD. The P-values are these of the t-tests.
Cerebral Cortex 5
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Figure 4. Evolution of NIRS signals over time during a sustained attention RT task of 30 min. *P < 0.05 after Bonferroni correction. Gray traces represent Δ[O2Hb] changes.
Significant changes are the results of post hoc tests and horizontal bars represent comparisons with cortical activation after 1 min of task over the respective area (except for the
mPFC where the significant changes are compared with the cortical activation after 5 min of task). Black circles represent the cortical areas investigated by the NIRS probes.
Vertical bars represent SD.
TMS
A significant increase in MEP amplitude was observed over
time for the TMS group (Fr (13, 8) = 38.31, P < 0.001) but not
for the control subjects (Fr(4, 8) = 5.33, P = 0.72). These results
are presented in Figure 5. The Student’ t-tests for paired
samples showed no significant difference between the pretask
and the post-task in MEPsup/M (t = 0.58, P = 0.57), MEP/M
(t = 0.64, P = 0.53), MEPsup/Hsup (t = 0,07, P = 0.95), and SP
duration (t = 0.08, P = 0.93). These results are presented in
Table 1.
Discussion Figure 5. Evolution of the largest motor evoked potential (MEP) amplitude over time
during a sustained attention RT task of 30 min (experimental group) and at rest (control
The aim of this study was to highlight how the activity of group). **P < 0.01. Significant changes are the results of post hoc tests and
motor structures, in concert with attention-related cortical horizontal bars represent comparisons with pre- and post-task MEP amplitude values.
areas, adapts to the occurrence of the TOT effect. Our exper- Vertical gray dotted lines delimit the beginning and the end of the sustained attention
imental design produced a TOT effect after, on average, 9 min RT task. Pretask and post-task values were measured in the 2 min before, and in the 1
min after the task, respectively. It should be noted that post-task MEP values of the
of sustained attention as revealed by the significant increases
experimental group returned to the baseline level (i.e., the pretask values) and no
in RT (P < 0.001). Our measurements and analysis demonstrate significant difference was found between pre- and post-test MEP values (P > 0.05).
a significant increase (P < 0.05) in NIRS-measured lateral PFC This finding highlights a link between the act of sustaining attention and the rise in
(right and left) and right parietal areas activity concomitant MEP amplitude. Vertical bars represent SD.
Cerebral Cortex 7
This suggests that the increase in MEP amplitude may be the cortical area, in response to the TOT effect occurrence during a
product of an increase in cortical neurons excitability and/or in sustained attention RT task. As it has been previously proposed
spinal neurons excitability (for review, see Reis et al. 2008). As for some attention-related areas, we suggest that these motor
the timing of increase in amplitude for both the MEP and the structures undergo increased activation because they have to
NIRS-measured Δ[O2Hb] over the M1 area (i.e., 15 min of task) cope with the increasing task demand. We report that the in-
are similar, one may suppose that the excitability was mainly in- creased CSE and M1 activity occurs significantly later than the
creased at the cortical level. However, H-reflex results in increase in lateral PFC and the right parietal areas activity (for
humans (e.g., Schiepatti 1986) and intraspinal neural recordings this task) which suggests that the motor structures are only re-
in monkeys (e.g., Fetz et al. 2002) reported a facilitatory effect of cruited at a later stage of the process. To the best of our knowl-
motor preparation on spinal neurons activity. Further, it is edge, this study is the first to approach the question of the
notable that the NIRS-measured M1 activation resulted, in part, adaptations of the motor structures to lapses in attention. This
from the neuronal activation related to the execution of the work answers and opens new questions as regards the adap-
motor response as well (i.e., it did not arise only as a result of tation of motor structures’ activity to the observed rise in RT
the motor preparation neural activity). The hypothesis that there over time, the so-called TOT effect.
are motor preparation-related changes in spinal excitability after
15 min of task (maybe in parallel to the increase in M1 area
activity) cannot be totally excluded. Further investigations of the Funding
modulation of spinal excitability with the TOT are required to
This work was supported by the LabEx “Numerisation and
test this hypothesis. Because of differences in excitability of the
Modelisation for Health and Environment” (ANR-10-LABX-20-
Cerebral Cortex 9