Eleonora Patitucci1, Michael Germuska1, James Kolasinski1, Valentina Tomassini1,2,3, and Richard G Wise1,2
1CUBRIC, Cardiff University, Cardiff, United Kingdom, 2Institute for Advanced Biomedical Technologies (ITAB), Department of Neurosciences, Imaging and Clinical Sciences, University of Chieti-Pescara, Chieti, Italy, 3MS Centre, Neurology Unit, SS. Annunziata University Hospital, Chieti, Italy
Synopsis
Functional MRI can detect modifications
in the brain’s resting state with learning-related behavioural improvements. However,
the impact of learning on local cerebral blood flow after task execution remains
unclear. Here we investigate changes in CBF after the execution of a motor task
and demonstrate a sustained increase in resting CBF that is localised in
regions relevant for the learning of the task. Our results show that learning induces
sustained changes of local cerebral blood flow (over a timescale of minutes).
Introduction
Motor tasks during fMRI have been
extensively used to probe neuroplasticity1,2. Changes in BOLD
resting state signal fluctuations following motor training have been observed3,
suggesting a sustained pattern of altered neuronal activity and/or
microvascular function for a period of time following the cessation of a motor
task. Although studies have employed arterial spin labelling (ASL) techniques
to study fluctuations in resting state CBF4-9, evidence for
sustained changes in brain perfusion following the learning of a motor task
remains incomplete.
Here, we investigate voxel-wise changes in CBF following 10 minutes of motor
learning task in order to test the hypothesis that sustained changes in
CBF occur to support changes in energy demand, under the assumption of a stable
neurovascular coupling10; these
changes in CBF would subserve task-related neural plasticity or
represent microvascular plasticity.Methods
Healthy volunteers underwent two 3T
MRI (Siemens Prisma) sessions (“task” and “control”) a week apart (Fig. 1).
Participants were randomised to start with the “task” or with the “control”
session; half of the participant did the task session first, while the other
half did the control session first.
At each session, structural (T1-weighted
scan, 1mm isotropic, 200 slices, TR/TE = 2100/3.24ms) and perfusion (a
dual-excitation pseudo-continuous arterial spin labelling acquisition; TE1:
10ms, TR1: 3600ms, TE2: 30ms, TR2: 800ms, labelling duration: 1.5s,
post-labelling delay: 1.5s, slice thickness: 7mm, and GRAPPA acceleration
factor 3) images were acquired. During the “task” session, participants were
asked to perform a motor learning task; during the “control” session, they were
asked to lay still in the scanner. FEAT (https://fsl.fmrib.ox.ac.uk/) was used
to fit a linear model to the voxel-wise data in order to produce maps of
significant task related CBF activation.
CBF maps of resting periods (before
and after the task periods in both sessions) were created from the TE=10ms data
and converted to units of ml/100g/min using BASIL toolbox11. For each subject, the CBF map of post-task
resting period was subtracted from the CBF map of the pre-task resting period to
estimate differences in CBF following the task. Permutation testing
(FSL-RANDOMISE) was used to investigate differences between conditions (“task” vs. “control”) in the resting post-task
(rest 2) vs. pre-task (rest 1) CBF maps
at a voxel-wise level.
During the “task” session,
participants practised a motor task while perfusion data acquisition continued
(Fig. 1). They used an
MRI-compatible right hand 5DT Data Glove 16 MRI (https://5dt.com/5dt-data-glove-ultra/) with fibreoptic sensors to control the size of a green circle (participant
controlled), which they had to match to
the size of a white circle (target) by squeezing their hand into a fist. The
white circle expanded and contracted in a fixed sequence. A temporal Pearson’s correlation between the diameter
of the white circle (pre-fixed sequence) and the diameter of the green circle
drawn by the participant’s fist (behavioural response) was calculated. A
one-way ANOVA was performed with the correlation index as the dependent
variable and each block of the experiment as the independent variable.Results
We recruited 20 participants, who
were 27.5±3.8 years old; 11 were female.
There was an increasing temporal
correlation between the size of the target circle and the size of the participant
controlled circle (F(1,9)
= 10.89, p < 0.001) (Fig. 2), indicating improvement of
performance with task practice. Most of the improvement occurred during the
first 3 blocks of sequence repetition.
Main
areas of positive CBF responses to the task were found bilaterally in the
postcentral gyrus, inferior occipital cortex, superior parietal lobule,
cerebellum (lobules V-VI) and left precentral gyrus (Fig.
3).
We
observed an increase in resting CBF in the 8-minute period post “task” compared
to the same period post “control” (Fig. 4) suggesting that the observed changes
were due to the performance of the task rather than an effect of time. Areas
with significantly increased resting CBF (on average 15.8%) following
completion of the task included the cerebellum (bilaterally crus I, lobules VIII,
right V-VI lobules), the inferior temporal gyri, the supramarginal gyri, the right
angular gyrus, the precentral gyri, the right postcentral gyrus, visual cortex
(V5) bilaterally (Fig. 4).Discussion/Conclusion
We demonstrated a sustained and localised
increase in resting CBF after the completion of motor learning task. The
increase was measured over a period of 8 minutes and localised in functional
regions that were relevant for the task performance. This increase in CBF may reflect
a task-related change in local neural activity as a result of increased energy
supply and/or an initial stage of microvascular plasticity. It remains to be
investigated how long the elevated post-task CBF lasts, the specificity of its
association with motor learning and whether it subserves long term brain
plasticity.Acknowledgements
The study was funded by the
Wellcome Trust.
References
-
Mozolic, J. L., Hayasaka, S., & Laurienti, P. J. (2010).
A cognitive training intervention increases resting cerebral blood flow in
healthy older adults. Frontiers in Human Neuroscience, 4(March),
1–10. https://doi.org/10.3389/neuro.09.016.2010
- Thomas,
A. G., Marrett, S., Saad, Z. S., Ruff, D. A., Martin, A., & Bandettini, P.
A. (2009). Functional but not structural changes associated with learning: An
exploration of longitudinal Voxel-Based Morphometry (VBM). NeuroImage, 48(1),
117–125. https://doi.org/10.1038/jid.2014.371
- Albert, N. B., Robertson, E. M., Miall, R. C., & Hall, G.
(2009). The Resting Human Brain and Motor Learning. Current Biology, 19(12),
1023–1027. https://doi.org/10.1016/j.cub.2009.04.028
- Biswal, B. B., Kylen, J. Van, & Hyde, J. S. (1997).
Simultaneous Assessment of Flow and BOLD Signals in Resting-State Functional
Connectivity Maps. NMR in Biomedicine, 10, 165–170
- Chuang, K., Gelderen, P. Van, Merkle, H., Bodurka, J.,
Ikonomidou, V. N., Koretsky, A. P., … Talagala, S. L. (2008). Neuroimage, 40, 1595–1605.
https://doi.org/10.1016/j.neuroimage.2008.01.006
- Fukunaga, M., Horovitz, S. G., Zwart, J. A. De, Gelderen, P.
Van, Balkin, T. J., Braun, A. R., & Duyn, J. H. (2008). Metabolic origin of
BOLD signal fluctuations in the absence of stimuli, JCBFM, 1377–1387. https://doi.org/10.1038/jcbfm.2008.25
- Liang, X., Zou, Q., He, Y., & Yang, Y. (2013). Coupling
of functional connectivity and regional cerebral blood flow reveals a
physiological basis for network hubs of the human brain, PNAS, 110(5),
1929–1934. https://doi.org/10.1073/pnas.1214900110
- Viviani, R., Messina, I., & Walter, M. (2011). Resting
State Functional Connectivity in Perfusion Imaging : Correlation Maps with BOLD
Connectivity and Resting State Perfusion. PLoS ONE, 6(11). https://doi.org/10.1371/journal.pone.0027050
- Zou, Q., Wu, C. W., Stein, E. A., Zang, Y., & Yang, Y.
(2009). Static and Dynamic Characteristics of Cerebral Blood Flow during the
Resting State. NeuroImage, 48(19), 515–524. https://doi.org/10.1016/j.neuroimage.2009.07.006.Static
- Iadecola, C.
(2017). The Neurovascular Unit Coming of Age: A Journey through Neurovascular
Coupling in Health and Disease. Neuron, 96(1), 17–42. https://doi.org/10.1016/J.NEURON.2017.07.030
11.
- Chappell, M. A.,
Groves, A. R., Whitcher, B., & Woolrich, M. W. (2009). Variational Bayesian
Inference for a Nonlinear Forward Model. IEEE Transactions on Signal
Processing, 57(1), 223–236