Cerebral Metabolic Changes During Visuomotor Adaptation Assessed Using Quantitative fMRI

Abstract

The brain retains a lifelong ability to adapt through learning and in response to injury or disease-related damage, a process known as functional neuroplasticity. The neural energetics underlying functional brain plasticity have not been thoroughly investigated experimentally in the healthy human brain. A better understanding of the blood flow and metabolic changes that accompany motor skill acquisition, and which facilitate plasticity, is needed before subsequent translation to treatment interventions for recovery of function in disease. The aim of the current study was to characterize cerebral blood flow (CBF) and oxygen consumption (relative CMRO₂) responses, using calibrated fMRI conducted in 20 healthy participants, during performance of a serial reaction time task which induces rapid motor adaptation. Regions of interest (ROIs) were defined from areas showing task-induced BOLD and CBF responses that decreased over time. BOLD, CBF and relative CMRO₂ responses were calculated for each block of the task. Motor and somatosensory cortices and the cerebellum showed statistically significant positive responses to the task compared to baseline, but with decreasing amplitudes of BOLD, CBF, and CMRO₂ response as the task progressed. In the cerebellum, there was a sustained positive BOLD response in the absence of a significant CMRO₂ increase from baseline, for all but the first task blocks. This suggests that the brain may continue to elevate the supply energy even after CMRO₂ has returned to near baseline levels. Relying on BOLD fMRI data alone in studies of plasticity may not reveal the nature of underlying metabolic responses and their changes over time. Calibrated fMRI approaches may offer a more complete picture of the energetic changes supporting plasticity and learning.

Keywords: calibrated fMRI; cerebral blood flow; functional MRI; motor adaptation; oxygen metabolism.

FIGURE 1

Schematic of the Serial Reaction Time task presentation, inter-stimulus intervals on the left indicate example times between trials. This figure shows an example of the presentation of the first three items of the 12-item sequence. Participants responded to each star position using a handheld 4-button response box.

FIGURE 2

Average [mean ± standard error of the mean (SEM)] response accuracy per block (A), and average response latency (B) per task block. Error bars represent the standard error of the mean across participants. Blocks S1–S6 represent the 6 sequence blocks, responses to these blocks were the focus of the analysis. Blocks R1, R2, and R3 (shown in red) represent pseudorandom sequence blocks.

FIGURE 3

Maps (A–C) show the mean BOLD signal response to the task across all subjects and sequence blocks (green), the CBF response (blue), and regions with overlapping BOLD and CBF task-related signal increases from rest (red). Maps (D–F) show areas of BOLD signal decrease over time during the SRT task (green), decreasing CBF responses (blue) and overlapping BOLD and CBF signal decreases across the task. Random blocks were not included in this analysis.

FIGURE 4

Plots showing the mean ± SEM responses for each task block in the global mean reduction ROI shown in Figure 3F. S1 = SRT sequence block 1, R1 = pseudorandom block 1. Y = Yes to indicate statistically significant (p < 0.05), signal changes from baseline and between first and second and first and last SRT blocks. BOLD and CBF showed significant increases from baseline across all blocks except the final sequence block S6. CMRO₂ was significantly higher than baseline in the first sequence block only. For BOLD, CBF, and CMRO₂, there were significant reductions in the responses between the first and second and first and last sequence blocks.

FIGURE 5

Mean ± SEM SRT task responses in M1. Plots show a mean reduction in BOLD and CBF across task blocks. S1 = SRT block 1, R1 = random block 1. Y = Yes to indicate statistically significant (p < 0.05), signal changes from baseline and between first and second and first and last SRT blocks. BOLD and CBF showed significant increases from baseline across all sequence and pseudorandom task blocks. There were also significant reductions in BOLD and CBF between sequence blocks S1 and S2 and S1 and S6. The CMRO₂ was significantly elevated from baseline across all blocks except squence blocks S2 and S6. There was also a significant reduction in CMRO₂ between S1 and S6.

FIGURE 6

Mean ± SEM SRT task responses in S1. Plots show a mean reduction in BOLD and CBF across task blocks. S1 = SRT block 1, R1 = random block 1. Y = Yes to indicate statistically significant (p < 0.05), signal changes from baseline and between first and second and first and last SRT blocks. BOLD and CBF showed significant increases from baseline across all sequence and pseudorandom task blocks, except S6. There were also significant reductions in BOLD and CBF between sequence blocks S1 and S2 and S1 and S6. There was a sustained CMRO₂ increase across all random blocks and the first, fourth and fifth sequence blocks but CMRO₂ was not different from baseline in the second, third or final sequence blocks. As in M1, there was only a significant difference between S1 and S6 in CMRO₂.

FIGURE 7

Mean ± SEM SRT task responses in the cerebellum. Plots show a mean reduction in BOLD and CBF across task blocks. S1 = SRT block 1, R1 = random block 1. Y = Yes to indicate statistically significant (p < 0.05), signal changes from baseline and between first and second and first and last SRT blocks. BOLD and CBF showed significant increases from baseline across all sequence and pseudorandom task blocks, except S5 and R3 for BOLD, and R3 for CBF. There were also significant reductions in BOLD and CBF between sequence blocks S1 and S2 and S1 and S6. CMRO₂ increases from baseline were only detected in the first sequence blocks and there were significant reductions from S1 in S2, and S6.