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Table 1 Information summaries of studies focusing on associations between dynamic GABA modulation and behavior

From: MRS-assessed brain GABA modulation in response to task performance and learning

Author, year

Sample size

Strength

Coil

Sequence

Voxel (mm3)

Time Points

Metabolite/RC

Data analysis software

Task/intervention

Behavioral measures

Modulation and correlation

Perceptual performance and learning

     

Bang et al. 2018

24 H

3T

32-channel

MEGA-PRESS

PRESS

OCC 20 × 20 × 20

3 time points:

pre-, post-, 3.5 h post-learning

GABA

Glu/NAA

LCModel

An orientation detection learning task

(1) detection threshold

E/I modulation:

E/I ratio increased after reactivation and returned to baseline 3.5 h after reactivation

Bednařík et al. 2015

12 H

7T

Gradient/shim

sLASER

OCC 20 × 20 × 20

continuously measure during visual stimulation and rest

Glu

Lac

GABA/

LCModel

Red–black flickering checkerboard

No

GABA and Glu modulations:

GABA did not change significantly with visual stimulation

Glu increased with visual stimulation

Boillat et al. 2020

20 H (posBOLD)

21 H (negBOLD)

7T

quadrature coil

Semi-adiabatic SPECIAL

OCC 18 × 18 × 18

continuously measure during STIM and REST

GABA

Glu

La/water

Home-built MATLAB functions and LCModel

A full screen radial checkerboard (posBOLD)

A small central checkerboard (negBOLD)

No

GABA and Glu modulations:

GABA decreased during the stimulation of negBOLD

GABA did not change significantly during the stimulation of posBOLD

Glu decreased during the stimulation of negBOLD but increased during posBOLD

Frangou et al. 2018

Cohort 1:

SN 17H

FD 21H

cohort 2:

SN 17H

FD 21H

3T

32-channel

2D J-PRESS

Right OCT 25 × 25 × 25

2 time points:

Pre- and post-task

OCT and PPC 25 × 25 × 25

2 time points:

Pre- and post-task

GABA/tCr

ProFit

A radial or concentric Glass patterns learning task

(1) Learning rate of perceptual sensitivity (d’) across runs

(2) Change in perceptual sensitivity (d’)

(early vs late run)

GABA modulation:

GABA did not change significantly in either voxel

GABA correlation:

cohort 1:

(r = − 0.43, CI = [− 0.74, 0.07]) measure (1) in SN & OCT GABA change

(r = 0.54, CI = [0.05, 0.85]) measure (2) in FD—OCT GABA change

cohort 2:

(r = − 0.43, CI = [− 0.75, − 0.02]) measure (1) in SN—OCT GABA

(r = 0.55, CI = [0.10, 0.78]) measure (2) in FD—OCT GABA

Frangou et al. 2019

47 H

7T

32-channel

sLASER

Left OCT and PPC 20 × 20 × 20

4 time points:

baseline, first (block 1,2), second (3,4), third (5,6)

GABA

Glu/tCr

LCModel

A radial or concentric Glass patterns learning task

(1) Learning improvement in each block

(2) Individual biggest improvement

GABA modulation:

In OCT, GABA levels decreased in SN and increased in FD

In PPC, GABA levels increased in both SN and FD, no significant difference between tasks

GABA correlation:

(n = 16, r = − 0.43, CI = [− 0.75, − 0.02]) measure (2) in SN—OCT GABA change

(n = 19, r = 0.55, CI = [0.10, 0.78]) measure (2) in FD—OCT GABA change

Frank et al. 2022

13 Children

14 Adults

3T

64-channel

MEGA-PRESS

Early visual cortex

20 × 20 × 20

Continuously measure at pre-, during and post-training

GABA/NAA + NAAG

LCModel

An orientation detection learning task

(1) Detection threshold

GABA modulation:

GABA increased during visual training in children, and it persisted after training ended

GABA did not change significantly during visual training in adults

Heba et al. 2016

24 H

3T

32-channel

MEGA-PRESS

left and right SM1 30 × 30 × 30

2 time points:

Baseline, post-stimulation

GABA/water

Gannet

Repetitive somatosensory stimulation

(1) 2ptD changes before and after the stimulation

GABA modulation:

GABA did not change significantly after the perceptual stimulation

Ip et al. 2019

24 H

7T

32-channel

semi-LASER

OCC 20 × 20 × 20

4 time points:

Baseline, visual stimulation

(4 types)

GABA

Glu/water

MRspa

LCModel

Full field checkerboards with contrast (3.1%, 12.5%, 50%, and 100%)

No

GABA and Glu modulations:

GABA did not change significantly under different contrast levels as compared to baseline

Glu increased significantly in stimulation with 100% contrast as compared to baseline

Koush et al. 2021

20 H

4T

Single-channel quadrature coil

MRGA-STEAM

OCC and PCC

Continuously measure during visual stimuli and auditory emotion task

GABA

Glx

Lac/NAA

 

A flashing checkboard (OCC activation)

Identification of auditory emotion (PCC deactivation)

No

GABA and Glx modulations:

GABA decreased during visual stimuli but increased during identification of auditory emotion task

Glx increased during visual stimuli but did not change during identification of auditory emotion task

Kurcyus et al. 2018

30 H

3T

12-channel

MEGA-PRESS

OCC 25 × 25 × 25

3 time points:

In eye closed

In open in dark

In open with stimuli

GABA

Glx/Cr

Gannet

LCModel

An increasing visual input task

(1) Discrimination threshold

GABA and Glx modulations:

GABA decreased significantly from eye-closed to eye-open state

GABA did not change significantly with visual checkerboard stimuli

Glx increased with visual checkerboard stimuli

GABA correlation:

[r (23) = − 0.54, p = 0.008] measure (1) and GABA with visual checkerboard stimuli

Lea-Carnall et al. 2020

14 H

3T

8-channel

MEGA-PRESS

Left S1 20 × 30 × 20

2 time points:

First 12 m of tactile stimulation, last 12 m of tactile stimulation

GABA

Glx/NAA

jMRUI

AMARES

Tactile stimulation at resonance frequency (23 Hz)

tactile stimulation above resonance frequency (39 Hz)

(1) Tactile discrimination test

GABA and Glx modulations:

GABA decreased in response to above-resonance stimulation

GABA did not change significantly in response to at-resonance stimulation

Glx did not change significantly in both stimulation frequencies

Lin et al. 2012

10 H

7T

16-channel

STEAM

OCC 20 × 20 × 20

3 time points:

Rest, stimuli, recovery

GABA

Glu

NAA/water

jMRUI

LCModel

A visual perceptual task

No

GABA and Glu modulations:

GABA decreased under visual stimulation but did not reach significance and back to resting state in recovery

Glu increased during the visual stimulation and back to rest state in recovery

Lunghi et al. 2015

19 H

7T

16-channel

sLASER

OCC, PCC 20 × 20 × 20

2 time points:

Pre- and post- monocular deprive

GABA/water/tNAA

LCModel

A binocular rivalry task (pre-, post-),

150 min monocular deprivation

(1) Mean duration (pre)

(2) Mean duration (post)

GABA modulation:

GABA decreased after monocular deprivation, in OCC not in PCC

GABA correlation:

(r = 0.62, p = 0.006) reduction of OCC GABA & increasement of the predominance of the dominant eye

Mangia et al. 2007

12 H

7T

Head gradient coil

STEAM

OCC 20 × 22 × 20

Continuously measure during visual stimulation on and off

Glu

Lac

GABA/water

LCModel

A radial red/black checkboard

No

GABA and Glu modulations:

GABA did not change significantly during the visual stimulation

Glu increased during the visual stimulation

Mekle et al. 2017

20 H

7T

Quadrature coil

SPECIAL

Right OCC

20 × 22 × 20

2 time points:

Active stimulation

Control stimulation

GABA

Glx/no

LCModel

Half of a rotating checkerboard in the form of a torus

No

GABA modulation:

GABA decreased in the active stimulation condition as compared to the control stimulation condition

Schaller et al. 2013

6 H (active)

4 H (control)

7T

quadrature coil

SPECIAL

OCC & POC

20 × 22 × 32

Continuously measure during visual stimulation on and off

GABA

Glu

Lac/no

FIDs

LCModel

A black–grey checkerboard

No

GABA and Glu modulations:

GABA did not modulate significantly

Glu increases within the first two minutes of the primary visual activation

Shibata et al. 2017

12 H (no-overlearning)

12 H (overlearning)

3T

32-channel

MEGA-PRESS

PRESS

OCC 20 × 20 × 20

Overlearning (3)

Pre-, post1, post2 Interference (2) pre-, between training 1 and 2

Glu/GABA/Cr

LCModel

An orientation detection learning task

(1) Detection threshold

E/I modulation:

The modulation of E/I was specific to learning and not to non-learning training

E/I increased in non-overlearning and decreased in overlearning 30 min after training

E/I returned close to baseline in both groups at 3.5 h after training

E/I correlation:

(r = 0.64, p = 0.024) E/I reduction and anterograde interference to training 2

van Vugt et al. 2020

25 H

3T

32-channel

PRESS

Left SM1 30 × 30 × 20

During task (16 min)

GABA

lactate/tNAA

FID-A

LCModel

An audio-motor mapping learning task

(1) Tracking error

GABA modulation:

GABA increased during motor learning

GABA correlation:

(r = − 0.49, p = 0.014) GABA increase & audio-motor learning

Ziminski et al. 2023

22 M

3T

32-channel

MEGA-PRESS

OCT & PPC

20 × 20 × 25

3 time points:

Baseline, pre-, post-training

GABA

Glu/water/NAA

MRspa

LCModel

A radial or concentric Glass patterns learning task (SN task)

(1) Task accuracy

GABA modulation:

It did not report

GABA and Glu correlations:

(r = − 0.60, p = 0.012) bigger reduction of OCT GABA and bigger behavioral progress

(r = 0.36, p = 0.154) no correlation between PCC GABA changes & behavioral progress

Motor performance and learning

     

Andrushko

et al. 2023

15 H

3T

32-channel

MRSI

Left M1, right M1,

Left SMA, right SMA

2 time points:

Before and after the force matching task

GABA

Glx/tCr

In-house scripts

A handgrip force matching task (right hand)

A response task

(1) Reaction times

GABA modulation:

GABA did not modulate significantly after the task

GABA correlation:

The faster measure (1) & larger decreased GABA levels in left M1, left SMA and right SMA respectively

The faster measure (1) & larger increased Glx levels in right M1

Bell et al. 2023

9 H

3T

32-channel

MEGA-PRESS

left SM1

25 × 25 × 25

Continuously measure through baseline and 6 blocks about 30 min

GABA

Glu

Glx/tCr

Gannet

LCModel

A serial reaction time task

(1) Reactions times

GABA and Glu modulations:

No significant modulation in GABA and Glu in either task

Glx correlation:

higher Glx levels in Block 1 & worse progress in block 6, median progress and progress of the best block

Chalavi et al. 2018

32 Y

28 O

3T

32-channel

MEGA-PRESS

OCC and left SM1

4 time points:

Day 1-pre

Day 1-post

Day 3-pre

Day 3-post

GABA/water

Gannet

A bimanual coordination task

(1) Initial error rate

(2) Retention error

GABA modulation:

OCC GABA decreased in random and increased in blocked group from pre- to post-training in combined YA and OA. The difference of GABA modulation following two schedules is significant in OA (p = 0.018, corrected), not in YA (p = 0.22, corrected)

OCC GABA levels decreased in the blocked group and increased in the random group from Day 1 to Day 3 in OA (p = 0.008, corrected) but not in YA (p > 0.1)

GABA correlation:

(t = 0.26, p = 0.021) measure (1) & baseline SM1 GABA levels

Chen et al. 2017

16 H

7T

32-channel

MM-eliminated MEGA-sLASER

Left SM1

15 × 20 × 30

Continuously measure during the 20-min task

GABA

Glx

NAA/tCr

In-house scripts

A hand clenching task

No

GABA modulation:

GABA levels slowly decreased (− 15 ± 2%) to a stable level

Glx levels increased (8 ± 2%) rapidly during the 10-min clenching period

Both of them recovered towards baseline during the rest period after clenching

Coxon et al. 2018

10 H

3T

32-channel

MEGA-PRESS

SM1, DLPFC

2 time points:

Pre-, post-exercise

GABA

Glx

/water,Cr,NAA

LCModel

High-intensity interval exercise

No

GABA modulation:

SM1 GABA increased post-exercise compared with the pre-measure

DLPFC GABA did not change significantly

Glx levels did not change significantly in both SM1 and DLPFC

Floyer-Lea et al. 2006

13 H

(learn)

10 H (move)

7 H (rest)

3T

coil: NS

MEGA-PRESS

Left SM1 20 × 20 × 20

Continuously measure during 30-min task and 20 min after task

GABA

Glx, Cr

NAA/Cr

LCModel

A force tracing task

(1) Tracking errors

GABA modulation:

Left SM1 GABA levels decreased (18%) during sequence learning and did not change in movement and rest condition. Right SM1 GABA levels did not change significantly

Left SM1 GABA levels recovered 40% of the maximum decrease during 20 min after stop learning

Kolasinski et al. 2019

11 H (learn)

12 H (move)

11 H (rest)

7T

32-channel

sLASER

Left SM1 20 × 20 × 20

Continuously measure through 6 blocks about 40 min

GABA/tCr

LCModel

A visually cued serial reaction time task

(1) Learning gain (RT)

(2) Best performance

GABA modulation:

In the learning group, SM1 GABA levels decreased significantly in the block 6 compared with the block 1, not in movement group and rest group

GABA correlation:

(r = 0.515, p = 0.049) measure (1) & block 1 GABA levels

(r = 0.613, p = 0.015) measure (2) & block 1 GABA levels

King et al. 2020

36 O

3T

32-channel

MEGA-PRESS

Right SM1 30 × 30 × 30

2 time points:

Pre-, post-learning

GABA/water

Gannet

A motor sequence task, anodal (1 mA, 15 min), sham tDCS

(1) Reaction times

GABA modulation:

GABA did not change significantly

GABA correlation:

SM1 GABA change & motor learning magnitude (r = − 0.41, p = 0.013), age (r = 0.45, p = 0.06), and baseline GABA (r = − 0.51, p = 0.001)

Maddock et al. 2016

38 H

3T

32-channel

MEGA-PRESS

PRESS

OCC, ACC 30 × 25 × 25

2 time points:

Pre-, post-exercise

GABA

Glu/NAA/water/Cr

jMRUI

LCModel

Exercise on a bicycle ergometer

No

GABA and Glu modulations:

OCC GABA, OCC Glu and ACC Glu increased following exercise

Maruyama et al. 2021

25 H (learning)

12 H (control)

7T

32-channel

STEAM

Right M1 20 × 20 × 20

3 time points:

Pre-, during, post-task

GABA

Glu/tCr

LCModel

Motor sequence learning task

(1) Reaction times

GABA modulation:

GABA did not change significantly during these 3 time points

GABA correlation:

Bigger GABA/Glu ratio reduction is associated with better performance improvement in the learning group

Maes et al. 2022

28 Y

29 O

3T

32-channel

MEGA-PRESS

Left SM1

3 time points:

Pre-, during, post-task

GABA/water

Gannet

Multidigit task

(1) Accuracy

GABA modulation:

GABA decreased significantly during the task and returned to pre-levels in the post measurement

GABA correlation:

A bigger reduction of GABA was significantly related to better performance in older but poorer performance in young adults

Nettekoven et al. 2022

17 H

3T

32-channel

MRSI

Semi-LASER

Bilateral cerebellum

4 Time points:

Baseline, early task, late task, post-task

GABA

Glu /tCr

In-house scripts

A visuomotor task with no adaptation

A visuomotor task with adaptation

(1) Error

GABA modulation:

Learning-driven GABA levels in the left cerebellar nuclei, as measured by the difference between these two tasks, decreased, but not in the right cerebellar nuclei

GABA correlation:

Greater decreased GABA levels in the right cerebellar nuclei in the early training phase & better motor adaptation

Sampaio-Baptista et al. 2015

22 H (high)

18 H (low)

20 H

(control)

3T

12-channel

SPECIAL

Left SM1 20 × 20 × 20

3 time points:

baseline, post 1: after 6-week train, post 2: after subsequent 4-week

GABA/Cr

LCModel

A three-ball juggling task

(1) Daily scores

(2) learning rates

GABA modulation:

GABA levels decreased significantly in Post 1 compared with the baseline measure and increased significantly in Post 2 compared with Post 1 in the low-intensity group

GABA levels did not change significantly among three measures in the high-intensity group

Streeter et al. 2010

34 H

4T

MEGA-PRESS

Left thalamus

3 time points:

Baseline, after 12w but before 60 m intervention, after 60 s intervention

GABA/Cr

LCModel

Yoga

Walking

(1) Mood and anxiety scales

GABA modulation:

GABA did not change significantly in either group

GABA correlation:

Bigger GABA changes from scan 2 to scan 1 was related to better mood and lower anxiety

Cognitive performance and learning

      

Bezalel et al. 2019

31 H

3T

12-channel

MEGA-PRESS

dACC 40 × 25 × 10

3 times points:

Baseline, during task, final rest

GABA

Glx/water

In-house scripts

A reinforcement learning task

(1) Gain options/10 times

(2) Overall gain options/condition

(3) Learning rates

GABA and Glx modulations:

dACC GABA and Glx did no change significantly between the initial and final rest

Compared to the discrimination condition, dACC GABA levels increased and Glx/GABA levels decreased in the uncertainty condition (p < 0.05)

GABA correlation:

(r = − 0.592, p = 0.001) measure (1) & dACC GABA levels in NULL condition

Frank et al. 2021

20 H

3T

MEGA-PRESS

PRESS

Right PIVC

25 × 25 × 25

2 time points:

Low attention load

High attention load

GABA

Glx/water

LCModel

Visual tracking task (low attention load and high attention load)

(1) Accuracy

GABA and Glx modulations:

GABA did not change significantly in these 2 states

Glx decreased from low to high visual attentional load

Koolschijn et al. 2021

19 H

7T

32-channel

fMRI-fMRS sequence

OCC 20 × 20 × 20

Continuously measure during the task

GABA

Glu/tCr

MRspa

LCModel

Three stage interference tasks

(1) Accuracy

GABA and Glu/GABA modulations:

GABA as well Glu/GABA ratio decreased in the right inferences relative to erroneous answers

Kühn et al. 2016

19 H

3T

32-channel

SPECIAL

ACC 25 × 35 × 20

3 time points:

Pre-, during, post-task

GABA

Glu

Gln

tCr/water

LCModel

A color/word Stroop task

(1) Reaction times

(2) errors

GABA and Glu modulations:

GABA and Glu levels increased during the task and decreased at the post-task measure

Michels et al. 2012

16 H

3T

MEGA-PRESS

Left DLPFC

25 × 40 × 30

Baseline and continuously measure during the task

GABA

Glx/water

LCModel

Working memory task

(1) Accuracy

GABA and Glx modulations:

GABA increased significantly initially and then decreased in the following runs

Glx did not change significantly across the conditions

Namgung et al. 2021

19 F

3T

32-channel

MEGA-PRESS

PFC 30 × 30 × 30

2 time points:

Baseline, after training program

GABA/water

Gannet

10-day relaxation training program

(1) Stress

GABA modulation:

GABA decreased significantly after 10 days training program as compared to baseline

Spurny et al. 2020

20 H

3T

64-channel

3D-MRSI MEGA-LASER

(1) Hippocampus, insula, thalamus

(2) 2 Time points:

pre-, post-21-day

GABA

Glx

tNAA/tCr

In-house scripts

An associative facial learning task

(1) IRS

(2) FRS

(3) RI

GABA and Glx modulations:

GABA or Glx did not change significantly in the three tested regions from the pre- to post-training

GABA correlation:

(r = 0.69, p = 0.013) measure (1) & hippocampal GABA levels

no correlation between GABA in thalamus or insula and measure (1), (2) or (3)

no correlation between Glx before or after learning and measure (1), (2) or (3)

Vijayakumari et al. 2018

10 H

3T

32-channel

PRESS

Left DLPFC 20 × 20 × 20

3 time points:

Baseline, during and post-task

GABA

Glu

Glx/no

LCModel

A working memory task

(1) Accuracy

GABA modulation:

GABA did not change significantly during this task

  1. 3D-MRSI: three-dimensional magnetic resonance spectroscopic imaging; ACC: anterior cingulate cortex; Cr: creatine; DLPFC: dorsolateral prefrontal cortex; E/I: excitation/inhibition; F: female; FD: feature difference; FRS: final-retrieval-success; GABA: γ-aminobutyric acid; Gln: glutamine; Glu: glutamate; Glx: glutamate and glutamine; H: healthy subjects; IRS: initial-retrieval-success; Lac: lactate; M: male; M1: primary motor cortex; MEGA-PRESS: Meshcher-Garwood Point Resolved spectroscopy; MM: macro-molecular; NAA: N-acetyl-aspartate; NAA + NAAG: N-acetyl-aspartate + N-acetyl-aspartyl-glutamate; negBOLD: negative BOLD signal; posBOLD: positive BOLD signal; NS: not specified; O: older subjects; OCC: occipital cortex; OCT: occipito-temporal; PCC: posterior cingulate cortex; PFC: prefrontal cortex; PPC: posterior cingulate cortex; POC: parieto-occipital cortex; PRESS: Point Resolved Spectroscopy; PIVC: parietoinsular vestibular cortex; RI: retrieval improvement; sLASER: semi-localized by adiabatic selective refocusing; S1: primary somatosensory cortex; SM1: sensorimotor cortex; SMA: supplementary motor cortex; SN: signal-in-noise; SPECIAL: spin-echo full-intensity acquired localized; STEAM: Stimulated Echo Acquisition Mode; STIM: stimulation; tCR: total creatine; tDCS: transcranial direct current stimulation; tNAA: total N-acetylaspartate; Y: young subjects