Table 1.
Imaging studies on GABAergic alterations in Parkinson’s disease
| First author [Ref.] | Year | Imaging technique | Cohort | Disease duration, Avg., (SD), {range} in years | Medication state during imaging/clinical assessment | Results | Area of interest | GABA levels in patients with PD vs. HCs |
|---|---|---|---|---|---|---|---|---|
| Delli Pizzi [23] | 2020 | 3-T MRS | 42 PD/19 HC |
PD: 3.5 (2.3) PD (+ SDD): 4.6 (2.1) |
OFF/ON |
(1) No difference between GABA levels in the medial prefrontal cortex between PD patients and healthy controls (2) GABA was elevated in patients with SDD compared to non-SDD |
Medial prefrontal cortex | No difference |
| Dharmadhikari [20] | 2015 | 3-T MRS | 19 PD/18 HC | N/A | OFF/OFF | (1) GABA levels in the thalamus were elevated in patients, but not in the striatum | Striatum, thalamus |
No difference (striatum) ↑ (thalamus) |
| Elmaki* [17] | 2018 | 3-T MRS | 21 PD/15 HC | 3.5 (2.7) | OFF/OFF | (1) GABA levels in the basal ganglia were lower in patients than in controls | Basal ganglia | ↓ |
| Emir [12] | 2012 | 7-T MRS | 13 PD/12 HC | N/A | OFF/OFF | (1) GABA levels in the pons and putamen were higher in patients | Pons and putamen | ↑ |
| Firbank [30] | 2018 | 3-T MRS | 36 PD/20 HC |
No hallucinations: 9.6 (6.5) With hallucinations: 11.0 (7.4) |
N/A | (1) Higher GABA levels in patients with PD and hallucinations compared to PD patients without hallucinations and healthy controls | Visual cortex | N/A |
| Gong* [18] | 2018 | 3-T MRS | 22 PD/16 HC |
PIGD: 3.3 (1.7) TD: 3.8 (3.4) |
N/A |
(1) GABA levels were lower in patients with PD (2) Inverse correlation in PIGD patients between GABA levels and UPDRS |
Basal ganglia | ↓ |
| Gröger [24] | 2014 | 3-T MRS | 21 PD/24 HC | [3–7, 8••, 9, 10, 11•, 12, 13] | N/A | (1) Slight, non-significant elevation of GABA in substantia nigra | Substantia nigra | No difference |
| Kawabata [9] | 1996 | 123I-iomazenil SPECT | 15 PD | N/A | N/A | (1) Inverse relationship between the availability of GABAA receptors and motor symptoms | Cortex | N/A |
| van Nuland [22•] | 2020 | 3-T MRS | 60 PD/22 HC | N/A | ON and OFF/ON and OFF | (1) No alterations in GABA levels due to PD, clinical phenotype with tremor or medication | Thalamus, motor cortex and visual cortex | No difference |
| O’Gorman Tuura [13] | 2018 | 3-T MRS | 20 PD/17 HC | 9.25 (4.3) [2–7, 8••, 9, 10, 11•, 12–18] | ON/ON |
(1) Elevated GABA levels in the basal ganglia of patients (2) This elevation in GABA correlated with the degree of gait disturbance (3) No difference in prefrontal GABA levels between groups |
Basal ganglia | ↑ |
| Oz [25] | 2006 | 4-T MRS | 10 PD/11 HC | 2.3 (1.5) | OFF/ON | (1) No difference between GABA levels in patients compared to healthy controls | Substantia nigra | No difference |
| Pesch [19] | 2019 | 3-T MRS | 35 PD/35 HC | 4.7 | ON/ON | (1) No difference between GABA levels in patients compared to healthy controls | Basal ganglia, thalamus | No difference |
| Piras [29] | 2020 | 3-T MRS | 20 PD/20 HC | 3.51 (1.78) | ON/ON |
(1) In the right cerebellar hemisphere, there was an inverse correlation between GABA levels and cognitive scoring on the Stroop word-color test in patients with PD, while this was positive in healthy controls (2) This correlation was positive in both groups in analyses of the left cerebellar hemisphere and the overall mean of cerebellum |
Cerebellum | No difference |
| Takashima [8••] | 2022 | 11C-FMZ PET | 13 PD/15 HC | 13.8 (8.1) | OFF/OFF |
(1) GABAergic binding potential was reduced in the striatum as well as frontal, parietal and temporal cortical areas of patients (2) There was an inverse correlation between GABAergic and dopaminergic signals in the putamen in patients |
Striatum and frontal cortex | ↓ |
| Trujillo [37] | 2022 | 3-T MRS | 14 PD/19 PD + ICB |
PD: 7.2 (4.2) PD + ICB: 4.3 (3.3) |
OFF and ON/OFF and ON | (1) Patients with ICB had a reduced GABAergic response to dopaminergic therapy only in the thalamus | Thalamus, motor cortex | N/A |
| Seger [11•] | 2021 | 7-T MRS | 19 PD/13 HC | 5.7 (4.2) | ON/OFF and ON |
(1) GABA levels in putamen were significantly elevated in patients (2) Patients’s putaminal GABA correlated inversely with dopaminergic treatment response |
Putamen | ↑ |
| Song** [26] | 2021 | 3-T MRS | 18 PD/18 HC | 2.9 (1.5) | OFF/ON | (1) GABA levels in the upper brainstem were lower in patients than in controls | Upper brainstem | ↓ |
| Song** [32] | 2021 | 3-T MRS | 11 PD/11 HC | 3.4 (1.8) | OFF and ON/OFF and ON |
(1) GABA levels were lower in patients than controls (2) Dopaminergic therapy improved GABA levels in the upper brainstem of patients |
Upper brainstem | ↓ |
Twelve out of 17 papers found in our literature search were published within the last 5 years. Upwards arrow (↑) indicates significant or non-significant elevation of GABA in patients with PD compared to HCs. Downwards arrow (↓) indicates a significant decrease of GABA level in patients with PD compared to HCs
T tesla, MRS magnetic resonance spectroscopy, PD Parkinson’s disease, HCs healthy controls, N/A information not available, PET Positron emission tomography, 11C-FMZ 11C-flumazenil, SDD somatic symptom disorder, ICB impulsive compulsive behaviour
*/**Possible overlap in the participants