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27-07-2018 | Parkinson's disease | News | Article

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Occipital GABA levels reduced in Parkinson’s patients with visual hallucinations

medwireNews: Reduced levels of γ-aminobutyric acid (GABA) in the primary visual cortex are linked to visual hallucinations in patients with Parkinson’s disease (PD), study findings indicate.

“Our findings support the hypothesis that poor input to the visual cortex leads to levels of inhibitory GABA being reduced to optimize visual processing, at the price of increased misclassifications of ambiguous stimuli,” report Michael Firbank (Newcastle University, UK) and co-researchers.

They used magnetic resonance spectroscopy to determine occipital GABA levels in 36 patients with PD, of whom 19 had complex visual hallucinations, and 20 healthy individuals without hallucinations.

The patients with PD and visual hallucinations had a ratio of GABA to creatinine of 0.091, which was not significantly different to that of controls, at 0.099, but was significantly lower compared with the PD patients without visual hallucinations, at 0.101. The difference between PD patients with and without visual hallucinations remained significant after taking into account cognitive ability.

Patients with visual hallucinations had worse acuity than the other participants and this correlated with reduced GABA in the PD group, notes the team.

But there was no association between reduced GABA and the severity of hallucinations. This suggests that “low GABA levels may predispose people to hallucinate, but the occurrence of visual hallucinations is controlled by other factors, including attention and the visual environment,” say Firbank and colleagues.

They add: “If visual hallucinations are partly facilitated by decreased levels of GABA in the occipital cortex causing hyperexcitability, one therapeutic strategy might be to utilize antiepileptic drugs.”

Structurally, there was a significant cluster of grey matter loss in the right anterior temporal lobe in PD patients with hallucinations, compared with those without hallucinations and controls, as well as grey matter reductions in V4 of the occipital lobe compared with controls.

This suggests “disrupted communication between the ventral visual stream and lateral frontal cortex as being mechanistically involved in the generation of visual hallucinations,” says the team in Neurology.

Widespread reductions in white matter integrity were seen in the PD patients with hallucinations versus the other groups, but they were no longer significant after taking into account cognitive function.

And there were no differences across the groups in functional activity in response to visual excitation by checkerboard stimulus, which the team says “fits with the suggestion that visual hallucinations are a side effect of neural changes aimed at preserving visual function in the face of worsening visual input or connectivity.”

They conclude that further studies to investigate the connection between structural changes in the ventral stream and GABA alterations and their influence on visual hallucinations “may have important translational implications, as remediation of GABAergic function or reduction in visual cortical hyperexcitability may represent a novel treatment approach for visual hallucinations in PD.”

In a related editorial, Marco Onofrj (Universit`a Chieti-Pescara, Chieti, Italy) and Gordon Gilbert (University of South Florida, Tampa, USA) describe the study as “remarkable,” but note the existence of a few limitations associated with the use of magnetic resonance spectroscopy, including not knowing how GABAergic receptors are affected or whether GABA signalling is impaired.

They say that the study therefore “poses the question of how […] pharmacologic studies fare: Will GABAergic drugs prove effective, or should research focus on GABA interactions with other neurotransmitters or neurotrophic factors?”

By Lucy Piper

medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group