To investigate the relationship between visual hallucinations in Parkinson disease (PD) and levels of γ-aminobutyric acid (GABA) in the primary visual cortex.
Methods
We utilized magnetic resonance spectroscopy to investigate occipital GABA levels in 36 participants with PD, 19 with and 17 without complex visual hallucinations, together with 20 healthy controls without hallucinations. In addition, we acquired T1-weighted MRI, whole-brain fMRI during a visual task, and diffusion tensor imaging.
Results
We found lower GABA+/creatine in PD with visual hallucinations (0.091 ± 0.010) vs those without (0.101 ± 0.010) and controls (0.099 ± 0.010) (F2,49 = 4.5; p = 0.016). Reduced gray matter in the hallucinations group was also observed in the anterior temporal lobe. Although there were widespread reductions in white matter integrity in the visual hallucinations group, this was no longer significant after controlling for cognitive function.
Conclusions
The data suggest that reduced levels of GABA are associated with visual hallucinations in PD and implicate changes to the ventral visual stream in the genesis of visual hallucinations. Modulation of visual cortical excitability through, for example, pharmacologic intervention, may be a promising treatment avenue to explore.
Treatment of visual hallucinations in neurodegenerative disorders is not well advanced. The complexity of underlying mechanisms presents a number of potential avenues for developing treatments, but also suggests that any single one may be of limited efficacy. Reducing medication, with the careful introduction of antidementia medication if needed, is the mainstay of current management. Antipsychotic medication leads to excessive morbidity and mortality and should only be used in cases of high distress that do not otherwise respond. Education, reduction of risk factors and psychological treatments have limited evidence of efficacy, but are unlikely to cause harm.
To resolve differences in the literature, we have systematically reviewed 21 controlled comparisons of the cognitive performance of patients with dementia with Lewy bodies (DLB) These were identified by end May 2002 by Medline and PsycInfo searches, checking reference lists and contacting authors. Nine had comparisons between DLB patients (total n = 180) and age-matched controls (n = 172). Sixteen had comparisons between DLB (n = 312) and Alzheimer’s disease (AD, n = 380). Three compared DLB (n = 48) with Parkinson’s disease (PD, n = 65). Two raters independently scored the methodological quality. This was variable with a lack of high-quality studies (median rating 3 on a 0–7 scale, K<sub>w</sub> = 0.41). There was a significant heterogeneity in results with marked discrepancies between studies. In a meta-analysis, DLB patients were more cognitively impaired than were AD or PD patients (95% CI of inverse variance weighted average of effect size relative to controls DLB 2.0–2.2; AD 1.4–1.6; PD 0.7–1.0). To permit an analysis of impairments in specific cognitive areas, the cognitive abilities underpinning the wide variety of tasks used were classified by a group of experienced neuropsychologists. Reducing overlapping task classifications using factor analysis showed large effect sizes relative to controls, AD and PD on two factors (combined variance 30%): attentional/executive impairment (effect sizes 1.1–2.9) and visual-perceptual impairment (0.7–3.6). There were small differences on two other factors (combined variance 39%): general verbal/non-verbal impairment (–0.12 to –0.5) and relative verbal memory impairment (–0.33 to 0.21). The cognitive performance is also more variable in DLB than in controls or in AD, but not PD (ratio of DLB to comparator standard deviations estimated from linear regression: DLB/controls 2.5–3.6; DLB/AD 2.1–2.6; DLB/PD 0.8–1.0). The greater variability of patients with DLB is seen only on tasks needing timed or motor responses, visual learning, executive or attentional abilities, or with visual content. Further stratification indicated that recent consensus diagnostic criteria, clinical diagnoses, and milder dementia were all associated with a more distinctive cognitive profile. The uniquely profound visual-perceptual and attentional-executive impairments that characterize DLB are consistent with the most frequent locations of Lewy bodies in frontal, cingulate, and inferior temporal cortex and may be related to the characteristic visual hallucinations and clinical fluctuations of this disease. These findings need to be confirmed in prospective, longitudinal, clinicopathological studies.
Abstract Understanding of visual hallucinations is developing rapidly. Single‐factor explanations based on specific pathologies have given way to complex multifactor models with wide potential applicability. Clinical studies of disorders with frequent hallucinations—dementia, delirium, eye disease and psychosis—show that dysfunction within many parts of the distributed ventral object perception system is associated with a range of perceptions from simple flashes and dots to complex formed figures and landscapes. Dissociations between these simple and complex hallucinations indicate at least two hallucinatory syndromes, though exact boundaries need clarification. Neural models of hallucinations variably emphasize the importance of constraints from top down dorsolateral frontal systems, bottom up occipital systems, interconnecting tracts, and thalamic and brainstem regulatory systems. No model has yet gained general acceptance. Both qualitative (a small number of necessary and sufficient constraints) and quantitative explanations (an accumulation of many nonspecific factors) fit existing data. Variable associations of hallucinations with emotional distress and thought disorders across and within pathologies may reflect the roles of cognitive and regulatory systems outside of the purely perceptual. Functional imaging demonstrates that hallucinations and veridical perceptions occur in the same brain areas, intimating a key role for the negotiating interface between top down and bottom up processes. Thus, hallucinations occur when a perception that incorporates a hallucinatory element can provide a better match between predicted and actual sensory input than does a purely veridical experience. Translational research that integrates understandings from clinical hallucinations and basic vision science is likely to be the key to better treatments. WIREs Cogn Sci 2010 1 781–786 This article is categorized under: Psychology > Perception and Psychophysics Neuroscience > Cognition
Abstract Visual hallucinations (VH) are ill-understood phenomena, and can be distressing and disabling to people with psychosis. Current models of VH emphasise that the appraisal of the VH helps explain the distress associated with the experiences. However, we were also interested in the content of what people saw in order to determine if distressing content and perceived control may help us understand the distress reported. We report the prevalence and phenomenology of VH in a large number (176) of people experiencing their first episode of psychosis. Care coordinators working with service users in an early intervention in psychosis service were asked about the experiences reported, using a semi structured interview. The findings indicate that around one third of service users at some point report visual hallucinations but only around 11% continue to report distressing visual hallucinations. Most report seeing a human-like figure, some with a particularly unpleasant content and many report having little perceived control over the experiences. For some, then, understanding and addressing the content of the experience, and perceived control, may be important if we are to help people better manage these upsetting experiences. Keywords: psychosisvisual hallucinationphenomenologydistress Acknowledgements We would like to thank the staff members of the Sunderland, Gateshead and South Tyneside Early Intervention in Psychosis services. This work was in part supported by a grant from NTW Foundation Trust.
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