A neuroimaging measure to capture heterogeneous patterns of atrophy in Parkinson's disease and dementia with Lewy bodies.

INTRODUCTION: Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) show heterogeneous brain atrophy patterns which group-average analyses fail to capture. Neuroanatomical normative modelling overcomes this by comparing individuals to a large reference cohort. Patient-specific atrophy patterns are measured objectively and summarised to index overall neurodegeneration (the 'total outlier count'). We aimed to quantify patterns of neurodegenerative dissimilarity in participants with PD and DLB and evaluate the potential clinical relevance of total outlier count by testing its association with key clinical measures in PD and DLB. MATERIALS AND METHODS: We included 108 participants with PD and 61 with DLB. PD participants were subclassified into high and low visual performers as this has previously been shown to stratify those at increased dementia risk. We generated z-scores from T1w-MRI scans for each participant relative to normative regional cortical thickness and subcortical volumes, modelled in a reference cohort (n = 58,836). Outliers (z < -1.96) were aggregated across 169 brain regions per participant. To measure dissimilarity, individuals' Hamming distance scores were calculated. We also examined total outlier counts between high versus low visual performance in PD; and PD versus DLB; and tested associations between these and cognition. RESULTS: There was significantly greater inter-individual dissimilarity in brain-outlier patterns in PD poor compared to high visual performers (W = 522.5; p < 0.01) and in DLB compared to PD (W = 5649; p < 0.01). PD poor visual performers had significantly greater total outlier counts compared to high (ß = -4.73 (SE = 1.30); t = -3.64; p < 0.01) whereas a conventional group-level GLM failed to identify differences. Higher total outlier counts were associated with poorer MoCA (ß = -0.55 (SE = 0.27), t = -2.04, p = 0.05) and composite cognitive scores (ß = -2.01 (SE = 0.79); t = -2.54; p = 0.02) in DLB, and visuoperception (ß = -0.67 (SE = 0.19); t = -3.59; p < 0.01), in PD. CONCLUSIONS: Neuroanatomical normative modelling shows promise as a clinically informative technique in PD and DLB, where patterns of atrophy are variable.

Thalamic white matter macrostructure and subnuclei volumes in Parkinson's disease depression.

Depression is a common non-motor feature of Parkinson's disease (PD) which confers significant morbidity and is challenging to treat. The thalamus is a key component in the basal ganglia-thalamocortical network critical to the pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not been identified. We performed structural and diffusion-weighted imaging (DWI) on 76 participants with PD to evaluate the relationship between PD depression and grey and white matter thalamic subnuclear changes. We used a thalamic segmentation method to divide the thalamus into its 50 constituent subnuclei (25 each hemisphere). Fixel-based analysis was used to calculate mean fibre cross-section (FC) for white matter tracts connected to each subnucleus. We assessed volume and FC at baseline and 14-20 months follow-up. A generalised linear mixed model was used to evaluate the relationship between depression, subnuclei volume and mean FC for each thalamic subnucleus. We found that depression scores in PD were associated with lower right pulvinar anterior (PuA) subnucleus volume. Antidepressant use was associated with higher right PuA volume suggesting a possible protective effect of treatment. After follow-up, depression scores were associated with reduced white matter tract macrostructure across almost all tracts connected to thalamic subnuclei. In conclusion, our work implicates the right PuA as a relevant neural structure in PD depression and future work should evaluate its potential as a therapeutic target for PD depression.

Rewarding feedback after correct visual discriminations has both general and specific influences on visual cortex.

Reward can influence visual performance, but the neural basis of this effect remains poorly understood. Here we used functional magnetic resonance imaging to investigate how rewarding feedback affected activity in distinct areas of human visual cortex, separating rewarding feedback events after correct performance from preceding visual events. Participants discriminated oriented gratings in either hemifield, receiving auditory feedback at trial end that signaled financial reward after correct performance. Greater rewards improved performance for all but the most difficult trials. Rewarding feedback increased blood-oxygen-level-dependent (BOLD) signals in striatum and orbitofrontal cortex. It also increased BOLD signals in visual areas beyond retinotopic cortex, but not in primary visual cortex representing the judged stimuli. These modulations were seen at a time point in which no visual stimuli were presented or expected, demonstrating a novel type of activity change in visual cortex that cannot reflect modulation of response to incoming or anticipated visual stimuli. Rewarded trials led on the next trial to improved performance and enhanced visual activity contralateral to the judged stimulus, for retinotopic representations of the judged visual stimuli in V1. Our findings distinguish general effects in nonretinotopic visual cortex when receiving rewarding feedback after correct performance from consequences of reward for spatially specific responses in V1.

Neural correlates of hemianopic completion across the vertical meridian.

Hemianopic completion refers to the perceptual completion of figures located across the vertical meridian in the context of hemianopia, such that one half of the figure falls within the blind hemifield. It can occur whether the figure is itself complete (veridical completion) or incomplete (paracompletion). Psychophysical evidence suggests that this phenomenon may be a constructive one, and may share features with completion phenomena in normal vision. The neural structures mediating hemianopic completion are unknown. Here we studied the neural activity evoked by hemianopic completion using event-related fMRI in an individual (POV) with a large right visual field homonymous hemianopic scotoma due to left occipital damage. Either a large achromatic circular contour straddling the vertical meridian or a semicircular contour within the left hemifield just crossing the vertical meridian was presented to POV on each trial. POV indicated by button press whether he perceived a semicircular contour, a patchy circular contour or a complete circular contour. On trials where he reported perceiving a complete circular contour despite being presented with a semicircular contour (paracompletion), activity was increased in a region of ipsilateral extrastriate cortex (contralateral to the lesion, ipsilateral to the illusory edge of the circle). These results are discussed in the context of illusory contour completion in healthy subjects and more generally in the recovery of function after brain damage.

Neural correlates of perceptual completion of an artificial scotoma in human visual cortex measured using functional MRI.

When a featureless achromatic target is placed on a textured pattern and steadily viewed in peripheral vision, after a few seconds it seems to fill-in with the surrounding texture, similar to the perceptual experience of patients with scotomas from damage to the visual pathways. Such "artificial scotomas" are thought to arise early in visual processing, but their neural basis in humans has not been fully explored. Here we used functional MRI to show that perceptual completion of an artificial scotoma is associated with selective reductions in activity in the retinotopic representation of the target in human primary visual cortex (V1) and area V2. Moreover, the persistence of signals associated with the target, even after perceptual completion had been reported, indicate the presence of a persistent representation of the now invisible target.

Neural correlates of perceptual filling-in of an artificial scotoma in humans.

When a uniformly illuminated surface is placed eccentrically on a dynamic textured background, after a few seconds, it is perceived to disappear and be replaced by the background texture. Such texture filling-in is thought to occur in retinotopic visual cortex, but it has proven difficult to distinguish the contributions of invisible target and visible background to signals measured in these areas. Here, we used magnetoencephalography to measure time-dependent brain responses in human observers experiencing texture completion. We measured responses specifically associated with the filled-in target, by isolating neural population signals entrained at the frequency of flicker of the target. When perceptual completion occurred, and the target became invisible, there was significant reduction in the magnetoencephalography power at the target frequency over contralateral posterior sensors. However, even a subjectively invisible target nevertheless evoked frequency-specific signals compared with a no-target baseline. These data represent evidence for a persistent target-specific representation even for stimuli rendered invisible because of perceptual filling-in.

Optimal dose of stereotactic radiosurgery for acoustic neuromas: A systematic review.

Radiosurgery is increasingly employed in the treatment of acoustic neuroma, but the optimal dose in terms of long-term tumour control and minimal adverse effects has not been established. We performed a systematic review of the published literature of radiosurgery of acoustic neuroma to assess whether the use of low dose radiosurgery is as effective as high dose treatment. Reports of radiosurgery for acoustic neuroma were identified through a Medline search. Studies with at least 15 patients and a median follow-up longer than 12 months were included. The relationship between actuarial 5-year progression-free survival (PFS), and tumour and treatment parameters was examined. Forty-two studies were included. Tumour control following lower radiosurgery doses was similar to that reported following high doses. Only 12 studies reported actuarial outcomes at 5 years. There was no relationship between PFS at 5 years and dose to the tumour margin. Radiosurgery of larger tumours was associated with lower 5 year PFS (p < 0.05). Although on initial inspection radiosurgery of acoustic neuroma with doses of 12 - 13 Gy seems to be as effective as higher dose treatment, the available reports are subject to a number of confounding factors, are not sufficiently statistically powered and there is only limited long-term actuarial outcome data. Currently, available studies do not provide sufficient confidence to support the claim that low dose radiosurgery is equally effective as higher doses in the long-term control of acoustic neuroma.