International Multicenter Analysis of Brain Structure Across Clinical Stages of Parkinson's Disease.

BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated. OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging. METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score. RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (dmax  = -0.20, dmin  = -0.09). The bilateral putamen (dleft  = -0.14, dright  = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures. CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The role of linguistic and indexical information in improved recognition of dysarthric speech.

This investigation examined perceptual learning of dysarthric speech. Forty listeners were randomly assigned to one of two identification training tasks, aimed at highlighting either the linguistic (word identification task) or indexical (speaker identification task) properties of the neurologically degraded signal. Twenty additional listeners served as a control group, passively exposed to the training stimuli. Immediately following exposure to dysarthric speech, all three listener groups completed an identical phrase transcription task. Analysis of listener transcripts revealed remarkably similar intelligibility improvements for listeners trained to attend to either the linguistic or the indexical properties of the signal. Perceptual learning effects were also evaluated with regards to underlying error patterns indicative of segmental and suprasegmental processing. The findings of this study suggest that elements within both the linguistic and indexical properties of the dysarthric signal are learnable and interact to promote improved processing of this type and severity of speech degradation. Thus, the current study extends support for the development of a model of perceptual processing in which the learning of indexical properties is encoded and retained in conjunction with linguistic properties of the signal.

A follow-up investigation into the mechanisms that underlie improved recognition of dysarthric speech.

Differences in perceptual strategies for lexical segmentation of moderate hypokinetic dysarthric speech, apparently related to the conditions of the familiarization procedure, have been previously reported [Borrie et al., Language and Cognitive Processes (2012)]. The current follow-up investigation examined whether this difference was also observed when familiarization stimuli highlighted syllabic strength contrast cues. Forty listeners completed an identical transcription task following familiarization with dysarthric phrases presented under either passive or explicit learning conditions. Lexical boundary error patterns revealed that syllabic strength cues were exploited in both familiarization conditions. Comparisons with data previously reported afford further insight into perceptual learning of dysarthric speech.

Submovements in visually-guided and memory-guided reaching tasks: changes in Parkinson's disease.

Movements in people with Parkinson's disease are often hypometric, although we have found that this was not the case in an experimental visually-guided reaching task. We wished to explore our hypotheses that (1) people with Parkinson's disease produce hypometric primary submovements but(2) are able to use visual feedback to accurately reach the target in a single overall movement, and (3) this effect may be greater in memory-guided tasks in which an internal representation of the target location is used instead of a fixation-centered representation of the target.Visually- and memory-guided reaching movements were examined in 22 people with mild to moderate severity Parkinson's disease on medication, along with age-matched and sex-matched controls. Primary submovements were extracted from 5149 movements using a method based upon zero crossings of jerk(3rd derivative of position), with several additional criteria to minimize the detection of submovements due to noise or tremor.There was no difference in the end position of the overall reaching movement between the two groups, although the movement was smaller in the memory-guided task. In contrast,the gain of the primary submovement was smaller in the Parkinson's disease group than the control group, with this difference being greater on the memory-guided task. There was no task effect on the primary submovement gain in the control group.Our results show that the underlying primary submovement in visually-guided movements in people with Parkinson's disease is hypometric, and that the degree of hypometria is even greater in memory-guided movements.