Aberrant neurophysiological signaling associated with speech impairments in Parkinson’s disease

Aberrant neurophysiological signaling associated with speech impairments in Parkinson’s disease

Parkinson’s disease (PD) is a neurological disorder that progressively degrades the motor and cognitive abilities of affected patients. Although motor impairments are much more commonly studied in patients with PD, the cognitive symptoms that these patients experience are also debilitating and deserve more focus.

Patients with PD who experience issues with speech are impacted particularly negatively. The ability to speak intelligibly is essential for not only communicating needs and desires, but also for maintaining social bonds, the loss of which leads to worsened clinical declines in PD. Speech requires the integration of complex cognitive and motor processes, which are processed in different parts of the human brain. It is unclear from previous research whether speech impairments in PD are due to difficulties with the cognitive components (e.g., planning) of speech, or with the movements necessary to produce it.

Our study identified the origins of speech impairments in the brain of patients with PD. To do this, we mapped brain activity in a large group of patients with magnetoencephalography (MEG) imaging. MEG allows for examination of not only the spatial origins of brain activity with high precision, but also how they change over time, millisecond by millisecond. We also recruited healthy older adults in the study, for comparison to the patients with PD. For each patient, we derived a brain map of deviations in their brain activity relative to healthy levels.

To measure speech intelligibility, we used a new toolbox (audio-tokens; Figure 1A) that allows human listeners to interactively rate speech recordings each patient. We then tested how these speech impairments were related to changes in brain activity relative to healthy levels, in the patients with PD. In other words, we looked for unusual patterns in the brain activity of patients that were stronger in patients who had the greatest difficulties producing intelligible speech.

Figure 1. (A) Depiction of the audio-tokens graphical user interface. Each rater assessed three different speech samples from each patient participant. (B) The brain map shows the cortical region where brain activity deviations relative to healthy levels (measured with magnetoencephalography; MEG) were related to speech impairments. Line plots show the line of best fit for this relationship in each frequency band (δ: 2 – 4 Hz; θ: 5 – 7 Hz; α: 8 – 12 Hz; β: 15 – 29 Hz), demonstrating that patients with worse speech impairments (y-axis) had stronger activity in the faster (α and β) bands and weaker activity in the slower (δ and θ) bands.

We found that brain activity in a specific region of the cortex, the left inferior frontal gyrus (LIFC), is related to speech intelligibility: speech impairments are more pronounced in patients whose brain activity in this region deviates the most from healthy levels (Figure 1B). Decades of previous research have shown that this region is especially important for the cognitive aspects of speech production, rather than the mouth movements needed for articulating. This signaled that, at least in part, the speech impairments seen in patients with PD are due to problems with speech planning.

We then examined the frequency-content of the brain changes in the LIFC that were related to speech impairments in patients with PD, which tells us how the relative speed of neurophysiological signaling is changing. We saw that these brain changes reveal an acceleration of brain activity in this region: patients with worse speech impairments have faster patterns of LIFC brain signaling than those who remained more intelligible (Figure 1B).

Importantly, we also saw that speech impairments are also related to the amount of functional communication between the LIFC and the other parts of the brain that control movement – patients with more “functional connectivity” between such regions produced more intelligible speech. This tells us that the integration of cognitive and motor processes across the brain is beneficial for speech production, and that the breakdown of this integration leads to worse speech impairments in PD.

Together, these results give us new information regarding the brain-bases of speech impairments in Parkinson’s disease. Speech impairments that lead to worse intelligibility are attributable to problems with speech planning, as well as the integration of these plans with the movements required to produce them. We hope that these new findings will inspire novel clinical interventions to ameliorate speech impairments in PD through, for instance, brain stimulation – our results suggest that such therapies should aim to (1) decrease the speed of LIFC signaling and (2) increase the connectivity between the LIFC and motor regions of the brain.

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