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Novel Network-Based Approaches for Studying Cognitive Dysfunction in Behavioral Neurology

Periodic Reporting for period 2 - CoBeN (Novel Network-Based Approaches for Studying Cognitive Dysfunction in Behavioral Neurology)

Reporting period: 2019-03-01 to 2022-02-28

To conclude the action, we were able to identify neural networks engaged in language processing of words and non-words in the language with shallow orthography (i.e. Czech). The extent of involvement of the dorsal and ventral language networks was similar to that having been previously described described by our partners in the language with deep orthography (i.e. English). No data has been available in this regard for the Czech language so far. We were also able to describe changes occurring in task-specific (language) and task general (frontoparietal) networks due to physiological aging and in relation to age-related structural brain changes. In patients with Parkinson’s disease, a comparison of English, Czech, and Hungarian acoustic data revealed specific commonalities and differences that underlie hypokinetic dysarthria in these patient groups based on their mother tongue.

We were also able to identify structural and functional brain alterations in PD patients as compared to age-matched healthy controls in specific articulatory networks that underlie motor speech problems in PD. The structural volumetric decreases were accompanied by increased functional connectivity between specific regions of interest and demonstrated compensatory mechanisms in PD patients yet without any subjective and objective symptoms of hypokinetic dysarthria. Enhancing excitability of these regions by repetitive transcranial magnetic stimulation (rTMS) led to improved motor speech in PD and was accompanied by increased connectivity of the articulatory networks. This was shown in the prove-of-concept study as well as in a larger randomized controlled parallel-group study.

We also examined handwriting and drawing of intersecting pentagons (from the MMSE) using digitized tablets and the results showed that Shannon entropy of the in-air drawing might be a useful marker of early attention and executive function changes prior to the development of mild cognitive impairment in PD (MCI-PD). Whole-brain voxel-based morphometry revealed that the changes were related to volumes of the right superior parietal lobule.

Lastly, we focused on top-down and bottom-up control of visual processing in PD (and AD groups) using visual working memory tasks. Both behavioral and fMRI-related brain changes were identified in PD as compared to healthy controls. Early changes in PD were particularly related to altered engagement of the superior parietal lobule, i.e. area involved in both attention and spatial orientation. In AD subjects, it was rather specific frontal regions that showed changes in task-related activations. The results may assist in the early diagnosis of MCI in PD and AD as well as in monitoring disease progression and specific treatment effects.
For short report on recruiting and data collection in individual WPs as well as annotations of the articles please see the Technical report.
As part of this WP, 5 deliverables were submitted altogether, we developed and tested an fMRI protocol to assess the reading and spelling of words and non-words. Three manuscripts are in preparation and are expected to be submitted in 2022.
In prep.: The functional neuroanatomy of reading in Czech: evidence for a dual-route processing architecture in a shallow orthography by Bartoň M., et al.
Preliminary data has been presented at conferences for example: Bartoň et al. (2018). 21-Brain network activity during reading and writing of Czech words and nonwords. Clinical Neurophysiology

In prep.: Manuscript by Bartoň, et al.
Preliminary data has been presented at Course on Cognitive impairment and dementia, fMRI course and workshop XVI in 2019
In prep.: Kovac, et al.
Results of this work were already presented: Kovac, D., et al. (2021, July). Multilingual Analysis of Speech and Voice Disorders in Patients with Parkinson’s Disease. 44th International Conference on Telecommunications and Signal Processing
As part of this WP, 11 deliverables were submitted altogether; we developed and tested a short speech task protocol in Czech, English, and Hungarian. Four publications are relevant to this WP:
• Brabenec, L., et al. (2019). Non-invasive stimulation of the auditory feedback area for improved articulation in Parkinson's disease. Parkinsonism & related disorders
• Klobusiakova, et al. (2021). Articulatory network reorganization in Parkinson's disease as assessed by multimodal MRI and acoustic measures. Parkinsonism & Related Disorders
• Brabenec, L., et al. (2021). Non-invasive brain stimulation for speech in Parkinson’s disease: A randomized controlled trial. Brain Stimulation
• Submitted to the Parkinsonism and Related Disorders: Brabenec, L., et al. Repetitive transcranial magnetic stimulation for hypokinetic dysarthria in Parkinson’s disease enhances white matter integrity in the auditory-motor loop tract.
As part of this WP, 10 deliverables were submitted, and we also developed and evaluated a handwriting protocol. The following manuscripts were published relevant to this WP:
• Mucha, J., et al. (2018). Identification and monitoring of Parkinson’s disease dysgraphia based on fractional-order derivatives of online handwriting. Applied Sciences
• Brabenec, L., et al. (2022). Shannon entropy: A novel parameter for quantifying pentagon copying performance in non-demented Parkinson's disease patients. Parkinsonism & related disorders
As part of WP,4 seven deliverables were submitted altogether. We developed an fMRI visual working memory task to assess top-down and bottom-up control of visual attention and test it in the patient group (PD) and in control groups of subjects. The following manuscripts were or will be published relevant to this WP:
• In prep.: Klobušiaková, P. et al.
• In prep.: Veréb, D., et al. Modulation of cortical resting state functional connectivity during a visuospatial attention task in Parkinson’s disease.
• Elfmarkova, N. N., et al. (2017). Neural evidence for defective top-down control of visual processing in Parkinson's and Alzheimer's disease. Neuropsychologia
• Veréb, D., et al. (2021). Altered brain network function during attention-modulated visual processing in multiple sclerosis. Multiple Sclerosis Journal
• Minsterova, A. S., et al. (2020). Patterns of diffusion kurtosis changes in Parkinson's disease subtypes. Parkinsonism & related disorders
During the project duration we organized several events for the public where we summarized the generated knowledge of the project. You can see the detailed list of public events and their reach in the question Dissemination and Communication activities and in the Technical report.
In Brabenec et al. (2021), we successfully implemented our knowledge and state-of-the-art techniques into a novel therapeutic approach, i.e. use of non-invasive brain stimulation for the treatment of hypokinetic dysarthria in PD. All these results are novel and ready to be transferred to clinical practice since no good treatment exists for hypokinetic dysarthria in PD except for long-lasting Lee Silverman Voice Treatment (LSVT). In the future research, we will combine online home-based LSVT with either home-based transcranial direct current stimulation (tDCS) of the same region of interest, or sham stimulation.
Finally, comprehensive knowledge gained from the project was summarized in two reviews addressing PD manifestation and treatment (Rektorová, 2019) and brain correlates of PD and AD (Krajcovicova et al., 2019).
Bold signal changes
multilingual dataset - samples