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Relating Response Inhibition, Brain Connectivity, and Freezing of Gait in People with Parkinson’s Disease

Published online by Cambridge University Press:  09 December 2020

Daniel S. Peterson Open the ORCID record for Daniel S. Peterson [Opens in a new window] ,
Katrijn Smulders ,
Martina Mancini ,
John G. Nutt ,
Fay B. Horak  and
Brett W. Fling
Daniel S. Peterson*
Affiliation:
College of Health Solutions, Arizona State University, Phoenix, AZ, USA VA Phoenix Health Care System, Phoenix, AZ, USA
Katrijn Smulders
Affiliation:
Department of Research, Sint Maartenskliniek, Nijmegen, the Netherlands
Martina Mancini
Affiliation:
Department of Neurology, Oregon Health & Science University, Portland, OR, USA
John G. Nutt
Affiliation:
Department of Neurology, Oregon Health & Science University, Portland, OR, USA
Fay B. Horak
Affiliation:
Department of Neurology, Oregon Health & Science University, Portland, OR, USA VA Portland Healthcare Systems, Portland, OR, USA
Brett W. Fling
Affiliation:
Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA
*
*Correspondence and reprint requests to: Daniel Peterson, PhD, Assistant Professor, College of Health Solutions, Arizona State University, 425 N 5th St., Phoenix, AZ 85004, USA. Mailcode 9020, Tel.: +1 602 827 2279; Fax: +1 602 827 2253. Email: [email protected]
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Abstract

Objective:

Freezing of gait (FoG) in Parkinson’s disease (PD) has been associated with response inhibition. However, the relationship between response inhibition, neural dysfunction, and PD remains unclear. We assessed response inhibition and microstructural integrity of brain regions involved in response inhibition [right hemisphere inferior frontal cortex (IFC), bilateral pre-supplementary motor areas (preSMA), and subthalamic nuclei (STN)] in PD subjects with and without FoG and elderly controls.

Method:

Twenty-one people with PD and FoG (PD-FoG), 18 without FoG (PD-noFoG), and 19 age-matched controls (HC) completed a Stop-Signal Task (SST) and MRI scan. Probabilistic fiber tractography assessed structural integrity (fractional anisotropy, FA) among IFC, preSMA, and STN regions.

Results:

Stop-signal performance did not differ between PD and HC, nor between PD-FoG and PD-noFoG. Differences in white matter integrity were observed across groups (.001 < p < .064), but were restricted to PD versus HC groups; no differences in FA were observed between PD-FoG and PD-noFoG (p > .096). Interestingly, worse FoG was associated with higher (better) mean FA in the r-preSMA, (β = .547, p = .015). Microstructural integrity of the r-IFC, r-preSMA, and r-STN tracts correlated with stop-signal performance in HC (p ≤ .019), but not people with PD.

Conclusion:

These results do not support inefficient response inhibition in PD-FoG. Those with PD exhibited white matter loss in the response inhibition network, but this was not associated with FoG, nor with response inhibition deficits, suggesting FoG-specific neural changes may occur outside the response inhibition network. As shown previously, white matter loss was associated with response inhibition in elderly controls, suggesting PD may disturb this relationship.

Keywords

InhibitionStop-signal taskFreezing of gaitParkinson’s diseaseNeuroimagingDiffusion tensor imaging
Type
Regular Research
Information
Journal of the International Neuropsychological Society , Volume 27 , Issue 7 , August 2021 , pp. 733 - 743
Copyright
Copyright © INS. Published by Cambridge University Press, 2020

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References

REFERENCES

Aron, A. R., Behrens, T. E., Smith, S., Frank, M. J., & Poldrack, R. A. (2007). Triangulating a cognitive control network using diffusion-weighted magnetic resonance imaging (MRI) and functional MRI. Journal of Neuroscience, 27(14), 3743–3752. doi: 10.1523/JNEUROSCI.0519-07.2007 CrossRefGoogle ScholarPubMed
Aron, A. R., Robbins, T. W., & Poldrack, R. A. (2014). Inhibition and the right inferior frontal cortex: One decade on. Trends in Cognitive Sciences, 18(4), 177–185. doi: 10.1016/j.tics.2013.12.003 CrossRefGoogle Scholar
Beaulne-Seguin, Z., & Nantel, J. (2016). Conflicting and non-conflicting visual cues lead to error in gait initiation and gait inhibition in individuals with freezing of gait. Gait & Posture, 49, 443–447. doi: 10.1016/j.gaitpost.2016.08.002 CrossRefGoogle ScholarPubMed
Behrens, T. E., Berg, H. J., Jbabdi, S., Rushworth, M. F., & Woolrich, M. W. (2007). Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? Neuroimage, 34(1), 144–155. doi: 10.1016/j.neuroimage.2006.09.018 CrossRefGoogle ScholarPubMed
Behrens, T. E., Woolrich, M. W., Jenkinson, M., Johansen-Berg, H., Nunes, R. G., Clare, S., … Smith, S. M. (2003). Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magnetic Resonance in Medicine, 50(5), 1077–1088. doi: 10.1002/mrm.10609 CrossRefGoogle ScholarPubMed
Bharti, K., Suppa, A., Pietracupa, S., Upadhyay, N., Gianni, C., Leodori, G., … Pantano, P. (2019). Aberrant functional connectivity in patients with Parkinson’s disease and freezing of gait: A within- and between-network analysis. Brain Imaging and Behavior. doi: 10.1007/s11682-019-00085-9 Google Scholar
Bissett, P. G., Logan, G. D., van Wouwe, N. C., Tolleson, C. M., Phibbs, F. T., Claassen, D. O., & Wylie, S. A. (2015). Generalized motor inhibitory deficit in Parkinson’s disease patients who freeze. Journal of Neural Transmission, 122(12), 1693–1701. doi: 10.1007/s00702-015-1454-9 CrossRefGoogle ScholarPubMed
Bohnen, N. I., & Albin, R. L. (2011). White matter lesions in Parkinson disease. Nature Reviews Neurology, 7(4), 229–236. doi: 10.1038/nrneurol.2011.21 CrossRefGoogle ScholarPubMed
Boucher, L., Palmeri, T. J., Logan, G. D., & Schall, J. D. (2007). Inhibitory control in mind and brain: An interactive race model of countermanding saccades. Psychological Review, 114(2), 376–397. doi: 10.1037/0033-295X.114.2.376 CrossRefGoogle Scholar
Claassen, D. O., van den Wildenberg, W. P., Harrison, M. B., van Wouwe, N. C., Kanoff, K., Neimat, J. S., & Wylie, S. A. (2015). Proficient motor impulse control in Parkinson disease patients with impulsive and compulsive behaviors. Pharmacology Biochemistry and Behavior, 129, 19–25. doi: 10.1016/j.pbb.2014.11.017 CrossRefGoogle ScholarPubMed
Coxon, J. P., Van Impe, A., Wenderoth, N., & Swinnen, S. P. (2012). Aging and inhibitory control of action: Cortico-subthalamic connection strength predicts stopping performance. Journal of Neuroscience, 32(24), 8401–8412. doi: 10.1523/JNEUROSCI.6360-11.2012 CrossRefGoogle ScholarPubMed
Davidsdottir, S., Cronin-Golomb, A., & Lee, A. (2005). Visual and spatial symptoms in Parkinson’s disease. Vision Research, 45(10), 1285–1296. doi: 10.1016/j.visres.2004.11.006 CrossRefGoogle ScholarPubMed
Di Caprio, V., Modugno, N., Mancini, C., Olivola, E., & Mirabella, G. (2020). Early-stage Parkinson’s patients show selective impairment in reactive but not proactive inhibition. Movement Disorders, 35(3), 409–418. doi: 10.1002/mds.27920 CrossRefGoogle Scholar
Eagle, D. M., Bari, A., & Robbins, T. W. (2008). The neuropsychopharmacology of action inhibition: Cross-species translation of the stop-signal and go/no-go tasks. Psychopharmacology, 199(3), 439–456. doi: 10.1007/s00213-008-1127-6 CrossRefGoogle ScholarPubMed
Eickhoff, S. B., Jbabdi, S., Caspers, S., Laird, A. R., Fox, P. T., Zilles, K., & Behrens, T. E. (2010). Anatomical and functional connectivity of cytoarchitectonic areas within the human parietal operculum. Journal of Neuroscience, 30(18), 6409–6421. doi: 10.1523/JNEUROSCI.5664-09.2010 CrossRefGoogle ScholarPubMed
Factor, S. A., Scullin, M. K., Sollinger, A. B., Land, J. O., Wood-Siverio, C., Zanders, L., … Goldstein, F. C. (2014). Freezing of gait subtypes have different cognitive correlates in Parkinson’s disease. Parkinsonism & Related Disorders, 20(12), 1359–1364. doi: 10.1016/j.parkreldis.2014.09.023 CrossRefGoogle ScholarPubMed
Fearon, C., Butler, J. S., Newman, L., Lynch, T., & Reilly, R. B. (2015). Audiovisual processing is abnormal in Parkinson’s disease and correlates with freezing of gait and disease duration. Journal of Parkinson’s Disease, 5(4), 925–936. doi: 10.3233/JPD-150655 CrossRefGoogle ScholarPubMed
Fling, B. W., Cohen, R. G., Mancini, M., Carpenter, S. D., Fair, D. A., Nutt, J. G., & Horak, F. B. (2014). Functional reorganization of the locomotor network in Parkinson patients with freezing of gait. PLoS One, 9(6), e100291. doi: 10.1371/journal.pone.0100291 CrossRefGoogle ScholarPubMed
Fling, B. W., Cohen, R. G., Mancini, M., Nutt, J. G., Fair, D. A., & Horak, F. B. (2013). Asymmetric pedunculopontine network connectivity in parkinsonian patients with freezing of gait. Brain, 136(Pt 8), 2405–2418. doi: 10.1093/brain/awt172 CrossRefGoogle ScholarPubMed
Gauggel, S., Rieger, M., & Feghoff, T. A. (2004). Inhibition of ongoing responses in patients with Parkinson’s disease. Journal of Neurology, Neurosurgery and Psychiatry, 75(4), 539–544. doi: 10.1136/jnnp.2003.016469 CrossRefGoogle ScholarPubMed
Georgiades, M. J., Gilat, M., Ehgoetz Martens, K. A., Walton, C. C., Bissett, P. G., Shine, J. M., & Lewis, S. J. (2016). Investigating motor initiation and inhibition deficits in patients with Parkinson’s disease and freezing of gait using a virtual reality paradigm. Neuroscience, 337, 153–162. doi: 10.1016/j.neuroscience.2016.09.019 CrossRefGoogle ScholarPubMed
Gilat, M., Shine, J. M., Walton, C. C., O’Callaghan, C., Hall, J. M., & Lewis, S. J. G. (2015). Brain activation underlying turning in Parkinson’s disease patients with and without freezing of gait: A virtual reality fMRI study. npj Parkinson’s Disease, 1, 15020. doi: 10.1038/npjparkd.2015.20 CrossRefGoogle ScholarPubMed
Goetz, C. G., Tilley, B. C., Shaftman, S. R., Stebbins, G. T., Fahn, S., Martinez-Martin, P., … Movement Disorder Society, U. R. T. F. (2008). Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Scale presentation and clinimetric testing results. Movement Disorders, 23(15), 2129–2170. doi: 10.1002/mds.22340 CrossRefGoogle ScholarPubMed
Hair, J., Anderson, R., Tatham, R., & Black, W. (1998). Multivaiate data analysis (5 ed.). Englewood Cliffs, NJ: Prentice-Hall.Google Scholar
Hoeft, F., Barnea-Goraly, N., Haas, B. W., Golarai, G., Ng, D., Mills, D., … Reiss, A. L. (2007). More is not always better: Increased fractional anisotropy of superior longitudinal fasciculus associated with poor visuospatial abilities in Williams syndrome. Journal of Neuroscience, 27(44), 11960–11965. doi: 10.1523/JNEUROSCI.3591-07.2007 CrossRefGoogle Scholar
Hoehn, M. M., & Yahr, M. D. (1967). Parkinsonism: Onset, progression and mortality. Neurology, 17(5), 427–442. doi: 10.1212/wnl.17.5.427 CrossRefGoogle ScholarPubMed
Hughes, A. J., Daniel, S. E., Kilford, L., & Lees, A. J. (1992). Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: A clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery and Psychiatry, 55(3), 181–184.CrossRefGoogle ScholarPubMed
Isaacs, B. R., Trutti, A. C., Pelzer, E., Tittgemeyer, M., Temel, Y., Forstmann, B. U., & Keuken, M. C. (2019). Cortico-basal white matter alterations occurring in Parkinson’s disease. PLoS One, 14(8), e0214343. doi: 10.1371/journal.pone.0214343 CrossRefGoogle ScholarPubMed
Kohl, S., Aggeli, K., Obeso, I., Speekenbrink, M., Limousin, P., Kuhn, J., & Jahanshahi, M. (2015). In Parkinson’s disease pallidal deep brain stimulation speeds up response initiation but has no effect on reactive inhibition. Journal of Neurology, 262(7), 1741–1750. doi: 10.1007/s00415-015-7768-6 CrossRefGoogle ScholarPubMed
Lewis, S. J., & Barker, R. A. (2009). A pathophysiological model of freezing of gait in Parkinson’s disease. Parkinsonism & Related Disorders, 15(5), 333–338. doi: 10.1016/j.parkreldis.2008.08.006 CrossRefGoogle ScholarPubMed
Mancini, M., Smulders, K., Cohen, R. G., Horak, F. B., Giladi, N., & Nutt, J. G. (2017). The clinical significance of freezing while turning in Parkinson’s disease. Neuroscience, 343, 222–228. doi: 10.1016/j.neuroscience.2016.11.045 CrossRefGoogle ScholarPubMed
Manza, P., Schwartz, G., Masson, M., Kann, S., Volkow, N. D., Li, C. R., & Leung, H. C. (2018). Levodopa improves response inhibition and enhances striatal activation in early-stage Parkinson’s disease. Neurobiology of Aging, 66, 12–22. doi: 10.1016/j.neurobiolaging.2018.02.003 CrossRefGoogle ScholarPubMed
Morris, R., Smulders, K., Peterson, D. S., Mancini, M., Carlson-Kuhta, P., Nutt, J. G., & Horak, F. B. (2020). Cognitive function in people with and without freezing of gait in Parkinson’s disease. npj Parkinson’s Disease, 6, 9. doi: 10.1038/s41531-020-0111-7 CrossRefGoogle ScholarPubMed
Naismith, S. L., Shine, J. M., & Lewis, S. J. (2010). The specific contributions of set-shifting to freezing of gait in Parkinson’s disease. Movement Disorders, 25(8), 1000–1004. doi: 10.1002/mds.23005 CrossRefGoogle ScholarPubMed
Nasreddine, Z. S., Phillips, N. A., Bedirian, V., Charbonneau, S., Whitehead, V., Collin, I., … Chertkow, H. (2005). The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment. Journal of the American Geriatrics Society, 53(4), 695–699. doi: 10.1111/j.1532-5415.2005.53221.x CrossRefGoogle ScholarPubMed
Nieuwboer, A., & Giladi, N. (2013). Characterizing freezing of gait in Parkinson’s disease: Models of an episodic phenomenon. Movement Disorders, 28(11), 1509–1519. doi: 10.1002/mds.25683 CrossRefGoogle ScholarPubMed
Nieuwboer, A., Rochester, L., Herman, T., Vandenberghe, W., Emil, G. E., Thomaes, T., & Giladi, N. (2009). Reliability of the new freezing of gait questionnaire: Agreement between patients with Parkinson’s disease and their carers. Gait & Posture, 30(4), 459–463. doi: 10.1016/j.gaitpost.2009.07.108 CrossRefGoogle ScholarPubMed
Nutt, J. G., Bloem, B. R., Giladi, N., Hallett, M., Horak, F. B., & Nieuwboer, A. (2011). Freezing of gait: Moving forward on a mysterious clinical phenomenon. The Lancet Neurology, 10(8), 734–744. doi: 10.1016/S1474-4422(11)70143-0 CrossRefGoogle ScholarPubMed
Obeso, I., Wilkinson, L., Casabona, E., Bringas, M. L., Alvarez, M., Alvarez, L., … Jahanshahi, M. (2011). Deficits in inhibitory control and conflict resolution on cognitive and motor tasks in Parkinson’s disease. Experimental Brain Research, 212(3), 371–384. doi: 10.1007/s00221-011-2736-6 CrossRefGoogle ScholarPubMed
Obeso, I., Wilkinson, L., Casabona, E., Speekenbrink, M., Luisa Bringas, M., Alvarez, M., … Jahanshahi, M. (2014). The subthalamic nucleus and inhibitory control: Impact of subthalamotomy in Parkinson’s disease. Brain, 137(Pt 5), 1470–1480. doi: 10.1093/brain/awu058 CrossRefGoogle ScholarPubMed
Rae, C. L., Hughes, L. E., Anderson, M. C., & Rowe, J. B. (2015). The prefrontal cortex achieves inhibitory control by facilitating subcortical motor pathway connectivity. Journal of Neuroscience, 35(2), 786–794. doi: 10.1523/JNEUROSCI.3093-13.2015 CrossRefGoogle ScholarPubMed
Shine, J. M., Naismith, S. L., Palavra, N. C., Lewis, S. J., Moore, S. T., Dilda, V., & Morris, T. R. (2013). Attentional set-shifting deficits correlate with the severity of freezing of gait in Parkinson’s disease. Parkinsonism & Related Disorders, 19(3), 388–390. doi: 10.1016/j.parkreldis.2012.07.015 CrossRefGoogle ScholarPubMed
Smulders, K., Esselink, R. A., Bloem, B. R., & Cools, R. (2015). Freezing of gait in Parkinson’s disease is related to impaired motor switching during stepping. Movement Disorders, 30(8), 1090–1097. doi: 10.1002/mds.26133 CrossRefGoogle ScholarPubMed
Snijders, A. H., Takakusaki, K., Debu, B., Lozano, A. M., Krishna, V., Fasano, A., … Hallett, M. (2016). Physiology of freezing of gait. Annals of Neurology, 80(5), 644–659. doi: 10.1002/ana.24778 CrossRefGoogle ScholarPubMed
Stefanova, E., Lukic, M. L. Z., Markovic, V., Stojkovic, T., Tomic, A., … Kostic, V. (2014). Acquisition and discrimination set learning deficits in Parkinson’s disease with freezing of gait. Journal of the International Neuropsychological Society, 20(9), 929–936.CrossRefGoogle ScholarPubMed
Sylvester, C. Y., Wager, T. D., Lacey, S. C., Hernandez, L., Nichols, T. E., Smith, E. E., & Jonides, J. (2003). Switching attention and resolving interference: fMRI measures of executive functions. Neuropsychologia, 41(3), 357–370. doi: 10.1016/s0028-3932(02)00167-7 CrossRefGoogle ScholarPubMed
Uribe, C., Segura, B., Baggio, H. C., Abos, A., Garcia-Diaz, A. I., Campabadal, A., … Junque, C. (2018). Gray/white matter contrast in Parkinson’s disease. Frontiers in Aging Neuroscience, 10, 89. doi: 10.3389/fnagi.2018.00089 CrossRefGoogle ScholarPubMed
Vandenbossche, J., Deroost, N., Soetens, E., Spildooren, J., Vercruysse, S., Nieuwboer, A., & Kerckhofs, E. (2011). Freezing of gait in Parkinson disease is associated with impaired conflict resolution. Neurorehabilitation and Neural Repair, 25(8), 765–773. doi: 10.1177/1545968311403493 CrossRefGoogle ScholarPubMed
Verbruggen, F., Aron, A. R., Band, G. P., Beste, C., Bissett, P. G., Brockett, A. T., … Boehler, C. N. (2019). A consensus guide to capturing the ability to inhibit actions and impulsive behaviors in the stop-signal task. Elife, 8. doi: 10.7554/eLife.46323 CrossRefGoogle ScholarPubMed
Verbruggen, F., Chambers, C. D., & Logan, G. D. (2013). Fictitious inhibitory differences: How skewness and slowing distort the estimation of stopping latencies. Psychological Science, 24(3), 352–362. doi: 10.1177/0956797612457390 CrossRefGoogle ScholarPubMed
Verbruggen, F., Logan, G. D., & Stevens, M. A. (2008). STOP-IT: Windows executable software for the stop-signal paradigm. Behavior Research Methods, 40(2), 479–483.CrossRefGoogle ScholarPubMed
Vercruysse, S., Leunissen, I., Vervoort, G., Vandenberghe, W., Swinnen, S., & Nieuwboer, A. (2015). Microstructural changes in white matter associated with freezing of gait in Parkinson’s disease. Movement Disorders, 30(4), 567–576. doi: 10.1002/mds.26130 CrossRefGoogle ScholarPubMed
Vriend, C., Gerrits, N. J., Berendse, H. W., Veltman, D. J., van den Heuvel, O. A., & van der Werf, Y. D. (2015). Failure of stop and go in de novo Parkinson’s disease – a functional magnetic resonance imaging study. Neurobiology of Aging, 36(1), 470–475. doi: 10.1016/j.neurobiolaging.2014.07.031 CrossRefGoogle ScholarPubMed
Walton, C. C., Shine, J. M., Hall, J. M., O’Callaghan, C., Mowszowski, L., Gilat, M., … Lewis, S. J. (2015). The major impact of freezing of gait on quality of life in Parkinson’s disease. Journal of Neurology, 262(1), 108–115. doi: 10.1007/s00415-014-7524-3 CrossRefGoogle ScholarPubMed
Wessel, J. R., & Aron, A. R. (2015). It’s not too late: The onset of the frontocentral P3 indexes successful response inhibition in the stop-signal paradigm. Psychophysiology, 52(4), 472–480. doi: 10.1111/psyp.12374 CrossRefGoogle Scholar
Wylie, S. A., van Wouwe, N. C., Godfrey, S. G., Bissett, P. G., Logan, G. D., Kanoff, K. E., … van den Wildenberg, W. P. M. (2018). Dopaminergic medication shifts the balance between going and stopping in Parkinson’s disease. Neuropsychologia, 109, 262–269. doi: 10.1016/j.neuropsychologia.2017.12.032 CrossRefGoogle ScholarPubMed
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