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Generalized motor inhibitory deficit in Parkinson’s disease patients who freeze

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Freezing of gait is a disabling symptom of Parkinson’s disease (PD) that involves failure to initiate and continue motor activity appropriately. PD disrupts fronto-basal ganglia circuitries that also implement the inhibition of responses, leading to the hypothesis that freezing of gait may involve fundamental changes in both initiation and inhibition of motor actions. We asked whether PD patients who show freezing of gait show selective deficits in their ability to inhibit upper and lower extremity reactions. We compared older healthy controls, older PD controls without freezing of gait, and older PD participants with freezing of gait, in stop-signal tasks that measured the initiation (go trials) and inhibition (stop trials) of both hand and foot responses. When only go trials were presented, all three groups showed similar initiation speeds across lower and upper extremity responses. When stop-signal trials were introduced, both PD groups slowed their reactions nearly twice as much as healthy controls. While this adjustment helped PD controls stop their actions as quickly as healthy controls, PD patients with freezing showed significantly delayed inhibitory control of both upper and lower extremities. When anticipating the need to stop their actions urgently, PD patients show greater adjustments (i.e., slowing) to reaction speed than healthy controls. Despite these proactive adjustments, PD patients who freeze show marked impairments in inhibiting both upper and lower extremity responses, suggesting that freezing may involve a fundamental disruption to the brain’s inhibitory control system.

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Notes

  1. We considered the appropriateness of ANCOVA for our analyses, especially for our critical analyses of SSRT across groups. However, two assumptions for ANCOVA are violated: (1) given the significant relationship between multiple demographic variable (depression rating, years since diagnosis, FOG-Q, and Levodopa Dose) and the independent variable Group, the assumption of independence between independent variables and covariates is violated (Miller and Chapman 2001), and (2) given the significant correlation between several pairs of covariates (e.g., UPDRS and Years Since Diagnosis, Levodopa Dose and Years Since Diagnosis, Levodopa Dose and FOG-Q, CES-D and FOG-Q, and a negative correlation between MOCA and Age), the assumption that covariates are not overly correlated with each other is violated. Additionally, given the lack of a significant correlation between any demographic variables and dependent measures, the assumption of a linear relationship between covariate and dependent variable may be violated. In spite of these violations that we believe undermine any conclusions that can be drawn from ANCOVA, we ran a 2 (Effector: Hands Vs. Feet) × 2 (Group: FOG+ Vs. FOG-) mixed ANCOVA on SSRT with all eight demographic variables from Table 1 as covariates. The group effect on SSRT remained significant (p < 0.05).

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Acknowledgments

This research was supported by grant number BCS-0957074 and BCS-1257272 from the National Science Foundation and grant number R01-EY021833-01 from the National Eye Institute to GDL. This work was also supported by grant number K23 NS080988 to DOC and K23 AG028750 to SAW from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Psychology, Stanford University, Stanford, CA, USA

    Patrick G. Bissett

  2. Department of Psychology, Vanderbilt University, Nashville, TN, USA

    Gordon D. Logan

  3. Department of Neurology, Vanderbilt University, Nashville, TN, USA

    Nelleke C. van Wouwe, Christopher M. Tolleson, Fenna T. Phibbs, Daniel O. Claassen & Scott A. Wylie

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  1. Patrick G. Bissett
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  2. Gordon D. Logan
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Correspondence to Patrick G. Bissett.

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Financial Disclosures of All Authors (for the preceding 12 months)

P.G.B.: None, G.D.L.: Grants: NSF, NEI, N.C.V.W.: None, C.M.T.: None, F.T.P.: Consultancies: Medtronic, Boston Scientific, Grant: Medtronic, D.O.C.: Consultancies: Lundbeck, Advisory Boards: Teva Neuroscience, Lundbeck, Honoraria: Lundbeck, Teva Neuroscience, Grants: K23 NS080988, Michael J Fox Foundation, Auspex, Teva Neuroscience, Lundbeck, S.A.W: Grant: K23AG028750.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Bissett, P.G., Logan, G.D., van Wouwe, N.C. et al. Generalized motor inhibitory deficit in Parkinson’s disease patients who freeze. J Neural Transm 122, 1693–1701 (2015). https://doi.org/10.1007/s00702-015-1454-9

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