Prefrontal Cortex Activation in Patients Tied to Severity of Parkinson’s Disease

In patients with Parkinson’s disease (PD), those with increased disease severity depend more on the prefrontal cortex (PFC) when negotiating anticipated obstacles — perhaps to compensate for motor and attention deficits, according to a study published in the journal Parkinsonism & Related Disorders.

The researchers sought to evaluate how different obstacle difficulty levels, related to anticipation and height, impact an individual’s PFC activation levels with the progression of PD (eg, different Hoehn & Yahr [H&Y]). They theorized that individuals with more advanced PD will exhibit higher PFC activation levels compared with those with mild disease. Further, with an increasing level of difficulty (eg, the involvement of higher and unanticipated obstacles), compensatory mechanisms will decrease in their efficacy as disease severity rises, leading to patients with more advanced disease needing higher levels of the PFC to compensate for decreased motor and cognitive resources.

A total of 74 patients with PD residing in Israel were divided into 3 groups, based on H&Y stage, as follows: Group 1: 20 participants with H&Y stage 1 to 1.5; Group 2: 38 participants with H&Y stage 2 to 2.5; and Group 3: 16 participants with H&Y stage 3. Overall, 62.2% of the participants were men. The average patient age was 68.26±7.54 years.

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Study inclusion criteria were age between 50 and 85 years, PD diagnosis with the Movement Disorders Society Criteria for PD, H&Y stage 1 to 3 (evaluated during the “ON” medication state), and the ability to walk unassisted for 15 minutes or more. All patients needed to walk alongside an obstacle course while negotiating anticipated and unanticipated obstacles — long/low available response time — at heights of 50 mm and 100 mm. PFC activation was measured via the use of functional near-infrared spectroscopy, with comparisons made between groups and tasks using mixed model analyses. All of the participants wore a safety harness to guarantee safety during the evaluation.

Study findings revealed that participants who had more advanced PD (H&Y stage 3) compared with those with milder PD (H&Y stages 1 and 2) exhibited significantly higher PFC activation levels when negotiating anticipated obstacles. Additionally higher levodopa equivalent daily dose was associated with greater PFC activation during the higher anticipated obstacle. On the other hand, during the negotiation of unanticipated obstacles, the differences in PFC activation did not demonstrate a correlation with disease severity in a linear manner.

The current study had several limitations. Although a number of brain regions are involved in the negotiation of obstacles, brain activation was measured only from the PFC. Nonetheless, function undoubtedly plays an important role in obstacle negotiation. Technical limitations of the study included the fact that walking with a safety harness may have affected a patient’s gait pattern. Further, all participants with PD were assessed in their “ON” medication state only.

The researchers concluded that future studies in patients with PD in the “OFF” medication state might prove informative. “This knowledge should be considered while developing effective interventions to decrease falls in everyday environments in PD patients and even older adults.”

Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.


Assad M, Galperin I, Giladi N, Mirelman A, Hausdorff JM, Maidan I. Disease severity and prefrontal cortex activation during obstacle negotiation among patients with Parkinson’s disease: Is it all as expected? Parkinsonism Related Disord. Published online June 19, 2022. doi:10.1016/j.parkreldis.2022.06.006

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