Interval timing and midfrontal delta oscillations are impaired in Parkinson’s disease patients with freezing of gait

Abstract

Gait abnormalities and cognitive dysfunction are common in patients with Parkinson's disease (PD) and get worst with disease progression. Recent evidence has suggested a strong relationship between gait abnormalities and cognitive dysfunction in PD patients and impaired cognitive control could be one of the causes for abnormal gait patterns. However, the pathophysiological mechanisms of cognitive dysfunction in PD patients with gait problems are unclear. Here, we collected scalp electroencephalography (EEG) signals during a 7-second interval timing task to investigate the cortical mechanisms of cognitive dysfunction in PD patients with (PDFOG+, n=34) and without (PDFOG-, n=37) freezing of gait, as well as control subjects (n=37). Results showed that the PDFOG+ group exhibited the lowest maximum response density at around 7 seconds compared to PDFOG- and control groups, and this response density peak correlated with gait abnormalities as measured by FOG scores. EEG data demonstrated that PDFOG+ had decreased midfrontal delta-band power at the onset of the target cue, which was also correlated with maximum response density and FOG scores. In addition, our classifier performed better at discriminating PDFOG+ from PDFOG- and controls with an area under the curve of 0.93 when midfrontal delta power was chosen as a feature. These findings suggest that abnormal midfrontal activity in PDFOG+ is related to cognitive dysfunction and describe the mechanistic relationship between cognitive and gait functions in PDFOG+. Overall, these results could advance the development of novel biosignatures and brain stimulation approaches for PDFOG+.

Evoked midfrontal activity predicts cognitive dysfunction in Parkinson’s disease

“…Each of these paradigms have been extensively studied from the perspective of cognitive control and PD, and were specifically selected to study cognitive control in PD. 15,16,18,41–43…”

“…We performed a modified version of the peak-interval-timing task as described in detail previously. 14,41 43 control, 43 PD, 32 PDMCI, and 19 PDD participants estimated the duration of an interval after reading instructions displayed as text at the center of a video screen. White instructional text on the center of a black screen was presented that read “Short interval” on 3-second interval trials and “Long interval” on 7-second interval trials.…”

“…The actual interval durations were never communicated to the patient; we only analyzed long interval trials in this manuscript because our previous study observed no significant differences between PD and control subjects during short interval trials. 14,41 After the instructions were displayed for 1 second, the start of the interval was indicated by the appearance of an image of a solid box in the center of the computer screen (Fig. 1C), which was displayed for the entire 18–20 seconds for 7-second intervals.…”

“…Each of these paradigms have been extensively studied from the perspective of cognitive control and PD, and were specifically selected to study cognitive control in PD. 15,16,18,[41][42][43] Simon task: This and all subsequent tasks were presented using Psychtoolbox-3. 48 control, 47 PD, 34 PDMCI, and 18 PDD subjects were able to complete the Simon task (Fig.…”