Unravelling the Alteration of Brain Structure and Function in Parkinson´s Disease With Ultra-high Field MRI

Primary Outcomes (23)

• SN contrast ratio on neuromelanin sensitive images

  Mean SI(SN)/mean SI(cerebral peduncles), SI=signal intensity. We expect that PD patients will have decreased SN contrast ratio compared with age-matched healthy participants and that SN contrast ratio will correlate with UPDRS-3 subscore.

  Baseline

• SN volume on neuromelanin sensitive images

  Voxels in SN with mean SI \> SI+2 standard deviations(cerebral peduncles) , SI=signal intensity). We expect that PD patients will have decreased SN volume compared with age-matched healthy participants and that SN volume will correlate with UPDRS-3 subscore.

  Baseline

• LC contrast ratio on neuromelanin sensitive images

  Mean SI(LC)/mean SI(pontine tegmentum), SI=signal intensity. We expect that PD patients will have decreased LC contrast ratio compared with age-matched healthy participants and that LC contrast ratio will correlate with NMSS, LARS and BDI-II scores.

  Baseline

• LC volume on neuromelanin sensitive images

  Voxels in LC with mean SI \> SI+4 standard deviations(pontine tegmentum), SI=signal intensity). We expect that PD patients will have decreased LC volume compared with age-matched healthy participants and that LC volume will correlate with NMSS, LARS and BDI-II scores.

  Baseline

• Total SN iron accumulation: SWI

  SN mean signal intensity on SWI. We expect that PD patients will have lower mean SN SWI signal intensity compared to healthy.

  Baseline

• Total SN iron accumulation: R2*

  SN mean R2\* values (unit=1/s). We expect that PD patients will have higher mean SN R2\* values compared to healthy.

  Baseline

• Total SN iron accumulation: QSM

  SN mean QSM values (unit=ppb). We expect that PD patients will have higher mean SN QSM values compared to healthy.

  Baseline

• Nigrosome-1 iron accumulation: SWI

  Nigrosome-1 signal visibility on SWI assessed by blinded raters. We expect that iron accumulation in nigrosome-1 will be greater in PD patients leading to a loss of discrimination on SWI.

  Baseline

• Nigrosome-1 iron accumulation: R2*

  Mean R2\* values in the nigrosome-1 region (unit=1/s). We expect that PD patients will have higher R2\* values in the nigrosome-1 region.

  Baseline

• Nigrosome-1 iron accumulation: QSM

  Mean QSM values in the nigrosome-1 region (unit=ppb). We expect that PD patients will have higher QSM values in the nigrosome-1 region.

  Baseline

• Functional brain activation pattern in the LC, SN, VTA, and striatum

  Revealed by task related blood oxygenation level dependent (BOLD) signal changes. We expect that functional activation in these regions will be attenuated in PD patients corresponding to their loss of brainstem nuclei integrity (see hypotheses).

  ON & OFF PD medication in a period within 24 weeks from baseline.

• Motor disease severity

  Unified Parkinson's Disease Rating Scale (UPDRS)-3 subscore (Motor severity, range 0-108, higher values = worse outcome). Measured while subjects are taking their usual medication.

  Baseline

• Overall disease severity

  Total Unified Parkinson's Disease Rating Scale (UPDRS) score (sum of all 4 subscores listed below, range 0-199, higher values = worse outcome), UPDRS-1 (Cognitive and mental disease severity, range 0-16, higher values = worse outcome), UPDRS-2 (disease severity in relation to activities of daily living, range 0-52, higher values = worse outcome) and UPDRS-3 (Motor severity, range 0-108, higher values = worse outcome), UPDRS-4 (Complications of therapy, range 0-23, higher values = worse outcome) subscores. Measured while subjects are taking their usual medication.

  Baseline

• Non-motor disease severity

  Total Non-Motor Symptom Scale (NMSS) score (range 0-360, higher values = worse outcome). Measured while subjects are taking their usual medication.

  Baseline

• Modified Hoehn and Yahr Staging

  Modified Hoehn and Yahr Staging (Crude measure of disease severity, range 0-5, higher score = worse outcome). Measured while subjects are taking their usual medication.

  Baseline

• Schwab and England Activities of Daily Living Scale

  Schwab and England Activities of Daily Living Scale (Measure of ADL function, range 100-0%, higher score = better outcome). Measured while subjects are taking their usual medication.

  Baseline

• Apathy

  Total Lille Apathy Rating Scale (LARS) score (range -36-36, higher score = better outcome).

  Baseline

• Mood

  Total Beck's Depression Inventory-II (BDI-II) score (range 0-63, lower score = better outcome).

  Baseline

• Autonomic emotional-arousal response: Pupillary response

  Change in pupil size in response to arousing stimuli compared with non-arousing stimuli (unit=difference in mm). We expect that PD patients will have a smaller pupillary response following arousing stimuli compared to healthy participants.

  ON & OFF PD medication in a period within 24 weeks from baseline.

• Autonomic emotional-arousal response: Skin conductance response

  Change in skin conductance (unit=micro Siemens) in response to arousing stimuli compared with non-arousing stimuli. We expect that PD patients will show an attenuated skin conductance response to arousing stimuli compared to healthy participants.

  ON & OFF PD medication in a period within 24 weeks from baseline.

• Behavioural outcome measures: Choices

  Learning in reinforcement learning paradigm: Choices, reaction times, parameters describing degree of action-value vs. stimulus value learning from computational model.

  ON & OFF PD medication in a period within 24 weeks from baseline.

• Behavioural outcome measures: Reaction times

  Learning in reinforcement learning paradigm: Reaction times (unit=ms) describing degree of action-value vs. stimulus value learning from computational model.

  ON & OFF PD medication in a period within 24 weeks from baseline.

• Behavioural outcome measures: Model parameters

  Learning in reinforcement learning paradigm: Model parameters describing degree of action-value vs. stimulus value learning from computational model.

  ON & OFF PD medication in a period within 24 weeks from baseline.

Conditions