Striatum and Hippocampus on Different Time Scales (e-Time)

Role of the Striatum and Hippocampus on Different Time Scales

Time processing is fundamental to survival and goal reaching in humans. Different time scales (seconds, minutes, and beyond) are processed through specific cognitive processes involving different neural representations. It is generally agreed that time scale in seconds-to-minutes range named "interval timing" would be anatomically linked to the striatum. Indeed, it is possible to demonstrate a deficit of interval timing processes in patients suffering from striatal damage (Huntington's disease). However, recent findings show involvement of a second brain structure, the hippocampus, in interval timing processing in the minutes range, suggesting an interaction between the striatum and hippocampus. Presumably, patients with hippocampal damage (Alzheimer's disease) would specifically show a decrease in performance for this minutes-range time scale. This study aims to provide a better understanding of the role of the striatum in the treatment of time and its interactions with other brain structures such as the hippocampus. More specifically, it is unclear whether the striatum plays a platform role that would always be involved regardless of the time scale, as suggested by the unified model of time or whether different brain structures is solicited according to the time scale, as suggested by the modular system model. In order to elucidate these issues, a potential double dissociation between brain structures and time scales will be tested.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Huntington Disease
• Intervention / Treatment: Other: Temporal perception tasks

Detailed Description

In that aim, we will evaluate patients with Huntington's disease and patients with Alzheimer's disease by developing and using time processing paradigms comparing short and long time scales.

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne-Catherine BACHOUD-LEVI, MD, PhD; Phone Number: +33 01 49 81 23 10; Email: anne-catherine.bachoud-levi@aphp.fr
• Study Contact Backup: Name: Laurie LEMOINE; Phone Number: +33 01 49 81 21 11; Email: laurie.lemoine@aphp.fr

Study Locations

• France
  • Créteil, France, 94010
    • Recruiting
    • Assistance Publique Hopitaux de Paris - Hôpital Henri Mondor
    • Contact: Anne-Catherine BACHOUD-LEVI, MD,PHD; Phone Number: +33 01 49 81 23 10; Email: anne-catherine.bachoud-levi@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Huntington's disease gene carriers

  • Patient included in the BioHD protocol
  • Age from 18 to 90 years old
  • Symptomatic patient
  • TFC ≥ 11
  • UHDRS motor> 5
  • Native language: French
  • Affiliation to a social security or to another social protection

  • Signature of informed consent

    • Patients with Alzheimer's disease

  • MMS from 20 to 26 (included)
  • Age: from 60 to 90 years old
  • Native language: French
  • Progressive deterioration of memory reported by patient or caregiver for more than 6 months
  • Profile at RL /RI 16: no significant improvement with indexing
  • Episodic memory disorder isolated or associated with other cognitive disorders
  • MRI: Atrophy of the median temporal lobe
  • Affiliation to a social security or to another social protection

  • Signature of informed consent

    • Healthy subjects

  • Healthy subject included in the BioHD protocol
  • MMS ≥ 26
  • Age from 18 to 90 years old
  • Native language: French
  • Affiliation to a social security or to another social protection
  • Signature of informed consent

Exclusion Criteria:

• Huntington's disease gene carriers

  • Intellectual deterioration preventing understanding of the protocol
  • Other dementia than Huntington's disease
  • Patient living alone at home
  • Major depression
  • Patient under legal protection
  • Patient deprived of liberty
  • Pregnant or breastfeeding woman, situation known to the investigator
  • Inability to handle an electronic tablet

• Patients with Alzheimer's disease

  • Intellectual deterioration preventing understanding of the protocol
  • Patient living alone at home
  • Sudden onset of memory impairment
  • Early onset of the following symptoms: difficulty in walking, convulsions, changes in behavior
  • Focal neurological characteristics including hemiparesis, sensory loss, visual field deficit
  • Early extrapyramidal sign
  • Other dementia than Alzheimer's disease
  • Major depression
  • Cerebrovascular disease
  • Toxic, metabolic or infectious anomaly
  • Patient under legal protection
  • Patient deprived of liberty
  • Pregnant or breastfeeding woman, situation known to the investigator
  • Inability to handle an electronic tablet

• Healthy subjects

  • Intellectual deterioration preventing understanding of the protocol
  • Known neurological or psychiatric illness
  • Patient under legal protection
  • Subject deprived of liberty
  • Pregnant or breastfeeding woman, situation known to the investigator
  • Inability to handle an electronic tablet

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients carrying the Huntington's gene; A "long" temporal perception task and a "short" temporal perception task	Other: Temporal perception tasks; A "long" temporal perception task in which the duration of the stimulus, around 2 min, is materialized by a video. For each trial, two videos are displayed to the participants, and then the task of the participant is to indicate the longest video and to give his level of confidence in his answer. A "short" temporal perception task which will take place in the same way as the "long" task except that the duration of the stimulus, around 2 seconds, is materialized by still frames from the videos used in the previous task.
Experimental: Alzheimer's disease patients; A "long" temporal perception task and a "short" temporal perception task	Other: Temporal perception tasks; A "long" temporal perception task in which the duration of the stimulus, around 2 min, is materialized by a video. For each trial, two videos are displayed to the participants, and then the task of the participant is to indicate the longest video and to give his level of confidence in his answer. A "short" temporal perception task which will take place in the same way as the "long" task except that the duration of the stimulus, around 2 seconds, is materialized by still frames from the videos used in the previous task.
Active Comparator: Healthy Volunteers; A "long" temporal perception task and a "short" temporal perception task	Other: Temporal perception tasks; A "long" temporal perception task in which the duration of the stimulus, around 2 min, is materialized by a video. For each trial, two videos are displayed to the participants, and then the task of the participant is to indicate the longest video and to give his level of confidence in his answer. A "short" temporal perception task which will take place in the same way as the "long" task except that the duration of the stimulus, around 2 seconds, is materialized by still frames from the videos used in the previous task.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability to discriminate durations	Ability to discriminate durations of a few seconds and durations of the order of minutes	25 months and 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risks's prediction of temporal disorientation.	Analysis of the answers (true/false) to the questionnaire assessing temporal orientation in daily life	26 months
Identification of neural correlations with temporal perception tests	Brain magnetic resonance imaging analysis	27 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Director: Anne-Catherine BACHOUD-LEVI, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2023
• Primary Completion (Estimated): March 30, 2025
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: March 4, 2022
• First Submitted That Met QC Criteria: July 5, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Hippocampus; Striatum; Huntington's disease; Time processing
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Tauopathies; Cognition Disorders; Chorea; Alzheimer Disease; Huntington Disease
• Other Study ID Numbers: APHP20211105; 2021-A01008-33 (Other Identifier: N° IDRCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No