Striatum and Hippocampus on Different Time Scales

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Role of the Striatum and Hippocampus on Different Time Scales

Conditions
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Huntington Disease, Alzheimer Disease

Intervention / Treatment
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* Other: Temporal perception tasks


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients carrying the Huntington's gene<br>A long temporal perception task and a short temporal perception task | Other: Temporal perception tasks<br>* 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.<br>|
| Experimental: Alzheimer's disease patients<br>A long temporal perception task and a short temporal perception task | Other: Temporal perception tasks<br>* 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.<br>|
| Active Comparator: Healthy Volunteers<br>A long temporal perception task and a short temporal perception task | Other: Temporal perception tasks<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Time processing, Huntington's disease, Alzheimer's disease, Striatum, Hippocampus