Temporal Disorders in Left and Right Brain-Damaged Patients

Study Overview
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Brief Summary
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Time is an important function that permeates our everyday activities but it has been so far significantly under-investigated in neurological patients. For instance, it is known that right brain damaged (RBD) patients with spatial attentional deficit (neglect) are impaired in both the ability to estimate the duration of an event (Time Estimation), showing a time underestimation, and the ability of mentally moving in past and future time (Mental Time Travelling), showing a deficit in processing future events when they are projected in the past. After a leftward shift of spatial attention induced by prismatic adaptation (PA), both the underestimation and the ability to travel in time ameliorate. However, less is known about these abilities in left brain damaged (LBD) patients. Aims of this study are to investigate: i) the performance (in terms of accuracy and reaction times) of LBD and RBD patients on Mental Time Travelling; ii) the correlation between Mental Time Travelling and Time Estimation abilities; iii) the efficacy of a single session of PA inducing a leftward (L-PA) and a rightward (R-PA) attentional shift on Mental Time Travelling and Time Estimation abilities. A group of control subjects will be involved for comparison among groups.

Detailed Description
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Time processing involves different abilities - i.e. estimating the duration of an event (Time Estimation) and moving in past and future time (Mental Time Travelling) - and it is a fundamental ability in everyday life. However, in neuropsychology, time processing is routinely neglected in the assessment of cognitive deficits in brain-damaged patients. This is surprising since time is an important function that permeates our activities: it is involved in perceiving mismatches in lip reading (milliseconds), estimating how long it takes to be ready for work (minutes), and planning how long it will take a manuscript to be accepted (usually months). Thus, impairment in processing time has important consequences in daily life. For instance, it is known that right brain damaged (RBD) patients with spatial attentional deficit (neglect) underestimate durations of milliseconds and show a deficit in processing future events when they are projected in the past. Moreover, previous studies have demonstrated that a leftward shift of spatial attention induced by prismatic adaptation (PA) determines an amelioration of both, time underestimation and the deficit in mental travel in time. The Mental Time Travelling, in particular, seems to involve different cognitive functions, among others, episodic memory and the ability to anticipate the future. Recent evidence suggests that these functions are mediated by neural circuits localized in the left hemisphere but no studies have investigated the ability of mentally moving in past and future time in left brain damaged (LBD) patients. Aims of this study are to investigate: i) the performance (in terms of accuracy and reaction times) of LBD and RBD patients on Mental Time Travelling; ii) the correlation between Mental Time Travelling and Time Estimation abilities; iii) the efficacy of a single session of PA inducing a leftward (L-PA) and a rightward (R-PA) attentional shift on Mental Time Travelling and Time Estimation abilities. A group of control subjects will be involved for comparison among groups.

Official Title
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The Relationship Between Our Ability in Travelling in Time and in Estimating Time Duration and Their Interaction With Spatial Attention: a Neuropsychological Study.

Conditions
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Brain Disease

Intervention / Treatment
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* Behavioral: Rightward Attentional Shift (R-PA)
* Behavioral: Leftward Attentional Shift (L-PA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with focal (right or left) brain-damage Exclusion Criteria: generalized cognitive impairment (score lower than 24 at the Mini Mental State Examination) psychiatric disorders additional neurological disorders abusive use of alcohol or illicit drugs

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| LBD patients R-PA<br>A group of 10 left brain damaged (LBD) patients will attend two sessions: First session - before prismatic adaptation (pre-PA): they will perform a computerized test battery to measure time abilities (Mental Time Travel and Time Estimation) and a neuropsychological test battery to assess cognitive abilities. Second session - after prismatic adaptation (post-PA): they will perform the Mental Time Travel and Time Estimation tasks immediately after a single session of pointing with prismatic goggles inducing rightward attentional shift (R-PA). | Behavioral: Rightward Attentional Shift (R-PA)<br>* Patients will perform a session of 90 pointing movements toward a visual target presented on the right, the left or at the center of the visual field. This pointing task will be performed with prismatic googles inducing a rightward attentional shift.<br>|
| LBD patients L-PA<br>A group of 10 left brain damaged (LBD) patients will attend two sessions: First session - before prismatic adaptation (pre-PA): they will perform a computerized test battery to measure time abilities (Mental Time Travel and Time Estimation) and a neuropsychological test battery to assess cognitive abilities. Second session - after prismatic adaptation (post-PA): they will perform the Mental Time Travel and Time Estimation tasks immediately after a single session of pointing with prismatic goggles inducing leftward attentional shift (L-PA). | Behavioral: Leftward Attentional Shift (L-PA)<br>* Patients will perform a session of 90 pointing movements toward a visual target presented on the right, the left or at the center of the visual field. This pointing task will be performed with prismatic googles inducing a leftward attentional shift.<br>|
| RBD patients R-PA<br>A group of 10 right brain damaged (RBD) patients will attend two sessions: First session - before prismatic adaptation (pre-PA): they will perform a computerized test battery to measure time abilities (Mental Time Travel and Time Estimation) and a neuropsychological test battery to assess cognitive abilities. Second session - after prismatic adaptation (post-PA): they will perform the Mental Time Travel and Time Estimation tasks immediately after a single session of pointing with prismatic goggles inducing rightward attentional shift (R-PA). | Behavioral: Rightward Attentional Shift (R-PA)<br>* Patients will perform a session of 90 pointing movements toward a visual target presented on the right, the left or at the center of the visual field. This pointing task will be performed with prismatic googles inducing a rightward attentional shift.<br>|
| RBD patients L-PA<br>A group of 10 right brain damaged (RBD) patients will attend two sessions: First session - before prismatic adaptation (pre-PA): they will perform a computerized test battery to measure time abilities (Mental Time Travel and Time Estimation) and a neuropsychological test battery to assess cognitive abilities. Second session - after prismatic adaptation (post-PA): they will perform the Mental Time Travel and Time Estimation tasks immediately after a single session of pointing with prismatic goggles inducing leftward attentional shift (L-PA). | Behavioral: Leftward Attentional Shift (L-PA)<br>* Patients will perform a session of 90 pointing movements toward a visual target presented on the right, the left or at the center of the visual field. This pointing task will be performed with prismatic googles inducing a leftward attentional shift.<br>|
| HC R-PA<br>A group of 10 healthy controls (HC) will attend two sessions: First session - before prismatic adaptation (pre-PA): they will perform a computerized test battery to measure time abilities (Mental Time Travel and Time Estimation) and a neuropsychological screening (Mini Mental State Examination) to assess inclusion/exclusion criteria. Second session - after prismatic adaptation (post-PA): they will perform the Mental Time Travel and Time Estimation tasks immediately after a single session of pointing with prismatic goggles inducing rightward attentional shift (R-PA). | Behavioral: Rightward Attentional Shift (R-PA)<br>* Patients will perform a session of 90 pointing movements toward a visual target presented on the right, the left or at the center of the visual field. This pointing task will be performed with prismatic googles inducing a rightward attentional shift.<br>|
| HC L-PA<br>A group of 10 healthy controls (HC) will attend two sessions: First session - before prismatic adaptation (pre-PA): they will perform a computerized test battery to measure time abilities (Mental Time Travel and Time Estimation) and a neuropsychological screening (Mini Mental State Examination) to assess inclusion/exclusion criteria. Second session - after prismatic adaptation (post-PA): they will perform the Mental Time Travel and Time Estimation tasks immediately after a single session of pointing with prismatic goggles inducing leftward attentional shift (L-PA). | Behavioral: Leftward Attentional Shift (L-PA)<br>* Patients will perform a session of 90 pointing movements toward a visual target presented on the right, the left or at the center of the visual field. This pointing task will be performed with prismatic googles inducing a leftward attentional shift.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mental Time Travel Ability on the Mental Time Travel (MTT) Task | In the MTT task participants are listened to auditory stimuli consisting of brief descriptions of personal and non-personal events. They are required to project themselves in the past (10 years ago), present or future (10 years from now) and to verbally determine whether each event has already happened (relative past event) or is yet to happen (relative future event) with respect to the specific self-location in time (past, present and future). Error rates and reaction times will be recorded and analyzed. The improvement will be defined as changes in the Inverse Efficiency (IE) ability: reaction times/accuracy. | pre-PA and immediately post-PA | 
| Change in Time Estimation Ability on the Time Estimation Task | The Time Estimation task consists of a red square that is displayed for different durations (1400, 1700, 2000, 2300, 2600 ms) on the computer screen. Participants are instructed to verbally judge whether the duration of each stimulus is short or long with respect to previously acquired pair of reference durations (1400 and 2600 ms). A psychophysical response function will be created for each participant by calculating the proportion of long responses: the Point of Subjective Equality (PSE) is the duration at which a participant is equally likely to classify the stimuli as short or long. An increase of long response after treatment, as compared to baseline performance, induces a decreased PSE, reflecting a relative shift towards overestimation of temporal midpoint. Conversely, an increase of short responses after treatment, as compared to baseline performance, induces an increased PSE, reflecting a relative shift towards underestimation of temporal midpoint. | pre-PA and immediately post-PA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Unilateral Spatial Neglect on the Behavioral Inattention Test (BIT) | The BIT is composed of two scales, the Conventional scale and the Behavioral scale. Participants will be administered the Conventional scale, which includes 6 tasks: line crossing, letter cancellation, star cancellation, figure and shape copying, line bisection and representational drawing. The score ranges from 0 to 146 (cut-off = 129). | baseline | 
| Assessment of Unilateral Spatial Neglect on the Bells Cancellation Test | The subject is required to cross out the bells that are scattered among several different shapes on a sheet of paper. Two indices of neglect will be calculated: total number of omissions (cut-off < 5) and number of left omissions (cut-off < 5), i.e. the difference between the number of targets crossed out on the right side and the number of targets crossed out on the left side (asymmetry score). | baseline | 
| Assessment of Unilateral Spatial Neglect on the Apples Cancellation Test | This is a cancellation task in which outline drawings of 150 apples are shown pseudorandomly scattered over a sheet of A4 paper presented in a landscape orientation. All of the apples are presented in an upright position. One-third of the apples are full (targets) and two-thirds are open on either the left or the right side (distractors). Participants are asked to cross out all the full apples and to ignore the distractors. Three scores will be calculated: full apples barrage (cut-off = 45), full apples asymmetry (cut-off = 2), and incomplete apples asymmetry (cut-off = 1). The full apples asymmetry (the difference between the number of targets selected on the right side and the number of targets selected on the left side) represents the score for egocentric neglect. The incomplete apples asymmetry (total left openings minus total right openings) represents the score for allocentric neglect. | baseline | 
| Assessment of General Cognitive Functioning on the Mini Mental State Examination (MMSE) | The MMSE is a 30-point questionnaire that examines functions including registration (repeating named prompts), attention and calculation, recall, language, ability to follow simple commands and orientation. The score ranges from 0 to 30 (cut-off = 24). | baseline | 
| Assessment of Verbal Comprehension on the Token Test | The Token test is a test of auditory language processing in which participants are asked to manipulate tokens of different shapes, sizes, and colors in response to increasingly complex instructions. One point is credited for a correct performance on the first presentation and 0.5 point if the performance is correct only on the second presentation. The score ranges from 0 to 36 (cut-off = 26,50). | baseline | 
| Assessment of Frontal Functions on the Frontal Assessment Battery (FAB) | The FAB is a brief battery of six neuropsychological tasks designed to assess frontal lobe function at bedside. The six tasks explore: conceptualization and abstract reasoning, lexical verbal fluency and mental flexibility, motor programming and executive control of action, self-regulation and resistance to interference, inhibitory control, and environmental autonomy. Each task scores from 0 (pathologic) to 3 (best performance), for a total maximum score of 18. | baseline | 
| Assessment of Memory on the Rey's 15 Words Auditory Learning Test | The test is designed as a list-learning paradigm in which the participant hears a list of 15 nouns and is asked to recall as many words from the list as possible (five repetitions of free-recall). After a 15 min delay, the participant is asked to again recall the words from the list. It provides two scores: immediate (range 0-75) and delayed recall (range 0-15), i.e. the higher the score, the better the performance. | baseline | 
| Assessment of Ideomotor Apraxia on the Movement Imitation Test | The ability to carry out movements on imitation is assessed with a 24-item test. Each movement is presented for a maximum of 3 times and scores from 0 (pathologic) to 3 (best performance). The total score ranges from 0 to 72 (cut-off = 62). | baseline | 
| Assessment of Verbal Estimation Ability on the Time and Weight Estimation Test (STEP) | The STEP assesses aspects of executive functioning related to cognitive estimation ability. The questionnaire is composed of two distinct ten-item sections, focusing on time (e.g., How long does it take to have a shower?) and weight (e.g., How heavy is a pair of jeans?) estimations. Each item scores from 0 (bizarre estimation) to 3 (best estimation), for a total maximum score for each section of 30, with a cut-off value for normality above 20 for each section. | baseline | 
| Assessment of Verbal Estimation Ability on the Cognitive Estimation Task (CET) | The test comprised 21 questions that required participants to give oral, numerical responses. Two different scoring procedures will be considered: absolute error score and bizarreness. The total score for all 21 items ranges from a best of zero to a worst of 42. The greater the error score, the poorer the performance on the CET (cut-off = 18). The total bizarreness score ranges from 0 and 21 (cu-off = 4). The higher the bizarreness score, the greater the impairment in cognitive estimation. | baseline | 
| Correlation between Time Processing Abilities | MTT and Time Estimation Task will be correlated to investigate the relationship between different time processing abilities. | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Time perception, Mental Time Travel, Prismatic adaptation, Left and Right Brain Damaged Patients