Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT01506206 |
| Other study ID # |
2011P002546 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 2012 |
| Est. completion date |
January 10, 2024 |
Study information
| Verified date |
January 2024 |
| Source |
Massachusetts General Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The investigators propose a test of causality by examining a cohort of patients undergoing
deep brain stimulation (DBS) within the ventral striatum. The investigators will examine
behavior on and off stimulation across a range of tasks that index different forms of
impulsivity. Patients will be studied in both the ON and OFF state - that is, they will be
tested during active deep brain stimulation and 30 min to 1 hour after stimulation has been
stopped (order of state will be counterbalanced across subjects). The investigators specific
aim is to test the hypothesis that enhancing ventral striatal signaling (i.e. ON-state DBS)
will cause more impulsive patterns of behavior across several impulsivity tasks. The
investigators predict that ventral striatal DBS will increase stop-signal reaction time on
the stop-signal task and commission errors on the Go/NoGo task, and increase delay aversion
in a delay discounting paradigm.
Description:
The study will take place at a clinical office in the Charlestown Navy Yard (CNY), and will
consist of 4 or 4.5 hour visit. Study staff will schedule a convenient time for patients to
arrive, or the research visit may be paired with a regularly scheduled DBS programming visit.
A member of the Division of Neurotherapeutics authorized to manipulate DBS programming will
turn the device ON and OFF during the study. The subject's therapeutic parameters of the DBS
system will not be changed. The subject will be asked to complete 2 questionnaires. Following
these questionnaires, DBS stimulation will be turned off and a member of the study staff will
teach the subjects to perform the following tasks on the computer:
Stop-Signal Task To measure "impulsive action," the investigators will use the stop-signal
task (SST), a well-validated measure of response inhibition known to be impaired in substance
abusers. In each of the 192 trials (3 blocks of 64; 10s interval between blocks, 2s ISI),
subjects see a fixation cue (250ms) that is replaced by a shape (square or circle).
Participants are told to make a shape judgment by pressing the appropriate computer key. On
no-signal trials (75%), subjects are instructed to respond to the stimulus as fast and
accurately as possible. On stop-signal trials (25%), the stimulus is followed by an auditory
stop signal, and subjects are instructed to withhold responding. On stop-signal trials, a
stop signal is presented after a variable delay (SSD), initially set at 250 msec and adjusted
continuously with a staircase procedure by 50ms depending on whether inhibition is successful
(increases) or unsuccessful (decreases). The paradigm will be administered using precompiled
software provided by Gordon Logan, which automatically analyzes all relevant dependent
variables (e.g stop-signal reaction time [SSRT] and GoRT). This task takes approximately 20
minutes.
Rewarded Variant This task is a variant of the above, with an inclusion of a "points possible
cue" (2 or 50 points) for 500 ms, and followed by a brief delay (500-1500 ms) prior to the
target. The task will be presented in 13 blocks. The first contains only go trials, from
which the initial SSD will be calculated. The 12 subsequent blocks each consist of 40 trials;
18 standard go trials, 12 high reward (HR) go trials, 6 standard stop trials, and 4 HR stop
trials, presented in random order. The SSD will be determined by a simple staircase-tracking
algorithm as described by Logan, in which the SSD is adjusted up or down by 25 ms in order to
establish an SSD that produces 50% accuracy of successful performance, with separate
staircases calculated for the HR and standard trials. Outcome measures are the standard and
high reward GoRTs, the standard and HR SSRTs, and the proportion of responses that would have
been unsuccessfully stopped on HR trials if the standard SSD were utilized instead of the HR
SSD.
Rewarded Go/NoGo Task In this task, participants are asked to make, or withhold, a button
press to one of six stimuli (shapes), that correspond to six trial types: Go (no reward), Go
(low reward), Go (high reward), NoGo (no reward), NoGo (low reward), NoGo (high reward).
Participants are asked to press a button for Go stimuli and withhold a button press for NoGo
stimuli. The ratio of Go stimuli to NoGo stimuli is approximately 15:1. Participants win
money for correctly pressing a button for Go stimuli and for withholding a response for NoGo
stimuli; conversely, they lose money for failing to respond to a Go stimuli or for failing to
withhold a response to NoGo stimuli. There are 1260 trials, and each lasts 1 second. The task
takes about 20 minutes to complete. Task may be administered without reward contingencies. In
this case, there will only be two trial types: Go and NoGo.
Delay Discounting Task To measure "impulsive choice" the investigators will use a
delay-discounting (DD) paradigm101. On each trial, participants make a binary choice between
a smaller/sooner and a larger/later reward. The delay of the sooner reward is set as today, 2
weeks, & 1 month; the delay of the later reward ranges from 2 to 6 weeks after the early
reward. The sooner reward is from 1% to 50% less than the late reward (max = $40).
Participants will complete approximately 80 trials. Participants are told that two of their
choices will be randomly selected for payout at the appropriate time. Outcome variables
include the proportion of choices for immediate/sooner rewards, as well as discounting
parameter k, obtained by fitting choice data for each subject to a hyperbolic discount
function. The task takes approximately 15 minutes to complete.
30 minutes after turning OFF DBS stimulation, participants will either remain in the OFF
condition or will have the DBS turned ON, depending on their counter-balanced condition
assignment. Subjects will complete the tasks above in the first condition. Following task
completion, subjects will have DBS stimulation turned OFF or ON (again, depending on
condition assignment). After 30 minutes, participants will complete the same tasks in the
second condition. Following retesting, participants that were in the OFF condition will
return to ON DBS stimulation.
The investigators will be using the implanted pulse generator to deliver a safe current.
Because the investigators are not changing the therapeutic parameters of stimulation,
subjects should not experience any changes during the ON condition. Should any discomfort
arise in the OFF condition, the subject will be able to terminate the study and return to the
ON condition immediately. The computer will register the subject's performance.
Electroencephalography recordings (EEG) will be acquired during performance of the
aforementioned tasks. Continuous EEG data will be sampled at a maximum of 1024Hz using a
64-electrode cap. Eye movement artifacts will be assessed using bipolar electrodes.
Patients with just major depressive disorder or obsessive compulsive disorder will also be
recruited as a control group for the patients with deep brain stimulation.
