Michelle Hampson, PhD: The use of real-time fMRI to treat and study mental illness

Transcript

• 00:00My name is Michelle Hampson.
• 00:01I'm going to be talking today about
• 00:04some work that our group has been doing
• 00:06using real time fMRI neurofeedback to
• 00:08try to treat and study mental illness.
• 00:10So what do we mean by real time?
• 00:12fMRI neurofeedback?
• 00:13Well, this is a picture of somebody
• 00:15receiving this form of neurofeedback.
• 00:16They're lying in an MRI scanner
• 00:18and we're monitoring their brain
• 00:20activity patterns and we give them
• 00:21feedback over the course of the scan,
• 00:23showing them how some aspect of
• 00:25their brain activity is changing
• 00:27over the course of the of the scan
• 00:29and they get lots of practice trying
• 00:31to control that brain activity.
• 00:32Using the feedback that we give
• 00:34them as a training signal.
• 00:36So there's many different applications
• 00:38using this technique across the world
• 00:40to try to train people to control
• 00:42specific aspects of their brain function.
• 00:44I'm going to talk today about a
• 00:46specific application where we use
• 00:48this to try to train people to
• 00:49control contamination anxiety.
• 00:51So why am I focused on contamination anxiety?
• 00:54Well,
• 00:54it's a major symptom dimension
• 00:55of obsessive compulsive disorder,
• 00:57and it's also common in the healthy
• 00:59population.
• 00:59An regardless of whether you're a piece
• 01:02of patient with OC D or a healthy person.
• 01:05If you're experiencing contamination anxiety,
• 01:06we know that you have hyperactivity.
• 01:08And your orbital frontal cortex.
• 01:10So this is an area right at the front
• 01:12of your brain which provides kind of
• 01:14a biomarker of contamination anxiety.
• 01:16And we were wondering if we train people
• 01:19to control activity in this region,
• 01:21will that help them to better
• 01:23control their contamination anxiety?
• 01:24So that's the study I'm going
• 01:26to describe to you today.
• 01:27In this study we collected three
• 01:29different outcome measures.
• 01:30First of all,
• 01:31we assessed how well the training enabled
• 01:33people to control their target brain area.
• 01:35We also monitor brain connectivity,
• 01:37pattern changes.
• 01:38So we collected resting state data before
• 01:40the intervention after the intervention.
• 01:42To see if the training basically
• 01:44rewired their brain connectivity and
• 01:45then Thirdly and most importantly
• 01:47we had a measure of control over
• 01:49contamination anxiety that we collected
• 01:51before the training and after the
• 01:53training to see if the neurofeedback
• 01:54training improved people's ability to
• 01:56control their contamination anxiety.
• 01:58The last thing I'll mention before
• 01:59going on is that in addition to
• 02:02the subjects who got real neural
• 02:04feedback in this study,
• 02:05we had a control group that received
• 02:07a fake or sham form of neurofeedback.
• 02:10So just so you have a sense of what the.
• 02:13Neurofeedback is like for participants.
• 02:14I'm going to show you a video,
• 02:16which is exactly what one of our
• 02:18subjects saw in the neural feedback training.
• 02:20On the left is an arrow that cues
• 02:22the mess to their current task.
• 02:23When it's a white arrow pointing
• 02:25forward that tells them just to rest,
• 02:27relax and look at the neutral image
• 02:29at other periods of time it will be a
• 02:31red arrow pointing up or a blue arrow
• 02:33pointing down and that skewing them
• 02:34to try to increase or decrease
• 02:36activity in the target brain area.
• 02:37And during those periods of
• 02:39provocative images shown depicting
• 02:40some contamination related thing.
• 02:41So I've started playing the video
• 02:42and you can see the feedback is
• 02:44provided here in this line graph.
• 02:46At the bottom of the screen.
• 02:48And right now they're just
• 02:49resting and looking at what's
• 02:50happening in their orbital cortex,
• 02:51but now it's an increased block,
• 02:53so now they're trying to
• 02:54get the line to go up.
• 02:56They can look at this picture
• 02:57of a dirty stove and think,
• 02:59oh that's a food surface
• 03:00that really should be clean.
• 03:01Whatever is going to be helpful to
• 03:03activate this anxiety related brain
• 03:04area Now it's going to decrease block,
• 03:06so they're going to decrease.
• 03:07Block is to bring the activity
• 03:08in this area back down there
• 03:10supposed to look at the image,
• 03:11but they can be appraised it you
• 03:13know you're in is usually sterile.
• 03:15There's nothing to be worried about.
• 03:16Whatever they think is going to be helpful.
• 03:18For controlling that region and now
• 03:20it's arrest block so they basically
• 03:21cycle through these three blocks,
• 03:22getting lots and lots of practice
• 03:24trying to get activity in the target
• 03:26brain area to increase in the red
• 03:27blocks and decreasing the blue blocks.
• 03:29And the sham subjects.
• 03:32Our match one to one to the real
• 03:34neurofeedback subjects an are shown
• 03:35at the time courses from the real
• 03:37neural feedback subjects brains,
• 03:38but misled to believe that getting
• 03:39feedback from their own brain.
• 03:41So to the extent that the real
• 03:43neurofeedback subject got the
• 03:44line higher in the red than the
• 03:45blue blocks there Matcham subject
• 03:46is misled to believe they're
• 03:48having a similar level of success.
• 03:49So that was the kind of control that we used.
• 03:52If you want to know anything
• 03:53else about our methods,
• 03:54we have a job paper with a
• 03:56cheesy video you can watch,
• 03:57but I'm going to present to
• 03:59you now the results.
• 04:00So first of all,
• 04:01did the training help them better
• 04:02control their target region?
• 04:04We evaluated that ability to
• 04:05control the target region at
• 04:06four points throughout the study.
• 04:08The important thing to note is
• 04:09that at the end of the training,
• 04:11they had statistically significantly
• 04:13greater control than they did at
• 04:14the beginning of the training.
• 04:16So indeed,
• 04:16it seemed like the neurofeedback
• 04:17training did improve their ability
• 04:19to control their target brain area,
• 04:20which is encouraging.
• 04:21But the more important question is,
• 04:23does it actually translate into
• 04:24anything outside of the scanner so
• 04:26they actually get better at controlling
• 04:28their contamination anxiety?
• 04:28So for that,
• 04:29we turn to our behavioral measure
• 04:31that we collected before and
• 04:32after the intervention.
• 04:33Indeed,
• 04:33what we found.
• 04:34Is that the training did improve
• 04:36ability to control contamination
• 04:37anxiety in the neurofeedback
• 04:39subjects and it had no significant
• 04:41effect and the control group.
• 04:42So this was really exciting to
• 04:44us because it implies that this
• 04:45training can help people better
• 04:47control their contamination
• 04:48anxiety and contamination.
• 04:49Anxiety is a major symptom dimension of OC D,
• 04:52so that means that it has the same
• 04:54effects in the clinical population.
• 04:56This intervention would have
• 04:57direct clinical utility,
• 04:58but it raises the question well,
• 05:00what's going on in the brains of
• 05:02these people that they're better
• 05:04able to control their contamination
• 05:05anxiety after the training.
• 05:07So for that we looked at the resting
• 05:09state connectivity changes we used
• 05:11to measure of global connectivity,
• 05:12where we evaluate which parts of the
• 05:15brain changed their global amount
• 05:16of connectivity over the course of
• 05:18the training and what we found is
• 05:20that these areas shown with red,
• 05:22yellow colors,
• 05:23whereas it had significant
• 05:24increases in global connectivity
• 05:25in the neurofeedback subjects.
• 05:26These are prefrontal control areas
• 05:28and the areas shown in blue had
• 05:30decreases in global connectivity,
• 05:31so these are a lot of limbic
• 05:33emotion processing parts of
• 05:35the brain including insula,
• 05:36substantia nigra, amygdala, hippocampus.
• 05:37So it seemed like this is very
• 05:40consistent with neurobiological
• 05:41models of emotion regulation,
• 05:42whereby prefrontal control areas come
• 05:44online to help downregulate processing
• 05:46in limbic or emotion parts of the brain.
• 05:48And it seemed like the neural feedback
• 05:50was strengthening that circuitry an I
• 05:52should note that this is these effects
• 05:54were specific to the neurofeedback group.
• 05:57We did a similar analysis in the control
• 05:59group and there were no significant
• 06:01changes in global connectivity.
• 06:02But this is the pattern we see in the
• 06:05group of neurofeedback subjects as a whole.
• 06:08An within this group there are a lot
• 06:10of differences between subjects,
• 06:11so some subjects really get a lot from
• 06:13the intervention and other subjects find
• 06:15it frustrating and get very little from it.
• 06:17So we wanted to see what's happening in
• 06:19the brains of those good responders,
• 06:21and we computed correlation map
• 06:22examining which parts of the brain
• 06:24had changes in global connectivity,
• 06:25and the people who really responded well.
• 06:27And what we found jumping out
• 06:29of this analysis.
• 06:30This is analysis that treats every
• 06:31part of the brain in the same way,
• 06:33but what popped out of this
• 06:35analysis was our target region
• 06:36of the orbital frontal cortex.
• 06:38So the people who were rewiring
• 06:40this target area where the people
• 06:41who are really gaining control
• 06:43over their contamination anxiety,
• 06:44which is encouraging that we're
• 06:46targeting a reasonable part of the brain.
• 06:48If you manage to rewire the brain area,
• 06:50you get better control over your anxiety.
• 06:53So we thought all this data was
• 06:55really promising and we decided we
• 06:57wanted to move forward in studying
• 06:58this in an OC D population.
• 07:00So we applied for funding from NIH and
• 07:03we're now running a clinical trial in OC T.
• 07:05This is a randomized double blind
• 07:07placebo controlled trial which were
• 07:09actually close to wrapping up now.
• 07:11It's very similar to the study
• 07:13I just described to,
• 07:14except that we're running OC D
• 07:16patients and we're monitoring
• 07:17symptoms with classic symptom scales
• 07:18rather than a behavioral measure.
• 07:20But one interesting new aspect
• 07:21of the study is that
• 07:23we're following these subjects up clinically
• 07:25after they receive the neural feedback.
• 07:27So in the study I just described to you,
• 07:30we assess their ability,
• 07:31their, their contamination,
• 07:32symptoms of a few days after the training,
• 07:35and we do that in this
• 07:36clinical trial as well.
• 07:38But in addition, we bring them back
• 07:40two weeks later and assess them again.
• 07:42Then we also bring back a month
• 07:44later and assess their symptoms
• 07:45amonth after the training.
• 07:47So in this clinical trial we're
• 07:49actually following them from month
• 07:50post neurofeedback and the reason we're
• 07:52doing that as we wanted to rule out
• 07:54the possibility that the effects we
• 07:56are inducing were just transient so it
• 07:58wouldn't be super clinically useful.
• 08:00If you know participants who got
• 08:01real neurofeedback got better
• 08:02while they're receiving the neural
• 08:04feedback and their symptoms,
• 08:05you know decreased,
• 08:06and then as soon as you know feedback ended,
• 08:09they regressed back to baseline.
• 08:10That wouldn't be super clinically useful
• 08:12'cause you kind of need something
• 08:14that persists in a person's life.
• 08:16What we were hoping to show by doing
• 08:18this follow up is that the improvements
• 08:20in symptoms that we induced with the
• 08:22training were maintained during the
• 08:24month that we were following up afterwards,
• 08:26but we found was actually quite surprising.
• 08:28The subjects got better
• 08:29during the neurofeedback,
• 08:30but they continued to get better for
• 08:31a month after the neurofeedback so
• 08:33that the biggest differences between
• 08:35the control group and the real
• 08:37neurofeedback group were actually
• 08:38a month after training.
• 08:39So this was totally surprising
• 08:40to us and we thought,
• 08:42is this specific to OC D is
• 08:43this like an idiot?
• 08:45Syncratic phenomena for this application?
• 08:46But then we.
• 08:47We went and looked at another study
• 08:49we were running in Trett syndrome,
• 08:51which showed exactly the same pattern.
• 08:53This was a different population being
• 08:54trained on a different brain area,
• 08:56but we are assessing different
• 08:58type of symptoms.
• 08:59But we saw the same qualitative pattern,
• 09:01so we thought,
• 09:01well,
• 09:02maybe this is not an uncommon pattern
• 09:04in neurofeedback experiments and so we
• 09:05wrote this up and published in neuroimaging.
• 09:08It since heard from multiple groups
• 09:09that they are seeing similar
• 09:11patterns in other applications.
• 09:12So it's a really important for the people
• 09:15designing studies in our field to know this.
• 09:17Because if you're going to.
• 09:19Running her feedback study,
• 09:20it's very important to follow people
• 09:22up for a month or you might be missing
• 09:25the time point of greatest effect.
• 09:27So this that I've described here is just
• 09:29one of the studies were running at Yale.
• 09:31There are many different ongoing studies
• 09:33looking at all sorts of different disorders.
• 09:34If you're interested in using real
• 09:36time after a feedback to treat
• 09:38or study mental illness,
• 09:39please come talk to me.
• 09:42I want to just quickly acknowledge
• 09:44contributions of the people.
• 09:45This I can't possibly show everybody
• 09:47doing their feedback research at Yale.
• 09:49This is the subgroup that was involved
• 09:52specifically in that sub clinical OC D study,
• 09:54our primary clinical collaborator
• 09:56in that setting is Chris Pittenger.
• 09:58Teodora Stoica collected all that day.
• 10:00That I presented to you and Dustin
• 10:02Chinese has been really involved in,
• 10:04you know, creating and maintaining the
• 10:06real time imaging systems that we use.