SNI Study News
The trail of trauma
permalinkUMNnews - Health+Medicine - Deane M. Morrison - 2013-08-27When a disaster strikes, groups of people spontaneously form and start talking all at once.And your brain does the same thing in response to personal trauma. Groups of neurons in the cerebral cortex start firing at the same time, "talking" to each other, and get locked into a correlated pattern of activity. Previous work by University of Minnesota researchers identified a particular pattern so strongly associated with post-traumatic stress disorder (
Posttraumatic Stress Disorder) that they can clearly tell who has
PTSD. Now, a new study shows that in people with
PTSD, these patterns persist, just as do the intrusive, incapacitating memories or re-experiencing of the events, emotional numbing, and hyperarousal that define the disorder.
But, they found, in people who have not developed
PTSDdespite exposure to trauma, the patterns lack staying power. In them, "these patterns loosen and dissipate over weeks, months, or days," says lead researcher Lisa James, an assistant professor in the U's Department of Psychiatry and a researcher in the
Brain Sciences Centerat the Minneapolis
VA Medical Center, where the study took place. "This wipes the slate clean."
"Our work means that in resilient people the brain can actively adapt to traumatic experiences in a way that those with
PTSDcannot. The better we understand the brain mechanisms associated with
PTSD, the sooner we can apply that knowledge to evaluating treatment efficacy."
Co-author Apostolos Georgopoulos likens the situation in a trauma-exposed brain to an infection.
The advantage of
MEGis its ability to detect brain activity on a scale of milliseconds. The researchers placed an apparatus resembling a helmet over the heads of the subjects, who were asked to fixate on a stationary dot with their eyes for 60 seconds. The helmet contained 248 sensors, each of which detected the magnetic fields generated in a population comprising tens of thousands of cortical cells. Together, the sensors scanned the magnetic activity over the whole cortex.
'It's like having a disease, where you make antibodies," says Georgopoulos, a Regents Professor of neuroscience and director of the
BSC. "If you can't make antibodies, you don't adapt to the virus. Similarly, if you don't de-correlate your brain networks, you're still sick."
Short-term tracking of the
PTSD-linked patterns in people exposed to trauma could potentially identify those who are resilient vs. those who need treatment. Pattern tracking could also be used to monitor progress during
PTSDtreatments or to validate a simpler test for resilience, such as genetic or personality traits, the researchers say.
The work is published online in the journal JAMA Psychiatry.
How to eavesdrop on brain chatter
The researchers studied 86 veterans with
PTSDand 113 veterans who were resilient to trauma. A questionnaire revealed the extent of their exposure to trauma; those with trauma exposure but no
PTSDwere, by definition, resilient controls.
The team used a noninvasive technique called
MEG; see sidebar)) to study the magnetic fields generated in neurons of the right temporal lobe cortex as they received messages during neuronal "talk." Neurons receiving messages experience movements of ions across their outer membranes; these movements generate the magnetic fields.
MEGmeasured the strength of correlated patterns of activity in cell populations-i.e., simultaneous generation of magnetic fields-characteristic of
PTSD. They discovered:
Among controls, weaker
PTSD-related patterns tended to occur in those with highertrauma scores. In other words, "In controls, big trauma leads to a big adaptation," says Georgopoulos.
Also in controls, the right temporal cortex had a crucial node in which brain activity was decorrelated, a signal of adaptation. This area of the brain is a focus of future study.
Resilience isn't an all-or-nothing trait, but a continuum.
The trauma landscape
Most people are resilient to some events, so the question becomes: Why isn't everybody?
"About 60 to 90 percent of people will experience a potentially traumatic event in their lifetime, like a car accident or the sudden death of a loved one, but they are resilient. They don't develop symptoms of a psychiatric disorder," says James.
"Only seven percent of people in the general population and about 20 percent of veterans develop
PTSD. Most come back [from service] without
PTSD-what enables them to do that?"
To answer that question, the researchers are turning their attention to a search for genetic markers of resilience. If certain genes or, perhaps, personality traits, are found to be associated with resilience, that could allow researchers to predict one's degree of resilience before trauma hits.
PTSDsufferers have options that include medications, talk therapy, and interventions to treat nightmares," James says. "We're interested in what happens in the brain as individuals with
PTSDrespond to treatment."
Risk and Protective Factors Associated With Symptoms of Post-Traumatic Stress, Depression, and Alcohol Misuse in Operation Enduring Freedom - Afghanistan/Operation Iraqi Freedom Veterans
Neural Network Modulation by Trauma as a Marker of Resilience Differences Between Veterans With Posttraumatic Stress Disorder and Resilient Controls
permalinkJAMA Psychiatry - 2013-01-01James L, Engdahl B, Leuthold A, Lewis S, Kampen EV, Georgopoulos AP10.1001/jamapsychiatry.2013.878Importance
PTSDand resilience reflect 2 distinct outcomes after exposure to potentially traumatic events. The neural mechanisms underlying these different outcomes are not well understood.
Objective To examine the effect of trauma on
Synchronous Neural Interactionsfor veterans with
PTSDand resilient controls using magnetoencephalography.
Design Participants underwent diagnostic interviews, a measure of exposure to potentially traumatic events, and magnetoencephalography.
Setting US Department of Veterans Affairs medical center.
Participants Eighty-six veterans with
PTSDand 113 resilient control veterans recruited from a large Midwestern medical center.
Main Outcome Measures Multiple regression analyses were performed to examine the effect of lifetime trauma on global and local
SNI. In analyses examining the local
SNI, the partial regression coefficient indicates the strength and direction of the effect of trauma on the synchronous interactions between the 2 neural signals recorded by a pair of sensors. The partial regression coefficient, or slope, is the primary outcome measure for these analyses.
SNIwere significantly modulated downward with increasing lifetime trauma scores in resilient control veterans (P = .003) but not in veterans with
PTSD(P = .91). This effect, which was primarily characterized by negative slopes (ie, decorrelations) in small neural networks, was strongest in the right superior temporal gyrus. Significant negative slopes were more common, stronger, and observed between sensors at shorter distances than positive slopes in both hemispheres (P < .001 for all) for controls but not for veterans with PTSD.
Conclusions Neural modulation involving decorrelation of neural networks in the right superior temporal gyrus and, to a lesser extent, other areas distinguishes resilient veterans from those with
PTSDand is postulated to have an important role in healthy response to trauma.
Canonical correlation analysis of Synchronous Neural Interactions and cognitive deficits in Alzheimer's dementia
permalinkJournal of Neural Engineering - 2012-08-07Karageorgiou E, Lewis S, McCarten JR, Leuthold A, Hemmy LS, McPherson SE, Rottunda SJ, Rubins D, Georgopoulos AP10.1088/1741-2560/9/5/056003In previous work (Georgopoulos et al 2007 J. Neural Eng. 4 349-55) we reported on the use of magnetoencephalographic (
SNIas a functional biomarker in Alzheimer's dementia (AD) diagnosis. Here we report on the application of canonical correlation analysis to investigate the relations between
SNIand cognitive neuropsychological (NP) domains in AD patients. First, we performed individual correlations between each
SNIand each NP, which provided an initial link between
SNIand specific cognitive tests. Next, we performed factor analysis on each set, followed by a canonical correlation analysis between the derived
SNIand NP factors. This last analysis optimally associated the entire
MEGsignal with cognitive function. The results revealed that
SNIas a whole were mostly associated with memory and language, and, slightly less, executive function, processing speed and visuospatial abilities, thus differentiating functions subserved by the frontoparietal and the temporal cortices. These findings provide a direct interpretation of the information carried by the
SNIand set the basis for identifying specific neural disease phenotypes according to cognitive deficits.
Post-traumatic stress disorder: a right temporal lobe syndrome?
permalinkJournal of Neural Engineering - 2010-10-28Engdahl B, Leuthold A, Tan HRM, Lewis S, Winskowski AM, Dikel TN, Georgopoulos AP10.1088/1741-2560/7/6/066005In a recent paper (Georgopoulos et al 2010 J. Neural Eng. 7 016011) we reported on the power of the
SNItest to differentiate post-traumatic stress disorder (
PTSD) subjects from healthy control subjects and to classify them with a high degree of accuracy. Here we show that the main differences in cortical communication circuitry between these two groups lie in the miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas. This lateralized temporal-posterior pattern of miscommunication was very similar but was attenuated in patients with
PTSDin remission. These findings are consistent with observations (Penfield 1958 Proc. Natl Acad. Sci. USA 44 51-66, Penfield and Perot 1963 Brain 86 595-696, Gloor 1990 Brain 113 1673-94, Banceaud et al 1994 Brain 117 71-90, Fried 1997 J. Neuropsychiatry Clin. Neurosci. 9 420-8) that electrical stimulation of the temporal cortex in awake human subjects, mostly in the right hemisphere, can elicit the re-enactment and re-living of past experiences. Based on these facts, we attribute our findings to the re-experiencing component of
PTSDand hypothesize that it reflects an involuntarily persistent activation of interacting neural networks involved in experiential consolidation.
The Synchronous Neural Interactions test as a functional neuromarker for post-traumatic stress disorder (Posttraumatic Stress Disorder): a robust classification method based on the bootstrap
permalinkJournal of Neural Engineering - 2010-01-20Georgopoulos AP, Tan HRM, Lewis S, Leuthold A, Winskowski AM, Lynch J, Engdahl B10.1088/1741-2560/7/1/016011Traumatic experiences can produce post-traumatic stress disorder (
PTSD) which is a debilitating condition and for which no biomarker currently exists (Institute of Medicine (US) 2006
PTSD: Diagnosis and Assessment (Washington, DC: National Academies)). Here we show that the
SNItest which assesses the functional interactions among neural populations derived from magnetoencephalographic (
MEG) recordings (Georgopoulos A P et al 2007 J. Neural Eng. 4 349-55) can successfully differentiate
PTSDpatients from healthy control subjects. Externally cross-validated, bootstrap-based analyses yielded >90% overall accuracy of classification. In addition, all but one of 18 patients who were not receiving medications for their disease were correctly classified. Altogether, these findings document robust differences in brain function between the
PTSDand control groups that can be used for differential diagnosis and which possess the potential for assessing and monitoring disease progression and effects of therapy.
P2-027: Association of cognitive deficits with Synchronous Neural Interactions as revealed by magnetoencephalography: A canonical correlation analysis
permalinkAlzheimer's & Dementia - 2008-07-01Karageorgiou E, Lewis S, McCarten JR, Leuthold A, Hemmy LS, McPherson SE, Rottunda SJ, Georgopoulos AP10.1016/j.jalz.2008.05.1108In a recent study we showed that
MEGin a simple fixation test can be used as a functional biomarker for brain disorders (Georgopoulos et al., J. Neural Engineer. 4:349-355, 2007). The
SNIvariables consist of partial zero-lag cross-correlations estimated between pairs of 248 axial gradiometer sensors after prewhitening of the
MEGtime series. In this study we evaluated the relations between cognitive deficits and
Synchronous Neural Interactions assessed by magnetoencephalography: a functional biomarker for brain disorders
permalinkJournal of Neural Engineering - 2007-08-27Georgopoulos AP, Karageorgiou E, Leuthold A, Lewis S, Lynch J, Alonso A, Aslam Z, Carpenter A, Georgopoulos A, Hemmy LS, Koutlas I, Langheim F, McCarten JR, McPherson SE, Pardo J, Pardo P, Parry GJ, Rottunda SJ, Segal BM, Sponheim S, Stanwyck JJ, Stephane M, Westermeyer JJ10.1088/1741-2560/4/4/001We report on a test to assess the dynamic brain function at high temporal resolution using
MEG. The essence of the test is the measurement of the dynamic
SNI, an essential aspect of the brain function.
MEGsignals were recorded from 248 axial gradiometers while 142 human subjects fixated a spot of light for 45-60 s. After fitting an autoregressive integrative moving average (ARIMA) model and taking the stationary residuals, all pairwise, zero-lag, partial cross-correlations (PCCij0) and their z-transforms (zij0) between i and j sensors were calculated, providing estimates of the strength and sign (positive, negative) of direct synchronous coupling at 1 ms temporal resolution. We found that subsets of zij0 successfully classified individual subjects to their respective groups (multiple sclerosis, Alzheimer's disease, schizophrenia, Sj"ogren's syndrome, chronic alcoholism, facial pain, healthy controls) and gave excellent external cross-validation results.