Conjunct COST B27 and SAN Scientific Meeting, Swansea, UK, 16-18 September 2006

Low Resolution Electromagnetic Tomography (LORETA) in Monozygotic Twins Discordant for Chronic Fatigue Syndrome

Authors

 Leslie Sherlin, M.S.

 Thomas Budzynski, Ph.D.

 Helen Kogan Budzynski, Ph.D.

 Marco Congedo, Ph.D.

 Mary E. Fischer, Ph.D.

 Jack Goldberg, Ph.D.

 Suzanne Ashton, B.S.

 Dedra Buchwald, M.D.

Acknowledgements



Drs Tom and Helen Budzynski

Chronic Fatigue Syndrome



Chronic fatigue syndrome (CFS) is an illness characterized by profound fatigue lasting at least 6 months accompanied by disturbances of sleep, mood, musculoskeletal pain, and other symptoms (Fukuda et al., 1994).

Previous Applications  Attention Deficit Disorder (Chabot & Serfontein, 1996) - QEEG   Schizophrenia (Pascual-Marqui, 1999) LORETA Depression (Pizzagalli et al., 2002 ) – LORETA  Obsessive Compulsive Disorder (Prichep et al., 1993) – QEEG (Sherlin and Congedo, 2002) - LORETA

CFS & QEEG

 “ CFS and healthy twins differed significantly on qEEG theta and delta parameters.

” (Budzynski et al., Manuscript Submitted for publication) – Elevated levels of theta at FZ, CZ, & PZ – Elevated levels of delta at CZ, PZ

CFS & QEEG

 “ CFS microvolt levels were significantly higher in the 5-7 Hz range under [eyes closed] condition.

” (Billiot, Budzynski & Andrasik, 1997)

LORETA & CFS

 To date, there are no other studies using the techniques of LORETA with the CFS population.

 The current investigation compares current source density measures of monozygotic twins discordant for CFS.

Subject Selection

 Twins were part of a larger study designed to examine genetic contributions to the medical and psychological aspects of CFS (Buchwald et al., 2001)  A very extensive screening procedure took place beginning with 600 individuals which was then narrowed to 193 pairs obtained from the CFS Twin Registry (Buchwald et al, 1999)

Subject Selection

 Ultimately 22 sets of twins were selected for the clinical sample.

 Due to dropout in screening and constraints in data collection, 17 sets are described here.

Clinical Sample

 From those measures, – At least 18 years old – Reared together – Discordant for CFS (one twin met the Center for Disease Control criteria at the time of test and the co-twin was healthy and had no history of chronic fatigue) – Evidence of a recent negative HIV test

Clinical Sample

– Discontinued use of alcohol, caffeine, and all medications known to affect sleep, cognition, immune, or inflammatory function at least two weeks prior to and during all evaluations.

– Deny head trauma that was recurrent or accompanied by more than 5 minute loss of consciousness.

– Able to travel at the same time to the testing center in Seattle.

Subject Validation/Reliability

 Clinical diagnosis included: – Diagnostic Interview Schedule (Version III-A) – Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) – Clinical Interview – Medical record review

Subject Validation/Reliability

 Zygosity was determined – Using validated self report methods – Confirmed by restriction fragment length polymorphisms  Following 6 tests the probability of monozygosity was confirmed with 99.9% certainty

Instruments

 Neurosearch-24 – Lexicor Medical Technology, Inc  EureKa3! and MHyT3! from the

NTE Pack freeware

– Nova Tech EEG, Inc  LORETA-Key Viewer from the

LORETA-Key freeware

– Key Institute for Mind Brain Research

EEG Collection

 An EEG was collected on each of the subjects under standardized settings and procedure  EEG was digitally recorded on a LEXICOR Neurosearch-24 system from 19 scalp electrodes  The EEG was sampled in the awake state with eyes closed and serial 7s task  The recording was imported, visually edited for artifact and subjected to quantitative spectral analysis using EureKa3! software

EEG Analysis

  For each subject the cross spectral analysis was computed in 12 bands on the

eyes closed

condition recording Bands analyzed were: Delta 2-3.5 Hz Theta 4-7.5 Hz Alpha1 8-10 Hz Alpha2 10-12 Hz Alpha 8-12 Hz Beta1 12-16 Hz Beta2 16-20 Hz Beta3 20-24 Hz Beta4 24-28 Hz Beta5 24-32 Hz Beta 13-21 Hz Hi Frequency 13-32 Hz

Statistical Analysis

 The statistical T-sum procedure was utilized which is a multiple comparison procedure based on a combination of Test-Statistics

LORETA

 LORETA is a solution to the inverse problem that is the computation of images of electric neuronal activity based on scalp EEG measurements (Pascual-Marqui, 2002)  These measurements provide information on the time course and localization of brain function (Pascual Marqui, 2002)

Low Resolution Electromagnetic Tomography

 Cortical grey matter limited to 2394 voxels  Each voxel is 7x7x7 mm  Color is representing “current source density”

Results

 The average age for the 17 pairs of twins was 40.6 years, 88% were female, and 100% were white.   CFS twins differed from their co-twins in the frequency of being employed (53% versus 88%,

p

= 0.034), current depression (24% versus 0%,

p

= 0.046) and in educational level (13.7 versus 14.4 years,

p

= 0.048). Among the twins with CFS, 47% reported an acute onset with a flu-like illness with an average fatigue duration of 7.4 years.

Results

 The majority of the frequency band parameters were similar in the CFS and healthy twins: – alpha1 (-1.83 difference), – alpha2 (-2.46 difference), – – beta1 (2.01 difference), beta2 (-.42 difference), – – – beta3 (-.34 difference), beta4 (2.52 difference), and beta5 (-1.94 difference).

Results

 The maximum t-statistic, or maximum t value across the entire volume was  3.61 for delta and  6.08 and theta, which indicates that the effect for theta is much stronger than the effect for delta.

 LORETA current source density in the delta (2-3.5 Hz) band was higher in the CFS twins than among the healthy twins in the left uncus and parahippocampal gyrus (Brodmann areas 28, 36, 38 and 20).

 LORETA current source density in theta also was higher in the CFS group in the cingulate gyrus (Brodmann areas 24 and 32) and right precentral gyrus of the frontal lobe (Brodmann areas 6 and 8).

Discussion

   Previous studies have found that slowing of the deeper structures of the limbic system are associated with affect. This system appears to be involved in guiding behavior and regulation of mood. Functional imaging studies indicate that many of these areas also show volume changes and decreased glial number and density in mood-disordered subjects

Discussion

 This study demonstrates the utility of LORETA as a clinical tool.

 May help us understand CFS in new light…

mood disorder

?

 The obvious implications for our field are: – validation of the physiological markers for a disorder – that with advanced neurofeedback techniques the potential for clinically relevant treatment may fulfilled.