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

1
Low Resolution Electromagnetic Tomography
(LORETA) in Monozygotic Twins Discordant for
Chronic Fatigue Syndrome
Conjunct COST B27 and SAN Scientific Meeting,
Swansea, UK, 16-18 September 2006
2
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.

3
Acknowledgements

• Drs Tom and Helen Budzynski

4
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).

5
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

6
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

7
CFS QEEG

• CFS microvolt levels were significantly higher
  in the 5-7 Hz range under eyes closed
  condition. (Billiot, Budzynski Andrasik, 1997)

8
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.

9
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)

10
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.

11
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

12
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.

13
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

14
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

15
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

16
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

17
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 Beta2 16-20 Hz
• Theta 4-7.5 Hz Beta3 20-24 Hz
• Alpha1 8-10 Hz Beta4 24-28 Hz
• Alpha2 10-12 Hz Beta5 24-32 Hz
• Alpha 8-12 Hz Beta 13-21 Hz
• Beta1 12-16 Hz Hi Frequency 13-32 Hz

18
Statistical Analysis

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

19
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)

20
Low Resolution Electromagnetic Tomography

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

21
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.

22
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).

23
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.

24

• 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).

25

• 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).

26
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

27
Discussion

• This study demonstrates the utility of LORETA as
  a clinical tool.
• May help us understand CFS in new lightmood
  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.