Human volunteer studies using QEEG

1
Effects of nanoparticle exposure on brain function

• Human volunteer studies using QEEG

2
Effects of nanoparticle exposure on brain function
Björn Crüts1, Ludo van Etten1 , Flemming Cassee2,
Paul J.A. Borm1   1Centre of Expertise in Life
Sciences, Hogeschool Zuyd, Heerlen 2RIVM,
Bilthoven
3
Pathways
Translocation of NP
Inhalation UFP (Diesel)
Irritant receptors
Soluble Components, NP
QEEG
HRV
VR
4
Study designs
3 studies from 03.2005 10.2007
5
QEEG
Non-invasive measurement of effects in the brain
Quantitative EEG
6
Design

• Design study 1 Diesel exposure
• 14 subjects (18-38)
• Exposure diesel ( 1 hr, 300 ?g/ m3) and
• sham ( 1 hr), gt 48 hr between sham and diesel
• randomized trial
• pre- en post- QEEG (eyes-open, closed)
• continuous, synchronized measurement of HR,
• VR en QEEG
• No exercise (affects QEEG)

7
Design
Diesel
exposure (60 min)
post exposure (60 min)
preparation (30 min)
random order
Air
8
Lab Umeå
9
Results MPF
Median power frequency (MPF) of 11 subjects
gradually increases during and after exposure to
diesel, compared to sham
10
Results MPF
Mean absolute changes in median power frequency
(MPF) during different exposure conditions
11
Results MPF
Electrode localizations in relation to time of
response
12
Results MPF
13
Results MPF
DIESEL
Variability of median power frequency (MPF) at
left frontal cortex in time during and after
exposure
SHAM
14
Results frequency bands
Exposure
Post Exposure
14 12 10 8 6 4 2 0
fast wave activity
Amplitude (µV)
Amplitude (µV)
Exposure
Post Exposure
3025 20 15 10 5 0
0 60 120
slow wave activity
0 60 120
15
Summary
Wrap-up Diesel exposure affects average median
power of the QEEG during and up to 1 hour after
exposure. The effect moves in time from Fp1 and
FP2 in frontal cortex over the skull to F3 and
F4 Diesel exposure affects the variability of
the MPF mainly during post-exposure this effect
is present also in the frontal cortex. There is
an activation of fast wave activity (Beta2) in
the frontal cortex
16
Discussion
Discussion The effect is not likely caused by
sensory irritation due to gases or smell since
eye blinking not affected and reverse QEEG
response should be seen (direct effect). We
cannot discriminate between effect through NP
translocation and vagal afferent nerve reflex in
the airways. An shift to higher frequencies in
the frontal cortex is usually considered as a
stress response. In combination with increased
variability one may imagine that both central
information processing and systemic signaling are
affected.
17
Discussion
How does this connect to existing data on PM?

• Effect earlier than current kinetics of uptake in
  bulb and frontal cortex (Elder et al, 2006) in
  rats.
• Stress response in cortex may be related to
  increased HRV and arrythmias noted in earlier
  work.
• Physiological meaning however in this context
  largely unknown and needs combination with
  (f)MRI.
• Similar findings in fast wave activity have been
  observed in chronic disorders including headache,
  burnout, traumatic brain injury and
  post-traumatic stress.

18
Study 2 Effects of nanoparticle exposure on
brain activity
19
Design

• Design study 2 Nanoparticle exposure
• 10 subjects (18-28)
• Exposure CNP
• 40 ?g/ m3 (P40)
• 80 ?g/ m3 (P80)
• Air
• randomized trial, 1 hour exposure, 1 hour post
• pre- and post- QEEG (eyes-open, closed)
• continuous, synchronized measurement of HR,
• VR, QEEG and blood flow
• Questionnaires (fatigue, headache)

20
Mobile lab RIVM
21
Results frequency bands

• No significant increase of fast wave activity in
  frontal cortex
• Altered alpha activity in frontal cortex

AIR
P 40
22
Results frequency bands
AIR
P 40
Individual alpha activity (7.5-12 Hz) left
frontal cortex during air and P40 exposure
23
Alpha band exposure
Mean values 10 subjects
24
Alpha band post-exposure
Mean values 10 subjects
25
Alpha band post-exposure
Mean values 10 subjects
26
Results

• Results so far
• Alpha activity decreases during NP exposure
• No observable differences between P40 and P80
• Alpha activity indicator of ground state of
  brain activity (idling state of neocortex) ? link
  with blood flow
• Left/right differences could prove to be
  important for relationship with ECG (left side
  afferent inhibitory pathways with parasymp.)
• Connection Umeå data with RIVM data ratio
  alpha/beta increases during exposure (stress
  response vs. changes in cortical blood flow)

27
Future data analysis

• Analysis of data RIVM nanoparticles and diesel
• Quantification of dynamics of QEEG
• Coupling QEEG ECG
• Coupling QEEG neocortical blood flow
• More insight into causes of brain effects,
  possible pathways and cognitive effects

28
Ackownledgements
Centre of Expertise in Life Science, Hogeschool
Zuyd Paul Borm, Ludo van Etten, Bart Wauben,
Aloys Sipers RIVM Flemming Cassee, Paul
Fokkens Team University Hospital Umeå,
Sweden Hakan Törnqvist, Anders Blomberg, Thomas
Sandström Opleiding Biometrie, Hogeschool
Zuyd Erik Hinssen, Felipe Ernst, Paul Perreijn,
Rick Huijten, Thomas Baumgartner, Frank Keulen,
Mink Beaujean Biometrisch Centrum Gulpen Anique
Driessen