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RADIOFREQUENCY EFFECTS ON THE HUMAN ELECTROENCEPHALOGRAM: ITS RELEVANCE FOR HEALTH AND HOW DO WE EXPLAIN THIS PHENOMENON BLANKA POPHOF FEDERAL OFFICE FOR RADIATION PROTECTION

OUTLINE History Cognition Evoked and event related potentials Spontaneous waking EEG Sleep EEG Exposure and dosimetry Possible mechanisms Health relevance Charité Berlin, Competence Center of Sleep Medicine, Prof. H. Danker-Hopfe

HISTORY Low Energy Emission Therapy 27.12 MHz modulated at 42.7 Sleep inducing and promoting effect (Reite et al., Bioelectromagnetics, 1994) Effect of EMF on human brain activity Mega-Wave 150 (150 MHz) D1 Mobile phone 324, GSM Increase of EEG power in Alpha and Beta Band (Reiser, Eur. J. Med. Res., 1995)

COGNITION reaction time auditory and visual discrimination short and long term memory Callicot et al. 1999 Small, single blind, older studies: Effects in both directions, often improvement Large, double blind recent studies, correction for multiple testing: no or very small effects, failed replications. TETRA: 400 MHz, up to 10 W/kg, very few studies. Some minor effects on memory cannot be excluded, replication needed, ongoing study in Germany.

COGNITION Barth et al., Occup. Environ. Med. 2008: Results of the meta-analysis suggest that EMFs may have a small impact on human attention and working memory. van Rongen et al., J. Toxicol. Environ. Health. 2009: No consistent significant effects on cognitive performance in adults have been observed. If anything, any effect is small and exposure seems to improve performance. Effects in children did not differ from those in healthy adults. Valentini et al., Occup. Environ. Med. 2010: Mobile phone-like EMF do not seem to induce cognitive and psychomotor effects. Kwon and Hämäläinen, Bioelectromagnetics 2011: Behavioral studies previously reported improved cognitive performance under exposure, but it was likely to have occurred by chance due to multiple comparisons. Recent behavioral studies and replication studies with more conservative statistics found no significant effects compared with original studies. Recent German study (Sauter et al. 2011) no effect of EMF on cognition, but significant influence of time of day.

EVOKED AND EVENT RELATED POTENTIALS brain signals recorded by EEG sensory perception auditory, visual intention, awaiting and performing a task many parameters: amplitude, latency, frequency, power acoustically evoked potential movement related cortical potentials motion begin common acoustic signal rare acoustic signal ms Stöhr et al. 2005 Hegerl 1998

EVOKED AND EVENT RELATED POTENTIALS: Australia Changes in spectral power of EEG during an auditory task (Croft et al. 2002) and in amplitude and latency of auditory evoked potentials (Hamblin et al. 2004). Weak methodology dosimetry, single blind, small sample size. Larger, double blind replication study, with a power of 80% to detect a difference of 0.25 SD failed (Hamblin et al. 2006): There was no significant difference between exposure conditions for any auditory or visual event related potential (ERP) component or RT. As previous positive findings were not replicated, it was concluded that there is currently no evidence that acute MP exposure affects these indices of brain activity. Large study including adolescents, adults and elderly has shown effects on auditory evoked potentials (all age groups, 2G only) and event related desynchronization/ synchronization (all age groups, 2G and 3G) during an auditory task which was specially adjusted to individual abilities (Leung et al. 2011): The subtlety of mobile phone effect on cognition in our study suggests that it is important to account for individual differences in future mobile phone research.

EVOKED AND EVENT RELATED POTENTIALS: Finland Effects on brain oscillatory activity in the frequency range of 8-12 Hz during auditory and visual memory tasks (Krause et al. 2000) unable to replicate (Krause et al. 2004), but found again later (Krause at. al. 2007). The effects on the EEG were, however, varying, unsystematic and inconsistent with previous reports. We conclude that the effects of EMF on brain oscillatory responses may be subtle, variable and difficult to replicate for unknown reasons. Slight effects on event related desynchronisation/synchronisation during an auditory memory task in children (Krause et al. 2006), but no effect on auditory evoked potentials neither in adults (Kwon et al.2009) nor in children (Kwon et al. 2010). Kwon and Hämäläinen, Bioelectromagnetics 2011: Neurophysiological studies found no significant effects on cochlear and brainstem auditory processing, but only inconsistent results on spontaneous and evoked brain electrical activity. The inconsistent findings suggest possible false positives due to multiple comparisons and thus replication is needed.

SPONTANEOUS WAKING EEG Registration of brain electrical activity Frequency bands: δ (0.5 3.5 Hz) θ (3.5 7.5 Hz) α (7.5 12.5 Hz) β (12.5-30 Hz) eyes closed eyes open Charité Berlin, Competence Center of Sleep Medicine, Prof. H. Danker-Hopfe

SPONTANEOUS WAKING EEG significant changes with exposure year N Authors 1997 34 Rösche and Mann 2000 19 Hietanen et al. Increased α-power, decreased δ-power 2002 24 Croft et al. Increased α-power, decreased δ-power 2005 20 Curcio et al. 2007 12 Perentos et al. Increased α-power 2007 24 Regel et al. Interhemispheric synchronization in α-band 2007 10 Vecchio et al. 2008 15 Kleinogel et al Increased α-power 2008 120 Croft et al. Increased α-power (young adults, 2G) 2010 41,42,20 Croft et al. Interhemispheric synchronization in α-band 2010 16 Vecchio et al. Interhemispheric synchronization in α-band 2012 11 Vecchio et al.

SPONTANEOUS WAKING EEG Recent German study (Charité Berlin): of GSM and UMTS on waking EEG (power, α-attenuation) after correcting for multiple testing Significant influence of time of day. 10.0 Hz 10.25 Hz 10.5 Hz 10.75 Hz blue: time of day red: GSM Charité Berlin, Competence Center of Sleep Medicine Prof. H. Danker-Hopfe

SLEEP EEG

SLEEP EEG Laboratory studies: Sleep macrostructure significant changes with exposure year N Authors Reduced sleep latency 1996 12 Mann and Röschke Reduced REM-sleep (% SPT) 1996 34 Mann and Röschke 1998 22 Wagner et al. 2000 20 Wagner et al. Reduced wake after sleep onset 1999 24 Borbély et al. 2000,2003 16 Huber et al. 2002 16 Huber et al. 2005 13 Hinrichs et al. REM-sleep latency 2005 50 Loughran et al. Prolonged sleep latency 2007 10 Hung et al. 2007 10 Fritzer et al. 2007 15 Regel et al Reduced duration and prolonged latency of SWS 2011 48 Lowden et al.

SLEEP EEG German Study: GSM (Danker-Hopfe et al. 2011) NREM1-sleep whole night [min] REM-sleep whole night [min] REM-sleep whole night [% TST] Mean duration of REM-cycles REM-sleep middle sleep cycles [min] REM-sleep 3rd quarter of the night [min] REM-sleep 3rd quarter of the night [%] NREM2-sleep whole night [min] NREM2-sleep whole night [% TST] NREM2-sleep 3rd quarter of the night [min] NREM2-sleep 3rd quarter of the night [% TST] Stage shifts from SWS to NREM1 Movement time 1st sleep cycles [min] Movement time 1st quarter of the night [min] increased increased increased increased increased increased increased increased 14 observed, 12 expected by chance

SLEEP EEG German Study: UMTS (Danker-Hopfe et al. 2011) NREM1-sleep whole night [min] NREM1-sleep whole night [% TIB] NREM1-sleep during sleep period time [min] NREM1-sleep [% SPT] NREM1-sleep 2nd third of the night [min] NREM1-sleep 2nd third of the night [% TIB] Mean duration NREM cycles [min TIB] Mean duration REM cycles [min TIB] NREM2-sleep middle cycles [min] increased Less observed that expected by chance of GSM and UMTS on sleep macrostructure

SLEEP EEG Laboratory studies: Power spectral analysis significant changes with exposure year N Authors Increased mean power during REM sleep 1996 12 Mann and Röschke 1998 22 Wagner et al. 2000 20 Wagner et al. Increased mean power during NREM sleep Increased mean power during NREM sleep Increased mean power during NREM sleep Increased mean power during NREM sleep Increased mean power during NREM sleep 1999 2000,2003 2002 2007 2005 24 16 16 15 50 Borbély et al. Huber et al. Huber et al. Regel et al. Loughran et al. spindle frequency range 2005 13 Hinrichs et al. Increased mean power during NREM sleep Increased mean power during NREM sleep Increased mean power during NREM sleep Increased mean power during NREM sleep 2007 2012 2011 2012 10 20 48 30 Hung et al. Loughran et al. Lowden et al. Schmid et al. 1-4 Hz spindle frequency range

SLEEP EEG German Study: Spectral power, GSM (Somnolyzer, 400 variables) spindle frequency Charité Berlin, Competence Center of Sleep Medicine, Prof. H. Danker-Hopfe No changes of power in SWS and REM sleep; No changes under UMTS

SLEEP EEG German Study: spindle detection Automatic detection Somnolyzer 24x7: 810 variables GSM UMTS 23 significant results 11 significant results 41 statistically significant results are expected by chance No systematic changes in frequency, density, amplitude and duration of spindles Young healthy men no information about female, elderly Individual variability?

Exposure and dosimetry exposure intensity exposure duration pulsed continuous wave near field far field sleep: prior to sleep during sleep waking: tests during or before and after exposure mobile phone, simulated mobile phone, homogeneous exposure of a hemispehre left right side

Exposure and Dosimetry Nokia 6110 Patch antenna Planar antenna GSM UMTS Boutry et al. 2007, Murbach et al. 2012, Bahr et al. 2007

Possible mechanisms Thalamus: - central role in spindle generation - sensory and motor signals to the cerebral cortex, regulation of consciousness, sleep, and alertness Hypothalamus: thermoregulation, circadian rhythm, sleep Influence of EMF: direct, or via cortical stimulation Thermal or non-thermal? Sensitivity of neurons: ~ 0.1 C; neuronal Networks: 0.03 C Peak exposure of thalamus: Nokia 6110: Turku: 0.024 W/kg; Swinburne: 0.011 W/kg Patch antenna: 0.16 W/kg (Boutry et al. 2007) Planar antenna (TETRA, 6 W/kg) 0.08 W/g (Schmid et al. 2012) Temperature increase at 2 W/kg (simulated mobile phone): cortex < 0.1 C, thalamus < 0.01 C (Schmid et al. 2007)

Possible mechanisms Circadian rhythm Thermoregulation Sleep regulation Warming: sleep induction Activation of warm-sensitive neurons of Hypothalamus triggers NREM-sleep onset. These neurons are activated by direct warming as well as by peripheral thermo sensory input. Core body temperature N = 8 Kräuchi et al. 2007

Health relevance on cognition on evoked and event related potential on waking EEG on sleep macrostructure and sleep quality Possible effect on sleep EEG Probably sleep inducing and promoting effects, no sleep disturbance Apparently dose dependent Role of pulse modulation not clarified Possibly thermal Physiologically interesting, differences between laboratories should be clarified Age, gender and individual variability insufficiently investigated Probably no adverse health relevant effects