Effects of Cell Phone Radio frequency

  • Upload
    aupkp

  • View
    219

  • Download
    0

Embed Size (px)

Citation preview

  • 8/12/2019 Effects of Cell Phone Radio frequency

    1/6

    PRELIMINARY

    COMMUNICATION

    Effects of Cell Phone Radiofrequency SignalExposure on Brain Glucose MetabolismNora D. Volkow, MD

    Dardo Tomasi, PhD

    Gene-Jack Wang, MD

    Paul Vaska, PhD

    Joanna S. Fowler, PhD

    Frank Telang, MD

    Dave Alexoff, BSE

    Jean Logan, PhDChristopher Wong, MS

    THE DRAMATIC WORLDWIDE IN-crease in use of cellular tele-phones has prompted con-cerns regarding potential

    harmful effects of exposure to radiofre-quency-modulatedelectromagnetic fields(RF-EMFs). Of particular concern hasbeen the potential carcinogenic effectsfrom the RF-EMF emissions of cellphones. However, epidemiologic stud-iesof the association between cell phoneuseand prevalence of brain tumors havebeen inconsistent (some, but not all,studies showed increased risk), and theissue remains unresolved.1

    RF-EMFs emitted by cell phones areabsorbedinthebrain2 withinarangethatcould influence neuronal activity.3 Al-thoughthe intensityof RF-EMFs isverylow, the oscillatory frequencies corre-spondto some oftheoscillation frequen-ciesrecordedinneuronaltissueandcouldinterfere with neuronal activity.4 Ther-maleffectsfromRF-EMFshavealsobeen

    invokedasamechanismthatcouldaffectneuronalactivity,althoughtemperaturechanges producedby current cellphonetechnology are likely minimal.5 Studiesperformedin humans to investigate theeffects of RF-EMF exposures from cell

    phoneshaveyieldedvariableresults.6 Forexample, imaging studies that usedpositron emission tomography (PET)tomeasure changes in cerebral blood flow(CBF)withRF-EMFexposuresfromcellphones have reported increases,7,8 de-creasesandincreases,9,10 ornochanges11

    in CBF. The discrepancies among theseimaging studies likely reflect their rela-tively small sample sizes (9-14 partici-pants),and thepotential confoundingofCBFmeasuresreflectingvascular ratherthanneuronalsignals.12-14 ThishighlightstheneedforstudiestodocumentwhetherRF-EMFs from cell phone use affectsbrain function in humans.

    The objective of this study was to as-sess if acute cell phone exposure af-fected regional activity in the humanbrain. For this purpose we evaluated theeffects in healthyparticipants (N= 47)ofacute cell phone exposureson brain glu-cose metabolism, measured using PET

    with injection of (

    18

    F)fluorodeoxyglu-cose (18FDG). Brain glucose metabolic

    For editorial comment see p 828.

    Author Affiliations:National Institute on Drug Abuse,Bethesda,Maryland (DrVolkow); National Institute onAlcoholAbuse andAlcoholism, Bethesda (DrsVolkow,Tomasi,and Telangand MrWong);andMedicalDepart-ment,BrookhavenNationalLaboratory,Upton,NewYork(DrsWang, Vaska,Fowler, andLogan andMr Alexoff).Corresponding Author: NoraD. Volkow,MD, NationalInstituteonDrugAbuse,6001ExecutiveBlvd,Room5274,Bethesda, MD 20892 ([email protected]).

    Context The dramatic increase in use of cellular telephones has generated concernabout possible negative effects of radiofrequency signals delivered to the brain. How-ever, whether acute cell phone exposure affects the human brain is unclear.

    Objective To evaluate if acute cell phone exposure affects brain glucose metabo-lism, a marker of brain activity.

    Design, Setting, and Participants Randomized crossover study conducted be-tween January 1 and December 31, 2009, at a single US laboratory among 47 healthyparticipants recruited from the community. Cell phones were placed on the left and rightears and positron emission tomography with (18F)fluorodeoxyglucose injection was usedto measure brain glucose metabolismtwice, oncewith the right cellphone activated (soundmuted) for 50 minutes (on condition) and oncewith bothcell phones deactivated (offcondition). Statistical parametric mapping was used to compare metabolism between onand off conditions using paired ttests, and Pearson linear correlations were used to verifythe associationof metabolism and estimated amplitude of radiofrequency-modulatedelec-tromagnetic waves emitted by the cell phone. Clusters with at least 1000 voxels (volume8 cm3) andP .05 (corrected for multiple comparisons) were considered significant.

    Main Outcome Measure Brain glucose metabolism computed as absolute me-tabolism (mol/100 g per minute) and as normalized metabolism (region/whole brain).

    Results Whole-brain metabolism did not differ between on and off conditions. In con-trast, metabolism in the region closest to the antenna (orbitofrontal cortex and temporalpole) was significantly higher for on than off conditions (35.7 vs 33.3 mol/100 g perminute;meandifference, 2.4 [95%confidence interval,0.67-4.2];P=.004). The increaseswere significantly correlated withthe estimated electromagnetic fieldamplitudesboth for

    absolute metabolism (R=0.95, P.001) andnormalized metabolism (R=0.89; P .001).

    Conclusions In healthy participants and compared with no exposure, 50-minute cellphone exposure was associated with increased brain glucose metabolism in the re-gion closest to the antenna. This finding is of unknown clinical significance.

    JAMA. 2011;305(8):808-814 www.jama.com

    808 JAMA,February 23, 2011Vol 305, No. 8 (Reprinted) 2011 American Medical Association. All rights reserved.

    by guest on February 22, 2011jama.ama-assn.orgDownloaded from

    http://jama.ama-assn.org/http://jama.ama-assn.org/http://jama.ama-assn.org/http://jama.ama-assn.org/
  • 8/12/2019 Effects of Cell Phone Radio frequency

    2/6

    activity is a more proximal marker ofneuronal activity thanmeasures of CBF,which reflects vascular as well as neu-ronal components.15 Also, because brainglucose metabolic measures obtainedwith 18FDGreflect theaveraged brain ac-

    tivity occurring over a 30-minute pe-riod,16 this method allowed assessmentofthecumulative effects ofcell phoneex-posure on resting brain metabolism. Be-cause exposure to RF-EMFs from cellphones is well localized and is highestin brain regions closest to the antenna,2

    we hypothesizedthat theeffects on brainmetabolism would be greatest in infe-rior and anterior brain regions, the re-gions that would beexposed to thehigh-estRF-EMFamplitude forthe cell phonemodel used in this study.

    METHODSParticipants

    Thestudy wasconducted at BrookhavenNational Laboratory from January 1,2009, through December 31, 2009, andwas approved by the local institutionalreview board (Committee on ResearchInvolving Human Subjects, Stony BrookUniversity).Weenrolled 48 healthy par-ticipants recruited from advertisementsin local newspapersandscreened for ab-sence of medical, psychiatric, or neuro-logicdiseases. Special attention wasgiven

    to ensure that participantsdid not abuseaddictive substances (including alco-hol and nicotine), and urine toxicologystudies were performed prior to theimaging sessions to ensure lack of psy-choactive drug use. For technical rea-sons, data from one of the participantscould not be used (see below). TABLE 1providesdemographic characteristics andcell phone usage histories of the 47 par-ticipants whose data were used in theanalysis.Participants eachreceived $250for their participation in thestudy ($200

    for PET scans [$100 per scan] plus $50for the physical examination and labo-ratory work). All participants providedwritten informed consent after receiv-ing a complete description of the study.

    Experimental Conditions

    All participants had 2 scans performedon separate days using PET with 18FDG

    injection under resting conditions. Forboth scans 2 cell phones, one placed onthe left ear and one on the right, wereused to avoid confounding effects fromthe expectation of a signal from the sideof the brain at which the cell phone was

    located. For one of the days both cellphones were deactivated (off condi-tion). For the other day the right cellphone was on (activated but muted toavoid confounding from auditory stimu-lation) and the left cell phone was off(on condition). For the on conditionthecell phone was receiving a call (froma recorded text),although thesound wasmuted. Theorder of conditions was ran-domly assigned, and participants wereblinded to the condition. Themean timebetween the first and the second studywas 5 (SD, 3) days.

    Two Samsung model SCH-U310 cellphones,capableof transmitting at eithercellularor personalcommunicationsser-vice frequency bands with code divi-sion multiple access modulation, wereused for each study. Themaximum spe-cific absorption rate in the head for thiscell phone model corresponds to 0.901W/kg.Cellphoneswereplacedovereachear with microphones directed towardthe participants mouth and were se-cured to the headusing a muffler thatdidnot interfere with the lower part of the

    cell phone, where the antenna is lo-cated. Activation of the right cell phonewas started 20 minutes prior to 18FDGinjection and maintained for 30 min-utes afterward to correspond with the18FDG uptake period. During the 50-minuteperiodparticipantssaton a com-fortable chair in a quiet, dimly lit roomand with their eyes open, with a nursepresentto ensure that they kept their eyesopen and did not fall asleep.

    The RF-EMF emissions were re-corded once before the call (back-

    ground) andevery5 minutes during thestimulation periodto ensurethatthecallwas not terminated. This was accom-plished with a handheld spectrum ana-lyzer (model FSH6; Rohde & Schwarz,Munich, Germany) connected to a cel-lular wide-band log periodic direc-tional antenna (model 304411; WilsonElectronics, St. George, Utah) aimed at

    the head from a distance of 3 feet. Thecellular band was active, with a fre-

    quency of 837.8 MHz. This frequencywas monitored with a resolution band-width of 1 MHz. Activation of the cellphone for the experimental period wasalso corroborated with the records ob-tainedfrom thecell phone company.For1 participant the cell phone signal wasinterrupted at the time of18FDG injec-tion; this participants data were not in-cluded in the analysis.

    PET Scanning

    Inpreparationforthestudy,participants

    had2venouscathetersplaced,oneintheantecubital veinfor radiotracer injectionand theotherin a superficialvein onthedorsal surface of thehand forsamplingofarterializedblood.Arterialization wasachievedbywarmingthehandto44C.The participants were injected with18FDG (148-222 MBq [to convert tomillicuries, divide by 37]) and askedto refrain from moving or speakingduringthe 30-minute18FDGuptakepe-riod. At the end ofthe sessions, the cellphones were removed and the partici-

    pants were positioned in thePET scan-neraspreviouslydescribed. 17Participantswere scannedwith a whole-body tomo-graph (ECAT HR; Siemens/CTI,Munich, Germany),with a resolutionof4.64.64.2mm3 asmeasuredby Na-tionalElectricalManufacturersAssocia-tion protocols. Emission scans werestarted 35 minutesafter18FDGinjection

    Table 1.Characteristics and CellularTelephone Histories of Participants (N = 47)

    Characteristic No. (%)

    Age, mean (SD), y 31 (9)

    SexMen 23 (48.9)

    Women 24 (51.1)

    Body mass index, mean (SD)a 26 (3)

    HandednessRight-handed 43 (91.5)

    Left-handed 4 (8.5)

    Education mean (SD), y 14 (2)

    Cell phone use, mean(SD) [range], min/mo

    1500 (1850)[15-9000]

    Ear favored for useRight 38 (80.9)

    Left 9 (19.1)a Calculated asweightin kilogramsdividedby heightin me-

    ters squared.

    CELL PHONE SIGNALS AND BRAIN GLUCOSE METABOLISM

    2011 American Medical Association. All rights reserved. (Reprinted) JAMA,February 23, 2011Vol 305, No. 8 809

    by guest on February 22, 2011jama.ama-assn.orgDownloaded from

    http://jama.ama-assn.org/http://jama.ama-assn.org/http://jama.ama-assn.org/http://jama.ama-assn.org/
  • 8/12/2019 Effects of Cell Phone Radio frequency

    3/6

    and lasted 20 minutes. Transmissionscanswere performed simultaneously.

    Radiofrequency Field

    The average position of the antenna inthe stereotactic space of the MontrealNeurological Institute (r0) (r0=21 [SD,10] mmforx[left to right], 30 [SD, 11]mm for y [anterior to posterior], 160[SD, 7] mmfor z[superior to inferior])wasdetermined for21 participantsusingcalibrated orthogonal photography thatregistered orthogonal views (front andsides) of the cell phone positions on theparticipants head. The positions of the

    eyes were used as landmarks to deter-mine r0 withtheaidofthe standardbraintemplate (ch2.nii) provided in MRI-cron (availableat http://www.sph.sc.edu/comd/rorden/mricron/). The relativeamplitude of the cell phones electricfield, E(r), at every position in thebrain,r, wascomputedin Interactive Data Lan-guage version 6.0 (ITT Visual Informa-

    tionSolutions, Boulder,Colorado)usingthe far-field approximation,E(r)~||r-

    r0||3, of a dipole field (FIGURE1).

    Image Analysis

    Thedata were analyzed using statisticalparametricmapping(SPM)intheSPM2mapping package(WelcomeDepartmentofCognitiveNeurology,London,UnitedKingdom).18 TheSPManalyseswereper-formedontheabsoluteaswellasthenor-malized (to whole-brain metabolism)metabolicimages. Forthis purpose, theimages were spatially normalized usingtheSPM2PETtemplateanda2-mm32-

    mm

    32-mm

    3

    voxelsize andwere sub-sequently smoothed withan 8-mm iso-tropic Gaussian kernel. Voxel-wisepaired t testswereusedtoassessregionalchanges in glucose metabolism.

    Because the electric field,E(r), pro-duced by the cell phone decreases rap-idly with distance to theantenna, we hy-pothesized thatthe effectsof cell phones

    on glucose metabolism would occur inregions close to theantennaand that theregions farfromtheantenna wouldshowno effects.Therefore, the correctionsformultiple comparisonswererestricted tobrain regions in whichE(r) was higher

    than 50% of the maximum field value,E0, in the brain (E0/2E(r)E0)(Figure 1).Thus, theBonferroni methodwith a searching volume (Sv) of 201.3cm3 (Sv=25 161 voxels) was used to cor-rect cluster-levelP values for multiplecomparisonsas a function of the clustervolume (Cv) (Pcorr=PSv/Cv). Clusterswith at least 1000 voxels (Cv 8 cm

    3)andP.05(correctedfor multiple com-parisons) were considered significant.

    A simplemodel assuming a linear re-lationship between cell phonerelatedincreases in metabolism (18FDG; av-

    erage across participants) andE wasused. The paired values (18FDGi,Ei)from all voxelsthatwere statistically sig-nificant in the SPM2 t test analyses con-trasting on vs off conditions within Svwere sorted byE, clustered in groupsof 50 voxels, and averaged. These clus-ters were treated as independent. ThePearson linear correlation factor,R,wasused to assessthe linear relationshipbe-tween18FDG andE in Interactive DataLanguage version 6.0.

    Thesample-size calculation wasbased

    on our preliminary study of the effectoflow-frequency magnetic field gradientsin glucosemetabolism,19 which demon-strated metabolic differences betweenstimulation and sham conditions witheffectsize(ratiobetweenthe mean differ-enceand thepooledstandarddeviation)between0.65and0.80.Theminimalim-portant differencein glucosemetabolismused to determinethesamplesize was 1mol/100 g per minute. For such effectsizes, to achieve a power of at least 80%usingtheindependent-samples t testwith

    asignificancelevelof.05,atleast40par-ticipants were needed.

    RESULTS

    Whole-brain glucose metabolismdid notdiffer betweenconditions,which for theoffcondition correspondedto 41.2mol/100g perminute(95% confidenceinter-val [CI], 39.5-42.8) and for the on con-

    Figure 1.Amplitude of the Electric Field Emitted by the Right Cellular Telephone AntennaRendered on the Surface of the Human Brain

    LEFT HEMISPHERERIGHT HEMISPHERE

    Lateral view

    Medial view

    Lateral view

    Medial viewBoundary of clusters proximalto antenna (E0/2

  • 8/12/2019 Effects of Cell Phone Radio frequency

    4/6

    dition to 41.7 mol/100 g per minute(95%CI, 40.1-43.3).However,thereweresignificant regional effects. Specifically,the SPM comparisons14 on the absolutemetabolic measures showed significantincreases (35.7 vs 33.3 mol/100 g per

    minute for the on vs off conditions,respectively; mean difference, 2.4 [95%CI, 0.67-4.2];P=.004) in a region thatincluded the right orbitofrontal cortex(BA11/47)andthelowerpartoftherightsuperior temporal gyrus (BA 38)(FIGURE 2 and TABLE 2). No areasshowed decreases. Similar results wereobtainedfor theSPM analysis ofthenor-malized metabolic images (normal-ized to whole-brain glucose metabo-lism), which also showed significantincreases (1.048 vs 0.997 for the on vsoff conditions, respectively; mean dif-

    ference, 0.051 [95% CI, 0.017-0.091];P.001) in a regionthat included rightorbitofrontal cortex and right superiortemporal gyrus (BA 38) (Figure 2).

    The regression analysis between cellphonerelated increases in metabolism(18FDG) and E revealed a significantpositivecorrelation both forthe absolutemetabolic measures (R=0.95, P.001)and the normalized metabolic measures(R=0.89,P.001) (FIGURE3). This in-dicatesthattheregionsexpectedtohavethegreater absorption of RF-EMFsfrom

    the cell phone exposure were the onesthat showedthe largerincreases in glu-cose metabolism.

    CONCLUSIONS

    These results provide evidence that thehuman brain is sensitive to the effects ofRF-EMFs from acute cell phone expo-sures. The findings of increasedmetabo-lisminregionsclosest totheantenna dur-ing acute cell phone exposure suggestthat brain absorption of RF-EMFs mayenhance the excitability of brain tissue.

    This interpretation is supportedby a re-port of enhanced cortical excitability toshort transcranial magnetic stimulationpulses (1 msec) following 40-minuteRF-EMF exposures.20

    AlthoughincreasesinfrontalCBFdur-ing acute cell phone exposure had beenpreviouslyreportedby2independentPETlaboratories, such increases did not oc-

    curinbrainregionswiththehighestRF-EMFexposures.7-10 Moreover,oneofthesestudiesreportedCBFdecreasesin there-gion withmaximal RF-EMF exposure.10

    These discrepanciesare likely to reflect,amongothers,themethodsused,particu-larly because the 18FDG method is opti-

    malfor detecting long-lastingeffects(30minutes)in brain activity,whereas CBFmeasuresreflectactivityover60 seconds.In this respect, this study is an exampleofthevalueofthe 18FDG methodfor de-tecting cumulative effects in brain activ-itythatmaynotbeobservedwhenusingmore transientmeasures ofactivity. Dis-crepanciesalso could reflectuncouplingbetweenCBFandmetabolism.12-14 More-over, the relatively large sample size(n=47) improved our ability to detectsmall effects that may have been missed

    inpriorstudieswithsmallersamplesizes.

    11

    The experimental setup also differedfrom prior studies that used cell phonesfor which the antenna was closest to su-perior and middle temporal cortices.21

    However, this is unlikely to have ac-counted forthedifferences in results, be-cause the findings in this study showincreases in the region with maximal

    RF-EMF exposure, whereas findingsfrom other studies have shown de-creases in regions with the highest RF-EMFexposures, increasesin regions farfrom theantenna, or both.However, theincreases in frontal CBF previously re-ported with acute cell phone exposure

    possibly couldreflect a downstreameffectof connections with theregions that hadthe highest RF-EMF exposures.

    The linear association between cellphonerelated increases in metabolism(18FDG) andE suggests that the meta-bolic increases are secondary to theabsorption of RF-EMFsfromcellphoneexposures. The mechanisms by whichRF-EMFs from cell phones could affectbrain glucose metabolism are unclear.However,basedonfindingsfrominvivoanimal and in vitro experiments, it has

    beenhypothesizedthatthiscouldreflecteffectsof RF-EMFexposureonneuronalactivitymediatedbychangesincellmem-brane permeability, calcium efflux, cellexcitability, and/or neurotransmitter re-lease.4 A thermal effectof cell phonesonthebrainhasalsobeenproposed, 22butthisisunlikelytocontributetofunctionalbrainchanges.5 Disruption of the blood-brain

    Figure 2.Brain Glucose Metabolic Images Showing Axial Planes at the Level of theOrbitofrontal Cortex

    Cell phone on

    L R L R

    Cell phone off

    Rate of glucose metabolism,

    mol/100 g per min

    600

    Images are from a single participant representative of the study population. Glucose metabolism in right or-bitofrontal cortex (arrowhead) was higher for the on than for the off condition (see Methods for de-scription of conditions).

    CELL PHONE SIGNALS AND BRAIN GLUCOSE METABOLISM

    2011 American Medical Association. All rights reserved. (Reprinted) JAMA,February 23, 2011Vol 305, No. 8 811

    by guest on February 22, 2011jama.ama-assn.orgDownloaded from

    http://jama.ama-assn.org/http://jama.ama-assn.org/http://jama.ama-assn.org/http://jama.ama-assn.org/
  • 8/12/2019 Effects of Cell Phone Radio frequency

    5/6

    barrier hasalsobeeninvokedas a poten-tial mechanismbywhichRF-EMFs fromcellphoneexposurecouldaffect brain ac-tivity.23 A recent clinical study reported

    alterations in a peripheral biomarker ofblood-brainbarrier integrity(transthyre-tin) aftercellphoneexposure,but thesig-nificance of this finding is unclear.24

    The increasesin regional metabolisminducedbyRF-EMFs(approximately7%)aresimilarinmagnitudetothosereportedaftersuprathresholdtranscranialmagneticstimulation of the sensorimotor cortex(7%-8%).25 However, these increases aremuchsmaller thantheincreases after vi-sual stimulation reported by most stud-ies (range, 6%-51%).26 The large differ-

    enceinthemagnitudeofregionalglucosemetabolicincreasesislikelytoreflectmul-tiplefactors,includingdifferencesin gly-colytic rate between brain regions,27 theduration of the stimulation (transientstimulationincreasesglucosemetabolismmorethancontinuousstimulation26),andthe characteristics of the stimulationused.28 Indeed, whereas resting glucosemetabolismis predominantlysupportedbyglucoseoxidation(90%),withacutevisual stimulation the large increases inglucosemetabolismappear to reflectpre-

    dominantlyaerobicglycolysis,

    29

    whichisused for purposesother than energy ex-penditures, andactualenergyutilizationis estimated to be 8% at most.13

    Concern has been raised by the pos-sibility that RF-EMFs emitted by cellphones may induce brain cancer.30 Epi-demiologic studies assessing the rela-tionship betweencell phoneuseandrates

    Table 2.Statistical Parametric Mapping For Brain Regions Showing Higher Glucose Metabolism With Cellular Telephone On Than Off

    Brain Region Volumea Brodmann Area

    Region Coordinates,mm b

    Z Score,On vs Off Pcorr

    c

    On vs Off,Mean Difference

    (95% CI)x y z

    Absolute glucose metabolismRight inferior frontal 47 18 23 18 2.7

    Right superior temporal 2649 38 24 12 37 2.6 .05 2.4 (0.67-4.2)d

    Right middle frontal 11 23 38 15 2.6

    Normalized glucose metabolismRight superior temporal 38 27 2 35 3.1

    Right inferior frontal 2910 47 16 27 16 3.1 .05 7.8 (2.7-12.9)d

    Right middle frontal 11 23 38 15 3.1

    Abbreviation: CI, confidence interval.a No. of voxels. One voxel= 0.008 mm3.b Coordinates on the Montreal Neurological Institute stereotactic space corresponding to distance (in mm) for x(left to right), y(anterior to posterior), and z(superior to inferior).c See Methods for details of calculation of Bonferroni-correctedPvalue.dValues for absolute metabolism reported in mol/100 g per minute; those for normalized metabolism reported as percentages.

    Figure 3. Measures of Absolute and Normalized Glucose Metabolism and Correlation BetweenEstimated Electromagnetic Field Amplitudes and Increases in Measures (N=47 Participants)

    45

    40

    35

    30

    250.5 0.6 0.7 0.90.8 1.0

    E/E0

    mol/100gpermin

    OnCell phone

    OffOn

    Cell phone

    Off

    1.4

    1.2

    1.0

    0.80.5 0.6 0.7 0.90.8 1.0

    E/E0

    Region/WholeBrain

    8

    6

    4

    2

    0

    20.5 0.6 0.7 0.90.8 1.0

    E/E0

    %

    ChangeFromOff

    10

    0

    2

    4

    8

    6

    2

    4

    60.5 0.6 0.7 0.90.8 1.0

    E/E0

    %

    ChangeFromOff

    Absolute glucose metabolismA

    Change in absolute glucose metabolismC

    Normalized glucose metabolismB

    Change in normalized glucose metabolismD

    A and B, Mean measures of absolute glucose metabolism (mol/100 g per minute) and normalized glucosemetabolism (region/whole brain; units cancel) in regions with increased metabolism during on vs offconditions (see Methods for description of conditions) in the brain area within the spherical constraint,E0/2E(r)E0 (where E0 indicates maximal field value and E(r) indicates amplitude of the theoretical elec-

    tromagnetic field) and the E(r) emitted by the antenna of the right cellular telephone. Absolute=40 clusters;2000 voxels were activated within searching volume and grouped into clusters of 50 voxels each; normal-ized=48 clusters; 2400 voxels were activated within searching volume and grouped into clusters of 50voxels each. Range of variability (95% confidence interval [CI]): 9-21 mol/100 g per minute (panel A)and 0.29-0.57 (panel B). C and D, Regression lines between cell phonerelated increases in absolute andnormalized glucose metabolism (both expressed as % change from the off condition) in brain regionswithin the spherical constraint,E0/2E(r)E0, and the theoretical electric field, E(r), emitted by the antennaof the right cell phone. Increases significantly correlated with estimated electromagnetic field amplitudes(absolute: R =0.95, P.001; normalized: R =0.89, P.001). Data markers indicate mean metabolic mea-sures; error bars, 95% CIs. Linear regression lines were fitted to the data using Interactive Data Languageversion 6.0.

    CELL PHONE SIGNALS AND BRAIN GLUCOSE METABOLISM

    812 JAMA,February 23, 2011Vol 305, No. 8 (Reprinted) 2011 American Medical Association. All rights reserved.

    by guest on February 22, 2011jama.ama-assn.orgDownloaded from

    http://jama.ama-assn.org/http://jama.ama-assn.org/http://jama.ama-assn.org/http://jama.ama-assn.org/
  • 8/12/2019 Effects of Cell Phone Radio frequency

    6/6

    of brain cancers are inconclusive; somereport an association,31-33 whereas oth-ers do not.34-36 Results of this study pro-vide evidence that acute cell phone ex-posure affects brain metabolic activity.However, these results provide no infor-

    mationasto their relevance regarding po-tential carcinogenic effects (or lack ofsucheffects) fromchronic cellphoneuse.

    Limitations of this study include thatit isnotpossibleto ascertain whetherthefindings pertain to potential harmful ef-fectsofRF-EMFexposuresoronlydocu-mentthatthebrainisaffectedbytheseex-posures.Also,thisstudydoesnotprovideanunderstandingofthemechanism(s)bywhichRF-EMF exposuresincrease brainmetabolism, and although we interprettheseexposuresasindicatorsofneuronalexcitation, further studies are necessary

    to corroboratethis.Lastly,this modelas-sumes a linear relationshipbetween theamplitudeoftheradiofrequencyfieldanditseffectsinneuronaltissue,butwecan-notrule outthe possibility that this rela-tionship could be nonlinear.

    In summary, this study provides evi-dence thatin humansRF-EMFexposurefromcellphoneuseaffectsbrainfunction,asshownbytheregionalincreasesinmeta-bolicactivity. It also documents that theobservedeffectsweregreatestinbrainre-gions that had the highest amplitude of

    RF-EMF emissions (for the specific cellphones used in this study and their po-sition relative to the head when in use),which suggests that the metabolic in-creases are secondary to the absorptionof RF-EMF energy emitted by the cellphone.Further studies areneeded to as-sess if these effects could have potentiallong-term harmful consequences.

    Author Contributions: Drs Volkow and Tomasi hadfull access to all of the data in the study and take re-sponsibility for the integrity of the data and the ac-curacy of the data analysis.Study concept and design: Volkow.Acquisitionofdata:Wang,Vaska,Telang,Alexoff,Wong.

    Analysis and interpretation of data:Volkow, Tomasi,Vaska, Fowler, Telang, Logan.Drafting of the manuscript:Volkow, Wong.Critical revision of the manuscript for important in-tellectual content:Volkow, Tomasi, Wang, Vaska,Fowler, Telang, Alexoff, Logan.Statistical analysis:Tomasi.Obtained funding:Volkow, Fowler.Administrative, technical, or materialsupport:Wang,Fowler, Telang, Alexoff, Wong.Study supervision:Wang, Fowler.

    Conflict of Interest Disclosures: All authors have com-pletedand submitted theICMJE Form forDisclosureofPotential Conflicts of Interest andnone werereported.Funding/Support:This study was carried out atBrookhavenNational Laboratory(BNL) and was sup-ported by the Intramural ResearchProgram of the Na-tionalInstitutes of Health(NIH) andby infrastructuresupport from the Department of Energy.Roleof Sponsor:Thefundingagencieshadno rolein the

    designand conductof thestudy;the collection, manage-ment,analysis,andinterpretationofthedata;ortheprepa-ration, review, or approval of the manuscript.Additional Contributions: We are grateful toBNL em-ployees Donald Warner, AA, for positron emission to-mographyoperations;David Schlyer, PhD,and MichaelSchueller,PhD, forcyclotronoperations; PaulineCarter,RN,and Barbara Hubbard,RN, fornursing care;PaytonKing, BS,for plasmaanalysis; andLisaMuench, MS,You-wenXu,MS,and ColleenShea, MS,forradiotracerprepa-ration;and to NIH employees KarenAppelskog-Torres,AA,for protocolcoordination;MillardJayne,RN, forsub-jectrecruitmentandnursing care; andLinda Thomas,MS,foreditorialassistance.We alsothanktheindividualswhovolunteeredfor thesestudies. Noneof theindividualsac-knowledged werecompensatedin additionto theirsala-ries for their contributions.

    REFERENCES

    1. Dubey RB,Hanmandlu M, Gupta SK.Risk of braintumors from wireless phone use. J Comput AssistTomogr. 2010;34(6):799-807.2. Schnborn F, Burkhardt M, Kuster N. Differencesin energyabsorptionbetween heads of adults andchil-dren in the near field of sources. Health Phys. 1998;74(2):160-168.3. Kleinlogel H, DierksT, KoenigT, Lehmann H, MinderA , B e r z R . E f f e ct s o f w e a k m o b i l e p h o n eelectromagnetic fields (GSM, UMTS) on event re-l a t e d p o t e n t i a l s a n d c o g n i t i ve f u n c t i o ns .Bioelectromagnetics. 2008;29(6):488-497.4. HylandGJ. Physics and biology of mobiletelephony.Lancet. 2000;356(9244):1833-1836.5. Wainwright P. Thermal effects of radiation fromcellular telephones. Phys Med Biol. 2000;45(8):2363-2372.6. van Rongen E, Croft R, Juutilainen J, et al. Effectsof radiofrequency electromagnetic fields on the hu-

    man nervous system.J Toxicol Environ Health B CritRev. 2009;12(8):572-597.7. Huber R, Treyer V, Borbely AA, et al. Electromag-netic fields, such as those from mobile phones, alterregional cerebral bloodflow andsleepandwaking EEG.J Sleep Res. 2002;11(4):289-295.8. Huber R, Treyer V, Schuderer J, et al. Exposure topulse-modulatedradio frequency electromagneticfieldsaffects regional cerebral blood flow. Eur J Neurosci.2005;21(4):1000-1006.9. Haarala C, Aalto S, Hautzel H, et al. Effects of a902 MHz mobile phone on cerebral blood flow inhumans.Neuroreport. 2003;14(16):2019-2023.10. Aalto S, Haarala C, Bruck A, et al. Mobile phoneaffects cerebral blood flow in humans. J Cereb BloodFlow Metab. 2006;26(7):885-890.11. Mizuno Y, Moriguchi Y, Hikage T, et al. Effectsof W-CDMA 1950 MHz EMF emitted by mobilephones on regional cerebral blood flow in humans.Bioelectromagnetics. 2009;30(7):536-544.12. SirotinYB, DasA. Anticipatory haemodynamicsig-nals in sensory cortexnot predictedby local neuronalactivity.Nature. 2009;457(7228):475-479.13. FoxPT, Raichle ME,Mintun MA, Dence C. Non-oxidative glucose consumption during focal physi-ologic neural activity. Science. 1988;241(4864):462-464.14. Devor A, Hillman EM, Tian P, et al. Stimulus-induced changes in blood flow and 2-deoxyglucoseuptake dissociate in ipsilateral somatosensory cortex.J Neurosci. 2008;28(53):14347-14357.

    15. IadecolaC, Nedergaard M. Glialregulation of thecerebral microvasculature. Nat Neurosci. 2007;10(11):1369-1376.16. Sokoloff L, Reivich M, Kennedy C, et al. The[14C]deoxyglucose method for the measurement oflocalcerebral glucose utilization.J Neurochem. 1977;28(5):897-916.17. Wang G-J, Volkow ND, Roque CT, et al. Func-tional importance of ventricular enlargement andcor-tical atrophy in healthy subjects and alcoholics as as-sessed with PET, MR imaging, and neuropsychologictesting.Radiology. 1993;186(1):59-65.18. Friston KJ, Holmes AP, Worsley KJ, et al. Statis-tical parametric maps in functional imaging. Hum BrainMapp. 1995;2:189-210.19. Volkow ND, Tomasi D, Wang GJ, et al. Effectsof low-field magnetic stimulation on brain glucosemetabolism.Neuroimage. 2010;51(2):623-628.20. Ferreri F, Curcio G, Pasqualetti P, et al. Mobilephone emissions and human brain excitability. AnnNeurol. 2006;60(2):188-196.21. Cardis E, Deltour I, Mann S, et al. Distribution ofRF energy emitted by mobile phones in anatomicalstructures of the brain. Phys Med Biol. 2008;53(11):2771-2783.22. Cotgreave IA. Biological stress responses to ra-dio frequency electromagnetic radiation. Arch Bio-chem Biophys. 2005;435(1):227-240.23. Nittby H, GrafstrmG, EberhardtJL, et al.Radio-

    frequencyand extremely low-frequency electromag-netic field effects on the blood-brain barrier. Electro-magn Biol Med. 2008;27(2):103-126.24. Sderqvist F, CarlbergM, HanssonMild K, HardellL. Exposure to an 890-MHz mobile phone-like signaland serum levels of S100B and transthyretin involunteers.Toxicol Lett. 2009;189(1):63-66.25. Siebner HR, Peller M, Bartenstein P, et al. Acti-vation of frontal premotor areas during suprathresh-old transcranial magnetic stimulation of the leftprimary sensorimotor cortex: a glucose metabolicPET study. Hum Brain Mapp. 2001;12(3):157-167.26. Vlassenko AG, Rundle MM, Mintun MA. Hu-man brain glucose metabolism may evolve duringactivation.Neuroimage. 2006;33(4):1036-1041.27. Vaishnavi SN, Vlassenko AG, Rundle MM, et al.Regional aerobic glycolysis in the human brain. ProcNatl Acad Sci U S A. 2010;107(41):17757-17762.28. Sanganahalli BG, Herman P, HyderF. Frequency-

    dependent tactile responses in rat brain measured byfunctional MRI. NMR Biomed. 2008;21(4):410-416.29. Blomqvist G, Seitz RJ, Sjgren I, et al. Regionalcerebraloxidative andtotal glucose consumptiondur-ingrest andactivation studied withpositronemissiontomography. Acta Physiol Scand. 1994;151(1):29-43.30. Yakymenko I, Sidorik E. Risks of carcinogenesisfrom electromagnetic radiation of mobile telephonydevices.Exp Oncol. 2010;32(2):54-60.31. Lehrer S, Green S, Stock RG. Association be-tween number of cell phone contracts and brain tu-mor incidence in nineteen U.S. States.J Neurooncol.2011;101(3):505-507.32. Hardell L, Carlberg M. Mobile phones, cordlessphones and the risk for brain tumours. Int J Oncol.2009;35(1):5-17.33. Myung SK, Ju W, McDonnell DD, et al. Mobilephone use and risk of tumors: a meta-analysis. J ClinOncol. 2009;27(33):5565-5572.34. Inskip PD, Tarone RE, Hatch EE, et al. Cellular-telephoneuse and braintumors. NEngl J Med. 2001;344(2):79-86.35. INTERPHONE Study Group. Brain tumour risk inrelation to mobiletelephoneuse. IntJ Epidemiol. 2010;39(3):675-694.36. Inskip PD, Hoover RN, Devesa SS. Brain cancerincidence trends in relation to cellular telephone usein the United States. Neuro Oncol. 2010;12(11):1147-1151.

    CELL PHONE SIGNALS AND BRAIN GLUCOSE METABOLISM

    2011 American Medical Association. All rights reserved. (Reprinted) JAMA,February 23, 2011Vol 305, No. 8 813

    by guest on February 22, 2011jama.ama-assn.orgDownloaded from

    http://jama.ama-assn.org/http://jama.ama-assn.org/http://jama.ama-assn.org/http://jama.ama-assn.org/