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Alcohol induced changes in regional cerebral glucose metabolic rate during divided attention
\ PERGAMON
Personality and Individual Di}erences 15 "0888# 314Ð328
Alcohol induced changes in regional cerebral glucose metabolic rate during divided attention R[J[ Haiera\ \ S[L[ Schandlerb\ A[ MacLachlan\ E[ Soderling\ M[S[ Buchsbaumc\ M[J[ Cohend a
Departments of Pediatrics and Neurolo`y\ University of California\ Irvine\ U[S[A[ Department of Psychiatry and Human Behavior\ University of California\ Irvine\ U[S[A[ c Department of Psychiatry\ Mount Sinai School of Medicine\ U[S[A[ d Departments of Neurolo`y and Psychiatry and Human Behavior\ University of California\ Irvine\ U[S[A[ b
Received 15 February 0887
Abstract Under conditions of moderate alcohol intoxication "9[64 ml:kg# and an alcohol!disguised placebo\ eight non!alcoholic male volunteers performed a divided attention task after injection of 07!F!1!~uoro!1!deox! yglucose "FDG# for a Positron Emission Tomography "PET# study[ The administration of alcohol or placebo followed a random order double!blind protocol[ During 21 min of divided attention\ the subject performed a letter matching task or a spatial orientation task presented simultaneously on a computer!generated split display[ The task to be performed was indicated by an arrow on the display that changed randomly every few trials[ Alcohol intoxication was associated with a trend toward generally reduced performance[ Task performance di}erences between the alcohol and placebo conditions were signi_cantly correlated with cortical glucose metabolic rates "GMR# in the superior\ inferior\ and middle parietal lobes[ Impaired performance was associated with GMR decreases[ GMR in several subcortical and medial cortical areas were also correlated with performance changes\ including areas of the putamen and cingulate[ The major _nding is that individual di}erences in GMR change from placebo to alcohol in parietal cortex are related to individual di}erences in attention performance[ The application of PET with selective information processing paradigms provides a useful method for isolating and in identifying the e}ects of alcohol intoxication on the function of the central nervous system[ Þ 0888 Elsevier Science Ltd[ All rights reserved[ Key words] Alcohol^ Attention^ Positron emission tomography^ Glucose metabolism^ Parietal cortex
0[ Introduction Several decades of research have reliably established that acute and chronic alcohol use and abuse produce selective rather than global e}ects on operations of the human central nervous Corresponding author[ Fax] 838 713!2024^ e!mail] rjhaierÝuci[edu 9080Ð7758:88:, ! see front matter Þ 0888 Elsevier Science Ltd[ All rights reserved[ PII] S 9 0 8 0 Ð 7 7 5 8 " 8 7 # 9 9 0 8 6 Ð 3
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system "CNS#[ However\ the nature and location of alcohol|s e}ects remain unclear[ This is due primarily to the use of information processing probe paradigms that vary greatly in the demands placed on the CNS and the measurement of CNS activity during those demands[ Not unexpectedly\ the use of performance\ psychophysiological\ and electrophysiological measures of CNS operations during cognitive operations support several di}erent and often opposing hypotheses as to the nature and the location of alcohol|s e}ect on the information processing system[ New technological and statistical modeling developments in functional brain imaging now make this method highly suited to direct assessment of CNS operations in response to demands from selected information processing tasks[ Positron Emission Tomography "PET# has appeared as one method that is suited to this task[ Used together with standardized information processing probes and paradigms\ PET may both test the most prominent hypotheses of alcohol|s e}ects on information processing and illuminate the source"s# of these e}ects[ Once the sources are identi_ed\ it may be possible to develop and accurately evaluate cognitive interventions that address and ameliorate the e}ects of chronic alcohol abuse[ Early PET studies of alcohol|s e}ect on CNS operations have been more exploratory than focused on a speci_c hypothesis[ Although not employing a consistent paradigm for probing information processing\ these studies have shown regional cerebral changes in both blood ~ow and glucose metabolism following alcohol administration[ Volkow et al[ "0877# studied 02 normal social drinkers in a no!task paradigm with 04O!labeled water to assess blood ~ow[ Seven subjects received a low dose of alcohol "9[53 ml:kg# and six others a high dose "0[17 ml:kg#[ They reported signi_cantly decreased blood ~ow in the cerebellum with the high dose[ The high dose also signi_cantly increased blood ~ow in the right prefrontal and temporal cortex[ In a second study\ Volkow et al[ "0889# used FDG and PET to compare regional cerebral glucose metabolic rates "GMR# between six alcoholics and six normals[ Each subject was studied twice\ baseline "no task\ resting with eyes open# and during alcohol intoxication "based on 0[17 ml:kg#[ Both the normals and the alcoholics showed decreased GMR in cortex and cerebellum^ the basal ganglia\ thalamus\ and corpus callosum did not change[ The largest GMR decreases with alcohol were in the occipital and frontal cortex[ These areas have high concentrations of benzodiazapine receptors\ receptors hypothesized to be important in alcohol response[ De Wit\ Metz\ Wagner + Cooper\ "0889# studied eight healthy male volunteers with PET and two doses of alcohol "9[415 and 9[731 ml:kg#[ Following the lower dose\ whole brain glucose was higher than placebo in _ve subjects but lower in three subjects[ Finding no signi_cant group e}ect for alcohol\ they went on to relate these individual di}erences in cerebral glucose metabolic rate change with alcohol to cognitive and mood changes by examining correlation coe.cients[ The brain areas so identi_ed were similar to those found by Volkow et al[ "0889#\ in showing alcohol decreases and thus are partially consistent with the implication of benzodiazapine receptor rich areas in alcohol response[ Mathew and Wilson "0875# showed bilateral increases in blood ~ow after administration of alcohol in 15 normal controls in a double blind\ placebo controlled study using the xenon inhalation technique[ The largest increases were in parietal and frontal cortex bilaterally and in right temporal areas[ Whilst instructive regarding general alcohol e}ects\ the data are inconsistent in isolating infor! mation processing e}ects related to a speci_c cortical area[ This may be due to the lack of a meaningful task during the metabolic tracer uptake[ Attention tasks are known to be sensitive to
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alcohol e}ects and therefore may be of special interest for PET studies[ For example\ Moskowitz\ Burns and Williams "0874# used a battery of divided attention and information processing measures to test 09 normal males with mean blood alcohol levels "BAL# ranging from 9Ð48 mg:dl[ All measures showed impaired performance and impairment increased with increasing BAL[ The divided attention task was the most sensitive to alcohol impairment "Moskowitz\ 0862#[ Similarly\ Rohrbaugh et al[ "0877# found that increased blood alcohol levels "up to 0[94 gm ETOH:kg lean body mass# were negatively correlated with cognitive performance on a sustained attention task "the continuous performance test# testing visual vigilance in social drinkers "N 01#[ They concluded that alcohol reduces central processing capacity and capacity availability over time[ Interestingly\ when comparing the performance of nine intoxicated and detoxi_ed chronic alcoholics during a visual CPT and a visuoÐspatial learning task\ Schandler and his colleagues "Cohen\ Schandler + Nalibo}\ 0876^ Schandler\ Cohen\ McArthur\ Nalibo} + Hassell\ 0877# found the intoxicated chronic alcoholics to display enhanced orienting and attention operations[ The combining of attention!sensitive information processing paradigms with brain imaging dependent measures has begun yielding more direct information about the e}ects of alcohol on CNS function[ Corbetta\ Miezin\ Dobmeyer\ Schulman and Petersen "0880# studied cerebral blood ~ow using PET in a group of nine normals performing a divided attention task[ Subjects were scanned in six conditions] three scans set the baseline for three selective attention conditions "shape\ velocity\ and color#[ The divided attention stimuli required the detection of a change in either shape\ speed\ or color features[ During the divided attention trials\ blood ~ow was uniquely activated in the left collateral sulcus\ the left lateral occipital gyrus\ the anterior cingulate and the dorsolateral prefrontal cortex[ "Activation also occurred in area 06 and the lingual gyrus in visual cortex but this was not unique to divided attention#[ Buchsbaum et al[ "0889# used PET:FDG to study attention using the continuous performance test "CPT#[ Right frontal and right tem! poroparietal cortex showed GMR increases[ Attention appears as one CNS!mediated operation that is particularly sensitive to alcohol ingestion and intoxication[ Of the paradigms used to probe attention operations during information processing\ the divided attention paradigm may show a more pronounced alcohol induced e}ect in cognitive performance than other attention tasks "Moskowitz et al[\ 0874^ Moskowitz\ 0862^ Moskowitz + Depry\ 0857#[ Given the ability of PET to illuminate speci_c cortical areas involved in information processing\ it was the purpose of this exploratory study to use PET to determine whether the e}ect of alcohol on a divided attention task was correlated with activity "metabolic changes# in brain areas used for attention[
1[ Methods 1[0[ Subjects Eight healthy right!handed male volunteers "mean age 15 years\ SD 3[1# served individually in two sessions of PET scans performed at the University of California\ Irvine\ U[S[A[ Using a randomized\ double!blind procedure\ subjects consumed a moderate dose of alcohol on one session and a placebo on the other[ Subjects were drawn from the student population at the University of California at Irvine\ and\ based on academic performance\ they display normal neurocognitive
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function[ All subjects were light to moderate social drinkers\ reporting a mean average rate of consumption of less than one drink:day for the previous year[ Based on a standard structured interview\ potential subjects were excluded if they currently su}ered or had any history of signi_cant medical illness\ including head injury\ epilepsy\ or other indicators of neurological illness[ Additional exclusion criteria included any history of excessive alcohol or drug consumption or treatment\ past or current use of psychoactive medications\ and a history of alcohol abuse or alcoholism by the immediate biological family[ The relatively small sample size is similar to other studies "Volkow et al[\ 0877\ 0882^ N 5 and N 01 respectively^ de Wit et al[\ 0889\ N 7#[ Thus\ only moderate to large e}ects can be detected[ 1[1[ Instruments 1[1[0[ Blood alcohol concentration An Alco!Sensor III Breathalyzer "Intoximeters\ Inc[# obtained BAC[ Previous data show cor! relations of ¦9[87 between calibrated breathalyzer and blood chemistry values "Gibb\ Yee\ John! ston\ Martin + Scha}er\ 0873^ Poon\ Hodgson\ Hinberg + Rowatt\ 0876#[ 1[1[1[ Divided attention tasks The divided attention task was comprised of two well!studied attention tasks adapted to a Toshiba Model 0999 laptop computer display[ The component parts of the divided attention task were the manikin task "Carter + Woldstad\ 0874# and the Posner!Mitchell "0856# letter matching task[ The manikin task has been used to test visuoÐspatial ability "Bunnell + Horvath\ 0877#[ The version we used featured a stick _gure "manikin# in four possible orientations] "0# standing upright facing the subject^ "1# standing upright facing away from the subject^ "2# standing upside down facing the subject^ "3# standing upside down facing away from the subject[ In all four orientations\ the manikin had a ball in one hand and a box in the other[ The subject was required to indicate in which of the manikin|s hands "left or right# the box was located[ Both the order of the _gure|s orientation and the hand in which the box was held were randomly ordered and counter!balanced[ The manikin task tested the subject|s ability to perform rotations and transformations of a mental image[ The Posner!Mitchell task tested the subject|s ability to match symbols[ The symbols were letters to be matched by either identity or by case type "i[e[ upper or lower case#[ The letters matched if the identity "e[g[ Aa# or the case type "e[g[ AB or ab# of the letters were the same[ Two letters were displayed on the screen\ randomly chosen from the same set "A\ B\ C\ and E#[ Each letter appeared in both upper case and lower case during the task "randomly ordered and counter!balanced#[ Both the manikin and the letter tasks were computer controlled and displayed side by side on the 14 cm×7 cm computer display situated 49 cm from the subject[ An arrow presented in the middle of the display indicated which task was to be performed[ The arrow would shift tasks every few trials on a random schedule[ For the manikin task\ the subject indicated box location "left hand or right hand# by pushing one of two buttons marked L or R on the left side of the keyboard[ During the Posner!Mitchell task\ the subject indicated whether the letters were the same or di}erent by pressing one of two buttons marked S or D on the right side of the keyboard[ The subject was given 0 s to respond for each trial[ The subject performed this task\ using his right hand\ for a
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period of 21 min following the injection of the FDG[ During this time\ each subject was exposed to approximately 0499 stimuli[ The subject was instructed to work through the task as quickly and accurately as possible[ Performance was evaluated from eight dependent measures obtained from the divided attention task[ For the component tasks\ manikin and Posner!Mitchell\ we evaluated performance for each task separately using the dependent measures of reaction time "RT# and response accuracy "percentage correct of total possible correct responses#[ These measures excluded both the reaction time and the response accuracy when the subjects made the transition trials from task to task[ Transition reaction time "TRT# was de_ned as the response time to the _rst trial following the transition to the alternate task[ Transition accuracy was the subject|s percentage correct of total possible responses emitted when responding to the alternate task for the _rst trial following the transition[ 1[2[ Procedure Before the start of the protocol\ each subject received training on the divided attention task\ and practiced it for at least 29 min[ On two subsequent test days\ a week apart\ each subject received either alcohol or placebo\ randomly ordered and counter!balanced[ Subjects were tested in the afternoon\ after fasting at least 5 h[ 1[2[0[ Administration of alcohol and placebo On the day alcohol was administered\ each subject received 9[64 ml:kg of alcohol in a 19) by volume solution "cold tonic water#\ consumed in 6Ð09 min[ According to Schuckit "0873#\ this results in a peak blood alcohol level of about 69 mg:dl after 29Ð59 min\ falling to a blood level of about 49 mg:dl for approximately 29 min[ Following Schuckit\ on the placebo day the volume of liquid was kept constant but a few drops of alcohol were added to mimic the odor and taste of the alcoholic beverage[ Blood alcohol levels were evaluated by breathalyzer every 04 min following alcohol consumption "and placebo consumption to maintain the blind#[ Neither the subject nor the experimenter "except the breathalyzer operator# knew whether the subject had received alcohol or placebo[ The subject began the divided attention task 29 min after alcohol or placebo ingestion[ 1[2[1[ Positron emission tomography The PET procedure followed a standard PET protocol "Buchsbaum et al[\ 0889#[ After obtaining written informed consent and completing the structured screening interview on a prior day\ the subject was seated in an acoustically attenuated testing room[ An intravenous line with a 9[8) saline drip was inserted into the subject|s right arm for radioactive!tracer injection and a second line into the subject|s left arm with a plastic cannula for blood sampling[ The left arm was wrapped in a hot pack for arterialization of venous blood "which gives adequate glucose values "Phelps et al[\ 0868##[ Intravenous lines were started about 59 min before FDG injection[ About 1Ð2 min before injection\ the subject started the task so that the initial novelty of the presentation would not be FDG labeled[ After 21 min of FDG uptake\ the IV in the right arm was removed\ the subject was allowed to void\ and then was transferred to the adjacent PET scanner\ a NeuroECAT[ Resolution "FWHM# is 6[5 mm in plane and 09[8 mm in the Z!dimension[ An individually molded\ thermosetting plastic
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Fig[ 0[ This left lateral view of the cortex based on the Matsui + Hirano atlas "0867# shows how cortical peel PET slices are stacked[ Stereotactic!based locations for major lobe segments are shown[ Signi_cant correlations between alcohol induced changes in glucose metabolic rate and attention were found in the postcentral\ supramarginal\ superior parietal lobule\ and the angular gyrus segments "Table 2#[
head holder was used\ holding the head still and positioning the scanner to insure the same slices would be imaged on both days[ Nine or 09 slices parallel to the cm line were scanned at 09 mm intervals for each subject[ Scans were transformed to glucose metabolic rate "Buchsbaum et al[\ 0878#[ Each slice was then matched to a standard atlas "Matsui + Hirano\ 0867# by an observer without knowledge of treatment condition[ We then outlined the cortex\ and averaged metabolic rates in a strip along the slice perimeter as described elsewhere "Buchsbaum et al[\ 0878#[ A weighted average of these strip segments was then calculated across slices to obtain estimates of metabolic rate in the major gyri of the brain "05 per hemisphere^ see Fig[ 0#[ In addition to the cortical peel\ we applied our own standard template of 52 regions of interest "left and right separately#\ as described in Buchsbaum et al[ "0878# and illustrated in Fig[ 1[ All analyses were computed on GMR within the region!of!interest divided by whole slice "sub cortical areas# or whole brain "cortical areas# GMR[ This is termed relative GMR and corrects for the wide individual di}erences among people in overall brain GMR[ Relative GMR corresponds to {normalization| corrections[ Placement errors in stereotactic methods result primarily from inexact head positioning and from individual divergence from proportional co!ordinates[ Our head holder method results in placement errors of about 1 mm\ well within the spatial resolution of our scanner[ This was assessed
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Fig[ 1[ These axial slices show our standard anatomical template for sub and medial cortical areas[ Percentages next to each slice indicate percentage of head height above the canthomeatal line[ Black boxes show areas where there were signi_cant correlations between alcohol induced glucose metabolic rate and attention "Table 3#[
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on repeat MRI scans several weeks apart using the same PET headholder "Buchsbaum et al[\ 0881#[ Individual di}erences from proportional co!ordinates would be constant between scan 0 and scan 1^ therefore\ any di}erences would not produce spurious alcohol e}ects[ Moreover\ there is a close correspondence between many of our stereotactic regions!of!interest and MRI de_ned regions "Haier et al[\ 0881#[ 1[3[ Data reduction and analysis Glucose data were analysed using repeated measures analysis of variance "ANOVA^ BMDP 3V\ Dixon\ 0877# and post hoc t!tests[ ANOVA was chosen because multiple determinations within each subject arranged in discrete dimensions were obtained from the peel method "frontal\ parietal\ temporal and occipital lobes\ four gyri within each lobe\ left and right hemisphere#[ For the cortical peel\ this was a four way ANOVA with repeated measures for condition "placebo\ alcohol#\ and within nested factors of hemisphere\ lobe\ and gyrus[ The BMDP 3V option of structure was used to eliminate gyri e}ects not nested within lobe[ Correlations between relative GMR and task performance measures were also computed\ following the approach of de Wit et al[ "0889# and Haier et al[ "0877#[ Since earlier authors report data from a number of subcortical and medial brain areas\ a set of 52 brain regions were analysed^ these include divided attention areas reported by Corbetta et al[ "0880# and alcohol and lorazepam sensitive areas reported by Volkow et al[ "0882# and de Wit et al[ "0889#[ Although 52 regions are explored\ they are not fully statistically independent\ many showing intra!correlations ranging from 9[2Ð9[5[ Thus\ straight Bonneferoni correction is not appropriate[ We thought examination of areas already reported a}ected by alcohol and:or benzo! diazepines was appropriate^ exploratory analyses are performed for all other brain areas since the PET technique acquires data for the whole brain[
2[ Results During the 21 min FDG uptake period subjects displayed a mean BAC of 54 mg:dl "SD 02 mg:dl# in the alcohol condition and a mean BAC of 9 in the placebo condition[ A four way ANOVA "alcohol:placebo condition×cortical lobe×segment of lobe×cortical hemisphere# of the relative brain metabolic data showed no signi_cant interactions or e}ects for alcohol "C×L×S×H^ F 0[61\ HuynhÐFeldt df 7[33\ 007[03^ P 9[985#[ These data are shown in Table 0[ The mean task performances for each measure on alcohol and placebo are shown in Table 1[ Attention data were analysed using matched t!tests of performance data obtained during the alcohol vs the placebo conditions[ While no signi_cant di}erences were found between conditions\ under the in~uence of alcohol\ subjects displayed generally reduced performance on each task[ The data are commensurate with _ndings from other studies of acute alcohol e}ects employing sample sizes su.ciently large to allow acquisition of a more stable performance e}ect[ However\ the principal question of the present study was whether PET provides coherent evaluations of attention operations a}ected by acute alcohol intoxication[ We examined the correlation coe.cients between change in performance "alcoholÐplacebo# and change in the glucose
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Table 0 Relative glucose metabolic rates in each lobe for alcohol and placebo conditions Segment0
Frontal
Parietal
Temporal
Occipital
Placebo 0 1 2 3
0[95 0[10 0[07 0[15
0[10 0[07 0[11 0[19
9[86 9[83 9[80 9[79
0[00 0[15 0[14 0[97
Alcohol 0 1 2 3
0[96 0[05 0[05 0[13
0[19 0[06 0[08 0[11
9[86 9[83 9[80 9[68
0[98 0[12 0[06 0[94
0 Segments for each lobe are shown in Fig[ 0^ left and right hemispheres combined[ No main e}ects or interactions for alcohol:placebo comparisons were signi_cant by repeated measures ANOVA "condition×lobe×segment× hemisphere#[
Table 1 Attention performance on each attention variable for placebo and alcohol conditions
Posner RT Posner )0 Manikin RT Manikin ) correct Transition1 Posner RT Transition Posner ) correct Transition Manikin RT Transition Manikin ) correct 0 1
Placebo M "N 7#
Alcohol M "N 7#
428 ms SD 41[6 83[0) SD 2[8 527 ms SD 55[0 89[6) SD 5[7 444 ms SD 74[3 83[9) SD 3[6 541 ms SD 59[8 80[7) SD 5[2
459 ms SD 37[3 83[2) SD 2[4 552 ms SD 71[2 78[2) SD 4[4 485 ms SD 55[2 82[4) SD 3[7 579 ms SD 82[2 75[7) SD 7[1
) is percentage of trials correct[ Transition variables include only trials following a switch of the center arrow[
metabolic rate "alcohol!placebo# for the 21 cortical areas[ The only signi_cant correlations were in the parietal lobe^ better performance\ whether fewer errors or faster reaction times\ was always associated with higher metabolic rates[ The correlations between changes in attention and glucose metabolic rate for all four segments of the parietal lobe are shown in Table 2 and their location is illustrated in Fig[ 0[ None of the correlations was an artifact of outliers[ For reaction time "RT# variables\ a negative correlation means better performance "i[e[ shorter RT# goes with higher GMR on alcohol^ for percentage correct variables\ a positive correlation means the same[ Note in Table
323
Segments All four
Posner RT Posner ) Manikin RT Manikin ) Transition Posner RT Transition Posner ) Transition Manikin RT Transition Manikin RT
Post central
Supra margin
Angular
Superior
Left
Right
Left
Right
Left
Right
Left
Right
Left
Right
−9[70 9[57 −9[52 9[65 −9[50 9[55 −9[59 9[52
−9[67 9[57 −9[62 9[64 −9[53 9[56 −9[64 9[65
−9[77 9[49 −9[53 9[65 −9[51 9[37 −9[47 9[47
−9[75 9[44 −9[70 9[68 −9[61 9[44 −9[68 9[64
−9[21 9[18 −9[11 9[18 −9[47 9[13 −9[96 −9[05
−9[31 9[72 −9[34 9[43 −9[47 9[67 −9[34 9[33
−9[59 9[70 −9[32 9[52 −9[55 9[79 −9[27 9[29
−9[64 9[53 −9[62 9[68 −9[64 9[53 −9[60 9[53
−9[45 9[32 −9[37 9[41 −9[11 9[31 −9[44 9[60
−9[51 9[42 −9[44 9[42 −9[21 9[42 −9[51 9[61
Note] r × 9[60 signi_cant at P ³ 9[94\ 1!tailed^ r × 9[68 signi_cant at P ³ 9[91\ 1!tailed^ r × 9[72 signi_cant at P ³ 9[90\ 1!tailed[ 0 For RT a negative correlation is better performance with higher GMR with alcohol^ for ) correct a positive correlation is better performance with higher GMR with alcohol[
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Table 2 Correlations between change in attention "alcoholÐplacebo# and change in parietal lobe relative glucose metabolic rate "alcoholÐplacebo#0
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2 that there are 21 possible correlations in each hemisphere "3 segments×7 attention variables#[ Signi_cant correlations appear more often in the right hemisphere "03:21# than in the left hemi! sphere "4:21^ x1 3[68\ P ³ 9[914\ Yates corrected#[ Of the four regions Corbetta et al[ "0880# identi_ed as activated during their divided attention task "region of the left collateral sulcus\ left occipital gyrus\ anterior cingulate\ dorsolateral prefrontal cortex#\ none showed a signi_cant increase or decrease on alcohol in our relative data "the four Corbetta et al[ "0880# areas correspond\ respectively\ to our inferior:posterior temporal cortex\ area 08\ the anterior cingulate\ and middle frontal cortex\ all shown in Figs 0 and 1#[ We also applied our standard region!of!interest template of 52 areas "Fig[ 1#\ to explore additional areas throughout the brain "Buchsbaum et al[\ 0878#[ Two regions were signi_cantly decreased on alcohol\ the left precuneus\ and the left posterior putamen^ the right uncus signi_cantly increased on alcohol "P ³ 9[94\ 1!tailed matched t!test#[ For each of these three regions!of!interest that were signi_cantly di}erent between alcohol and placebo\ we correlated change in metabolic rate "alcoholÐplacebo# and change in attention performance "alcohol!placebo#[ Signi_cant correlations were found for precuneus and putamen^ the anterior cingulate\ activated in the Corbetta et al[ study\ also showed signi_cant correlations with several attention performance measures[ This is shown in Table 3 along with all other signi_cant correlations between change in metabolic rate and RT for the other sub and medial cortical regions examined "Fig[ 1#[ Negative correlations indicate better attention performance "i[e[ faster RT# as GMR with alcohol increases[ Positive correlations indicate worse performance "i[e[ slower RT# as GMR increases with alcohol[ This is presented as an exploratory analysis for future hypothesis testing[
3[ Discussion The data show that the use of PET within a controlled information processing paradigm is an e}ective means of explaining the nature and location of alcohol|s e}ects on central nervous system operations[ The major _nding of this study was the signi_cant correlations between alcohol changes in cognitive performance and alcohol changes in relative GMR in the superior\ inferior\ and middle parietal lobes[ This is consistent with other studies showing that the parietal lobes are important in both maintaining "Mesulam 0874\ Posner\ Walker\ Friedrich + Rafal\ 0876# and allocating attention "Farah\ Wong\ Monheit + Morrow\ 0878#[ Because the right parietal lobe is thought to be important in spatial orientation of objects "Di Mattia + Kesner\ 0877^ Mesulam\ 0874#\ our _nding more signi_cant correlations in the right hemisphere could be a function of the spatial nature of the manikin task and its relative sensitivity to alcohol e}ects[ The FDG technique\ however\ does not allow separation of the e}ects contributed from the manikin and letter matching tasks^ only cumulative e}ects for the 21 min uptake period can be determined[ It should be noted further that the letter matching task alone might be expected to activate the left frontal cortex\ parts of the temporal lobe\ and parts of the visual cortex[ The manikin task alone would activate right parietal\ dorsal lateral pre!frontal cortex\ and the same parts of the visual cortex as the letter matching task[ Since both the alcohol and the placebo conditions used the same combination of tasks and no control tasks were used\ alcoholÐplacebo comparisons would not necessarily show di}erences in these areas alone[
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Table 3 Correlations between change in attention "alcoholÐplacebo# and change in relative glucose metabolism "alcoholÐplacebo# for selected regions!of!interest0 Transition trials )1
Posner RT
Manikin RT
Posner RT
Manikin RT
L Precuneus L Precuneus L Ant Cingulate R Mid Cingulate
63 57 43 43
−9[56 −9[40 −9[48 −9[52
−9[65 −9[57 −9[31 −9[69
−9[56 −9[42 −9[63 −9[62
−9[72 −9[67 −9[11 −9[46
R Mid Corpus Callosum L Mid Corpus Callosum
36 36
9[51 9[68
9[58 9[63
R Post Calcarine R Ant Calcarine L Frontal White L Post Putamen
30 30 30 30
−9[63 −9[65 −9[64 9[66
−9[65 −9[47 −9[54 9[50
L Cingulate L Globus Pallidus
23 23
9[66 9[44
9[56 9[65
9[38 9[35
L Ant Cingulate L Putamen R Inf Colliculus
17 17 17
9[65 9[64 −9[51
9[79 9[66 −9[56
9[80 9[36 −9[67
9[66 9[61 −9[44
L Ant Rectal Gyrus L Hippocampus
10 10
−9[47 −9[33
−9[66 −9[31
−9[32 −9[62
−9[72 −9[14
9[67 9[76
−9[74 −9[43 −9[43 9[43
9[02 9[69 −9[55 −9[35 −9[48 9[36 9[53 9[79
r × 9[60 signi_cant at P ³ 9[94\ 1!tailed^ r × 9[68 signi_cant at P ³ 9[91\ 1!tailed^ r × 9[72 signi_cant at P ³ 9[90\ 1!tailed[ 0 Of 52 areas measured\ only the areas with at least one signi_cant correlation with RT performance are shown in this Table[ Negative correlations indicate that attention performance is better "i[e[ shorter RT# as GMR increases with alcohol^ positive correlations mean worse performance "i[e[ longer RT# as GMR increases with alcohol[ L is for left hemisphere^ R is right[ ANT is for anterior^ POST is for posterior^ INF is for inferior[ 1 ) head height of slice from the canthomeatal line^ see Matsui + Hirano "0867#[
In their PET study\ de Wit et al[ "0889# also investigated individual di}erence correlations after similarly failing to _nd main group alcohol e}ect for a low dose[ Their _nding of slower reaction times on alcohol for subjects whose glucose metabolic rate increased "their table 1\ occipital lobe and thalamus# is similar to ours although their parietal lobe data were not signi_cant[ The signi_cant correlations found in several areas of the limbic system are consistent with both memory and emotion function[ The anterior cingulate gyrus correlations are consistent with the Corbetta et al[ "0880# _nding[ It should be noted that di}erences between the Matsui and Hirano atlas used in this study and the Talairach atlas used by Corbetta et al[ "0880# are not large[
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Although the Matsui and Hirano atlas used the canthomeatal line\ a standard in clinical use\ and the Talairach atlas is based on the anteriorÐposterior commissure line\ both portray the brain of a single individual and are not statistical standards[ Our use of proportional rather than absolute mm co!ordinates and the cortical peel technique avoids potential problems associated with regions! of!interest at the brain|s margin found with the method used by Corbetta et al[ "0880# "Drevets\ Videen\ MacLeod\ Haller + Raichle\ 0881#[ Following Buchsbaum et al[ "0871#\ we use the statistical method of repeated measures ANOVA on data expressed as a ratio to whole brain mean to remove e}ects of individual variation in global brain metabolic rate and we use each individual structure as its own baseline for medication contrasts\ providing relative glucose values "regional area rate:whole slice rate#[ This achieves a similar aim as the subtraction procedure applied to normalized data used by Corbetta et al[ "0880#[ It has the advantage of yielding only a few F!ratios which provide a systematic test of hemisphere asymmetries and di}erences between structures[ The cortical areas which showed correlations between change in performance and change in metabolism are similar to those with high concentrations of benzodiazapine receptors "Buchsbaum et al[\ 0878^ de Wit et al[\ 0889^ Volkow et al[\ 0889#[ Volkow et al[ "0882# also found that chronic alcoholics had a blunted response to lorazepam in orbitofrontal cortex and basal ganglia\ areas with signi_cant correlations in our study "Table 3#[ Thus\ individual di}erences in alcohol response may re~ect di}erences in the GABA!benzodiazapine receptor distribution and:or density[ Evidence on this\ however\ is mixed "Litton et al[\ 0882^ Pauli et al[\ 0881#[ The e}ects reported here are for structures adequately imaged with 6[5 mm in plane and 09[8 mm axial resolution "FWHM#[ The major gyri of the cortical surface are all several cm in length[ While the cortical ribbon surface is 2Ð4 mm thick\ it is typically folded into a thicker strip similar in width to our cortical peel[ Thus\ our cortical regions are typically more than three times the FWHM[ The putamen\ caudate\ and cingulate gyrus all accommodate the 5×5 mm box easily in the horizontal plane and all are at least 19 mm or two 09 mm planes high[ Heterogeneity within the axial or horizontal plane would reduce the adequacy of the method[ However\ random variation caused by individual di}erences in brain proportions\ vertical position of the plane acquired and variation in head position and reposition would all tend to create random error and diminish any correlations[ Structures closer in size to the FWHM resolution are not so well quanti_ed so only large e}ects or e}ects re~ecting surrounding structures would be detected[ In conclusion\ alcohol improved performance on the divided attention task in some subjects and worsened performance in other subjects[ The degree of change in attention performance was correlated with change in GMR only in areas of the parietal cortex and several subcortical areas[ This study demonstrates the importance of individual di}erences of alcohol response in attention and implicates a small number of brain areas where alcohol may have e}ects at low levels[
Acknowledgments This study was funded by the Medical Management Division of the Atlantic Rich_eld Company[ The authors thank Dr Aleksandra Chicz!DeMet for her help in quantifying alcohol doses and NTI\ Ohio for providing computer software for the attention tests[ These data were presented at
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the Human Performance Conference\ Institute of Human Performance\ Lisbon\ Portugal\ January\ 0880[
References Buchsbaum\ M[ S[\ Gillan\ J[ C[\ Wu\ J[\ Hazlett\ E[\ Sicotte\ N[\ + DuPont\ R[ M[ "0878#[ Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography[ Life Science\ 34\ 0238Ð0245[ Buchsbaum\ M[ S[\ Ingvar\ D[ H[\ Kessler\ R[\ Waters\ R[ N[\ Cappelletti\ J[\ van Kammen\ D[ P[\ King\ A[ C[\ Johnson\ J[ J[\ Manning\ R[ G[\ Flynn\ R[ M[\ Mann\ L[ S[\ Bunney\ W[ E[\ + Sokolo}\ L[ "0871#[ Cerebral glucography with Positron Emission Tomography in normals and in patients with schizophrenia[ Arch[ Gen[ Psychiatry\ 28\ 140Ð148[ Buchsbaum\ M[ S[\ Nuechterlein\ K[ H[\ Haier\ R[ J[\ Wu\ J[\ Sicotte\ N[\ Hazlett\ E[\ Asarnow\ R[\ Potkin\ S[\ + Guich S[ "0889#[ Glucose metabolic rate in normals and schizophrenics during the Continuous Performance Test assessed by Positron Emission Tomography[ Br[ J[ Psychiatry\ 045\ 105Ð116[ Buchsbaum\ M[ S[\ Potkin\ S[\ Marshall\ J[ F[\ Lottenberg\ S[\ Teng\ C[\ Heh\ C[\ Tafalla\ R[\ Reynolds\ C[\ Abel\ L[\ + Plon\ L[ "0881#[ E}ects of clozapine and thiothixene on glucose metabolic rate in schizophrenia[ Neu! ropsychopharmacolo`y\ 5\ 044Ð052[ Bunnell\ D[ E[\ + Horvath\ S[ M[ "0877#[ Interactive e}ects of physical work and carbon monoxide on cognitive task performance[ Aviat[ Space Environ[ Med[\ December\ 0022Ð0027[ Carter\ R[\ + Woldstad\ J[ "0874#[ Repeated measurements of spatial ability with the manikin test[ Hum[ Factors\ 16\ 198Ð108[ Cohen\ M[ J[\ Schandler\ S[ L[\ + Nalibo}\ B[ D[ "0876#[ Psychophysiological measures from intoxicated and detoxi_ed alcoholics[ J[ Stud[ Alcohol\ 33\ 160Ð171[ Corbetta\ M[\ Miezin\ F[ M[\ Dobmeyer\ S[\ Shulman\ G[ L[\ + Petersen\ S[ E[ "0880#[ Selective and divided attention during visual discriminations of shape\ color\ and speed] Functional anatomy by Positron Emission Tomography[ J[ Neuroscience\ 00\ 1272Ð1391[ de Wit\ H[\ Metz\ J[\ Wagner\ N[\ + Cooper\ M[ "0889#[ Behavioral and subjective e}ects of ethanol] relationship to cerebral metabolism using PET[ Alcohol Clin[ Exp[ Res[\ 03\ 371Ð378[ Di Mattia\ B[ V[\ + Kesner\ R[ P[ "0877#[ Role of the posterior parietal association cortex in the processing of spatial event information[ Behav[ Neurosci[\ 091\ 286Ð392[ Dixon\ W[ J[ "0877#[ BMDP Biomedical Statistical Software[ Berkeley\ CA] University of California Press[ Drevets\ W[ C[\ Videen\ T[ Q[\ MacLeod\ A[ K[\ Haller\ J[ W[\ + Raichle\ M[ E[ "0881#[ PET images of blood ~ow changes during anxiety] Correction[ Science\ 145\ 0585[ Farah\ M[ J[\ Wong\ A[ B[\ Monheit\ M[ A[\ + Morrow\ L[ A[ "0878#[ Parietal lobe mechanisms of spatial attention] modality!speci_c or supramodal< Neuropsycholo`ia\ 16\ 350Ð369[ Gibb\ K[ A[\ Yee\ A[ S[\ Johnston\ C[ C[\ Martin\ S[ D[\ + Scha}er\ M[ A[ "0873#[ Accuracy and usefulness of a breath alcohol analyzer[ Ann[ Emer`[ Med[\ 02\ 405Ð419[ Haier\ R[ J[\ Siegel\ B[ V[\ MacLachlan\ A[\ Soderling\ E[\ Lottenberg\ S[\ + Buchsbaum\ M[ S[ "0881#[ Regional glucose metabolic changes after learning a complex visuoÐspatial:motor task] a Positron Emission Tomography study[ Brain Res[\ 469\ 023Ð032[ Haier\ R[ J[\ Siegel\ B[ V[\ Nuechterlein\ K[ H[\ Hazlett\ E[\ Wu\ J[\ Peak\ J[\ Browning\ H[\ + Buchsbaum\ M[ S[ "0877#[ Cortical glucose metabolic rate correlates of abstract reasoning and attention studied with positron emission tomography[ Intelli`ence\ 01\ 088Ð106[ Litton\ J[ E[\ Neiman\ J[\ Pauli\ S[\ Farde\ L[\ Hindmarsh\ T[\ Halldin\ C[\ + Sedvall\ G[ "0882#[ PET analysis of ð00CŁFlumazenil binding to benzodiazepine receptors in chronic alcohol!dependent men and healthy controls[ Psy! chiatry Research\ 49\ 0Ð02[ Mathew\ R[ J[\ + Wilson\ W[ H[ "0875#[ Regional cerebral blood ~ow changes associated with ethanol intoxication[ Stroke\ 06\ 0045Ð0048[ Matsui\ T[\ + Hirano\ A[ "0867#[ An Atlas of the Human Brain for Computerized Tomo`raphy[ Tokyo] Igku!Shoin[ Mesulam\ M[ M[ "0874#[ Principles of Behavioral Neurolo`y[ Philadelphia] F[A[ Davis Company[
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Moskowitz\ H[ "0862#[ Laboratory studies of the e}ects of alcohol on some variables related to driving[ J[ Safety Res[\ 4\ 074Ð088[ Moskowitz\ H[\ Burns\ M[ M[\ + Williams\ A[ F[ "0874#[ Skills performance at low blood alcohol levels[ J[ Stud[ Alcohol\ 35\ 371Ð374[ Moskowitz\ H[\ + Depry\ D[ "0857#[ Di}erential e}ect of alcohol on auditory vigilance and divided!attention tasks[ Quarterly J[ Stud Alcohol\ 43Ð52[ Pauli\ S[\ Liljequist\ S[\ Farde\ L[\ Swahn\ C[ G[\ Litton\ J[ E[\ + Sedevall\ G[ "0881#[ PET analysis of alcohol interaction with the brain disposition of ð00CŁFlumazenil[ Psychopharmacolo`y\ 096\ 079Ð074[ Phelps\ M[ E[\ Huang\ S[ C[\ Ho}man\ E[ J[\ Selin\ C[\ Sokolo}\ L[\ + Kuhl\ D[ E[ "0868#[ Tomographic measurement of local cerebral glucose metabolic rate in humans with "F!0#1!~uoro!1!deoxy!D!glucose] validation of method[ Ann[ Neuro[\ 5\ 260Ð27[ Poon\ R[\ Hodgson\ B[ T[\ Hinberg\ I[\ + Rowatt C[ "0876#[ Evaluation of three pocket!size breath alcohol analyzers[ J[ Can[ Sociolo`ical Forensic Science\ 19\ 08Ð16[ Posner\ M[ I[\ + Mitchell\ R[ F[ "0856#[ Chronometric analysis of classi_cation[ Psychol Rev[\ 63\ 281Ð398[ Posner\ M[ I[\ Walker\ J[ A[\ Friedrich\ F[ J[\ + Rafal\ R[ D[ "0876#[ How do the parietal lobes direct covert attention< Neuropsycholo`ia\ 17\ 024Ð034[ Rohrbaugh\ J[ W[\ Stapleton\ J[ M[\ Parasuram\ R[\ Frowein\ H[ W[\ Adino}\ B[\ Varner\ J[ L[\ Zubovic\ E[ A[\ Lane\ E[ A[\ Eckardt\ M[ J[\ + Linnoila\ M[ "0877#[ Alcohol intoxication reduces visual sustained attention[ Psy! chopharmacolo`y\ 85\ 331Ð335[ Schandler\ S[ L[\ Cohen\ M[ J[\ McArthur\ D[ L[\ Nalibo}\ B[ D[\ + Hassell\ A[ "0877#[ Activation peaking in intoxicated and detoxi_ed alcoholics during visuoÐspatial learning[ J[ Stud[ Alcohol\ 38\ 015Ð029[ Schuckit\ M[ A[ "0873#[ Subjective responses to alcohol in sons of alcoholic and control subjects[ Arch[ Gen[ Psychiatry\ 30\ 768Ð773[ Volkow\ N[ D[\ Mullani\ N[\ Gould\ L[\ Adler\ S[ S[\ Guynn\ R[ W[\ Overall\ J[ E[\ + Dewey\ S[ "0877#[ E}ects of acute! intoxication on cerebral blood ~ow measured with PET[ Psychiatry Res[\ 13\ 190Ð198[ Volkow\ N[ D[\ Hitzemann\ R[\ Wolf\ A[ P[\ Logan\ J[\ Fowler\ J[ S[\ Christman\ <[\ Dewey\ S[ L[\ Schlyer\ G[ B[\ Vitkun\ S[\ + Hirschowitz\ J[ "0889#[ Acute e}ects of ethanol on regional brain glucose metabolism and transport[ Psychiatry Res[\ 24\ 28Ð37[ Volkow\ N[ D[\ Wang\ G[ J[\ Hitzemann\ R[\ Fowler\ J[ S\ Wolf\ A[ P\ Pappas\ N[\ Biegon\ A[\ + Dewey\ S[ L[ "0882#[ Decreased cerebral response to inhibitory neurotransmission in alcoholics[ Am[ J[ Psychiatry\ 049\ 306Ð311[
Personality and Individual Di}erences 15 "0888# 314Ð328
Alcohol induced changes in regional cerebral glucose metabolic rate during divided attention R[J[ Haiera\ \ S[L[ Schandlerb\ A[ MacLachlan\ E[ Soderling\ M[S[ Buchsbaumc\ M[J[ Cohend a
Departments of Pediatrics and Neurolo`y\ University of California\ Irvine\ U[S[A[ Department of Psychiatry and Human Behavior\ University of California\ Irvine\ U[S[A[ c Department of Psychiatry\ Mount Sinai School of Medicine\ U[S[A[ d Departments of Neurolo`y and Psychiatry and Human Behavior\ University of California\ Irvine\ U[S[A[ b
Received 15 February 0887
Abstract Under conditions of moderate alcohol intoxication "9[64 ml:kg# and an alcohol!disguised placebo\ eight non!alcoholic male volunteers performed a divided attention task after injection of 07!F!1!~uoro!1!deox! yglucose "FDG# for a Positron Emission Tomography "PET# study[ The administration of alcohol or placebo followed a random order double!blind protocol[ During 21 min of divided attention\ the subject performed a letter matching task or a spatial orientation task presented simultaneously on a computer!generated split display[ The task to be performed was indicated by an arrow on the display that changed randomly every few trials[ Alcohol intoxication was associated with a trend toward generally reduced performance[ Task performance di}erences between the alcohol and placebo conditions were signi_cantly correlated with cortical glucose metabolic rates "GMR# in the superior\ inferior\ and middle parietal lobes[ Impaired performance was associated with GMR decreases[ GMR in several subcortical and medial cortical areas were also correlated with performance changes\ including areas of the putamen and cingulate[ The major _nding is that individual di}erences in GMR change from placebo to alcohol in parietal cortex are related to individual di}erences in attention performance[ The application of PET with selective information processing paradigms provides a useful method for isolating and in identifying the e}ects of alcohol intoxication on the function of the central nervous system[ Þ 0888 Elsevier Science Ltd[ All rights reserved[ Key words] Alcohol^ Attention^ Positron emission tomography^ Glucose metabolism^ Parietal cortex
0[ Introduction Several decades of research have reliably established that acute and chronic alcohol use and abuse produce selective rather than global e}ects on operations of the human central nervous Corresponding author[ Fax] 838 713!2024^ e!mail] rjhaierÝuci[edu 9080Ð7758:88:, ! see front matter Þ 0888 Elsevier Science Ltd[ All rights reserved[ PII] S 9 0 8 0 Ð 7 7 5 8 " 8 7 # 9 9 0 8 6 Ð 3
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system "CNS#[ However\ the nature and location of alcohol|s e}ects remain unclear[ This is due primarily to the use of information processing probe paradigms that vary greatly in the demands placed on the CNS and the measurement of CNS activity during those demands[ Not unexpectedly\ the use of performance\ psychophysiological\ and electrophysiological measures of CNS operations during cognitive operations support several di}erent and often opposing hypotheses as to the nature and the location of alcohol|s e}ect on the information processing system[ New technological and statistical modeling developments in functional brain imaging now make this method highly suited to direct assessment of CNS operations in response to demands from selected information processing tasks[ Positron Emission Tomography "PET# has appeared as one method that is suited to this task[ Used together with standardized information processing probes and paradigms\ PET may both test the most prominent hypotheses of alcohol|s e}ects on information processing and illuminate the source"s# of these e}ects[ Once the sources are identi_ed\ it may be possible to develop and accurately evaluate cognitive interventions that address and ameliorate the e}ects of chronic alcohol abuse[ Early PET studies of alcohol|s e}ect on CNS operations have been more exploratory than focused on a speci_c hypothesis[ Although not employing a consistent paradigm for probing information processing\ these studies have shown regional cerebral changes in both blood ~ow and glucose metabolism following alcohol administration[ Volkow et al[ "0877# studied 02 normal social drinkers in a no!task paradigm with 04O!labeled water to assess blood ~ow[ Seven subjects received a low dose of alcohol "9[53 ml:kg# and six others a high dose "0[17 ml:kg#[ They reported signi_cantly decreased blood ~ow in the cerebellum with the high dose[ The high dose also signi_cantly increased blood ~ow in the right prefrontal and temporal cortex[ In a second study\ Volkow et al[ "0889# used FDG and PET to compare regional cerebral glucose metabolic rates "GMR# between six alcoholics and six normals[ Each subject was studied twice\ baseline "no task\ resting with eyes open# and during alcohol intoxication "based on 0[17 ml:kg#[ Both the normals and the alcoholics showed decreased GMR in cortex and cerebellum^ the basal ganglia\ thalamus\ and corpus callosum did not change[ The largest GMR decreases with alcohol were in the occipital and frontal cortex[ These areas have high concentrations of benzodiazapine receptors\ receptors hypothesized to be important in alcohol response[ De Wit\ Metz\ Wagner + Cooper\ "0889# studied eight healthy male volunteers with PET and two doses of alcohol "9[415 and 9[731 ml:kg#[ Following the lower dose\ whole brain glucose was higher than placebo in _ve subjects but lower in three subjects[ Finding no signi_cant group e}ect for alcohol\ they went on to relate these individual di}erences in cerebral glucose metabolic rate change with alcohol to cognitive and mood changes by examining correlation coe.cients[ The brain areas so identi_ed were similar to those found by Volkow et al[ "0889#\ in showing alcohol decreases and thus are partially consistent with the implication of benzodiazapine receptor rich areas in alcohol response[ Mathew and Wilson "0875# showed bilateral increases in blood ~ow after administration of alcohol in 15 normal controls in a double blind\ placebo controlled study using the xenon inhalation technique[ The largest increases were in parietal and frontal cortex bilaterally and in right temporal areas[ Whilst instructive regarding general alcohol e}ects\ the data are inconsistent in isolating infor! mation processing e}ects related to a speci_c cortical area[ This may be due to the lack of a meaningful task during the metabolic tracer uptake[ Attention tasks are known to be sensitive to
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alcohol e}ects and therefore may be of special interest for PET studies[ For example\ Moskowitz\ Burns and Williams "0874# used a battery of divided attention and information processing measures to test 09 normal males with mean blood alcohol levels "BAL# ranging from 9Ð48 mg:dl[ All measures showed impaired performance and impairment increased with increasing BAL[ The divided attention task was the most sensitive to alcohol impairment "Moskowitz\ 0862#[ Similarly\ Rohrbaugh et al[ "0877# found that increased blood alcohol levels "up to 0[94 gm ETOH:kg lean body mass# were negatively correlated with cognitive performance on a sustained attention task "the continuous performance test# testing visual vigilance in social drinkers "N 01#[ They concluded that alcohol reduces central processing capacity and capacity availability over time[ Interestingly\ when comparing the performance of nine intoxicated and detoxi_ed chronic alcoholics during a visual CPT and a visuoÐspatial learning task\ Schandler and his colleagues "Cohen\ Schandler + Nalibo}\ 0876^ Schandler\ Cohen\ McArthur\ Nalibo} + Hassell\ 0877# found the intoxicated chronic alcoholics to display enhanced orienting and attention operations[ The combining of attention!sensitive information processing paradigms with brain imaging dependent measures has begun yielding more direct information about the e}ects of alcohol on CNS function[ Corbetta\ Miezin\ Dobmeyer\ Schulman and Petersen "0880# studied cerebral blood ~ow using PET in a group of nine normals performing a divided attention task[ Subjects were scanned in six conditions] three scans set the baseline for three selective attention conditions "shape\ velocity\ and color#[ The divided attention stimuli required the detection of a change in either shape\ speed\ or color features[ During the divided attention trials\ blood ~ow was uniquely activated in the left collateral sulcus\ the left lateral occipital gyrus\ the anterior cingulate and the dorsolateral prefrontal cortex[ "Activation also occurred in area 06 and the lingual gyrus in visual cortex but this was not unique to divided attention#[ Buchsbaum et al[ "0889# used PET:FDG to study attention using the continuous performance test "CPT#[ Right frontal and right tem! poroparietal cortex showed GMR increases[ Attention appears as one CNS!mediated operation that is particularly sensitive to alcohol ingestion and intoxication[ Of the paradigms used to probe attention operations during information processing\ the divided attention paradigm may show a more pronounced alcohol induced e}ect in cognitive performance than other attention tasks "Moskowitz et al[\ 0874^ Moskowitz\ 0862^ Moskowitz + Depry\ 0857#[ Given the ability of PET to illuminate speci_c cortical areas involved in information processing\ it was the purpose of this exploratory study to use PET to determine whether the e}ect of alcohol on a divided attention task was correlated with activity "metabolic changes# in brain areas used for attention[
1[ Methods 1[0[ Subjects Eight healthy right!handed male volunteers "mean age 15 years\ SD 3[1# served individually in two sessions of PET scans performed at the University of California\ Irvine\ U[S[A[ Using a randomized\ double!blind procedure\ subjects consumed a moderate dose of alcohol on one session and a placebo on the other[ Subjects were drawn from the student population at the University of California at Irvine\ and\ based on academic performance\ they display normal neurocognitive
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function[ All subjects were light to moderate social drinkers\ reporting a mean average rate of consumption of less than one drink:day for the previous year[ Based on a standard structured interview\ potential subjects were excluded if they currently su}ered or had any history of signi_cant medical illness\ including head injury\ epilepsy\ or other indicators of neurological illness[ Additional exclusion criteria included any history of excessive alcohol or drug consumption or treatment\ past or current use of psychoactive medications\ and a history of alcohol abuse or alcoholism by the immediate biological family[ The relatively small sample size is similar to other studies "Volkow et al[\ 0877\ 0882^ N 5 and N 01 respectively^ de Wit et al[\ 0889\ N 7#[ Thus\ only moderate to large e}ects can be detected[ 1[1[ Instruments 1[1[0[ Blood alcohol concentration An Alco!Sensor III Breathalyzer "Intoximeters\ Inc[# obtained BAC[ Previous data show cor! relations of ¦9[87 between calibrated breathalyzer and blood chemistry values "Gibb\ Yee\ John! ston\ Martin + Scha}er\ 0873^ Poon\ Hodgson\ Hinberg + Rowatt\ 0876#[ 1[1[1[ Divided attention tasks The divided attention task was comprised of two well!studied attention tasks adapted to a Toshiba Model 0999 laptop computer display[ The component parts of the divided attention task were the manikin task "Carter + Woldstad\ 0874# and the Posner!Mitchell "0856# letter matching task[ The manikin task has been used to test visuoÐspatial ability "Bunnell + Horvath\ 0877#[ The version we used featured a stick _gure "manikin# in four possible orientations] "0# standing upright facing the subject^ "1# standing upright facing away from the subject^ "2# standing upside down facing the subject^ "3# standing upside down facing away from the subject[ In all four orientations\ the manikin had a ball in one hand and a box in the other[ The subject was required to indicate in which of the manikin|s hands "left or right# the box was located[ Both the order of the _gure|s orientation and the hand in which the box was held were randomly ordered and counter!balanced[ The manikin task tested the subject|s ability to perform rotations and transformations of a mental image[ The Posner!Mitchell task tested the subject|s ability to match symbols[ The symbols were letters to be matched by either identity or by case type "i[e[ upper or lower case#[ The letters matched if the identity "e[g[ Aa# or the case type "e[g[ AB or ab# of the letters were the same[ Two letters were displayed on the screen\ randomly chosen from the same set "A\ B\ C\ and E#[ Each letter appeared in both upper case and lower case during the task "randomly ordered and counter!balanced#[ Both the manikin and the letter tasks were computer controlled and displayed side by side on the 14 cm×7 cm computer display situated 49 cm from the subject[ An arrow presented in the middle of the display indicated which task was to be performed[ The arrow would shift tasks every few trials on a random schedule[ For the manikin task\ the subject indicated box location "left hand or right hand# by pushing one of two buttons marked L or R on the left side of the keyboard[ During the Posner!Mitchell task\ the subject indicated whether the letters were the same or di}erent by pressing one of two buttons marked S or D on the right side of the keyboard[ The subject was given 0 s to respond for each trial[ The subject performed this task\ using his right hand\ for a
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period of 21 min following the injection of the FDG[ During this time\ each subject was exposed to approximately 0499 stimuli[ The subject was instructed to work through the task as quickly and accurately as possible[ Performance was evaluated from eight dependent measures obtained from the divided attention task[ For the component tasks\ manikin and Posner!Mitchell\ we evaluated performance for each task separately using the dependent measures of reaction time "RT# and response accuracy "percentage correct of total possible correct responses#[ These measures excluded both the reaction time and the response accuracy when the subjects made the transition trials from task to task[ Transition reaction time "TRT# was de_ned as the response time to the _rst trial following the transition to the alternate task[ Transition accuracy was the subject|s percentage correct of total possible responses emitted when responding to the alternate task for the _rst trial following the transition[ 1[2[ Procedure Before the start of the protocol\ each subject received training on the divided attention task\ and practiced it for at least 29 min[ On two subsequent test days\ a week apart\ each subject received either alcohol or placebo\ randomly ordered and counter!balanced[ Subjects were tested in the afternoon\ after fasting at least 5 h[ 1[2[0[ Administration of alcohol and placebo On the day alcohol was administered\ each subject received 9[64 ml:kg of alcohol in a 19) by volume solution "cold tonic water#\ consumed in 6Ð09 min[ According to Schuckit "0873#\ this results in a peak blood alcohol level of about 69 mg:dl after 29Ð59 min\ falling to a blood level of about 49 mg:dl for approximately 29 min[ Following Schuckit\ on the placebo day the volume of liquid was kept constant but a few drops of alcohol were added to mimic the odor and taste of the alcoholic beverage[ Blood alcohol levels were evaluated by breathalyzer every 04 min following alcohol consumption "and placebo consumption to maintain the blind#[ Neither the subject nor the experimenter "except the breathalyzer operator# knew whether the subject had received alcohol or placebo[ The subject began the divided attention task 29 min after alcohol or placebo ingestion[ 1[2[1[ Positron emission tomography The PET procedure followed a standard PET protocol "Buchsbaum et al[\ 0889#[ After obtaining written informed consent and completing the structured screening interview on a prior day\ the subject was seated in an acoustically attenuated testing room[ An intravenous line with a 9[8) saline drip was inserted into the subject|s right arm for radioactive!tracer injection and a second line into the subject|s left arm with a plastic cannula for blood sampling[ The left arm was wrapped in a hot pack for arterialization of venous blood "which gives adequate glucose values "Phelps et al[\ 0868##[ Intravenous lines were started about 59 min before FDG injection[ About 1Ð2 min before injection\ the subject started the task so that the initial novelty of the presentation would not be FDG labeled[ After 21 min of FDG uptake\ the IV in the right arm was removed\ the subject was allowed to void\ and then was transferred to the adjacent PET scanner\ a NeuroECAT[ Resolution "FWHM# is 6[5 mm in plane and 09[8 mm in the Z!dimension[ An individually molded\ thermosetting plastic
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Fig[ 0[ This left lateral view of the cortex based on the Matsui + Hirano atlas "0867# shows how cortical peel PET slices are stacked[ Stereotactic!based locations for major lobe segments are shown[ Signi_cant correlations between alcohol induced changes in glucose metabolic rate and attention were found in the postcentral\ supramarginal\ superior parietal lobule\ and the angular gyrus segments "Table 2#[
head holder was used\ holding the head still and positioning the scanner to insure the same slices would be imaged on both days[ Nine or 09 slices parallel to the cm line were scanned at 09 mm intervals for each subject[ Scans were transformed to glucose metabolic rate "Buchsbaum et al[\ 0878#[ Each slice was then matched to a standard atlas "Matsui + Hirano\ 0867# by an observer without knowledge of treatment condition[ We then outlined the cortex\ and averaged metabolic rates in a strip along the slice perimeter as described elsewhere "Buchsbaum et al[\ 0878#[ A weighted average of these strip segments was then calculated across slices to obtain estimates of metabolic rate in the major gyri of the brain "05 per hemisphere^ see Fig[ 0#[ In addition to the cortical peel\ we applied our own standard template of 52 regions of interest "left and right separately#\ as described in Buchsbaum et al[ "0878# and illustrated in Fig[ 1[ All analyses were computed on GMR within the region!of!interest divided by whole slice "sub cortical areas# or whole brain "cortical areas# GMR[ This is termed relative GMR and corrects for the wide individual di}erences among people in overall brain GMR[ Relative GMR corresponds to {normalization| corrections[ Placement errors in stereotactic methods result primarily from inexact head positioning and from individual divergence from proportional co!ordinates[ Our head holder method results in placement errors of about 1 mm\ well within the spatial resolution of our scanner[ This was assessed
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Fig[ 1[ These axial slices show our standard anatomical template for sub and medial cortical areas[ Percentages next to each slice indicate percentage of head height above the canthomeatal line[ Black boxes show areas where there were signi_cant correlations between alcohol induced glucose metabolic rate and attention "Table 3#[
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on repeat MRI scans several weeks apart using the same PET headholder "Buchsbaum et al[\ 0881#[ Individual di}erences from proportional co!ordinates would be constant between scan 0 and scan 1^ therefore\ any di}erences would not produce spurious alcohol e}ects[ Moreover\ there is a close correspondence between many of our stereotactic regions!of!interest and MRI de_ned regions "Haier et al[\ 0881#[ 1[3[ Data reduction and analysis Glucose data were analysed using repeated measures analysis of variance "ANOVA^ BMDP 3V\ Dixon\ 0877# and post hoc t!tests[ ANOVA was chosen because multiple determinations within each subject arranged in discrete dimensions were obtained from the peel method "frontal\ parietal\ temporal and occipital lobes\ four gyri within each lobe\ left and right hemisphere#[ For the cortical peel\ this was a four way ANOVA with repeated measures for condition "placebo\ alcohol#\ and within nested factors of hemisphere\ lobe\ and gyrus[ The BMDP 3V option of structure was used to eliminate gyri e}ects not nested within lobe[ Correlations between relative GMR and task performance measures were also computed\ following the approach of de Wit et al[ "0889# and Haier et al[ "0877#[ Since earlier authors report data from a number of subcortical and medial brain areas\ a set of 52 brain regions were analysed^ these include divided attention areas reported by Corbetta et al[ "0880# and alcohol and lorazepam sensitive areas reported by Volkow et al[ "0882# and de Wit et al[ "0889#[ Although 52 regions are explored\ they are not fully statistically independent\ many showing intra!correlations ranging from 9[2Ð9[5[ Thus\ straight Bonneferoni correction is not appropriate[ We thought examination of areas already reported a}ected by alcohol and:or benzo! diazepines was appropriate^ exploratory analyses are performed for all other brain areas since the PET technique acquires data for the whole brain[
2[ Results During the 21 min FDG uptake period subjects displayed a mean BAC of 54 mg:dl "SD 02 mg:dl# in the alcohol condition and a mean BAC of 9 in the placebo condition[ A four way ANOVA "alcohol:placebo condition×cortical lobe×segment of lobe×cortical hemisphere# of the relative brain metabolic data showed no signi_cant interactions or e}ects for alcohol "C×L×S×H^ F 0[61\ HuynhÐFeldt df 7[33\ 007[03^ P 9[985#[ These data are shown in Table 0[ The mean task performances for each measure on alcohol and placebo are shown in Table 1[ Attention data were analysed using matched t!tests of performance data obtained during the alcohol vs the placebo conditions[ While no signi_cant di}erences were found between conditions\ under the in~uence of alcohol\ subjects displayed generally reduced performance on each task[ The data are commensurate with _ndings from other studies of acute alcohol e}ects employing sample sizes su.ciently large to allow acquisition of a more stable performance e}ect[ However\ the principal question of the present study was whether PET provides coherent evaluations of attention operations a}ected by acute alcohol intoxication[ We examined the correlation coe.cients between change in performance "alcoholÐplacebo# and change in the glucose
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Table 0 Relative glucose metabolic rates in each lobe for alcohol and placebo conditions Segment0
Frontal
Parietal
Temporal
Occipital
Placebo 0 1 2 3
0[95 0[10 0[07 0[15
0[10 0[07 0[11 0[19
9[86 9[83 9[80 9[79
0[00 0[15 0[14 0[97
Alcohol 0 1 2 3
0[96 0[05 0[05 0[13
0[19 0[06 0[08 0[11
9[86 9[83 9[80 9[68
0[98 0[12 0[06 0[94
0 Segments for each lobe are shown in Fig[ 0^ left and right hemispheres combined[ No main e}ects or interactions for alcohol:placebo comparisons were signi_cant by repeated measures ANOVA "condition×lobe×segment× hemisphere#[
Table 1 Attention performance on each attention variable for placebo and alcohol conditions
Posner RT Posner )0 Manikin RT Manikin ) correct Transition1 Posner RT Transition Posner ) correct Transition Manikin RT Transition Manikin ) correct 0 1
Placebo M "N 7#
Alcohol M "N 7#
428 ms SD 41[6 83[0) SD 2[8 527 ms SD 55[0 89[6) SD 5[7 444 ms SD 74[3 83[9) SD 3[6 541 ms SD 59[8 80[7) SD 5[2
459 ms SD 37[3 83[2) SD 2[4 552 ms SD 71[2 78[2) SD 4[4 485 ms SD 55[2 82[4) SD 3[7 579 ms SD 82[2 75[7) SD 7[1
) is percentage of trials correct[ Transition variables include only trials following a switch of the center arrow[
metabolic rate "alcohol!placebo# for the 21 cortical areas[ The only signi_cant correlations were in the parietal lobe^ better performance\ whether fewer errors or faster reaction times\ was always associated with higher metabolic rates[ The correlations between changes in attention and glucose metabolic rate for all four segments of the parietal lobe are shown in Table 2 and their location is illustrated in Fig[ 0[ None of the correlations was an artifact of outliers[ For reaction time "RT# variables\ a negative correlation means better performance "i[e[ shorter RT# goes with higher GMR on alcohol^ for percentage correct variables\ a positive correlation means the same[ Note in Table
323
Segments All four
Posner RT Posner ) Manikin RT Manikin ) Transition Posner RT Transition Posner ) Transition Manikin RT Transition Manikin RT
Post central
Supra margin
Angular
Superior
Left
Right
Left
Right
Left
Right
Left
Right
Left
Right
−9[70 9[57 −9[52 9[65 −9[50 9[55 −9[59 9[52
−9[67 9[57 −9[62 9[64 −9[53 9[56 −9[64 9[65
−9[77 9[49 −9[53 9[65 −9[51 9[37 −9[47 9[47
−9[75 9[44 −9[70 9[68 −9[61 9[44 −9[68 9[64
−9[21 9[18 −9[11 9[18 −9[47 9[13 −9[96 −9[05
−9[31 9[72 −9[34 9[43 −9[47 9[67 −9[34 9[33
−9[59 9[70 −9[32 9[52 −9[55 9[79 −9[27 9[29
−9[64 9[53 −9[62 9[68 −9[64 9[53 −9[60 9[53
−9[45 9[32 −9[37 9[41 −9[11 9[31 −9[44 9[60
−9[51 9[42 −9[44 9[42 −9[21 9[42 −9[51 9[61
Note] r × 9[60 signi_cant at P ³ 9[94\ 1!tailed^ r × 9[68 signi_cant at P ³ 9[91\ 1!tailed^ r × 9[72 signi_cant at P ³ 9[90\ 1!tailed[ 0 For RT a negative correlation is better performance with higher GMR with alcohol^ for ) correct a positive correlation is better performance with higher GMR with alcohol[
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Table 2 Correlations between change in attention "alcoholÐplacebo# and change in parietal lobe relative glucose metabolic rate "alcoholÐplacebo#0
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324
2 that there are 21 possible correlations in each hemisphere "3 segments×7 attention variables#[ Signi_cant correlations appear more often in the right hemisphere "03:21# than in the left hemi! sphere "4:21^ x1 3[68\ P ³ 9[914\ Yates corrected#[ Of the four regions Corbetta et al[ "0880# identi_ed as activated during their divided attention task "region of the left collateral sulcus\ left occipital gyrus\ anterior cingulate\ dorsolateral prefrontal cortex#\ none showed a signi_cant increase or decrease on alcohol in our relative data "the four Corbetta et al[ "0880# areas correspond\ respectively\ to our inferior:posterior temporal cortex\ area 08\ the anterior cingulate\ and middle frontal cortex\ all shown in Figs 0 and 1#[ We also applied our standard region!of!interest template of 52 areas "Fig[ 1#\ to explore additional areas throughout the brain "Buchsbaum et al[\ 0878#[ Two regions were signi_cantly decreased on alcohol\ the left precuneus\ and the left posterior putamen^ the right uncus signi_cantly increased on alcohol "P ³ 9[94\ 1!tailed matched t!test#[ For each of these three regions!of!interest that were signi_cantly di}erent between alcohol and placebo\ we correlated change in metabolic rate "alcoholÐplacebo# and change in attention performance "alcohol!placebo#[ Signi_cant correlations were found for precuneus and putamen^ the anterior cingulate\ activated in the Corbetta et al[ study\ also showed signi_cant correlations with several attention performance measures[ This is shown in Table 3 along with all other signi_cant correlations between change in metabolic rate and RT for the other sub and medial cortical regions examined "Fig[ 1#[ Negative correlations indicate better attention performance "i[e[ faster RT# as GMR with alcohol increases[ Positive correlations indicate worse performance "i[e[ slower RT# as GMR increases with alcohol[ This is presented as an exploratory analysis for future hypothesis testing[
3[ Discussion The data show that the use of PET within a controlled information processing paradigm is an e}ective means of explaining the nature and location of alcohol|s e}ects on central nervous system operations[ The major _nding of this study was the signi_cant correlations between alcohol changes in cognitive performance and alcohol changes in relative GMR in the superior\ inferior\ and middle parietal lobes[ This is consistent with other studies showing that the parietal lobes are important in both maintaining "Mesulam 0874\ Posner\ Walker\ Friedrich + Rafal\ 0876# and allocating attention "Farah\ Wong\ Monheit + Morrow\ 0878#[ Because the right parietal lobe is thought to be important in spatial orientation of objects "Di Mattia + Kesner\ 0877^ Mesulam\ 0874#\ our _nding more signi_cant correlations in the right hemisphere could be a function of the spatial nature of the manikin task and its relative sensitivity to alcohol e}ects[ The FDG technique\ however\ does not allow separation of the e}ects contributed from the manikin and letter matching tasks^ only cumulative e}ects for the 21 min uptake period can be determined[ It should be noted further that the letter matching task alone might be expected to activate the left frontal cortex\ parts of the temporal lobe\ and parts of the visual cortex[ The manikin task alone would activate right parietal\ dorsal lateral pre!frontal cortex\ and the same parts of the visual cortex as the letter matching task[ Since both the alcohol and the placebo conditions used the same combination of tasks and no control tasks were used\ alcoholÐplacebo comparisons would not necessarily show di}erences in these areas alone[
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Table 3 Correlations between change in attention "alcoholÐplacebo# and change in relative glucose metabolism "alcoholÐplacebo# for selected regions!of!interest0 Transition trials )1
Posner RT
Manikin RT
Posner RT
Manikin RT
L Precuneus L Precuneus L Ant Cingulate R Mid Cingulate
63 57 43 43
−9[56 −9[40 −9[48 −9[52
−9[65 −9[57 −9[31 −9[69
−9[56 −9[42 −9[63 −9[62
−9[72 −9[67 −9[11 −9[46
R Mid Corpus Callosum L Mid Corpus Callosum
36 36
9[51 9[68
9[58 9[63
R Post Calcarine R Ant Calcarine L Frontal White L Post Putamen
30 30 30 30
−9[63 −9[65 −9[64 9[66
−9[65 −9[47 −9[54 9[50
L Cingulate L Globus Pallidus
23 23
9[66 9[44
9[56 9[65
9[38 9[35
L Ant Cingulate L Putamen R Inf Colliculus
17 17 17
9[65 9[64 −9[51
9[79 9[66 −9[56
9[80 9[36 −9[67
9[66 9[61 −9[44
L Ant Rectal Gyrus L Hippocampus
10 10
−9[47 −9[33
−9[66 −9[31
−9[32 −9[62
−9[72 −9[14
9[67 9[76
−9[74 −9[43 −9[43 9[43
9[02 9[69 −9[55 −9[35 −9[48 9[36 9[53 9[79
r × 9[60 signi_cant at P ³ 9[94\ 1!tailed^ r × 9[68 signi_cant at P ³ 9[91\ 1!tailed^ r × 9[72 signi_cant at P ³ 9[90\ 1!tailed[ 0 Of 52 areas measured\ only the areas with at least one signi_cant correlation with RT performance are shown in this Table[ Negative correlations indicate that attention performance is better "i[e[ shorter RT# as GMR increases with alcohol^ positive correlations mean worse performance "i[e[ longer RT# as GMR increases with alcohol[ L is for left hemisphere^ R is right[ ANT is for anterior^ POST is for posterior^ INF is for inferior[ 1 ) head height of slice from the canthomeatal line^ see Matsui + Hirano "0867#[
In their PET study\ de Wit et al[ "0889# also investigated individual di}erence correlations after similarly failing to _nd main group alcohol e}ect for a low dose[ Their _nding of slower reaction times on alcohol for subjects whose glucose metabolic rate increased "their table 1\ occipital lobe and thalamus# is similar to ours although their parietal lobe data were not signi_cant[ The signi_cant correlations found in several areas of the limbic system are consistent with both memory and emotion function[ The anterior cingulate gyrus correlations are consistent with the Corbetta et al[ "0880# _nding[ It should be noted that di}erences between the Matsui and Hirano atlas used in this study and the Talairach atlas used by Corbetta et al[ "0880# are not large[
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Although the Matsui and Hirano atlas used the canthomeatal line\ a standard in clinical use\ and the Talairach atlas is based on the anteriorÐposterior commissure line\ both portray the brain of a single individual and are not statistical standards[ Our use of proportional rather than absolute mm co!ordinates and the cortical peel technique avoids potential problems associated with regions! of!interest at the brain|s margin found with the method used by Corbetta et al[ "0880# "Drevets\ Videen\ MacLeod\ Haller + Raichle\ 0881#[ Following Buchsbaum et al[ "0871#\ we use the statistical method of repeated measures ANOVA on data expressed as a ratio to whole brain mean to remove e}ects of individual variation in global brain metabolic rate and we use each individual structure as its own baseline for medication contrasts\ providing relative glucose values "regional area rate:whole slice rate#[ This achieves a similar aim as the subtraction procedure applied to normalized data used by Corbetta et al[ "0880#[ It has the advantage of yielding only a few F!ratios which provide a systematic test of hemisphere asymmetries and di}erences between structures[ The cortical areas which showed correlations between change in performance and change in metabolism are similar to those with high concentrations of benzodiazapine receptors "Buchsbaum et al[\ 0878^ de Wit et al[\ 0889^ Volkow et al[\ 0889#[ Volkow et al[ "0882# also found that chronic alcoholics had a blunted response to lorazepam in orbitofrontal cortex and basal ganglia\ areas with signi_cant correlations in our study "Table 3#[ Thus\ individual di}erences in alcohol response may re~ect di}erences in the GABA!benzodiazapine receptor distribution and:or density[ Evidence on this\ however\ is mixed "Litton et al[\ 0882^ Pauli et al[\ 0881#[ The e}ects reported here are for structures adequately imaged with 6[5 mm in plane and 09[8 mm axial resolution "FWHM#[ The major gyri of the cortical surface are all several cm in length[ While the cortical ribbon surface is 2Ð4 mm thick\ it is typically folded into a thicker strip similar in width to our cortical peel[ Thus\ our cortical regions are typically more than three times the FWHM[ The putamen\ caudate\ and cingulate gyrus all accommodate the 5×5 mm box easily in the horizontal plane and all are at least 19 mm or two 09 mm planes high[ Heterogeneity within the axial or horizontal plane would reduce the adequacy of the method[ However\ random variation caused by individual di}erences in brain proportions\ vertical position of the plane acquired and variation in head position and reposition would all tend to create random error and diminish any correlations[ Structures closer in size to the FWHM resolution are not so well quanti_ed so only large e}ects or e}ects re~ecting surrounding structures would be detected[ In conclusion\ alcohol improved performance on the divided attention task in some subjects and worsened performance in other subjects[ The degree of change in attention performance was correlated with change in GMR only in areas of the parietal cortex and several subcortical areas[ This study demonstrates the importance of individual di}erences of alcohol response in attention and implicates a small number of brain areas where alcohol may have e}ects at low levels[
Acknowledgments This study was funded by the Medical Management Division of the Atlantic Rich_eld Company[ The authors thank Dr Aleksandra Chicz!DeMet for her help in quantifying alcohol doses and NTI\ Ohio for providing computer software for the attention tests[ These data were presented at
327
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the Human Performance Conference\ Institute of Human Performance\ Lisbon\ Portugal\ January\ 0880[
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