HEMISPHERIC SPECIALIZATION IN NORMAL MAN

Brain (1975) 98, 511-524

HEMISPHERIC SPECIALIZATION IN NORMAL MAN STUDIED BY BILATERAL MEASUREMENTS OF THE REGIONAL CEREBRAL BLOOD FLOW A STUDY WITH THE 133-XE INHALATION TECHNIQUE

JARL RISBERG, JAMES H. HALSEY, EDWARD L. WILLS AND EDVIN M. WILSON (From the Department of Neurology, University of Alabama School of Medicine, Birmingham, Ala., USA, and the Laboratory of Neuropsychology, University of Lund, Lund, Sweden)

IT is now well established that functional changes within the normal brain related to mental activity can be quantified by measurement of the regional cerebral blood flow (rCBF). In addition to significant increases of average hemispheric grey matter blood flow specific patterns of regional blood flow changes have been demonstrated during problem solving and memorization (Ingvar and Risberg, 1967; Risberg, 1973; Risberg and Ingvar, 1973), during speech and reading (Ingvar and Schwartz, 1974) and during sensorimotor activation (Olesen, 1971). The previous studies have all been done by means of the intra-carotid 138 Xenon injection technique (Lassen et ai, 1963; Hoedt-Rasmussen et a!., 1966). Since this technique only allows unilateral simultaneous measurements, the results obtained so far only apply to one hemisphere, in most cases to the one dominant for speech. No systematic studies of possible hemispheric differences in blood flow during different types of mental activation have previously been published. In the present study simultaneous bilateral rCBF measurements have been made in normal volunteers by the 133Xenon inhalation technique during verbal and spatial tests. For the first time interhemispheric differences in blood flow will be shown, indicating the possibilities for rCBF measurement in the study of hemispheric specialization. MATERIAL AND METHODS

Subjects The measurements were made on 24 right-handed normal male volunteers (mean age 24 ±6 years). A handedness questionnaire containing 17 items was filled out by all the subjects (Raczkowski et al., 1974). All of them had a high score for right-handedness (average 15 out of 17 items answered in favour of right-handedness). The rCBF Measurements The measurements were done by means of the lif Xenon inhalation method (Mallett and Veall, 1963, 1965) as modified by Obrist and collaborators (1967, 1971). The measurement procedure,

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the principles of calculation and the instrumentation used are described in detail elsewhere (Obrist et al., 1967, 1975; Wilson et al., 1975). Here only a brief description will be given. The subjects inhaled ll3Xenon in a concentration of 5 mG/1 during one minute by means of a face mask and a closed spirometer system. The relative concentration of isotope in 7 regions of each hemisphere was recorded during 11 min by collimated (length of collimator 1 in, ID 3/4 in.) scintillation detectors (3/4 in. x 3/4 in. Nal fTl) crystals) placed in parallel in two lead-lined detector holders. The detectors were placed at a right angle to the sides of the subject's head covering the same regions in both hemispheres in the approximate locations shown in fig. 3. The proper positioning of each subject in relation to the detectors was aided by the use of bony landmarks (nasion and ear canal) and a plexiglas grid with a coordinate system. The pulses from the detectors were fed to 14 pulse height analysers set to accept both gamma and x-ray radiation (20-100 KeV).

Ni(t)=awiXikie~ 0'

where t = a given time after start of l l r Xenon inhalation, Ni(t)=counts obtained from the i:th tissue component at time t (i = l, 2), a = a proportionality constant, wi=relative weight of the i:th tissue component (wi+wa=»=l), X.i=tissue-blood partition coefficient for the i:th tissue, ki=decay constant for the i:th component, CA(t)=concentration of isotope in arterial blood (expired air) at time t. To calculate the fast flow (fi; considered to represent mainly grey matter blood flow in normal man) the ki values (decay constants) were multiplied by a standard lamda (tissue-blood partition coefficient) of 0-80. In the present study only the fi values will be used, since the slower cerebral flow rates (white matter blood flow) are known not to change during mental activation (Ingvar and Risberg, 1967; Risberg and Ingvar, 1973), and in this two-compartmental analysis contain extracerebral contamination. Design All the 24 subjects were paid $20 for taking part in the investigation. In order to study the effects of motivational factors on rCBF 12 of the subjects were promised an extra money award ($10 for each of the two tests) if the result on a test was above a certain level (best quartile). The group to which this extra reward was promised will be referred to as the "Reward" group, while the remaining 12 subjects will be called the "Non-reward" group. Four rCBF measurements were made in each subject: two during resting with eyes closed, one during a verbal test and one during a spatial test. A measurement during testing was in a randomized order either preceded or followed by a reference study during resting. The time interval between a rest and a test measurement was 60-90 min. In most cases there was a one-day difference between the two pairs of measurements. The order in which the two tests were presented was randomized within the group.


The arterial concentration of lt3 Xenon was estimated by measurement of the radioactivity in the end-tidal air (Obrist et al., 1967; Wilson et at., 1975). The arterial concentration of COj was estimated from capnographic recordings of the same expired air sample (Obrist et al., 1975), and the blood pressure was measured by auscultation immediately after the end of the measurement. The calculation of the flow values was based on a two-compartmental analysis of the recorded curves using a NOVA 1230 computer and programmes developed by Obrist and collaborators (cf. Obrist et al., 1975). The following basic equation was used (Obrist et al., 1967):

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HEMISPHERIC SPECIALIZATION AND rCBF

Verbal Ten A test of verbal reasoning ability containing 32 items (analogies) was constructed based on published training examples of the Miller Analogies Test (Gruber, 1972). As exemplified in fig. 1

CORK

is T O F L O A T

1, CRYSTALLIZE A I R

2, DISSOLVE

i sT O K I T E

1, FJSH

1, TRUANT

3. DUCK

4. CONDENSE

i s TO 4. RAFT

is T O M E D I E V A L

2, FUTURE

3. RECENT

is T O V E G E T A R I A N 2. PRINCIPAL

AS C U R R E N T is T O

4, ELECTRIC

AS S C H O O L

3. LIBRARY

is T O

4. CLASSROOM

FIG. 1.—Four typical items from the Verbal test (Gruber, 1972). each item had one correct and three wrong alternatives. Four problems were shown on each of eight cards, which were held in an easily readable position in front of the subject. The presentation of the test began 30 s after the start of the 1MXe inhalation and continued until the subject had completed all the items, which took at least 6-5 min. The subjects were thus always actively working on the tests during the period during which the fi was mainly determined (the 2-7 min period after start of inhalation). The answers to the questions were given either immediately after the study by writing them down (Non-reward group) or during the measurement by raising the number of fingers on the left hand, which corresponded to the answer chosen (Reward group). All instructions about the tests including practice items were given immediately before the measurement. Spatial Test A test of perceptual closure, the Street test, was chosen (Thurstone, 1938) containing 24 incomplete pictures of the type shown in fig. 2. The pictures were shown to the subjects on 3 cards

FIG. 2.—Three typical incomplete pictures from the Spatial test (Thurstone, 1938).


MEAT

is T O

3. SWEETEN

AS W A T E R

2, SWIMMER

PREHISTORIC 1. MODERN

AS S U G A R

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in a similar routine as for the verbal test. A desire for a change of card was indicated by the subject by raising the right hand. Since the mask precluded verbal contact with the subject the answers (naming of the pictures) were given immediately after the measurement, when the pictures were again shown to the subject for a short time. The subjects were instructed to work as hard as possible on solving the problems during the rCBF measurement.

RESULTS

The results from the measurements during rest are shown in fig. 3 (average of both groups) and in Table 1. It is seen that the regional distributions of fx are very similar in the two hemispheres. In relation to the hemisphere mean, higher flows are seen frontally (5-15 per cent) and lower postcentrally, a finding confirming earlier results from rCBF-measurements in normal resting hemispheres with the intraarterial technique (Wilkinson et al., 1969; Sveinsdottir et al, 1971/72).

Fro. 3.—The regional distribution of fi in 24 normal resting subjects related to the hemisphere average (indicated in the boxes). The clock symbols should be read thus: 12 o'clock denotes a regional value which is equal to the hemisphere average. Black marking indicates a value above and a striped field denotes a value below the average (90 degrees=25 per cent).


Hypotheses The following hypotheses were established on the basis of well-known concepts about hemispheric specialization in normal right-handed subjects (presumed left hemisphere dominant for speech; cf. Nebes, 1974): (1) A verbal test is accompanied by larger increases of rCBF in the left than in the right hemisphere. (2) A spatial test is accompanied by larger increases of rCBF in the right than in the left hemisphere. Based on previous observations of presumed influence of motivational factors on the rCBF changes (Ingvar and Risberg, 1967; Risberg, 1968; Risberg and Ingvar, 1973) the following hypothesis was established: (3) The more highly motivated (paid) group will show the largest rCBF changes.


TABLE I . — M A I N RESULTS: fi in ml/100 g/min

heft 1 2 3 4 5 6 7 Mean

79-3 ±14-6 75-4+.15-1 69-2±12-4 69-2 ±13-1 66-4±ll-5 64-2±l(M 58-5±10-O 68-9±ll-6

Right 1 2 3 4 5 6 7 Mean

79-2±15-2 74-3 ±14-7 69-3±ll-9 69-6 ±12-4 65-6±ll-5 65-2+.11-2 58-3± 9-1 68-8+.11-6

Reward group Spatial test Verbal test 83-6±13-9 89-7± 9-6 77-3±ll-l* 82-5 ± 9-8 75-3±ll-8* 82-O± 9-9 71-7±ll-4 76-9± 9-2 69-2 ± 9-0 76-3 ± 9-3 7M±10-9 78-8±ll-3* 68-5±10-0 71-3± 7-9* 73-8 ±10-6 79-7± 8-7 85-3 ±14-8 79-6±12-6* 78-8±12-7* 72-0±10-5 710± 9-6 73-4±12-7 68-3 ± 9-4 75-5 + 11-0

88-4±13-l 82-8 ± 9-8 81-4±10-0 75-9± 9-3 74-4± 7-1 76-3±101* 67-8 ± 8-4* 78-1+ 8-7

Mean difference Left-Right 01 ± 1-8 - l - 7 ± l-9f l-6± 1-1J apCCh 39-9± 2-1 39-8± 1-7 4O0± 1-8

Non-reward group

Spatial test Rest 81-O±10-3 81-4±100 77-8± 7-8 80-4± 5-4 76-3 ± 9-8 74-0± 6-3 70-8 ± 9-2 75-3 ± 6-0 69-5 ± 7-6 71-1 ± 3-9 71-6± 8-6 73-2± 5-5 63-5± 7-9 68-8± 5-5 72-9 ± 8-5 74-8 ± 4-3

Verbal test 86-8±ll-3 83-9±ll-6 78-6±10-5 77-9±ll-2 75-3±10-2 78-2±ll-7 72-7 ± 9-9 791 ±10-4

80-7± 9-4 76-2± 8-7 76-2± 8-8 72-3±10-l 70-8 ± 7-7 69-1± 8-2 63-1 ± 8-5 72-6 ± 8-7

86-3 ± 9-7 85-5±ll-7 78-7 ± 9-4 78-l±lM 76-4±10-3 76-3 ±10-5 71-8±10-6 78-9± 9-9

83-8 ± 8-0 79-7± 6-4 75-1 ± 4-5 74-4± 3-7 71-6± 3-8 73-5± 6-1 71-9± 6-2 75-7± 4-5

O3± 2-0 - 0 - 9 ± 2-0 41-2± 2-3 39-8 ± 1-7

Significance of hemisphere differences (one-tailed t-test): *P