Cortical blood flow asymmetries during monaural verbal stimulation

BRAIN

AND

LANGUAGE

15,

1-l

1

(1982)

Cortical Blood Flow Asymmetries during Monaural Verbal Stimulation V.

ALEXANDER

MAXIMILIAN

The regional cerebral blood flow (rCBF) of nine healthy male subjects (dextrals) was used as an index of local neuronal activity to measure the effects of repeated monaural verbal stimulation in 32 hemispheric cortical locations. In contrast to more complex mental activations, processing and analysis of verbal auditory stimuli did not result in significant increases from the resting flow level. Differences were, however. obtained when the rCBF of homologous regions of the two hemispheres were compared. A significant blood flow asymmetry with higher flows in the left hemisphere was found in a temporoparietal location during leftas well as right-ear-stimulation measurements. In addition, significantly higher flows were found in a frontotemporal area of the right hemisphere but only during left-ear stimulation. These results were interpreted as a participation of the posterior language area of the left hemisphere in verbal processes regardless of the laterality of the stimulus input and as a possible indication of cross-hemispheric transfer of a partially processed verbal material from a right frontotemporal region.

Extensive experimentation in the area of language lateralization was initiated by Kimura’s (1961, 1967) dichotic stimulation experiments and the proposal of right-ear advantage (REA) for verbal material (see Studdert-Kennedy, 1975, and Prohovnik, 1978, for a review). Contrary to earlier views, it has been repeatedly shown that the stimulus conflict extant in the dichotic paradigm is not the necessary precursor of the REA (Bakker, 1967, 1968, 1969; Frankfurter & Honeck, 1973; Haydon & Spellacy, 1973). The premise of the stronger contralateral pathways found ample supporting evidence (Gross, Small, & Thompson, 1967; This study was carried out at the Laboratory of Neuropsychology, Lund University, Sweden (Director: Dr. Jarl Risberg). Supported by grants from the Swedish Council for Social Science Research, the Swedish Medical Research Council (Project 14x-04969). and the Swedish Work Environment Fund. The author is grateful to Ms. Helena Fern& B. A., and Ms. Siv Karlsson, Eng., for valuable technical assistance and Ms. M. Glaser for typing the manuscript. Requests for reprints should be sent to Dr. Maximilian, Novo Diagnostic Systems Research Laboratory, Novo Industrie, Kantstrasse 2, Postfach 2840, 65 Mainz, West Germany. 0093-934X182/010001-1

1$02.00/O

Copyright 0 1982 by Academic Press. Inc. All rights of reproduction in any form r&served.

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V. ALEXANDER

MAXIMILIAN

Majkowski, Both, Bocheneck, Kapik-Filjallkowska, & Kopek, 1971) but, for example, Morais and Landercy (1973) rejected the notion that “auditory laterality is dependent on an anatomical or functional feature of the system connecting the ears and the hemispheres.” According to Bever (1975) the resulting asymmetry is caused by the left-hemispheric processing and analysis of incoming information. This activity is presumably cortical and subject to quantification. Electrophysiological studies of language lateralization have, however, yielded ambiguous results. While left-hemisphere asymmetries were reported by some investigators (Morel1 & Salamy, 1971; Galin & Ellis, 1975; McKee, Humphrey, & McAdams, 1973) others found no marked interhemispheric differences during verbal stimulation (Galambos, Benson, Smith, SchulmannGalambos, & Osier, 1975; Friedman, Simson, Ritter, & Rapin, 1975). Neuronal activity changes in the cortex can also be measured via the concurrent alterations of the regional cerebral blood flow (rCBF) (Raichle, Grubb, Gado, Eichling, & Ter-Pogossian, 1976). This can be accomplished with the noninvasive ‘33Xe-inhalation technique, a powerful neuropsychological instrument, increasingly proficient in distinguishing between different psychological functions in the brain (Risberg, 1980; Risberg, Maximilian, 2% Prohovnik, 1977; Maximilian, Prohovnik, & Risberg, 1980a; Maximilian, Risberg, Prohovnik, Rehnstrom, & Haeger-Aronsen, 1980b). What distinguishes the electrophysiological from the cerebral blood flow method is that the former reacts to stimulation while the latter can “sift out only those phenomena which are tonic over time as well as saturated in a given region” (Wood, 1980). Consequently, cortical activity such as stimulus processing and analysis induced by continuous verbal stimulation should be amenable to regional cerebral blood flow measurements. The main purpose of the present investigation was to determine whether lateralized verbal input affects differently the neuronal activity in the ipsi- versus the contralateral hemisphere. By measuring the rCBF with a bilateral, multidetector system, inter- and intrahemispheric regional comparisons can be made during the monaural stimulation. The reliability of the eventual hemodynamic response will be tested by repeating the stimulus presentation to each ear. MATERIAL AND METHODS Subjects Nine male healthy volunteers (mean age 24.6) with na past history of head trauma and free from ongoing medication participated in the study. They were all right-handed as determined by the Edinburgh Handedness Inventory (Oldfield, 1971).

Apparatus The regional cerebral blood flow measurements were performed with a “‘Xe inhalation Cerebrograph (Novo Diagnostic Systems, Hadsund), monitoring simultaneously 16 homologous regions of both hemispheres (Fig. I). For a complete theoretical model of the

BLOOD

FIG. I. Average hemispheres.

detector

3

FLOW ASYMMETRIES

localization

over homologous

regions

of the cerebral

rCBF method and its technical details see Obrist, Thompson. Wang and Wilkinson, (1975) and Risberg, (1980). The method is entirely atraumatic, the subject breathing the inert and freely diffusible tracer ‘j’Xe mixed with air (2.5 mCi/liter) for I min via a facemask. This is followed by IO min of ambient room air breathing during which the washout of the isotope is recorded by 32 scintillation detectors placed in parallel at a right angle to the lateral surface of both cerebral hemispheres. The total radiation dose to the lungs is 0.7 mGy per measurement. To correct for the recirculation of the isotope a separate detector recorded continuously the “‘Xe concentration in a sample of the expired air. The rate of the isotope’s washout from the brain is the basis for the flow calculations. The data output from each detector was analyzed by a HP 9825 desk-top computer using a recently developed program for calculating CBF based upon Fourier transform (Jablonski, Prohovnik. Risberg. Stahl. Maximilian, & von Sabsay. 1979). The present paper constitutes a further test for the applicability and advantage of Fourier analysis (e.g., analysis of information contained in the early part of the curves after isolating the air passage artifact) in experimental studies of mental activation (Prohovnik, Hakansson, & Risberg, in press; Prohovnik, Risberg, & Jablonski, in press). Two resulting CBF parameters are used in this study, (I) f,, the flow of rapidly perfused gray matter compartment, and (2) the Initial Slope Index (ISZ: Risberg, Ah, Wilson, Wills, & Halsey, 1975a; Risberg, Halsey, Wills, & Wilson, 1975b) calculated between the initial 30 and 90 set after the start of the measurement. The IS2 is dominated by gray matter flow, has a very small measurement error, and is used here as control of local CBF changes measured with f,. The arterial pC0, was estimated from recordings of end-tidal CO, concentrations (Beckmann LB2 analyzer) and blood pressure was measured by auscultation. Procedure The CBF of all subjects was measured 6 times in a paradigm counterbalanced for leftand right-ear stimulation. An initial resting measurement was succeeded by two monaural continuous stimulus presentations to one ear, followed by a second resting session which was finally followed by two verbal stimulation measurements to the other ear (i.e.. rest,-right ear,-right ear,-rest!-left ear,-left ear?). Due to technical difficulties in some of the initial resting measurements (rest,). the data from that session have been excluded from the analysis. Hereafter “rest” denotes rest,. It should be mentioned, however, that subjects habituate to the measurement situation and the second resting session has been

4

V. ALEXANDER

MAXIMILIAN

shown to reflect “the true resting baseline” (Prohovnik et al., in press-a,b; Risberg et al.. 1977; Maximilian, Prohovnik, Risberg, & HPkansson, 1978). The stimulation consisted of parallel lists of meaningful two-syllable Swedish words (interstimulus interval was 3.5 set) and was presented monaurally via an earphone, with the other ear plugged. The subjects had their eyes closed through all six measurements. They were given several training trials and were informed in detail about the CBF measurements and testing procedure. In order to ensure the subject’s attention throughout the activation sessions, they were asked to give an affirmative response each time a word had the least common of the Swedish plural endings (five required responses).

RESULTS

A normal resting “landscape” consisting of flows 5-15% above the hemispheric mean frontally, 5-15% below postcentrally, and at a mean level in central regions (Prohovnik et al., in press-a,b) was also found in the present group. t tests for related samples were computed for flow distribution differences (regional flow deviation from the hemispheric mean) between homologous areas of both hemispheres, and as shown in Fig. 2, no asymmetries were found in the “resting” brain. Mean hemispheric perfusion increased during the first verbal stimulation of either ear and decreased below resting level during the second testing session. As can be seen in Table 1, these flow changes lacked statistical significance. No significant regional increases between the resting and activation sessions were obtained with either f, or ZSZ flow

Rt

Fro. 2. rCBF distribution during rest. Gray matter flow during the resting session (f, = ml/JOO g/min). The regional distribution is the percentual flow deviation from the hemispheric mean (25% = 90” in the clock symbols). Black shadowing indicates a flow value above, and striped a value below, the hemispheric mean. ZSZ resting distribution was identical to f,.

VALUES

4X2)

84( 13)

6’W)

84(13) 69(8)

41(2)

78(15) 64( IO)

77(15) 64( IO)

pCOl

rh

RESl

AVERAGE

Ih

(f, AND ISI),

rh

RES,

FLOW

Ih

HEMISPHERIC

Nofe: Ih = left hemisphere, rh = right hemisphere .f, = ml/l00 g/min, ISI = ISI units, pC0, in mm Hg.

PCQ

I 1.71

f --

MEAN

I

81(13)

68W

rh

DEVIATIONS

81(13)

432)

Rest

STANDARD .~

6W

Ih

AND

TABLE LEWIS

87(13) 74( IO)

Ih

422)

rh

FIVE

88( 14) 74( I I )

THE

LES,

DURING

CBF

66(8)

79( IO)

Ih

JIG?)

LES,

MEASUREMENT

638)

79( IO)

rh

SESSIONS

E

2E s

? 2 >

E

F

V. ALEXANDER

6

MAXIMILIAN

parameters (one-way ANOVA). However, the verbal stimulation elicited significant interhemispheric regional asymmetries. These asymmetries were not affected by the above-mentioned changes in cerebral perfusion level. During all listening sessions, significantly higher flows were found in a temporoparietal area of the left hemisphere compared to its right-hemispheric homologous counterpart. Another significant asymmetry was located in a frontotemporal region with higher flows in the right hemisphere. It was obtained during the first and second left-ear stimulations (LES, and LESJ only. Table 2 and Fig. 3 summarize the results during right- and left-ear stimulation. Only significant asymmetries found in both fi and ZSZ are here considered reliable and biologically significant. Noteworthy, however, was a tendency toward higher flows in prefrontal areas of the right hemisphere during both right- and left-ear stimulations (RES and LES). DISCUSSION It is not surprising that a simple language-processing task did not result in the rCBF increases found during complex mental activations such as TABLE DIFFERENCES

Det. no.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 ’ R and homologus represents * p i ** p <

IN

rCBF

COMPUTED

f, (9%) 3 (4)R

6 (6)R 0 I I 3 1 3 1

2 6* 0 3 1 0 5

(0) (l)R (2)R (3)R (IS (3)R Kw (I& (S*)L (0) (2)L (ON(0) (4)L

2

BY t TEST FOR RELATED LEFT- EAR STIMULATION”

ISI (%) 6 4 3 1 0 2

2 4* 0 3* 6** 3

2 2 I 4

(4”)R (4)R (3*)R (OH(I& (2*)R (O)L (3*)R (0) (I)L (3*)L (4*)R (1)L (w(OH(2)L

SAMPLES

DURING

RIGHT-AND

ISI (%)

.f, (5%) 4 (4)R 6* (S*)R 2 UN0 (l)L 0 (0) 5** (5**)R 1 QW 1 (I& 1 (O)L 1 (1)R 6** (4*)L 3 (1)L 2 (It 4* (3)L 1 KNL 0 (l)R

4

(4)R

2 CW 1 1 1 5** 0 1 1 1 5**

(O)R @JR UN(4**)R (0) (l)R (0% (OK (4’L)L

2 C‘V3 2 (1% 4** (3*)L 1 (I& 0 (0)

L denote detector location where rCBF distribution (or flow) is higher than its counterpart in right or left hemisphere, respectively. Number in parenthesis flow in ml/100 g/min for f; and ISI units. .05. .Ol.

BLOOD

FLOW ASYMMETRlES

7

FIG. 3. Average rCBF distribution asymmetries during right- and left-ear verbal stimulation. Shadowed area depicts cortical region within each hemisphere where CBF is higher than its homologous counterpart. The darker shade denotes a statistically significant asymmetry obtained with both flow parameters (6 und ISI).

verbal analogies (Risberg et al., 1975a), problem solving (Risberg et al., 1977; Maximilian & Prohovnik, 1980), and verbal memory (Maximilian et al., 1978). The effects of the stimulus modality can be definitely excluded. Ongoing studies at our laboratory have shown that an aurally presented continuous verbal memory test produced high regional, as well as hemispheric flow, increases. Despite the counterbalanced design with the resting measurement in the middle, flows increased during the first monaural presentation and decreased during the second, irrespective of ear and pre- or postresting sequence. Thus, it is very likely that CBF, due to a general arousal level related to the peculiarity of the lateralized stimulus input, initially increased, and then subsequently adapted to an optimal “homeostatic” level, sufficient, however, for processing the auditory stimulation, The main results of the present study were foremost the localized flow asymmetries in the left and right cerebral hemispheres. The obvious questions they raise are: (1) what caused the localized interhemispheric flow differences, and (2) were they related to the monaural stimulation? Regarding the temporoparietal area of the left hemisphere, Risberg et al. (1975b) found there a significant CBF asymmetry during a visually presented verbal analogy test but not during spatial perception. The lefthemispheric postcentral asymmetries are thus most probably induced by language-related functional processes, which may also be anatomically determined. Geschwind and Levitsky (1968) found a larger planum tem-

8

V. ALEXANDER

MAXIMILIAN

porale in the left hemisphere, and it was subsequently suggested that the degree of language function’s dominance may be directly linked to the relative cytoarchitectonic asymmetry of homologous temporoparietal structures (Galaburda, Sanides, & Geschwind, 1978). Nevertheless, while the interhemispheric blood flow differences were here attributed to language-related functional activity, other factors, besides the verbal processing component, may have been involved. According to Spellacy and Wilson (1978), an auditory asymmetry for both verbal and nonverbal stimulation is the result of left-hemispheric language-mediated selective attention. An additional condition, confounding the issue and inherent in most experiments, is the ongoing performance of a task. Actually the present subjects were not only listening to the verbal material but also engaged in simple grammatical operations with the stimulus words. Could this extra activity or attentional processes, superimposed upon the lateralized stimulation, have contributed to the higher rCBF in the dominant hemisphere? This possibility cannot be disregarded but if Spellacy and Wilson’s hypothesis is not restricted to the auditory modality, the previously mentioned results of Risberg and co-workers (1975a,b) link the postcentral left-hemispheric flow asymmetries to the language-processing component only, independent of task and/or selective attention. The significant higher flows in the right frontotemporal regions were found only during the two LES sessions. Sparks and Geschwind (1968), and Catlin and Neville (1976) proposed that in dextrals verbal stimulation presented to the left ear goes first via the crossed auditory pathways to the right hemisphere and then across to the left by way of the corpus callosum. Referring to the findings of Whitlock and Nauta (1956) that the anterior commissure connects the temporal neocortex of the rhesus monkey, Risse, LeDoux, Springer, Wilson, and Gazzaniga (1978) suggested that following callosal surgery, information presented to a patient’s left ear was transferred to the left hemisphere via the spared anterior commissure. In the present study, incoming verbal stimulation during LES could have been partially processed in the right hemisphere and subsequently transferred to the left. Monaural stimulation goes nevertheless to both cortices, and it is interesting to observe that even during RES, there was a tendency toward right-hemispheric asymmetry both in the prefrontal cortex and in a temporal region (Fig. 3). Possibly verbal material arriving in the right hemisphere via the ipsilateral auditory pathways also needs to be conveyed to the left hemisphere. Obviously, it is essential that the frontotemporal findings receive additional confirmation. Replications, as well as an inverse rCBF asymmetry during nonverbal stimulation, would make the transfer hypothesis more tenable. The present experiment demonstrated that the magnitude of cortical functional hemispheric asymmetry during auditory perception can be

BLOOD

FLOW ASYMMETRIES

9

quantified by rCBF determinations. A continuation of this study appears desirable. CBF recordings should be made during both monaural and binaural presentations of verbal, as well as nonverbal material. This would help to differentiate between the actual effects of the stimulusinput laterality and its processing and analysis in the cortex. An interesting paradigm would consist of dichotic presentation of verbal and nonverbal sounds to each ear during alternating sessions and determination of the effects upon the blood flow of homologous regions when one ear is selectively attended. REFERENCES Bakker, D. J. 1967. Left-right differences in auditory perception of verbal and non-verbal material by children. Quurrer/y Jortrnul of Psychology, 19, 334-336. Bakker, D. J. 1968. Ear asymmetry with monaural stimulation. Psychonomic Science, 12, 62. Bakker, D. J. 1969. Ear asymmetry with monaural stimulation: Task influences. Cortex, 5, 36-42. Bever, T. G. 1975. Cerebral asymmetries in humans are due to the differentiation of two incompatible processes, holistic and analytic. Annuls of rhe New, York Acudemy of Sciences, 263, 251-262. Catlin, J., & Neville, H. 1976. The laterality effect in reaction time to speech stimuli. Neuropsychologiu, 14, 141-143. Frankfurter, A., & Honeck. R. P. 1973. Ear differences in the recall of monaurally presented sentences. Quurterly Journal of Experimenrul Psychology, 25, 138-146. Friedman, D.. Simson, R., Ritter. W.. & Rapin. I. 1975. Cortical evoked potentials elicited by real speech words and human sounds. Elecrroencephulo,qruphy & CIinical Nerrrophysiology. 38, 13-19. Galaburda, A. M., Sanides, F., & Geschwind, N. 1978. Human brain: Cytoarchitectonic left-right asymmetries in the temporal speech region. Archives of Neurology, 35, 812-817. Galambos, R., Benson. P., Smith, T. S.. Schulman-Galambos, C., & Osier, H. 1975. On hemispheric differences in evoked potentials to speech stimuli. Electroencephalogruphy

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