Handedness and Lateralization

Handedness and Lateralization Handedness and LateralizationCortical Organisation and Lateralization Of The Brain In Handedness And Dominance According to Annett intimately people in our society define pass a counseledness as the consider that you use for writing (1970). Researchers define handedness as the hand that performs faster or specifically on physical tests. Paul Broca (1979), suggested that a persons handedness was opposite from that specialised hemisphere (so a respectablefulness-handed person probably has a remaining-hemispheric linguistic process strong point). However, a majority of go away-hemispheric brain specialise for paroles abilities. M all researchers have try to this correlation between handedness and brain lateralisation. The key reason that hand-brain connection is important and is an accepted methodology is that clinicians use handedness as a marker for brain lateralisation.Language is a distributed intellectual ne twork with differences in deme sne involvement that relate to specific lyric poem functions (Frith et al., 1991). Vital regions in network lateralize to one hemisphere and determine lesion (Ojemann, 1991). In most people this authorisation is to the odd. The only consistent information on the variability of hemispheric control between individuals are aphasias following a cam stroke or hemispheric def employ by procedure in patients with brain lesions (Wada and Rasmussen, 1960). Pertaining to the unevenness of lecture control there is a chance of useful hemispheric reform (Rasmussen and Milner, 1977). It assumes that variation from left hemisphere wrangle power is related to a difference analogous left-handedness. In honest-handed subjects there is puzzling correlation of verbal dustup and hand controller, both confines to a small area to the left hemisphere (Mayeux and Kandel, 1991). The actual variability of spoken communication laterality in the general population is a great deal unknown. Evaluati ons in a representative number of healthy subjects do not exist because, in the past, no technique was available to determine language lateralization effectively and non-invasively.This wish of information has hampered the taskment of language disturbances. There is an ongoing believe on the role of the right hemisphere in reco actually from aphasia by and by left hemispheric strokes (Weiller et al., 1993Go Heiss et al., 1997Go Mimura et al., 1998Go). Particularly, in retrospective evaluations it would be important to know how more(prenominal) patients with left hemispheric strokes and transient disturbance of language can be expected to have been right hemisphere language dominant and to have suffered speech impairment due to separate, more unspecific causes like decreased vigilance.More over, experience concerning the exact incidence of right hemisphere language strength in healthy righthanders would be important for utilitarian neuroimaging studies. Here, due to lack of information, researchers often ingest to rely on the assumption that restricting examinations to healthy right-handers will control for a assertable variability in hemispheric dominance.Recently, a simplified functional imaging technique, functional transcranial Doppler-ultrasonography (fTCD) has become available (Aaslid, 1987Go Hartje et al., 1994Go Silvestrini et al., 1994Go Rihs et al., 1995Go). It allows determination of hemispheric dominance in individual subjects in an effective, reliable and non-invasive way (Deppe et al., 1997Go Knecht et al., 1998). This technique has now do it possible to establish the variability in the side and score of language dominance in a representative number of healthy subjects. fTCD measures rational perfusion changes related to neuronal activation in a way comparable to functional MRI (fMRI) and 15O-PET (Kuschinsky, 1991Go Jueptner and Weiller, 1995Go Deppe et al., 1997Go, 1998Go). fTCD makes it possible to compare perfusion changes (by m easuring blood hang up velocities) within the territories of the two middle intellectual arteries (MCAs), which comprise the potential language areas (van der Zwan and Hillen, 1991Go). It thus provides an operational major power of laterality which, in many respects, resembles the one obtained by the intracarotid amobarbital procedure (Wada test) (Wada and Rasmussen, 1960Go). finish of language lateralization by fTCD matches precisely both the results of fMRI and the Wada test with concordance in every single case (Deppe et al., 1998Go Knecht et al., 1998aGo).As in many previous studies of this kind, word generation was chosen as an activation paradigm because it is one of the most effective measures of language production (Neils-Strunjas, 1998Go). On this basis language dominance was determined in a total of 188 healthy subjects. Left-handers were excluded from the subscribe to because of possible confounding do of handedness on hemispheric dominance (Kimura, 1983Go). A carefu l history for brain vituperate in the prenatal period or in infancy was taken in order to exclude subjects with possible plastic re system of rules of hemispheric dominance after brain lesions (Rasmussen and Milner, 1977Go).The work was part of the Munster functional imaging study on the variability of hemispheric specialization in health and disease (Deppe et al., 1997Go Knecht et al., 1998aGo, bGo). Hemispheric language dominance was assessed in 188 healthy volunteers with 111 females (mean age 26 5.5 years, cultivate 17-50 years) and 77 males (mean age 27 3.7 years, range 21-40 years). Subjects were excluded if, on a standardized questionnaire, they reported delayed or disturbed language development or a history of other neurological disorders, curiously perinatal asphyxia or kernicterus, head trauma, loss of consciousness, epileptic seizures, meningitis or encephalitis. They were further required to have successfully completed the equivalent of high coach (Realschule or Gy mnasium). Right-handedness was assessed by a handedness index in the Edinburgh Inventory of greater than 30% (Oldfield, 1971Go). Left-handers were excluded from the study, as were right-handers with a score for right-handedness decline than 30%, because, due to the small number of these subjects, an adequate evaluation of the effect of handedness on language lateralization would not have been possible. Approximately 75% of the subjects recruited had an index of more than 80% right-handedness. All subjects gave informed consent to participate in this study, which was approved by the Ethics Committee of the University of Mnster.Assessment of hemispheric language dominance was performed by a standardized fTCD technique (used in a number of previous studies) and a word generation task, validated by direct comparison with the intracarotid amobarbital injection and fMRI (Knecht et al., 1996Go, 1997Go, 1998aGo, bGo Deppe et al., 1997Go, 1998Go). Briefly, subjects were presented with a let ter on a computer screen 2.5 s after a cueing tone. Silently they had to control as many words as possible starting with the displayed letter. For fTCD an activation paradigm powerfully based on verbal fluency was used, corresponding to the field of reported female superiority (Basso et al., 1982Go Pizzamiglio et al., 1985Go). Task performance was controlled by instructing the subjects to report the words after a second auditory signal following 15 s after presentation of the letter. All words had to be reported within a 5-s time period. The next letter was presented in the same way after a relaxation period of 60 s. Letters were presented in random order and no letter was displayed more than once. Q, X and Y were excluded because very few words have these as initial letters.Changes in the cerebral blood stop speeding (CBFV) in the basal arteries were measured as an exponent of the downstream increase of the regional metabolic activity during the language task. Dual fTCD of the MCAs was performed with two 2 MHz transducer probes attached to a headband and placed zygomorphously at the blase skull windows (1Go). Details of the insonation technique, particularly the correct identification of the MCA, have been published elsewhere (Ringelstein et al., 1990Go). The spectral envelope curves of the Doppler signal were analysed off-line with the fTCD software AVERAGE veritable by one of the authors (M.D.) (Deppe et al., 1997Go).1 Schematic diagram of the way language lateralization was determined. Perfusion increases and hence neuronal activation during word generation were assessed in the vascular territories of the left (marked in red) and right (marked in green) MCAs, which comprise the language areas. This was achieved by fTCD measurements of the CBFV changes in these arteries. Systemic effects were eliminated by calculating the differences in perfusion changes between sides. Averaging the responses over 20 repetitions (on amount) in each individual do th e results highly reliable. (For details, see Deppe et al., 1997.)After automated artefact rejection, info were integrated over the corresponding cardiac cycles, segmented into epochs which related to the cueing tone and therefore averaged. The epochs were set to begin 15 s before and to end 35 s after the cueing tone. The mean velocity in the 15-s pre-cueing interval (Vpre.mean) was taken as the base-line value. The congenator CBFV changes (dV) during cerebral activation were calculated using the formula dV = V(t) Vpre.mean x 100 / Vpre.mean where V(t) is the CBFV over time. Relative CBFV changes from perennial presentations of letters (on average 20 runs) were averaged time-locked to the cueing tone. The number of repetitions was less than 22, because no letter was presented more than once during the word generation task.A functional TCD laterality index LIfTCDwas calculated using the formulaStatisticsThe Kolmogorov-Smirnov test was used to assess the dead reckoning that late rality indices in males and females were drawn from different populations. Unlike the parametric t-test for independent renders or the Mann-Whitney U test, which tests for differences in the location of two samples (differences in means, differences in average ranks, respectively), the Kolmogorov-Smirnov test is sensitive to differences in the general shapes of the distributions in the two samples, i.e. to differences in sprinkle and skewness (Spence et al., 1990Go). The Mann-Whitney test for equivalence (Wellek, 1996Go) was employed to confirm equivalence of laterality indices in men and women. A significant result in this test provides a strong plus measure for a lack of sexual practice differences in laterality indices. We tested the null hypothesis H0 PLImale LIfemale 1/2 =varepsilonversus the alternative hypothesis of equivalence H1 PLImale LIfemale 1/2 In six of the 194 right-handed subjects determination of language lateralization was not possible due to lack of a te mporal bone window, i.e. inadequate ultrasonographic penetration of the skull by the ultrasound beam. In the remaining 188 subjects (59% females, 41% males) the overall distribution of language lateralization was bimodal with 7.5% being right hemisphere and 92.5% left hemisphere language dominant (2Go).The distribution of language lateralization was equivalent in men and women (3Go). The Kolmogorov-Smirnov test did not detect any significant differences between females and males in the overall distribution (P 0.05). In the subgroup of left hemisphere language dominant subjects, the Mann-Whitney test for equivalence acquainted equivalence with P The average number of words found during the activation task per letter presented was not statistically different between men and women (Mann-Whitney U test, P = 0.81) or subjects with left or right hemisphere language dominance (Mann-Whitney U test, P = 0.26). It was also independent of the index of lateralization (correlation coefficient r = 0.027).These are the first data on the immanent distribution of language dominance in a large serial of healthy right-handed subjects. They demonstrate equivalence of language lateralization for word generation in males and females, and they suggest that 1 in 13 healthy right-handed subjects is right hemisphere dominant for language.MethodologyThere is debate whether language can be treated as a separate mental faculty or should be approached as part of a more general cognitive system (Fodor, 1983Go). Moreover, language comprises receptive and expressive aspects and is intertwined with prosody, storage and attention (Knecht et al., 1996Go Binder et al., 1997Go). Therefore, the assessment of language lateralization based on a single activation task provides just one index of the interindividual variability in language processing. This approach can nevertheless serve as a first step in elucidating the factors under(a)lying the diversity of large scale neural language organizat ion.fTCD lends itself to determination of hemispheric language dominance. The index of lateralization obtained by fTCD based on word generation is very reliable and closely corresponds to (i) the outcome of the intracarotid amobarbital procedure and (ii) the index of lateralization obtained by fMRI (Deppe et al., 1998Go Knecht et al., 1998aGo). Other techniques like head turning, event-related potentials, transcranial high frequency magnetised stimulation or the dichotic listening test used for the evaluation of language dominance have so cold failed to provide results that are reproducible and in sufficient concordance with the intracarotid amobarbital procedure (Bryden and Allard, 1981Go Jancke et al., 1992Go Jennum et al., 1994Go Segalowitz and Berge, 1995Go OLeary et al., 1996Go Hugdahl et al., 1997Go).Unlike the intracarotid amobarbital procedure and as opposed to brain lesions, functional imaging techniques including fTCD assess brain activation and not inactivation. They ar e set to determine the location and relative amount of the maximal activation while diffuse or bilateral activations are cancelled out. Thus, fTCD is insensitive to a lesser activation in the contralateral hemisphere. Moreover, fTCD cannot determine whether an activated region during a task is a decisive region that, when damaged, will result in a loss of that particular function. This shortcoming holds for all functional imaging techniques. However, the fact that determination of language lateralization by fMRI and fTCD correspond closely to that determined by the intracarotid amobarbital inactivation suggests that activated regions match critical regions and therefore provide essential information on the risk for language loss (Desmond et al., 1995Go Binder et al., 1996Go Knecht et al., 1998aGo).SexFuelled by the general interest in la petite diffrence, the lack of information about the natural distribution of language dominance has led to far-reaching speculations about possible differences in language lateralizations between the sexes. This discussion has been characterized by a high acceptance for positive results. Thus, despite considerable data to the contrary, there is a strong belief that language in women, on average, is less lateralized than in men (Bakan and Putnam, 1974Go Levy and Reid, 1976Go McGlone, 1980Go McKeever et al., 1983Go Hough et al., 1994Go Rugg, 1995Go). The whim of an increased bilaterality in women has received support by a recent fMRI study in 19 males and 19 females (Shaywitz et al., 1995Go) in which activation related to a rhyming task was found to be more bilateral in women than in men. It has been conjectured that an increased bilaterality of language in women would fly the coop to a decreased susceptibility to unilateral infarctions explaining a greater male than female proportion of aphasics (McGlone, 1980Go).Kertesz and Sheppard then showed that aphasias were as frequent in males as in females, as long as sex differences in the incidence of infarcts were taken into account (Kertesz and Sheppard, 1981Go). Similar results were obtained in a more recent epidemiological study (Pedersen et al., 1995Go). Recently, using fMRI, Frost and colleagues found no differences between sexes during a language comprehension task when group averages were compared (Frost et al., 1999Go). Our data provide the first direct express that language lateralization during word generation in men and women is also equivalent in variablity. In fact, they not only show a lack of significant differences but they positively demonstrate significance of equivalence in healthy subjects even though this finding is based on a word generation task, i.e. a field of reported female superiority (Kimura and Harshman, 1984Go). Equivalence of hemispheric lateralization between sexes during word generation does not exclude gender differences in subfunctions of language like rhyming, which we did not investigate. As was pointed out before, such a difference has been reported by Shaywitz and colleagues in a small series of subjects examined by fMRI (Shaywitz et al., 1995Go). However, in line with our results, these researchers did not find gender differences in other language tasks.Right hemisphere language dominanceThe predomination of right-handedness and left hemisphere language lateralization has led some theorists to suggest that a gestural system of communication with dominance of the right hand provided the neural architecture for vocal articulation in human evolution (Hewes, 1973Go Kimura, 1987Go). If indeed handedness and language were coupled because they share the same neural resources, then any deviation from this pattern would have to be pathological. Right hemisphere language dominance in right-handers or left hemisphere language dominance in left-handers reported from the intracarotid amobarbital procedure does not challenge this view, because this procedure is only performed in patients with brain pathology . However, the present findings in healthy subjects indicate that even under natural conditions the association between handedness and language dominance is not an absolute one. Because 75% of subjects were strongly right-handed (80%) and the remaining had handedness indices of 30%, the effect of the degree of handedness on language lateralization could not be evaluated in the present study. Comparison of left- and right-handers will be necessary to test whether a relative association between handedness and language dominance exists in healthy subjects.The extreme line of descent could be put forward that all of our presumed healthy subjects with right hemisphere dominance must have suffered covert brain damage resulting in a sky of language into the right hemisphere. A similar argument has been made to explain left-handedness in healthy subjects (Coren, 1990Go). We believe that covert brain damage was unlikely. The medical history in all subjects was unrevealing and the scholasti c achievement was similar. The average number of words produced during the task did not differ between subjects with left or right hemisphere language dominance and the pattern of language lateralization variability was bimodal with maxima for left- and right-hemisphere dominance (2Go). If there had been subclinical damage to language relevant areas in the left hemisphere resulting in a shift to the right, one would have expected impaired word fluency and more cases with little lateralization because of a bilateral representation of language functions. This was not the case. We therefore suggest that right hemisphere language dominance is not a pathological but a natural phenomenon.Previous estimates of atypical right hemisphere language dominance were either based on the results from the intracarotid amobarbital test in patients evaluated for resective neurosurgery or on the occurrence of crossed aphasia, i.e. aphasias after right hemispheric lesions. In patients with epilepsy sub mitted to the intracarotid amobarbital test the number of right-handers with right hemisphere language dominance was 4% in a large series and rose to 12% when a left hemisphere lesion was defined (Rasmussen and Milner, 1977Go). Because the Wada test is only performed in patients with brain lesions, which are often associated with a secondary transfer of cortical functions from the damaged to the intact hemisphere, these verse cannot be extrapolated to healthy subjects (Helmstaedter et al., 1994Go). By evaluation of stroke-patients with crossed aphasia, the incidence of right hemisphere language dominance in right-handers has been inferred to be between 1 and 2% in the majority of series (Gloning, 1977Go Borod et al., 1985Go Kertesz, 1985Go).On the one hand, this low estimate of right hemisphere language dominance in previously healthy subjects made aphasias in right-handers after right-sided lesions seem an exceptional event and has resulted in almost 100 reports on crossed aphasia in the last 30 years. On the other hand, difficulties in the assessment of language performance due to physical exhaustion and deficits in sustained attention in the early stages after stroke and reorganizational insurance in the later stages may have facilitated an underdiagnosis of aphasia in right hemispheric stroke patients in many studies. Not every patient with a cerebral infarction in the respective language dominant hemisphere will suffer damage of the language areas and become aphasic. The overall rate of aphasia due to stroke has been found to be 38% in the acute state and 18% at discharge from the hospital (Pedersen et al., 1995Go). Reasoning from the effects of brain activation to the effects of brain lesions is problematic but results from activation studies may be conceptually useful to the understanding of lesion-deficit variability in the clinical context (Willmes and Poeck, 1993Go). In a single recent study on 880 stroke patients it was reported, in passing, that of right-handed aphasics 9% had right hemispheric lesions (Pedersen et al., 1995Go). In a study on language deficits in servicemen who had suffered penetrating brain wounds, 18% of the aphasics had suffered right hemispheric lesions (Mohr et al., 1980Go). However, here the possible effects of diffuse brain damage by the impact of a bullet and the effect of variable handedness pose methodological limitations. Our cohort was similar in age to these soldiers. We found an incidence of 7.5% of right hemisphere dominance in our activation study of healthy subjects. This combined evidence suggests that about 1 in 13 previously healthy right-handed patients with a right hemispheric infarction could be at risk of suffering language impairments because this is the hemisphere dominant for word generation. Conversely, after left hemispheric infarctions right-handed patients, who in retrospective evaluations seem to have recovered well from language disturbances, and on fMRI or PET may even show language related activation in the right hemisphere, may do so because they had been right hemisphere language dominant to begin with.Presently, we do not know the relevancy of the extent of language lateralization by fTCD. Low indices of lateralization indicate that there is a bihemispheric activation during word generation. Although reported in studies based on the Wada test, bilateral language representation in stroke patients has probably been neglected because persistent aphasia in these subjects may only occur after bilateral damage (Benbadis et al., 1995Go). This is very rare and patients rarely survive. 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