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Right auditory cortex lesion in Mongolian gerbils impairs discrimination of rising and falling frequency-modulated tones
Neuroscience Letters 252 (1998) 115–118
Right auditory cortex lesion in Mongolian gerbils impairs discrimination of rising and falling frequency-modulated tones W. Wetzel*, F.W. Ohl, T. Wagner, H. Scheich Leibniz Institute for Neurobiology, P.O.B. 1860, 39008 Magdeburg, Germany Received 8 June 1998; received in revised form 1 July 1998; accepted 6 July 1998
Abstract Mongolian gerbils (Meriones unguiculatus) were trained in a shuttle box to discriminate the direction in frequency-modulated tones (FM). Whereas control animals easily acquired FM discrimination, animals with auditory cortex lesion on the right side showed considerable difficulties in learning this task. The discrimination performance of gerbils with left auditory cortex lesion, however, was not different from controls. This study, suggesting that the right auditory cortex plays a dominant role in FM discrimination learning in gerbils, describes a useful animal model for investigation of the basic mechanisms underlying hemispheric asymmetries in auditory perception. 1998 Elsevier Science Ireland Ltd. All rights reserved
Keywords: Auditory cortex; Unilateral lesion; Frequency modulation; Discrimination learning; Hemispheric asymmetry; Mongolian gerbils
Cumulative evidence exists that human speech and animal communication calls share common acoustic characteristics and general principles of processing and that, both in humans and in animals, temporally changing acoustic cues are of critical importance [3,18]. In particular, frequency modulation (FM) is a critical parameter of acoustic communication signals. In studies on children with receptive dysphasia, for example, it was found that these children show no evoked responses to FM tones and it was concluded that a deficit in FM analysis may underlie the disturbance in speech perception [16]. There is a lack of behavioral studies, however, on complex auditory processing in animals. In earlier investigations in Mongolian gerbils, we found that some proportion of neurons in the auditory cortex show different responses to the direction of frequency modulation in FM stimuli [14]. Moreover, we found different neuronal response patterns to the direction of FM in right and left auditory cortex (Schulze et al., in preparation). In humans the existence of cerebral asymmetries is well known. Thus, a left hemisphere dominance for verbal stimuli, and a right hemisphere advantage for nonverbal sti* Corresponding author. Tel.: +49 391 6263338; fax: +49 391 6263328; e-mail: [email protected]
muli (environmental sounds, melodies, prosody), was shown [3,6,19]. In animals, there are relatively few studies of lateralization in auditory perception. Mostly, a left hemisphere specialization for processing of complex acoustic stimuli was found, e.g. in perception of species-specific vocalization in monkeys [5,12], mice [1] and birds [11]. These results, although not unequivocally, support the suggestion that a functional hemispheric asymmetry is also existent in nonhuman species. There are, however, marked species differences in lateralization studies and, furthermore, the observed effects could be obscured by high individual variations in lateralization [6]. In the present study, we tested if there are different effects of left or right auditory cortex lesions on FM discrimination. To our knowledge, the ability of animals with unilateral auditory cortical lesions to discriminate rising and falling FM tones has not yet been determined. Due to their well known and elaborate auditory cortex organization [13] and trainability on FM discrimination [20], Mongolian gerbils (Meriones unguiculatus) are useful animal models for the present type of research. The gerbils, weighing 62–98 g, were obtained from the Tumblebrook Farm (USA) and housed in a temperature-controlled room (23°C) under a 12 h/12 h light/dark cycle (light on 0600–
0304-3940/98/$19.00 1998 Elsevier Science Ireland Ltd. All rights reserved PII S0304- 3940(98) 00561- 8
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W. Wetzel et al. / Neuroscience Letters 252 (1998) 115–118
Table 1 Effect of unilateral auditory cortex lesions on directional discrimination of frequency-modulated tones Group (n)
Response
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Con L (6)
CR FA ITC CR FA ITC CR FA ITC CR FA ITC
13.8 ± 2.2 11.2 ± 2.7 8.3 ± 3.5 7.4 ± 1.7 6.3 ± 1.1 15.4 ± 4.1 9.8 ± 2.7 7.0 ± 2.4 20.8 ± 7.5 14.1 ± 2.3 13.6 ± 2.5* 22.4 ± 4.8
23.3 ± 1.8 13.8 ± 1.4 13.2 ± 3.4 22.5 ± 2.5 13.8 ± 2.0 14.9 ± 2.9 20.4 ± 4.5 9.2 ± 3.7 12.8 ± 3.6 23.3 ± 2.7 20.1 ± 2.4* 14.9 ± 3.5
23.7 ± 1.8 13.8 ± 2.7 9.8 ± 3.2 22.5 ± 1.9 10.8 ± 2.1 13.5 ± 2.4 25.8 ± 2.3 11.4 ± 3.2 10.8 ± 3.0 22.8 ± 1.7 16.3 ± 2.5 21.1 ± 4.1
21.7 ± 2.6 8.8 ± 1.9 7.3 ± 3.2 21.6 ± 1.7 9.8 ± 2.4 16.8 ± 5.0 23.6 ± 2.1 11.0 ± 2.3 15.8 ± 7.1 19.0 ± 2.5 14.1 ± 2.7 13.1 ± 3.1
22.0 ± 1.9 7.0 ± 1.2 8.7 ± 1.7 23.9 ± 2.3 8.9 ± 2.4 13.9 ± 2.9 22.8 ± 2.0 10.4 ± 3.0 9.4 ± 3.6 17.5 ± 1.8* 10.8 ± 1.8 14.0 ± 3.4
23.3 ± 2.2 6.0 ± 1.1 6.0 ± 1.9 22.8 ± 2.0 6.1 ± 2.7 10.5 ± 2.6 22.6 ± 2.4 8.0 ± 3.2 15.5 ± 8.4 18.3 ± 1.7** 12.8 ± 2.5 14.7 ± 4.1
23.2 ± 1.5 6.3 ± 1.1 7.3 ± 2.1 24.1 ± 1.8 6.3 ± 3.0 11.1 ± 3.0 23.8 ± 2.3 8.6 ± 3.4 8.0 ± 3.0 20.1 ± 1.6 12.4 ± 1.9 15.2 ± 4.2
25.8 ± 1.1 6.2 ± 2.0 7.8 ± 2.0 26.3 ± 1.2 6.9 ± 2.0 10.3 ± 3.2 23.4 ± 3.7 8.2 ± 2.4 12.8 ± 9.9 19.8 ± 2.7 11.5 ± 1.8 10.9 ± 2.6
LesL (8)
Con R (5)
LesR (8)
CR, correct conditioned responses; FA, false alarms; ITC, intertrial crossings; shown for 8 days of training (number of responses per session; means ± S.E.M.). Groups: ConL, sham-lesion left; ConR, sham-lesion right; LesL, lesion left; LesR, lesion right. *P , 0.05 (LesR vs. ConR). **P ± 0.05 (LesR vs. ConR and ConL).
1800 h) in standard laboratory cages with free access to food and water. Cortical lesions were made under ketamine (l00 mg/kg)/xylazine (5 mg/kg) anesthesia by thermocoagulation of the whole auditory cortex on the left (group LesL) or the right side (group LesR). Gerbils with small openings in the skull on the left (ConL) or the right side (ConR) were used as sham-lesioned controls. After operation, the animals were allowed to recover for at least 5 days before the training was started. Conditioned stimuli (CS) consisting of 16-bit digitally synthesized linearly frequency-modulated tones (1–2 kHz rising frequency; 2–1 kHz falling frequency; 65–70 dB SPL; 250 ms duration; 250 ms interval) were delivered by a loudspeaker over the shuttle box and controlled by a Bruel & Kjaer spectrum analyzer (B&K 2033). The discriminative footshock avoidance go/no go training was carried out in a mouse shuttle box (Coulbourn) located in a sound-proof room. Animals were required to perform an active avoidance response when presented with rising tones (CS+) and to suppress the response when presented with falling tones (CS−) using a randomized order. If, during CS+, a response did not occur within 6 s, the animal was punished by footshock. The daily training session performed between 0800 and 1300 h, consisted of 60 trials, the mean intertrial interval was 15 s. Discrimination performance was calculated as the difference between responses to CS+ (correct conditioned responses, CR) and responses to CS− (false alarms, FA). Crossing reactions during the interval were counted as intertrial crossings (ITC). Training program and recording were controlled by an IBM PC using custom-made software. For statistical evaluation (number of responses, Table 1; response differences, Fig. 2), Kruskal–Wallis Htest and Mann–Whitney U-test were used (comparison between groups; two-tailed). If, on some training days, there was no significant difference between ConR and LesR animals, both control groups were pooled (‘ConR and ConL’) and compared with LesR.
After completion of training experiments, the localization of cortical lesions was examined by the 2-fluoro-2-deoxy-d[14C(U)]glucose (FDG) mapping technique [13]. Lesions in each animal were reconstructed by alignment of serial horizontal brain sections (Fig. 1). Only those animals were included in the final evaluation (n = 27) whose lesions covered but did not exceed the territory of auditory cortex using landmarks and labelling patterns of a previous study [13]. As shown in Table 1, the CR and FA responses of the leftside lesioned animals (LesL) were not different from the responses of the control group (ConL). In the right-side lesioned gerbils (LesR), however, there was a decrease of
Fig. 1. Unilateral auditory cortex (AC) lesion in Mongolian gerbils: example of FDG autoradiograph of horizontal brain section of a right auditory cortex lesioned (arrow) animal.
W. Wetzel et al. / Neuroscience Letters 252 (1998) 115–118
CR and an increase of FA, compared to ConR. Comparison between the two control groups revealed no differences. Thus, only the LesR animals have lower response differences compared to the other three groups (Fig. 2). No between-group differences in intertrial crossings (Table 1) and response latencies were found. Furthermore, there were no differences in the mean group values of footshock intensity (ConL: 335 ± 44 mA; LesL: 293 ± 32mA; ConR: 344 ± 33mA; LesR 324 ± 40mA; means ± SEM). As shown in Fig. 2, neither group reached a plateau-level of FM discrimination after 8 days of training. Thus, LesR gerbils may have slower discrimination learning compared to the other groups so that the right hemisphere lesion would cause a deficit in discrimination rate rather than in discrimination ability. It is known from lesion studies that the auditory cortex is not an essential structure for all auditory discriminations. Dependent on animal species and experimental conditions, discriminations of sound frequency, intensity, or localization can be successfully learned by animals with auditory cortex lesions [2,10]. On the other hand, the auditory cortex was found to be necessary for discrimination of complex acoustic patterns, e.g. frequency-modulated tones [9]. In view of the substantial species differences, it is difficult to come to a general conclusion. Until now, there are no rodent studies on auditory cortex lesion effects on FM discrimina-
Fig. 2. Effect of unilateral auditory cortex lesions on discrimination of frequency-modulated tones. The figure shows group mean values of response differences (correct conditioned responses minus false alarms) over 8 days of training. ConL, sham-lesion left; ConR, sham-lesion right; LesL, lesion left; LesR, lesion right. (1) P , 0.05 (LesR vs. ConR); (2) P , 0.05 (LesR vs. ConR and ConL); (3) P , 0.02 (LesR vs. ConR and ConL); (4) P , 0.01 (LesR vs. ConR and ConL).
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tion and no animal studies investigating the effect of unilateral auditory cortex lesion on FM discrimination. Previously, we found that bilateral auditory cortex ablation in gerbils blocks discrimination of the direction of FM sounds but not discrimination of pure tones (Ohl et al., in preparation). The present study shows that right auditory cortex lesioned gerbils were clearly impaired in FM directional discrimination learning, whereas, gerbils with leftside lesions were indistinguishable from controls. To our knowledge, this is the first study in animals showing that the right auditory cortex plays a dominant role in discrimination of direction of frequency modulations. Although the lesion technique provides a powerful analytic tool for examining interrelationships between brain structures and functions, limitations of the method must be considered [4,7]. Especially, in learning studies, the results of brain lesions require careful interpretation. We have to consider that the learning and memory loss resulting from brain damage may be confounded by other deficits. Thus lesion-induced changes in behavioral performance may be due to disturbances in motor function, sensory capacities, sensorimotor integration, attention, motivation and emotion, rather than impairment of information acquisition, storage and/or retrieval. As shown by our previous pure tone discrimination study, bilateral auditory cortex lesion in gerbils was not followed by a hearing loss. Also, our earlier results as well as the present data (intertrial crossings; footshock sensitivity do not suggest that motor or sensory functions and motivation or emotion are substantially affected by the lesion. Furthermore, since no lesion effects or response latencies were observed, it seems to be unlikely that the attention level was altered. Thus, our results favour the interpretation that auditory learning and/or memory may be disturbed by right auditory cortex lesion. It remains to be clarified, however, whether acquisition, storage, or retrieval are specifically affected by the lesion. Moreover, since we found lesion effects on both CR and FM (Table 1), it is not clear whether the right auditory cortex may be more critical for mediating the active go response or the passive no-go response. In a go/no go procedure as used in our experiments, it is difficult to explain altered behavior as an alteration of the different response tendencies or as changing of discrimination ability. This question could be studied by using a two-alternative forced-choice procedure. Nevertheless, the present results show that right auditory cortex lesion in gerbils is followed by an impairment of discrimination of direction in frequency-modulated tones. Since frequency modulation is an essential component of prosodic information, our results resemble the right hemisphere specialization for speech prosody found in humans. It must be considered, however, that – compared to specialized functions of the ‘dominant’ left hemisphere (LH) – abilities unique to the ‘minor’ right hemisphere (RH) are much less clear. Lesion studies have not yet unequivocally demonstrated brain lateralization during the recognition of speech prosody. It may be possible that, rather than being
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lateralized to a right hemisphere in a fashion analogous to semantic information, prosodic processes are made up of multiple functions depending on systems distributed in both cerebral hemispheres [17,19]. A number of studies, showing a LH dominance for verbal stimuli but a RH dominance for non-verbal sounds, suggest that hemispheric asymmetry is related to the linguistic relevance of acoustic signals, rather than their physical characteristics (e.g. [12]). In other studies, however, it was found that acoustic signals that change rapidly in time (30-ms 350 Hz ascending or descending frequency glides; consonantvowel syllables incorporating 40-ms formant transitions) seem to be preferentially processed by the LH, regardless whether the sound has a linguistic relevance or not [8,15]. These data suggest that the LH specialization for speech perception and the RH advantage for other sound characteristics, e.g. prosody, appears to reflect hemispheric differences in processing of rapidly changing acoustic signals. It seems to be likely that this different hemispheric processing is based on fundamental brain mechanisms which can be investigated in human as well as in animal research [3,18]. The present animal method, showing that right auditory cortex lesion in gerbils impairs directional discrimination of FM stimuli of relatively long duration (250 ms), may be a useful approach to study specializations of the right hemisphere, e.g. prosody. It could be used for further investigations trying to elucidate basic brain processes underlying lateralized perception of complex acoustic signals. The skilful technical assistance of Lydia Lo¨w, Ute Lerke, Janet Thunert and Elke Muller is gratefully acknowledged. Supported by DFG (We 2104/2-1). [1] Ehret, G., Left hemisphere advantage in the mouse brain for recognizing ultrasonic communication calls, Nature, 325 (1987) 249–251. [2] Elliott, D.N. and Trahiotis, C., Cortical lesions and auditory discrimination, Psychol. Bull., 77 (1972) 198–222. [3] Fitch, R.H., Miller, S. and Tallal, P., Neurobiology of speech perception, Annu. Rev. Neurosci., 20 (1997) 331–353. [4] Grobstein, P., Strategies for analyzing complex organization in the nervous system: I. Lesion experiments. In E.L. Schwarz (Ed.), Computational Neuroscience, MIT Press, Cambridge, MA, 1990, pp. 19-37. [5] Heffner, H.E. and Heffner, R.S., Temporal lobe lesions and perception of species-specific vocalizations by macaques, Science, 226 (1984) 75–76.
[6] Hellige, J.B., Hemispheric asymmetry, Annu. Rev. Psychol., 41 (1990) 55–80. [7] Isaacson, R.L., Brain lesion studies related to memory: a critique of strategies and interpretations. In H.J. Markowitsch (Ed.), Information Processing by the Brain, H. Huber Publishers, Toronto, 1988, pp. 87-105. [8] Johnsrude, I.S., Zatorre, R.J., Milner, B.A. and Evans, A.C., Left hemisphere specialization for the processing of acoustic transients, NeuroReport, 8 (1997) 1761–1765. [9] Kelly, J.B. and Whitfield, I.C., Effects of auditory cortical lesions on discriminations of rising and falling frequency-modulated tones, J. Neurophysiol., 34 (1971) 802–816. [10] Neff, W.D., Diamond, I.T. and Casseday, J.J., Behavioral studies of auditory discrimination: central nervous system. In W.D. Keidel and W.D. Neff (Eds.), Handbook of Sensory Physiology, Vol. V/2, Springer, Berlin, 1975. pp. 307-400. [11] Nottebohm, F., Stokes, T.M. and Leonard, C.M., Central control of song in the canary, Serinus canarius, J. Comp. Neurol., 165 (1976) 457–486. [12] Petersen, M.R., Beecher, M.D., Zoloth, S.R., Green, S., Marler, P.R., Moody, D.B. and Stebbins, W.C., Neural lateralization of vocalizations by Japanese macaques: communicative significance is more important than acoustic structure, Behav. Neurosci., 98 (1984) 779–790. [13] Scheich, H., Simonis, C., Ohl, F., Thomas, H. and Tillein, J., Functional organization and learning related plasticity in auditory cortex of the Mongolian gerbil, Prog. Brain Res., 97 (1993) 135–143. [14] Schulze, H., Ohl, F.W., Heil, P. and Scheich, H., Field-specific responses in the auditory cortex of the unanaesthetized Mongolian gerbil to tones and slow frequency modulations, J. Comp. Physiol. A, 181 (1997) 573–589. [15] Schwartz, J. and Tallal, P., Rate of acoustic change may underlie hemispheric specialization for speech perception, Science, 207 (1980) 1380–1381. [16] Stefanatos, G.A., Green, G.G.R. and Ratcliff, G.G., Neurophysiological evidence of auditory channel anomalies in developmental dysphasia, Arch. Neurol., 46 (1989) 871–875. [17] Stiller, D., Gaschler-Markefski, B., Baumgart, F., Schindler, F., Tempelmann, C., Tegeler, C., Heinze, H.J. and Scheich, H., Lateralized processing of speech prosodies in the temporal cortex: a 3T fMRI study, MAGMA, 5 (1997) 32–47. [18] Suga, N., Processing of auditory information carried by speciesspecific complex sounds. In M.S. Gazzaniga (Ed.), The Cognitive Neurosciences, MIT Press, Cambridge, MA, 1995, pp. 295313. [19] Van Lancker, D., Rags to riches: our increasing appreciation of cognitive and communicative abilities of the human right cerebral hemisphere, Brain Lang., 57 (1997) 1–11. [20] Wetzel, W., Wagner, T., Ohl, F.W. and Scheich, H., Categorical discrimination of direction in frequency-modulated tones by Mongolian gerbils, Behav. Brain Res., 91 (1998) 29–39.
Right auditory cortex lesion in Mongolian gerbils impairs discrimination of rising and falling frequency-modulated tones W. Wetzel*, F.W. Ohl, T. Wagner, H. Scheich Leibniz Institute for Neurobiology, P.O.B. 1860, 39008 Magdeburg, Germany Received 8 June 1998; received in revised form 1 July 1998; accepted 6 July 1998
Abstract Mongolian gerbils (Meriones unguiculatus) were trained in a shuttle box to discriminate the direction in frequency-modulated tones (FM). Whereas control animals easily acquired FM discrimination, animals with auditory cortex lesion on the right side showed considerable difficulties in learning this task. The discrimination performance of gerbils with left auditory cortex lesion, however, was not different from controls. This study, suggesting that the right auditory cortex plays a dominant role in FM discrimination learning in gerbils, describes a useful animal model for investigation of the basic mechanisms underlying hemispheric asymmetries in auditory perception. 1998 Elsevier Science Ireland Ltd. All rights reserved
Keywords: Auditory cortex; Unilateral lesion; Frequency modulation; Discrimination learning; Hemispheric asymmetry; Mongolian gerbils
Cumulative evidence exists that human speech and animal communication calls share common acoustic characteristics and general principles of processing and that, both in humans and in animals, temporally changing acoustic cues are of critical importance [3,18]. In particular, frequency modulation (FM) is a critical parameter of acoustic communication signals. In studies on children with receptive dysphasia, for example, it was found that these children show no evoked responses to FM tones and it was concluded that a deficit in FM analysis may underlie the disturbance in speech perception [16]. There is a lack of behavioral studies, however, on complex auditory processing in animals. In earlier investigations in Mongolian gerbils, we found that some proportion of neurons in the auditory cortex show different responses to the direction of frequency modulation in FM stimuli [14]. Moreover, we found different neuronal response patterns to the direction of FM in right and left auditory cortex (Schulze et al., in preparation). In humans the existence of cerebral asymmetries is well known. Thus, a left hemisphere dominance for verbal stimuli, and a right hemisphere advantage for nonverbal sti* Corresponding author. Tel.: +49 391 6263338; fax: +49 391 6263328; e-mail: [email protected]
muli (environmental sounds, melodies, prosody), was shown [3,6,19]. In animals, there are relatively few studies of lateralization in auditory perception. Mostly, a left hemisphere specialization for processing of complex acoustic stimuli was found, e.g. in perception of species-specific vocalization in monkeys [5,12], mice [1] and birds [11]. These results, although not unequivocally, support the suggestion that a functional hemispheric asymmetry is also existent in nonhuman species. There are, however, marked species differences in lateralization studies and, furthermore, the observed effects could be obscured by high individual variations in lateralization [6]. In the present study, we tested if there are different effects of left or right auditory cortex lesions on FM discrimination. To our knowledge, the ability of animals with unilateral auditory cortical lesions to discriminate rising and falling FM tones has not yet been determined. Due to their well known and elaborate auditory cortex organization [13] and trainability on FM discrimination [20], Mongolian gerbils (Meriones unguiculatus) are useful animal models for the present type of research. The gerbils, weighing 62–98 g, were obtained from the Tumblebrook Farm (USA) and housed in a temperature-controlled room (23°C) under a 12 h/12 h light/dark cycle (light on 0600–
0304-3940/98/$19.00 1998 Elsevier Science Ireland Ltd. All rights reserved PII S0304- 3940(98) 00561- 8
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Table 1 Effect of unilateral auditory cortex lesions on directional discrimination of frequency-modulated tones Group (n)
Response
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Con L (6)
CR FA ITC CR FA ITC CR FA ITC CR FA ITC
13.8 ± 2.2 11.2 ± 2.7 8.3 ± 3.5 7.4 ± 1.7 6.3 ± 1.1 15.4 ± 4.1 9.8 ± 2.7 7.0 ± 2.4 20.8 ± 7.5 14.1 ± 2.3 13.6 ± 2.5* 22.4 ± 4.8
23.3 ± 1.8 13.8 ± 1.4 13.2 ± 3.4 22.5 ± 2.5 13.8 ± 2.0 14.9 ± 2.9 20.4 ± 4.5 9.2 ± 3.7 12.8 ± 3.6 23.3 ± 2.7 20.1 ± 2.4* 14.9 ± 3.5
23.7 ± 1.8 13.8 ± 2.7 9.8 ± 3.2 22.5 ± 1.9 10.8 ± 2.1 13.5 ± 2.4 25.8 ± 2.3 11.4 ± 3.2 10.8 ± 3.0 22.8 ± 1.7 16.3 ± 2.5 21.1 ± 4.1
21.7 ± 2.6 8.8 ± 1.9 7.3 ± 3.2 21.6 ± 1.7 9.8 ± 2.4 16.8 ± 5.0 23.6 ± 2.1 11.0 ± 2.3 15.8 ± 7.1 19.0 ± 2.5 14.1 ± 2.7 13.1 ± 3.1
22.0 ± 1.9 7.0 ± 1.2 8.7 ± 1.7 23.9 ± 2.3 8.9 ± 2.4 13.9 ± 2.9 22.8 ± 2.0 10.4 ± 3.0 9.4 ± 3.6 17.5 ± 1.8* 10.8 ± 1.8 14.0 ± 3.4
23.3 ± 2.2 6.0 ± 1.1 6.0 ± 1.9 22.8 ± 2.0 6.1 ± 2.7 10.5 ± 2.6 22.6 ± 2.4 8.0 ± 3.2 15.5 ± 8.4 18.3 ± 1.7** 12.8 ± 2.5 14.7 ± 4.1
23.2 ± 1.5 6.3 ± 1.1 7.3 ± 2.1 24.1 ± 1.8 6.3 ± 3.0 11.1 ± 3.0 23.8 ± 2.3 8.6 ± 3.4 8.0 ± 3.0 20.1 ± 1.6 12.4 ± 1.9 15.2 ± 4.2
25.8 ± 1.1 6.2 ± 2.0 7.8 ± 2.0 26.3 ± 1.2 6.9 ± 2.0 10.3 ± 3.2 23.4 ± 3.7 8.2 ± 2.4 12.8 ± 9.9 19.8 ± 2.7 11.5 ± 1.8 10.9 ± 2.6
LesL (8)
Con R (5)
LesR (8)
CR, correct conditioned responses; FA, false alarms; ITC, intertrial crossings; shown for 8 days of training (number of responses per session; means ± S.E.M.). Groups: ConL, sham-lesion left; ConR, sham-lesion right; LesL, lesion left; LesR, lesion right. *P , 0.05 (LesR vs. ConR). **P ± 0.05 (LesR vs. ConR and ConL).
1800 h) in standard laboratory cages with free access to food and water. Cortical lesions were made under ketamine (l00 mg/kg)/xylazine (5 mg/kg) anesthesia by thermocoagulation of the whole auditory cortex on the left (group LesL) or the right side (group LesR). Gerbils with small openings in the skull on the left (ConL) or the right side (ConR) were used as sham-lesioned controls. After operation, the animals were allowed to recover for at least 5 days before the training was started. Conditioned stimuli (CS) consisting of 16-bit digitally synthesized linearly frequency-modulated tones (1–2 kHz rising frequency; 2–1 kHz falling frequency; 65–70 dB SPL; 250 ms duration; 250 ms interval) were delivered by a loudspeaker over the shuttle box and controlled by a Bruel & Kjaer spectrum analyzer (B&K 2033). The discriminative footshock avoidance go/no go training was carried out in a mouse shuttle box (Coulbourn) located in a sound-proof room. Animals were required to perform an active avoidance response when presented with rising tones (CS+) and to suppress the response when presented with falling tones (CS−) using a randomized order. If, during CS+, a response did not occur within 6 s, the animal was punished by footshock. The daily training session performed between 0800 and 1300 h, consisted of 60 trials, the mean intertrial interval was 15 s. Discrimination performance was calculated as the difference between responses to CS+ (correct conditioned responses, CR) and responses to CS− (false alarms, FA). Crossing reactions during the interval were counted as intertrial crossings (ITC). Training program and recording were controlled by an IBM PC using custom-made software. For statistical evaluation (number of responses, Table 1; response differences, Fig. 2), Kruskal–Wallis Htest and Mann–Whitney U-test were used (comparison between groups; two-tailed). If, on some training days, there was no significant difference between ConR and LesR animals, both control groups were pooled (‘ConR and ConL’) and compared with LesR.
After completion of training experiments, the localization of cortical lesions was examined by the 2-fluoro-2-deoxy-d[14C(U)]glucose (FDG) mapping technique [13]. Lesions in each animal were reconstructed by alignment of serial horizontal brain sections (Fig. 1). Only those animals were included in the final evaluation (n = 27) whose lesions covered but did not exceed the territory of auditory cortex using landmarks and labelling patterns of a previous study [13]. As shown in Table 1, the CR and FA responses of the leftside lesioned animals (LesL) were not different from the responses of the control group (ConL). In the right-side lesioned gerbils (LesR), however, there was a decrease of
Fig. 1. Unilateral auditory cortex (AC) lesion in Mongolian gerbils: example of FDG autoradiograph of horizontal brain section of a right auditory cortex lesioned (arrow) animal.
W. Wetzel et al. / Neuroscience Letters 252 (1998) 115–118
CR and an increase of FA, compared to ConR. Comparison between the two control groups revealed no differences. Thus, only the LesR animals have lower response differences compared to the other three groups (Fig. 2). No between-group differences in intertrial crossings (Table 1) and response latencies were found. Furthermore, there were no differences in the mean group values of footshock intensity (ConL: 335 ± 44 mA; LesL: 293 ± 32mA; ConR: 344 ± 33mA; LesR 324 ± 40mA; means ± SEM). As shown in Fig. 2, neither group reached a plateau-level of FM discrimination after 8 days of training. Thus, LesR gerbils may have slower discrimination learning compared to the other groups so that the right hemisphere lesion would cause a deficit in discrimination rate rather than in discrimination ability. It is known from lesion studies that the auditory cortex is not an essential structure for all auditory discriminations. Dependent on animal species and experimental conditions, discriminations of sound frequency, intensity, or localization can be successfully learned by animals with auditory cortex lesions [2,10]. On the other hand, the auditory cortex was found to be necessary for discrimination of complex acoustic patterns, e.g. frequency-modulated tones [9]. In view of the substantial species differences, it is difficult to come to a general conclusion. Until now, there are no rodent studies on auditory cortex lesion effects on FM discrimina-
Fig. 2. Effect of unilateral auditory cortex lesions on discrimination of frequency-modulated tones. The figure shows group mean values of response differences (correct conditioned responses minus false alarms) over 8 days of training. ConL, sham-lesion left; ConR, sham-lesion right; LesL, lesion left; LesR, lesion right. (1) P , 0.05 (LesR vs. ConR); (2) P , 0.05 (LesR vs. ConR and ConL); (3) P , 0.02 (LesR vs. ConR and ConL); (4) P , 0.01 (LesR vs. ConR and ConL).
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tion and no animal studies investigating the effect of unilateral auditory cortex lesion on FM discrimination. Previously, we found that bilateral auditory cortex ablation in gerbils blocks discrimination of the direction of FM sounds but not discrimination of pure tones (Ohl et al., in preparation). The present study shows that right auditory cortex lesioned gerbils were clearly impaired in FM directional discrimination learning, whereas, gerbils with leftside lesions were indistinguishable from controls. To our knowledge, this is the first study in animals showing that the right auditory cortex plays a dominant role in discrimination of direction of frequency modulations. Although the lesion technique provides a powerful analytic tool for examining interrelationships between brain structures and functions, limitations of the method must be considered [4,7]. Especially, in learning studies, the results of brain lesions require careful interpretation. We have to consider that the learning and memory loss resulting from brain damage may be confounded by other deficits. Thus lesion-induced changes in behavioral performance may be due to disturbances in motor function, sensory capacities, sensorimotor integration, attention, motivation and emotion, rather than impairment of information acquisition, storage and/or retrieval. As shown by our previous pure tone discrimination study, bilateral auditory cortex lesion in gerbils was not followed by a hearing loss. Also, our earlier results as well as the present data (intertrial crossings; footshock sensitivity do not suggest that motor or sensory functions and motivation or emotion are substantially affected by the lesion. Furthermore, since no lesion effects or response latencies were observed, it seems to be unlikely that the attention level was altered. Thus, our results favour the interpretation that auditory learning and/or memory may be disturbed by right auditory cortex lesion. It remains to be clarified, however, whether acquisition, storage, or retrieval are specifically affected by the lesion. Moreover, since we found lesion effects on both CR and FM (Table 1), it is not clear whether the right auditory cortex may be more critical for mediating the active go response or the passive no-go response. In a go/no go procedure as used in our experiments, it is difficult to explain altered behavior as an alteration of the different response tendencies or as changing of discrimination ability. This question could be studied by using a two-alternative forced-choice procedure. Nevertheless, the present results show that right auditory cortex lesion in gerbils is followed by an impairment of discrimination of direction in frequency-modulated tones. Since frequency modulation is an essential component of prosodic information, our results resemble the right hemisphere specialization for speech prosody found in humans. It must be considered, however, that – compared to specialized functions of the ‘dominant’ left hemisphere (LH) – abilities unique to the ‘minor’ right hemisphere (RH) are much less clear. Lesion studies have not yet unequivocally demonstrated brain lateralization during the recognition of speech prosody. It may be possible that, rather than being
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lateralized to a right hemisphere in a fashion analogous to semantic information, prosodic processes are made up of multiple functions depending on systems distributed in both cerebral hemispheres [17,19]. A number of studies, showing a LH dominance for verbal stimuli but a RH dominance for non-verbal sounds, suggest that hemispheric asymmetry is related to the linguistic relevance of acoustic signals, rather than their physical characteristics (e.g. [12]). In other studies, however, it was found that acoustic signals that change rapidly in time (30-ms 350 Hz ascending or descending frequency glides; consonantvowel syllables incorporating 40-ms formant transitions) seem to be preferentially processed by the LH, regardless whether the sound has a linguistic relevance or not [8,15]. These data suggest that the LH specialization for speech perception and the RH advantage for other sound characteristics, e.g. prosody, appears to reflect hemispheric differences in processing of rapidly changing acoustic signals. It seems to be likely that this different hemispheric processing is based on fundamental brain mechanisms which can be investigated in human as well as in animal research [3,18]. The present animal method, showing that right auditory cortex lesion in gerbils impairs directional discrimination of FM stimuli of relatively long duration (250 ms), may be a useful approach to study specializations of the right hemisphere, e.g. prosody. It could be used for further investigations trying to elucidate basic brain processes underlying lateralized perception of complex acoustic signals. The skilful technical assistance of Lydia Lo¨w, Ute Lerke, Janet Thunert and Elke Muller is gratefully acknowledged. Supported by DFG (We 2104/2-1). [1] Ehret, G., Left hemisphere advantage in the mouse brain for recognizing ultrasonic communication calls, Nature, 325 (1987) 249–251. [2] Elliott, D.N. and Trahiotis, C., Cortical lesions and auditory discrimination, Psychol. Bull., 77 (1972) 198–222. [3] Fitch, R.H., Miller, S. and Tallal, P., Neurobiology of speech perception, Annu. Rev. Neurosci., 20 (1997) 331–353. [4] Grobstein, P., Strategies for analyzing complex organization in the nervous system: I. Lesion experiments. In E.L. Schwarz (Ed.), Computational Neuroscience, MIT Press, Cambridge, MA, 1990, pp. 19-37. [5] Heffner, H.E. and Heffner, R.S., Temporal lobe lesions and perception of species-specific vocalizations by macaques, Science, 226 (1984) 75–76.
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