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In both the aged and the young, the cortical activation elicited by the speech stimuli was of a larger amplitude than that elicited by the sinusoidal stimuli. Thus, aging does not seem to deteriorate the early stages of neural processing with respect to how the brain differentiates between stimuli of varying spectral complexity. Deteriorations in speech processing in the aged subjects, at the level of comprehension (Divenyi et al., 2005; Murphy et al., 2006; Pichora-Fuller and Souza, 2003; Bertoli et al., 2005; Schneider et al., 2005), could therefore be due to alterations in higher-level cortical functions. The alterations in response characteristics as a function of aging have been explained by, for example, aging resulting in deteriorated auditory attentive skills (Gaeta et al., 2003; Bennett et al., 2004). However, in the present study, attentional engagement to the stimuli enhanced the response amplitude similarly in both subject groups and thus, no support for diminished attentive functioning during auditory processing in the aged was gained. Furthermore, the percentage of behaviorally correctly detected sinusoidal stimuli in the present study was lower for the aged than for the young subjects, whereas the speech sounds were detected equally accurately in both subject groups. However, as the current observations are contrary to the results of Geal-Dor et al. (2006), further research into this issue is clearly warranted. 4.2. The processing of speech and non-speech stimuli In the present study, speech stimuli elicited a transient brain response significantly larger in amplitude than that elicited by sinusoids. This was observed in both the young and aged subjects. The finding parallels the results of previous N1(m) studies (Tiitinen et al., 1999; Kirveskari et al., 2006), and suggests that the transient brain response is highly sensitive to spectral complexity. In contrast to previous results showing right-hemispheric dominance for the transient brain response to sinusoidal stimuli (Mäkinen et al., 2004; Tiitinen et al., 2005) the responses were of similar amplitude in the two hemispheres in both subject groups. Further, in contrast to N1m studies (Gootjes et al., 1999; Kirveskari et al., 2006) suggesting that speech sounds elicit more prominent activation in the left than in the right hemisphere among right-handed subjects, the solely right-handed subject groups of the present study demonstrated no amplitude differences between the two hemispheres. The results of the present study show that even during relatively early stages of cortical processing of auditory information (i.e., when auditory cortex is initially activated by the stimuli), speech sounds elicit more prominent responses than sinusoids, even when voluntary attention is not focused on the stimuli. This may imply that early processing of the spectrotemporal structure of an auditory stimulus does not require attentive engagement. Consistent with previous studies (Mäkinen et al., 2004; Tiitinen et al., 2005) the amplitude of the transient brain response was enhanced when the subjects attended to the stimuli. In the young subjects, attentive engagement enhanced the response amplitude to sinusoids notably more than expected based on previous results and when compared to the attention effect in the aged subject group. This finding is somewhat surprising as it cannot be explained by learning effects due to the counterbalanced presentation order of the stimuli. 4.3. Prospects of the transient brain response In previous research, the results on the effects of aging on cortical sound processing have remained inconsistent, presumably due to methodological variations. Thus, non-invasive research might benefit from a more unified approach in studies of aging-related effects in brain function. Complementing ABRs and long-latency responses such as the P1–N1–P2 complex, the transient L.E. Matilainen et al. / Clinical Neurophysiology 121 (2010) 902–911 909 brain response addressed here might provide a valuable tool for this research. The current findings indicate that the use of a longduration, rising-intensity speech stimulus (as opposed to clicks or sinusoids of a duration in the range of 1–200 ms) could be used in future studies. Results show that for any particular transient auditory stimulus different sets of neurons respond to the stimulus onset and to its spectral structure (Wang et al., 2005), and the N1(m) response includes contributions from both types of neurons (Gutschalk et al., 2004). Importantly, because of the slow rise time of the stimulus, the transient brain response under current investigation is arguably a reflection of the activity of cells responding selectively to stimulus structure and is free of the ‘‘contamination” caused by stimulus onsets (which are part of the ABR and N1 responses). It might therefore offer a unique method for investigating stimulus-selective activation in cortex. In the current experimental design, the transient brain response could be reliably extracted in after only a few minutes of recording time, and was directly observable without offline analyses. This contrasts the mismatch negativity (MMN) response (Tiitinen et al., 1994) which has been offered as an objective measure of various clinical conditions (e.g., Näätänen and Escera 2000). The MMN is observed in the oddball paradigm in which subjects are exposed to a train of frequently occurring standard stimuli interspersed with occasional mismatching deviant stimuli. Thus, registering the MMN requires long recording times, relies on the use of offline subtraction procedures, and leads to a poor signal-to-noise ratio (usually not allowing conclusions to be made on the single-subject level). Taken together, these seriously limit the usefulness of this response in, for example, studies on clinical subject groups, and criticism towards the use of the MMN in clinical studies seems to be accumulating (e.g., Picton et al., 2000; Tremblay and Kraus, 2002; Sharma et al., 2006; May and Tiitinen, 2010). Further, the MMN recordings are carried out in the passive recording condition, leading to difficulties in linking the measured brain activity to behaviorally indexed sound detection. One is tempted to note that the transient brain response elicited by rising-intensity sounds bypasses all the above problems associated with the MMN and therefore offers a viable and interesting option for future basic and clinical investigations of auditory processing. In this study, we had no opportunity to measure the hearing thresholds of the subjects, and only an informal assessment of hearing ability was conducted. This poses a problem for the interpretation of the observed latency effect as an age-related elevation of hearing threshold has been demonstrated (Brant and Fozard, 1990; Lee et al., 2005). However, in a study by Harkrider et al. (2005), only minimally (0.8 dB) higher 2000 Hz pure-tone hearing thresholds were observed among the aged (average age 55.2 years) compared to the young subjects (average age 27 years). Thus, although the current subject population closely resembles that of the Harkrider et al. (2005) study, an elevation of the hearing threshold as a function of age can be expected and could be reflected in the latency of the transient brain response. The degree of dependence between the brain response latency and the individual hearing threshold obviously needs further investigation. Finally, in the present study, the age range of the aged subjects was quite wide and, thus, it could be valuable to examine the effects of aging indicated by more restricted sets of age groups. As normal aging results in atrophy changes in the brain, carrying out computer tomography (CT) or magnetic resonance imaging (MRI) scans could provide valuable information of the possible connection between the degree and location of cortical atrophy and the transient brain response. The experimental procedure used here was designed to be suitable for studying clinical subject groups (supine position, relatively short recording time, no requirements for verbal communication, no motor responses in the passive condition). Thus, the applicability of the transient brain
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