**8. Pre-attentive processing and lateralization of sound duration changes**

The finding indicated that the prominent response to both sounds elicited MMN peaking at 128 to 212 ms from stimulus onset. The grand-averaged ERPs showed that the MMN mean amplitude of both sounds was statistically significant (*t*-test). The paired sample *t*-test revealed a significant difference between conditions (*t* (10) = 73.00; *p* < 0.0001) showing that both sounds equally elicited a MMN. The magnitude of the acoustic difference between the stimulus pairs was reflected by the MMN amplitude, showing larger MMN amplitudes in long sound compared to the short one. The difference in MMN latencies to both sounds might reflect differential processing of the human auditory cortex. The delay in the MMN to the long sound might reflect additional time required to process sound perception. This processing apparently involves activation of a memory trace, or cell assembly, which possibly represents and the processes the sounds.

Estimated source localization of the average MMN responses evoked by both sounds was clearly identified. The current source density values in the time frame 128-212 ms poststimulus were calculated with LORETA. Stronger activation for long sound was found at 212 ms in the left middle temporal gyrus (MTG) (-59, -32, 1; *t*-value, 1.81), while the short sound most strongly activated at 128 ms in the left superior temporal gyrus (STG) (-59, -39, 8; *t*-value, 1.03) (see Figure 1). Analysis of the MMN responses indicated left-hemispheric laterality in both sound durations (*F* (3,30) = 47.02; *p* < 0.0001). The source analysis indicated strongest MMN response tentatively originating in the left hemisphere and possibly involving the perisylvian area in both sounds, with a more superior distribution for the long sound and a more medial distribution for the short one.

Pre-Attentive Processing of Sound Duration Changes:

have a frequency-dependant tonotopy.

Low Resolution Brain Electromagnetic Tomography Study 231

As it was well established that the MMN amplitude indexes the change detection accuracy (Näätänen, 1999), the MMN to short sound was significantly smaller than those for the long one. The source analysis for the long sound revealed that the source for long sound was located significantly more superior than for short sound in the left hemisphere. In addition, the estimated source strength was not difference between long and short sounds. It is thus the source location rather than its signal strength that might be a primary reason for the reduced responses for short with long sounds. These results may be comparable to those of a previous report by Tiitinen *et al.* (1993) indicating that the MMN sources as well as N100m

Additionally, source analysis suggested MMN sources to be in the vicinity of the left perisylvian area with a more medial distribution for the long deviant and more superior distribution for the short one. It may be that these similar topographies of the neurophysiological brain response do not reflect differential cortical distributions of the underlying neuronal assemblies. The finding of a significantly left-lateralized electric MMN in the present study supports to the previous study indicating a particularly strong asymmetry between the activated neuronal generators in the two hemispheres. There are two possible interpretations for this laterality. First, the functional information tied to the sound no matter of the type of the sounds underlies this laterality. As a second possibility, it may be that it is the functional information related to the stimulus contrasts that is crucial for the strong involvement of left hemispheric processes. Therefore, the MMN response topography and latency in the present study may reveal cortical distribution and activity dynamics of these memory traces. One possible explanation of this hemispheric discrepancy in the MMN effect is that the temporal window of integration (Näätänen and Winkler, 1999; Sussman *et al.,* 1999) differs between two hemispheres. The left hemisphere is suggested to be more sensitive than the right hemisphere to high-frequency temporal patterns of sounds including the stimulus duration. In fact, the perceptual right-ear advantage, regarded as an index of the left hemisphere dominance, can be observed for high-frequency sounds and this advantage is reversed for low-frequency sounds. This may relate to the lack of frequency and duration effect in the right hemisphere, since the long and short distinction mainly rests on the difference of the relatively high frequencies for each of the stimuli. Additionally, the sources for the short stimuli were located more posterior and superior in the left hemisphere than in the right hemisphere. The results replicated previous studies (Alho *et al.,* 1998; Rinne *et al.,* 1999; Tervaniemi *et al.,* 1999). For the source strength of the long and short stimuli, no hemispheric difference was observed. It should be also noted that MMN to short and long sounds showed significant left hemisphere dominance. These results might be in accordance with the findings of Mathiak et al. (1999) rather than studies reporting the left lateralized MMN for speech sounds (Näätänen *et al.,* 1992; Tervaniemi *et al.,* 1999). However, the present study used only one single pair of sounds (i.e., long and short) as an exemplar, which imposes certain limitations on generalization of the current results to all other long and short sounds. Studying this issue using different long and short

sounds thus appears to be a fruitful target for further experiments.

The prominent MMN component was elicited and more sensitive to the long sound than the short one. The MMN presumably reflect the early stage of processing of different sound

**9. Conclusion** 

Fig. 1. Graphical representation of the low-resolution electromagnetic tomography (LORETA *t*-statistic comparing the event-related potentials for mismatch negativity (MMN) responses at the time point of the individual peak over Fz for the long sound (A) and short sound (B) activated in the left hemisphere. Red color indicates local maxima of increased electrical activity for both sounds responses in an axial, a saggital and a coronal slice through the reference brain. Blue dots mark the center of significantly increased electric activity.

Fig. 1. Graphical representation of the low-resolution electromagnetic tomography

activity.

(LORETA *t*-statistic comparing the event-related potentials for mismatch negativity (MMN) responses at the time point of the individual peak over Fz for the long sound (A) and short sound (B) activated in the left hemisphere. Red color indicates local maxima of increased electrical activity for both sounds responses in an axial, a saggital and a coronal slice through the reference brain. Blue dots mark the center of significantly increased electric

As it was well established that the MMN amplitude indexes the change detection accuracy (Näätänen, 1999), the MMN to short sound was significantly smaller than those for the long one. The source analysis for the long sound revealed that the source for long sound was located significantly more superior than for short sound in the left hemisphere. In addition, the estimated source strength was not difference between long and short sounds. It is thus the source location rather than its signal strength that might be a primary reason for the reduced responses for short with long sounds. These results may be comparable to those of a previous report by Tiitinen *et al.* (1993) indicating that the MMN sources as well as N100m have a frequency-dependant tonotopy.

Additionally, source analysis suggested MMN sources to be in the vicinity of the left perisylvian area with a more medial distribution for the long deviant and more superior distribution for the short one. It may be that these similar topographies of the neurophysiological brain response do not reflect differential cortical distributions of the underlying neuronal assemblies. The finding of a significantly left-lateralized electric MMN in the present study supports to the previous study indicating a particularly strong asymmetry between the activated neuronal generators in the two hemispheres. There are two possible interpretations for this laterality. First, the functional information tied to the sound no matter of the type of the sounds underlies this laterality. As a second possibility, it may be that it is the functional information related to the stimulus contrasts that is crucial for the strong involvement of left hemispheric processes. Therefore, the MMN response topography and latency in the present study may reveal cortical distribution and activity dynamics of these memory traces. One possible explanation of this hemispheric discrepancy in the MMN effect is that the temporal window of integration (Näätänen and Winkler, 1999; Sussman *et al.,* 1999) differs between two hemispheres. The left hemisphere is suggested to be more sensitive than the right hemisphere to high-frequency temporal patterns of sounds including the stimulus duration. In fact, the perceptual right-ear advantage, regarded as an index of the left hemisphere dominance, can be observed for high-frequency sounds and this advantage is reversed for low-frequency sounds. This may relate to the lack of frequency and duration effect in the right hemisphere, since the long and short distinction mainly rests on the difference of the relatively high frequencies for each of the stimuli. Additionally, the sources for the short stimuli were located more posterior and superior in the left hemisphere than in the right hemisphere. The results replicated previous studies (Alho *et al.,* 1998; Rinne *et al.,* 1999; Tervaniemi *et al.,* 1999). For the source strength of the long and short stimuli, no hemispheric difference was observed. It should be also noted that MMN to short and long sounds showed significant left hemisphere dominance. These results might be in accordance with the findings of Mathiak et al. (1999) rather than studies reporting the left lateralized MMN for speech sounds (Näätänen *et al.,* 1992; Tervaniemi *et al.,* 1999). However, the present study used only one single pair of sounds (i.e., long and short) as an exemplar, which imposes certain limitations on generalization of the current results to all other long and short sounds. Studying this issue using different long and short sounds thus appears to be a fruitful target for further experiments.

#### **9. Conclusion**

The prominent MMN component was elicited and more sensitive to the long sound than the short one. The MMN presumably reflect the early stage of processing of different sound

Pre-Attentive Processing of Sound Duration Changes:

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**12** 

*Romania* 

**White Matter Changes in** 

Anca Hâncu, Irene Răşanu and Gabriela Butoi *County Emergency Clinical Hospital Constanta,* 

**Cerebrovascular Disease: Leukoaraiosis** 

The term 'leukoaraiosis', derived from the Greek 'leuko' meaning white and 'araios' meaning rarefied, was introduced in 1987, as a "neutral term, exact enough to define whitematter changes in the elderly or the demented, general enough that it serves as a description and a label, and demanding enough that it calls for a precise clinical and imaging description accompanied when possible by pathologic correlations" (Hachinski et al., 1987). When the term leukoaraiosis (LA) was introduced, only CT imaging was widely available. Similar appearance is conspicuous, and more florid on T2-weighted magnetic resonance imaging (MRI), particularly on fluid attenuated inversion recovery (FLAIR) images. Leukoaraiosis is currently defined as diffuse, confluent white matter abnormality (low density on CT, hyperintensity on T2-weighted or FLAIR MRI), often with irregular margins, commonly seen in the normal elderly and in association with vascular risk factors such as hypertension, or in context of cognitive impairment. The term was introduced to avoid confusing an imaging appearance with a specific pathology (O'Sullivan, 2008). Leukoaraiosis can be focal, patchy or diffuse area in the white matter and it is located

Leukoaraiosis severity has traditionally been graded by visual scales. Simples scales like that of van Swieten divide the appearances into only two grades of severity; more complex scales like the Fazekas scale discriminates "punctate", "early confluent" and "confluent" white matter lesions, while the Sheltens scale adopts a 0-6 scale in multiple anatomical regions (including periventricular and nonperiventricular white matter lesions - WML; periventricular hyperintensities are further separated into frontal, occipital, and lateral aspects) (O' Sullivan, 2008; Scheltens et al., 1993, as cited by Bohnen et al., 2009). Other rating scales of WML are the Brant-Zawadzki Scale and the Cardiovascular Health Study Scale both of which place relatively more emphasis on periventricular WML (Bohnen et al., 2009). However, even fully quantitative volumetric measurements of leukoaraiosis correlate weakly with cognitive and physical function, suggesting that T2-weighted MRI provides only a rough impression of the severity of the underlying pathology (O' Sullivan, 2008).

T2-weighted imaging is sensitive to liquid, gliosis and the effects of demyelination. FLAIR images are heavily T2-weigtened with cerebrospinal fluid suppression. This makes it

**1. Introduction** 

periventricularly or deeper in the white matter.

