J Huazhong Univ Sci Technol [Med Sci] 33(5):748-753,2013 DOI 10.1007/s11596-013-1191-y J Huazhong Univ Sci Technol [Med Sci] 33(5):2013
748
40 Hz Auditory Steady State Response to Linguistic Features of Stimuli during Auditory Hallucinations* Jun YING (应 俊)1, 2, Zheng YAN (闫 铮)3, Xiao-rong GAO (高小榕)1# 1 Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China 2 Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing 100853, China 3 Institute of Information Engineering & Technology, Huaqiao University, Xiamen 362021, China © Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2013
Summary: The auditory steady state response (ASSR) may reflect activity from different regions of the brain, depending on the modulation frequency used. In general, responses induced by low rates (≤40 Hz) emanate mostly from central structures of the brain, and responses from high rates (≥80 Hz) emanate mostly from the peripheral auditory nerve or brainstem structures. Besides, it was reported that the gamma band ASSR (30–90 Hz) played an important role in working memory, speech understanding and recognition. This paper investigated the 40 Hz ASSR evoked by modulated speech and reversed speech. The speech was Chinese phrase voice, and the noise-like reversed speech was obtained by temporally reversing the speech. Both auditory stimuli were modulated with a frequency of 40 Hz. Ten healthy subjects and 5 patients with hallucination symptom participated in the experiment. Results showed reduction in left auditory cortex response when healthy subjects listened to the reversed speech compared with the speech. In contrast, when the patients who experienced auditory hallucinations listened to the reversed speech, the auditory cortex of left hemispheric responded more actively. The ASSR results were consistent with the behavior results of patients. Therefore, the gamma band ASSR is expected to be helpful for rapid and objective diagnosis of hallucination in clinic. Key words: auditory steady state response; gamma band; speech recognition; auditory hallucination; electroencephalograph
Abnormal auditory steady state response (ASSR) was found from electroencephalography (EEG) and magnetoencephalography (MEG) of schizophrenia patients (SZ)[1]. Classically, ASSR was evoked by repeated clicks or amplitude modulated (AM) tones at a constant and rapid rate[2, 3]. In general, the evoked potential which is phase-locked with the stimuli can be observed after each tone is heard. As such, the ASSR response which is characterized by a significant amount of power at the modulation frequency of the stimuli can be determined by a fast Fourier transform (FFT). ASSR has extensive applications in clinical study, such as testing hearing sensitivity and as a marker of consciousness state during anesthesia. Studies reported that synchronous neural oscillations in the gamma band (30–90 Hz) of EEG played an important role in the process of grouping neurons into cell assemblies both in the local and inter-regional communications of the brain[4]. For this reason, the gamma band is believed to bear a particularly close connection to the cognition and working memory[5–7]. As researchers recognize that the gamma band ASSR is a useful tool for Jun YING, E-mail: [email protected] # Corresponding author, E-mail: [email protected] * This work was supported by the National Natural Science Foundation of China (No. 90820304, 61105123, and 31100714) and National Basic Research Program of China (No. 2011CB933204).
understanding the working memory and speech recognition, in recent years an increasing number of studies have been concentrated on investigating the brain mechanism using gamma band ASSR. A recent study compared the gamma band ASSR induced by speech and reversed speech, in which a significant hemispheric difference was found in the power of ASSR in response to the speech stimuli characterized by their meaningfulness[8]. It was suggested that the difference between the speech and reversed speech stimuli is due to the presence or lack of conceptual meaning, which may contribute to the lateralization effect. In another study, it was found that left hemisphere gamma band ASSR demonstrated sensitivity to linguistic aspects of stimuli, especially the presence and absence of conceptual meaning[9]. It was shown that difference between gamma band ASSR of normal people and patients with SZ could be observed. In an observation of SZ and healthy control (HC) subjects, Mulert found that the current source density of 40 Hz ASSR response was significantly diminished in SZ in comparison to HC in the right superior and middle temporal gyrus[10]. Furthermore, the interhemispheric phase locking in the primary auditory cortices was reduced in SZ compared with HC[11]. As is known, SZ is a mental disorder characterized by a breakdown of thought processes and by poor emotional responsiveness[12]. Therefore, the studies on SZ proved that the
J Huazhong Univ Sci Technol [Med Sci] 33(5):2013
gamma band ASSR was closely associated with perception and cognition. ASSR could be an effective method to investigate the brain rhythm of the patients with SZ. It was observed that gamma band ASSR at 40 Hz was higher than those at other frequencies. Besides, the 40 Hz ASSR had a close connection to the process of cognition[13]. However, most researches focused on the difference of distribution or power of ASSR between patients and healthy subjects. At present, the ASSR during the speech recognition process of SZ with auditory hallucination who had cognitive deficits was not specified. In present study, EEG was used to extract the gamma band ASSR for evaluation of the speech recognition of patients with auditory hallucination and normal healthy subjects. Two issues were addressed. First, were there differences between ASSR to meaningful speech and meaningless sound in brain regions? Second, what were the differences between the two groups under the two kinds of auditory stimulation while the patients had fantasy speech recognition evoked by meaningless sound? To address those two issues, the gamma band ASSRs were analyzed and compared in strength and cerebral distribution. The study found the responses were increased in auditory cortex of temporal lobe and rapidly decreased in parietal. It was expected that dysfunction of neuropathology in hallucinations during speech recognition process led to abnormal ASSR. 1 MATERIALS AND METHODS 1.1 Participants Ten healthy subjects (including 3 females, mean age: 27 years, standard deviation: 3.2 years, range: 20–40 years), and five patients suffering from hallucination for more than a year (including 1 female, mean age: 35 years, standard deviation: 4.7 years, range: 20–45 years) participated in the experiments. The diagnosis of hallucination was made in a consensus meeting of different specialists. All subjects were all right-handed and with nor-
749 mal hearing. According to the declaration of Helsinki, informed consent was obtained from all subjects before the experiments. 1.2 Experimental Paradigm In the experiment, all participants sat in a comfortable armchair in a shielded and quiet room. Stimuli were delivered binaurally through the headphones at an intensity of 65 dB sound pressure level. Experimental stimuli included Chinese speech phrase and same reversed phrase (fig. 1). To control attention, following each sweep, participants were requested to report the speech meaning as behavior results in order to ensure the speech was perceived and understood correctly. Before presented to participants, the stimuli were modulated by a 40 Hz sine wave, with a 100% modulation depth. Both the normal speech and the reversed speech were presented to all participants in the experiment. The speech consisted of 10 common Chinese phrases in woman voice and the time length of the speech was 20 s for every sweep. The reversed speech was produced by playing the speech stream from the end to the beginning, thus discarding semantic information and acoustic cues to speech, and the two kinds of sounds were the same at intensity and spectrum (fig. 2). As a result, the reversed speech could be categorized as meaningless and noise-like sound which was presented with no semantic content. The sounds were controlled by the digital signal processor (DSP) TMS320C5515 (TI. Inc.). And the sounds had been tested and found to be precise enough. The Etymotic Research ER2 insert earphones were selected since it can effectively avoid the electro-magnetic interference. 1.3 EEG Recording Multichannel EEG signals were recorded by 64 channels Synamps2 system (NeuroScan Inc.). The reference channel was at the nasion. And the impedance was kept below 10 kΩ. Data were recorded at a sampling rate of 1000 Hz and then band-pass filtered at 0.05 and 200 Hz.
Fig. 1 The demonstration of experiment paradigm Firstly, Chinese speech was reversed as meaningless sound. Secondly, speech and reversed speech were modulated by 40 Hz sine in amplitude. Then the two sounds were released to subjects separately and ASSR was extracted from EEG for further signal analysis such as topographic maps and parameter analysis.
750
J Huazhong Univ Sci Technol [Med Sci] 33(5):2013
For statistical analysis, a paired one-tailed t-test was used to calculate the significance and a P1. In order to obtain the distribution of cortical signal, all SNRs and RSNR were plotted in brain mapping with functions of the EEGLAB[14].
2.1 Behavior Results The behavior results showed that all healthy subjects perceived the modulated speech and correctly understood, and got no meaning from modulated reversed speech. By contrast, the patients with hallucination could perceive meaningful words not only from the modulated speech but also from the reversed speech stimuli. Unlike the healthy subjects, the patients reported that they could hear whispered speech or human voice while being given the modulated meaningless reversed speech (table 1). Table 1 The behavior results of the patients with hallucination attending to the speech and reversed speech Patient Speech Reversed speech 1 Correct perception Repeated human voice 2
Correct perception
3
Correct perception
4
Correct perception
5
Correct perception
Occasional whispered speech occasionally Continuous human voice Occasional whispered speech Repeated human voice
2.2 Distribution of RSNR The averaged ASSR SNR of two groups with different stimuli was computed and plotted (fig. 3). When the two groups were listening to speech phrase, there was maximal ASSR at the frontal-central and temporal regions with a symmetrical distribution. For the healthy subjects, on the left temporal regions, the ASSR was significantly greater in response to speech than to reversed speech (P
748
40 Hz Auditory Steady State Response to Linguistic Features of Stimuli during Auditory Hallucinations* Jun YING (应 俊)1, 2, Zheng YAN (闫 铮)3, Xiao-rong GAO (高小榕)1# 1 Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China 2 Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing 100853, China 3 Institute of Information Engineering & Technology, Huaqiao University, Xiamen 362021, China © Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2013
Summary: The auditory steady state response (ASSR) may reflect activity from different regions of the brain, depending on the modulation frequency used. In general, responses induced by low rates (≤40 Hz) emanate mostly from central structures of the brain, and responses from high rates (≥80 Hz) emanate mostly from the peripheral auditory nerve or brainstem structures. Besides, it was reported that the gamma band ASSR (30–90 Hz) played an important role in working memory, speech understanding and recognition. This paper investigated the 40 Hz ASSR evoked by modulated speech and reversed speech. The speech was Chinese phrase voice, and the noise-like reversed speech was obtained by temporally reversing the speech. Both auditory stimuli were modulated with a frequency of 40 Hz. Ten healthy subjects and 5 patients with hallucination symptom participated in the experiment. Results showed reduction in left auditory cortex response when healthy subjects listened to the reversed speech compared with the speech. In contrast, when the patients who experienced auditory hallucinations listened to the reversed speech, the auditory cortex of left hemispheric responded more actively. The ASSR results were consistent with the behavior results of patients. Therefore, the gamma band ASSR is expected to be helpful for rapid and objective diagnosis of hallucination in clinic. Key words: auditory steady state response; gamma band; speech recognition; auditory hallucination; electroencephalograph
Abnormal auditory steady state response (ASSR) was found from electroencephalography (EEG) and magnetoencephalography (MEG) of schizophrenia patients (SZ)[1]. Classically, ASSR was evoked by repeated clicks or amplitude modulated (AM) tones at a constant and rapid rate[2, 3]. In general, the evoked potential which is phase-locked with the stimuli can be observed after each tone is heard. As such, the ASSR response which is characterized by a significant amount of power at the modulation frequency of the stimuli can be determined by a fast Fourier transform (FFT). ASSR has extensive applications in clinical study, such as testing hearing sensitivity and as a marker of consciousness state during anesthesia. Studies reported that synchronous neural oscillations in the gamma band (30–90 Hz) of EEG played an important role in the process of grouping neurons into cell assemblies both in the local and inter-regional communications of the brain[4]. For this reason, the gamma band is believed to bear a particularly close connection to the cognition and working memory[5–7]. As researchers recognize that the gamma band ASSR is a useful tool for Jun YING, E-mail: [email protected] # Corresponding author, E-mail: [email protected] * This work was supported by the National Natural Science Foundation of China (No. 90820304, 61105123, and 31100714) and National Basic Research Program of China (No. 2011CB933204).
understanding the working memory and speech recognition, in recent years an increasing number of studies have been concentrated on investigating the brain mechanism using gamma band ASSR. A recent study compared the gamma band ASSR induced by speech and reversed speech, in which a significant hemispheric difference was found in the power of ASSR in response to the speech stimuli characterized by their meaningfulness[8]. It was suggested that the difference between the speech and reversed speech stimuli is due to the presence or lack of conceptual meaning, which may contribute to the lateralization effect. In another study, it was found that left hemisphere gamma band ASSR demonstrated sensitivity to linguistic aspects of stimuli, especially the presence and absence of conceptual meaning[9]. It was shown that difference between gamma band ASSR of normal people and patients with SZ could be observed. In an observation of SZ and healthy control (HC) subjects, Mulert found that the current source density of 40 Hz ASSR response was significantly diminished in SZ in comparison to HC in the right superior and middle temporal gyrus[10]. Furthermore, the interhemispheric phase locking in the primary auditory cortices was reduced in SZ compared with HC[11]. As is known, SZ is a mental disorder characterized by a breakdown of thought processes and by poor emotional responsiveness[12]. Therefore, the studies on SZ proved that the
J Huazhong Univ Sci Technol [Med Sci] 33(5):2013
gamma band ASSR was closely associated with perception and cognition. ASSR could be an effective method to investigate the brain rhythm of the patients with SZ. It was observed that gamma band ASSR at 40 Hz was higher than those at other frequencies. Besides, the 40 Hz ASSR had a close connection to the process of cognition[13]. However, most researches focused on the difference of distribution or power of ASSR between patients and healthy subjects. At present, the ASSR during the speech recognition process of SZ with auditory hallucination who had cognitive deficits was not specified. In present study, EEG was used to extract the gamma band ASSR for evaluation of the speech recognition of patients with auditory hallucination and normal healthy subjects. Two issues were addressed. First, were there differences between ASSR to meaningful speech and meaningless sound in brain regions? Second, what were the differences between the two groups under the two kinds of auditory stimulation while the patients had fantasy speech recognition evoked by meaningless sound? To address those two issues, the gamma band ASSRs were analyzed and compared in strength and cerebral distribution. The study found the responses were increased in auditory cortex of temporal lobe and rapidly decreased in parietal. It was expected that dysfunction of neuropathology in hallucinations during speech recognition process led to abnormal ASSR. 1 MATERIALS AND METHODS 1.1 Participants Ten healthy subjects (including 3 females, mean age: 27 years, standard deviation: 3.2 years, range: 20–40 years), and five patients suffering from hallucination for more than a year (including 1 female, mean age: 35 years, standard deviation: 4.7 years, range: 20–45 years) participated in the experiments. The diagnosis of hallucination was made in a consensus meeting of different specialists. All subjects were all right-handed and with nor-
749 mal hearing. According to the declaration of Helsinki, informed consent was obtained from all subjects before the experiments. 1.2 Experimental Paradigm In the experiment, all participants sat in a comfortable armchair in a shielded and quiet room. Stimuli were delivered binaurally through the headphones at an intensity of 65 dB sound pressure level. Experimental stimuli included Chinese speech phrase and same reversed phrase (fig. 1). To control attention, following each sweep, participants were requested to report the speech meaning as behavior results in order to ensure the speech was perceived and understood correctly. Before presented to participants, the stimuli were modulated by a 40 Hz sine wave, with a 100% modulation depth. Both the normal speech and the reversed speech were presented to all participants in the experiment. The speech consisted of 10 common Chinese phrases in woman voice and the time length of the speech was 20 s for every sweep. The reversed speech was produced by playing the speech stream from the end to the beginning, thus discarding semantic information and acoustic cues to speech, and the two kinds of sounds were the same at intensity and spectrum (fig. 2). As a result, the reversed speech could be categorized as meaningless and noise-like sound which was presented with no semantic content. The sounds were controlled by the digital signal processor (DSP) TMS320C5515 (TI. Inc.). And the sounds had been tested and found to be precise enough. The Etymotic Research ER2 insert earphones were selected since it can effectively avoid the electro-magnetic interference. 1.3 EEG Recording Multichannel EEG signals were recorded by 64 channels Synamps2 system (NeuroScan Inc.). The reference channel was at the nasion. And the impedance was kept below 10 kΩ. Data were recorded at a sampling rate of 1000 Hz and then band-pass filtered at 0.05 and 200 Hz.
Fig. 1 The demonstration of experiment paradigm Firstly, Chinese speech was reversed as meaningless sound. Secondly, speech and reversed speech were modulated by 40 Hz sine in amplitude. Then the two sounds were released to subjects separately and ASSR was extracted from EEG for further signal analysis such as topographic maps and parameter analysis.
750
J Huazhong Univ Sci Technol [Med Sci] 33(5):2013
For statistical analysis, a paired one-tailed t-test was used to calculate the significance and a P1. In order to obtain the distribution of cortical signal, all SNRs and RSNR were plotted in brain mapping with functions of the EEGLAB[14].
2.1 Behavior Results The behavior results showed that all healthy subjects perceived the modulated speech and correctly understood, and got no meaning from modulated reversed speech. By contrast, the patients with hallucination could perceive meaningful words not only from the modulated speech but also from the reversed speech stimuli. Unlike the healthy subjects, the patients reported that they could hear whispered speech or human voice while being given the modulated meaningless reversed speech (table 1). Table 1 The behavior results of the patients with hallucination attending to the speech and reversed speech Patient Speech Reversed speech 1 Correct perception Repeated human voice 2
Correct perception
3
Correct perception
4
Correct perception
5
Correct perception
Occasional whispered speech occasionally Continuous human voice Occasional whispered speech Repeated human voice
2.2 Distribution of RSNR The averaged ASSR SNR of two groups with different stimuli was computed and plotted (fig. 3). When the two groups were listening to speech phrase, there was maximal ASSR at the frontal-central and temporal regions with a symmetrical distribution. For the healthy subjects, on the left temporal regions, the ASSR was significantly greater in response to speech than to reversed speech (P
