Approach to impaired corollary discharge in patients with schizophrenia: An analysis of self-induced somatosensory evoked potentials and fields.

Background: Difficulty in distinguishing between self-generated actions and those generated by others is a core feature of schizophrenia. This is thought to be underpinned by the failure of corollary discharge. However, few studies have investigated these events using somatosensory evoked potentials (SEPs) and somatosensory evoked magnetic fields (SEFs). Methods: The study included 15 right-handed patients with schizophrenia and 16 healthy controls. SEP and SEF were elicited by electrical stimuli to the left median nerve at intervals of 1-3 s. In the external condition, stimuli were externally induced by a machine. In the self-condition, stimuli were induced by tapping the participants' own right index finger. Peak amplitude at C4' in SEP and root mean square in 10 channels on the right primary somatosensory area in SEF were analyzed. Results: Although there was a significant main effect of condition at N20m, and a significant main effect of condition and group at P30m, no significant interactions of condition and group were found in either N20m or P30m. The post-hoc Wilcoxon signed-rank test revealed that the peak value of P30m in the external condition was significantly higher than that in the self-condition in the healthy control group only. In addition, there was a significant positive correlation between the peak value of P30m in the self-condition and a positive symptom score. Conclusion: In the current study, we did not find abnormalities of corollary discharge in primary sensory areas in patients with schizophrenia. Further investigations with more cases may reveal the possibility of corollary discharge disturbance in the primary sensory cortex.

Comprehension of degraded speech sounds with m-sequence modulation: an fMRI study.

In a recent electroencephalography (EEG) study (Takeichi et al., 2007a), we developed a new technique for assessing speech comprehension using speech degraded by m-sequence modulation and found a correlation peak with a 400-ms delay. This peak depended on the comprehensibility of the modulated speech sounds. Here we report the results of a functional magnetic resonance imaging (fMRI) experiment comparable to our previous EEG experiment. We examined brain areas related to verbal comprehension of the modulated speech sound to examine which neural system processes this modulated speech. A non-integer, alternating-block factorial design was used with 23 Japanese-speaking participants, with time reversal and m-sequence modulation as factors. A main effect of time reversal was found in the left temporal cortex along the superior temporal sulcus (BA21 and BA39), left precentral gyrus (BA6) and right inferior temporal gyrus (BA21). A main effect of modulation was found in the left postcentral gyrus (BA43) and the right medial frontal gyri (BA6) as an increase by modulation and in the left temporal cortex (BA21, 39), parahippocampal gyrus (BA34), posterior cingulate (BA23), caudate and thalamus and right superior temporal gyrus (BA38) as a decrease by modulation. An interaction effect associated specifically with non-modulated speech was found in the left frontal gyrus (BA47), left occipital cortex in the cuneus (BA18), left precuneus (BA7, 31), right precuneus (BA31) and right thalamus (forward>reverse). The other interaction effect associated specifically with modulation of speech sound was found in the inferior frontal gyrus in the opercular area (BA44) (forward>reverse). Estimated scalp projection of the component correlation function (Cao et al., 2002) for the corresponding EEG data (Takeichi et al., 2007a, showed leftward dominance. Hence, activities in the superior temporal sulcus (BA21 and BA39), which are commonly observed for speech processing, as well as left precentral gyrus (BA6) and left inferior frontal gyrus in the opercular area (BA44) is suggested to contribute to the comprehension-related EEG signal.

Effects of feature and spatial attention on visual change detection.

In event-related brain potential studies using a visual S1-S2 matching task, stimulus changes elicit change-related positivity, which reflects the detection of visual changes. To investigate the effects of attention on change detection, we tested the elicitation of change-related positivity in response to changes in color and spatial frequency under three attention conditions: (i) changes in an unattended feature at an attended location, (ii) in an attended feature at an unattended location, and (iii) in an unattended feature at an unattended location. The results suggest that stimulus changes can be detected even when both feature and spatial attention are withdrawn, but change detection can also be inhibited, which might be because of biased-competition determined by the combination of feature and spatial attention conditions.

Attention switching function of memory-comparison-based change detection system in the visual modality.

To elucidate the attention switching function of a memory-comparison-based change detection system in the visual modality, the effects of task-irrelevant infrequent stimulus-size decrements that engaged memory-comparison-based change detection as well as stimulus-size increments that engaged memory-comparison-based change detection and refractoriness-based rareness detection on behavioral and event-related brain potential (ERP) measures were assessed using the distraction paradigm. Both size increments and size decrements caused distraction in forced-choice task performance, which was mirrored by a posterior negativity (peaking at around 240-260 ms, posterior N2) and a broad positivity (420-460 ms, P3a) that reflected attentional capture. Preceding these effects, size increments elicited a posterior negativity (120-140 ms, change-related negativity), while size decrements elicited a posterior positivity (140-160 ms, change-related positivity) and an anterior positivity (160-180 ms, frontal positivity). Taken together, these results indicate an attention switching function of a memory-comparison-based change detection system in the visual modality, which is most probably indexed by change-related positivity.

Neural responses to feedback information produced by self-generated or other-generated decision-making and their impairment in schizophrenia.

Several studies of self-monitoring dysfunction in schizophrenia have focused on the sense of agency to motor action using behavioral and psychophysiological techniques. So far, no study has ever tried to investigate whether the sense of agency or causal attribution for external events produced by self-generated decision-making is abnormal in schizophrenia. The purpose of this study was to investigate neural responses to feedback information produced by self-generated or other-generated decision-making in a multiplayer gambling task using even-related potentials and electroencephalogram synchronization. We found that the late positive component and theta/alpha synchronization were increased in response to feedback information in the self-decision condition in normal controls, but that these responses were significantly decreased in patients with schizophrenia. These neural activities thus reflect the self-reference effect that affects the cognitive appraisal of external events following decision-making and their impairment in schizophrenia.

Independent processing of visual stimulus changes in ventral and dorsal stream features indexed by an early positive difference in event-related brain potentials.

In event-related brain potential (ERP) studies of brain activity using a visual S1-S2 matching task, change stimuli elicit a posterior positive component with a latency of 100-200 ms. To elucidate the hierarchical organization of the processing of a visual stimulus change based on multiple stimulus features, ERPs were recorded in 12 participants performing an S1-S2 matching task with stimuli defined by color (mediated by the ventral stream) and motion direction (mediated by the dorsal stream). Each trial consisted of two sequentially presented stimuli (S1-S2), where S2 was either (1) the same as S1 (i.e., no change), (2) different from S1 in color only (color change), (3) different in motion direction only (motion direction change), or (4) different in both color and motion direction (color-motion direction change). These trials were presented in random order with equal probability, and the participants were asked to respond to one of these trials in separate blocks. Relative to the no-change stimulus, the three types of change stimuli elicited posterior positivities. The scalp-topography of change positivities differed according to the feature changed. In addition, the amplitude and scalp-topography of change positivities in response to a conjunction change were the respective sums of those in response to changes in the corresponding single features. These results suggest that the change detection system reflected by the change positivity is separate for each feature dimension, and these operate independently.

An ERP study of visual change detection: effects of magnitude of spatial frequency changes on the change-related posterior positivity.

In event-related brain potential (ERP) studies using a visual S1-S2 matching task, change stimuli elicit a posterior positivity at around 100-200 ms. In the present study, we investigated the effects of magnitude of spatial frequency changes on change-related positivity. Each trial consisted of two sequentially presented stimuli (S1-S2), where S2 was either (1) the same as S1 (i.e., NO-change, p=.40), (2) different from S1 in spatial frequency only (SF-change, .40), (3) different in orientation only (OR-change, .10), or (4) different in both spatial frequency and orientation (BOTH-change, .10). Further, three magnitude conditions (Large, Medium, and Small) were used to examine the effect of the magnitude of the spatial frequency change. Participant's (N=12) task was to respond to S2 with a change in orientation (from vertical to horizontal, or from horizontal to vertical) regardless of the spatial frequency of the stimulus. Changes in the spatial frequency elicited change-related positivity at a latency range of about 120-180 ms, which was followed by a central negativity (N270) and a late positive component (LPC). The amplitude of the change-related positivity tends to be enhanced as the magnitude of the change is increased. These results support the notion that the change-related positivity reflects memory-based change detection in the human visual system.

Discrepancy between feedback negativity and subjective evaluation in gambling.

Feedback negativity is a negative event-related potential elicited by feedback indicating incorrect performance or monetary loss. It is unclear whether this negativity is elicited by neutral feedback (e.g. a draw in gambling) or is affected by the subjective rating of punishment. To investigate these issues, we performed a modified and computerized game of 'rock-paper-scissors' as a gambling task and measured feedback negativity in response to feedback indicating the outcome, which was accompanied by a monetary reward. The data demonstrated that feedback negativity was elicited not only by a monetary loss but also by an even outcome and was independent of the magnitude of monetary loss. Our results suggest feedback negativity is not always specific to both monetary loss and subjective rating of punishment.

Neural correlates of pre-attentive and attentive processing of visual changes.

To identify electrophysiological correlates of pre-attentive and attentive processing of visual changes, we compared event-related brain potentials in response to color changes at attended and unattended spatial locations using a visual S1-S2 matching task. The results showed that compared to no change, change stimuli elicited occipito-temporal positivity at around 100-160 ms (change-related positivity) and subsequent central negativity at around 220-300 ms (N270). Change-related positivity was observed in response to changes at both attended and unattended locations, while N270 was observed only when attention was directed to the location of the changes. These results suggest that change-related positivity reflects the pre-attentive processing of visual changes and N270 reflects the attentive processing of visual changes in the human brain.

Attention that covers letters is necessary for the left-lateralization of an early print-tuned ERP in Japanese hiragana.

Extensive experience with reading develops expertise in acquiring information from print, and this is reflected in specific enhancement of the left-lateralized N170 component in event-related potentials. The N170 is generally considered to reflect visual/orthographic processing; while modulations of its left-lateralization related to phonological processes have also been indicated. However, in our previous study, N170-like response to Hiragana strings lacked left-lateralization when the stimuli were completely task-irrelevant in rapid-presentation sequences [Okumura et al. (2014). Early print-tuned ERP response with minimal involvement of linguistic processing in Japanese Hiragana strings. Neuroreport 25, 410-414]. This suggests that, despite the highly transparent character-to-syllable correspondence, the phonological mapping of Hiragana strings requires some kind of attention toward print. To verify this notion, the present study examined ERPs under the same experimental condition as in the previous study, except that the task required attention to a stimulus attribute (i.e., color). As a result, Hiragana words and nonwords elicited left-lateralized negative deflection in the occipito-temporal region during 130-170ms post-stimulus in comparison to symbol strings, but only when the print had a narrow intercharacter spacing. Moreover, we observed the enhancement of very early occipital ERP in response to words during 70-100ms. The present results suggest that visual attention plays a role in early print processing, which may contribute to our understanding of the mechanisms that underlie expert as well as impaired reading.

Early print-tuned ERP response with minimal involvement of linguistic processing in Japanese Hiragana strings.

The act of reading leads to the development of specific neural responses for print, the most frequently reported of which is the left occipitotemporal N170 component of event-related potentials. However, it remains unclear whether this electrophysiological response solely involves print-tuned neural activities. The present study examined an early print-tuned event-related potential response with minimal involvement of linguistic processing in a nonalphabetic language. Japanese Hiragana words, nonwords, and alphanumeric symbol strings were presented rapidly and the task was to detect the change in color of a fixation cross to restrict linguistic processing. As a result, Hiragana words and nonwords elicited a larger posterior N1 than alphanumeric symbol strings bilaterally, irrespective of intercharacter spacing. The fact that this N1 was enhanced specifically for rapidly presented Hiragana strings suggests the existence of print-tuned neural processes that are relatively independent of the influence of linguistic processing.

Individuals with Asperger's disorder exhibit difficulty in switching attention from a local level to a global level.

The purpose of the present study was to determine whether individuals with Asperger's disorder exhibit difficulty in switching attention from a local level to a global level. Eleven participants with Asperger's disorder and 11 age- and gender-matched healthy controls performed a level-repetition switching task using Navon-type hierarchical stimuli. In both groups, level-repetition was beneficial at both levels. Furthermore, individuals with Asperger's disorder exhibited difficulty in switching attention from a local level to a global level compared to control individuals. These findings suggested that there is a problem with the inhibitory mechanism that influences the output of enhanced local visual processing in Asperger's disorder.

Working memory capacity affects the interference control of distractors at auditory gating.

It is important to understand the role of individual differences in working memory capacity (WMC). We investigated the relation between differences in WMC and N1 in event-related brain potentials as a measure of early selective attention for an auditory distractor in three-stimulus oddball tasks that required minimum memory. A high-WMC group (n=13) showed a smaller N1 in response to a distractor and target than did a low-WMC group (n=13) in the novel condition with high distraction. However, in the simple condition with low distraction, there was no difference in N1 between the groups. For all participants (n=52), the correlation between the scores for WMC and N1 peak amplitude was strong for distractors in the novel condition, whereas there was no relation in the simple condition. These results suggest that WMC can predict the interference control for a salient distractor at auditory gating even during a selective attention task.

Discrepancy of neural response between exogenous and endogenous task switching: an event-related potentials study.

Task switching is a well-known cognitive paradigm to explore task-set reconfiguration processes such as rule shifting. In particular, endogenous task switching is thought to differ qualitatively from stimulus-triggered exogenous task switching. However, no previous study has examined the neural substrate of endogenous task switching. The purpose of the present study is to explore the differences between event-related potential responses to exogenous and endogenous rule switching at cue stimulus. We modified two patterns of cued switching tasks: exogenous (bottom-up) rule switching and endogenous (top-down) rule switching. In each task cue stimulus was configured to induce switching or maintaining rule. In exogenous switching tasks, late positive deflection was larger in the switch rule condition than in the maintain rule condition. However, in endogenous switching tasks late positive deflection was unexpectedly larger in the maintain-rule condition than in the switch-rule condition. These results indicate that exogenous rule switching is explicit stimulus-driven processes, whereas endogenous rule switching is implicitly parallel processes independent of external stimulus.

Role of the prefrontal cortex in the cognitive control of reaching movements: near-infrared spectroscopy study.

To elucidate the role of the prefrontal cortex in cognitive control of reaching movements, by multichannel near-infrared spectroscopy we examine changes in oxygenated hemoglobin (oxy-Hb) as an indicator of changes in regional cerebral blood flow in the bilateral dorsolateral (DLPFC), ventrolateral prefrontal cortex (VLPFC), and frontopolar cortex (FPC) during a reaching task with normal visual feedback (a consistent task) and a reaching task with flipped horizontal visual feedback (an inconsistent task). Subjects first perform 12 trials of the consistent task, and then perform six blocks of the inconsistent task, each of which consists of six trials. During the consistent task, oxy-Hb is increased only in the right VLPFC. During the first block of the inconsistent task, increases in oxy-Hb are observed in the bilateral DLPFC and the right VLPFC, whereas the increased oxy-Hb was gradually reduced as the block proceeded, which was accompanied by an improvement in the task performance. Eventually, there were no differences in the degree of change in oxy-Hb between the consistent and inconsistent tasks in the DLPFC and VLPFC. These findings suggest that the DLPFC is engaged in higher order cognitive control, while the right VLPFC is engaged in both higher and lower order cognitive controls.

Underlying mechanisms of the P3a task-difficulty effect.

In three-stimulus oddball studies, even typical deviant stimuli elicited a large P3a event-related brain potential (ERP) when target/standard discrimination was difficult. To investigate the underlying mechanisms, the effects of task difficulty on early deviant-related ERPs were assessed. Four visual stimuli defined by an orthogonal combination of task-relevant size (nontarget 80%, target 20%) and task-irrelevant luminance (standard 80%, deviant 20%) were presented randomly, where two task difficulties (easy, difficult) were defined by target/nontarget discriminability. An increase in task difficulty enhanced P3a as well as a posterior negativity (change-related negativity) and an anterior positivity (frontal positivity) elicited by deviant nontarget stimuli. These results suggest that attentional modulation of refractoriness-based rareness detection and an attention-triggering process underlie the P3a task-difficulty effect.

Involvement of memory-comparison-based change detection in visual distraction.

The involvement of memory-comparison-based change detection in visual distraction was elucidated. Not only luminance increments that engaged memory-comparison-based change detection and refractoriness-based rareness detection but also luminance decrements that engaged only memory-comparison-based change detection caused behavioral distraction, which was mirrored by a posterior negativity (240-260 ms, posterior N2) and a broad positivity (420-460 ms, P3a) that reflected attentional capture. Preceding these effects, luminance increments elicited a posterior positivity (100-120 ms, change-related positivity) and a posterior negativity (120-140 ms, change-related negativity), whereas luminance decrements elicited only a posterior positivity (160-180 ms, change-related positivity). These results suggest that memory-comparison-based change detection indexed by change-related positivity is involved in visual distraction as a result of attentional capture.

Probability-independent and -dependent ERPs reflecting visual change detection.

In ERP studies, two posterior components with different polarities have been identified as ERP correlates of visual change detection. To compare these components in terms of sensitivity to the preceding stimulus sequence, two peripheral stimuli of different colors (red and blue) were presented with equal (50:50) or different probabilities (20:80 or 80:20), while 12 participants performed shape discrimination at a central location. A posterior positivity at around 90-140 ms was observed with similar amplitude to all stimuli immediately preceded by a different stimulus. In contrast, a posterior negativity at around 140-180 ms was observed to increase in amplitude with increasing number of preceding different stimuli. These results suggest the existence of probability-independent and -dependent change processing in the human visual system. The functional significance is discussed in terms of memory-based comparison and stimulus-specific refractoriness.

Positive difference in ERPs reflects independent processing of visual changes.

To elucidate the nature of the processing of visual stimulus changes, ERPs were recorded while 12 participants performed an S1-S2 matching task with multifeature stimuli. Each trial consisted of two sequentially presented stimuli (S1-S2), where S2 was either the same as S1, different from S1 only in color, different only in shape, or different in both color and shape. The four trial types were presented in random order with equal probability, and participants responded to one of these types in separate blocks. Relative to the no-change stimuli, the change stimuli elicited posterior positivity with different topography according to changing features ranging from 100 to 180 ms in all tasks. The amplitude and topography of the positivity in response to the both changes were the respective sums of those to changes in the corresponding single features. These results suggest that a feature-specific change detection system exists in the human visual system.