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2.
Sci Rep ; 9(1): 16454, 2019 11 11.
Article in English | MEDLINE | ID: mdl-31712599

ABSTRACT

Research has found auditory spatial processing deficits in patients with schizophrenia (SCZ), but no study has examined SCZ patients' auditory spatial processing at both pre-attentional and attentional stages. To address this gap, we investigated schizophrenics' brain responses to sounds originating from different locations (right, left, and bilateral sources). The event-related potentials (ERPs) of 25 chronic schizophrenic patients and 25 healthy subjects were compared. Mismatch negativity (MMN) in response to frequency and duration deviants was assessed. Two P3 components (P3a and P3b) were elicited via a frequency discrimination task, and MMN and P3 were recorded through separate monaural and dichotic stimulation paradigms. Our results corroborated the previously published finding that MMN, P3a, and P3b amplitudes are reduced in SCZ patients, but they showed no significant effect of stimulus location on either MMN or P3. These results indicated similarity between the SCZ patients and healthy individuals as regards patterns of ERP responses to stimuli that come from different directions. No evidence of auditory hemispatial bias in the SCZ patients was found, supporting the existence of non-lateralized spatial processing deficits in such patients and suggesting compensatory changes in the hemispheric laterality of patients' brains.


Subject(s)
Brain/physiopathology , Contingent Negative Variation/physiology , Electrophysiological Phenomena , Evoked Potentials, Auditory/physiology , Functional Laterality/physiology , Schizophrenia/physiopathology , Spatial Processing/physiology , Acoustic Stimulation , Auditory Perception , Case-Control Studies , Electroencephalography , Evoked Potentials , Female , Humans , Male , Signal Processing, Computer-Assisted
3.
Behav Neurosci ; 133(4): 414-427, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31169383

ABSTRACT

Although the neural markers of interval timing have been widely studied, the events that determine the onset and offset of an interval have only recently started to gain attention. In the present study, I compare the predictions of the perceptual (preonset and start-gun) and decisional bias hypotheses with respect to onset N1P2 amplitude, the point of subjective equality (PSE) and delta/theta activity. The onsets of the comparison intervals (CIs) were manipulated to begin earlier, later, or on-time with regard to a standard interval (SI). Results supported the start-gun account by demonstrating an increase in the N1P2 amplitude and delta power in the "early" and "late" onset conditions due to temporal mismatch. Delayed or premature initiation of timing with respect to the predicted temporal point were associated with rightward and leftward shifts in the PSEs of the "early" and "late" onset conditions, respectively. In addition to the observed increase in temporal prediction-related delta activity in the "early" and "late" onset conditions, higher theta power in the "early" onset suggested an additional neural response for unexpected events that might be linked to response caution. Moreover, the ramping activity during the CIs, namely the contingent negative variation (CNV), showed a decision-related attenuation toward the end of an interval in the "late" onset. The latter finding was supported by the changes in offset N1P2 amplitude. The present study contributes to the interval-timing literature by presenting support in favor of the hypothesis that the onset N1P2 is a neural marker for the initiation of timing. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Subject(s)
Contingent Negative Variation/physiology , Time Perception/physiology , Acoustic Stimulation/methods , Adult , Attention , Brain/physiology , Delta Rhythm/physiology , Electroencephalography/methods , Female , Humans , Male , Psychomotor Performance/physiology
4.
Neuropsychologia ; 129: 179-190, 2019 06.
Article in English | MEDLINE | ID: mdl-30928337

ABSTRACT

Responsiveness to suggestions while hypnotized is termed hypnotic susceptibility. An association between reaction time and hypnotic susceptibility has been demonstrated, but whether distinct changes in brain activity accompany this relationship remains unclear. We investigated the effect of hypnotic susceptibility on the speed of information processing and motor cortical preparatory activity. Twenty-one "low" (LowHS) and fifteen "high" (HighHS) hypnotically susceptible right-handed participants performed precued simple (SRT) and choice (CRT) reaction time key-press tasks under hypnotized and non-hypnotized conditions. Force and surface electromyography data were recorded from left and right index fingers. The contingent negative variation (CNV) was derived from electroencephalography data. Mean reaction time and premotor time was shorter in HighHS participants than LowHS participants for both simple and choice reaction time tasks. HighHS participants in the hypnotized state performed fewer errors than HighHS participants in the non-hypnotized state and LowHS participants in either state for the SRT task. HighHS participants made fewer errors overall than LowHS participants for the CRT task. Mean C3/C4 CNV amplitude was larger in HighHS than in LowHS participants. Furthermore, larger CNV amplitude was associated with shorter premotor time. Our findings indicate that shorter reaction time in the high hypnotically susceptible group is associated with a greater change in brain activity during motor preparation. One interpretation is that hypnotic susceptibility and neural mechanisms of arousal and selective attention are linked.


Subject(s)
Attention/physiology , Contingent Negative Variation/physiology , Hypnosis , Motor Activity/physiology , Motor Cortex/physiology , Psychomotor Performance/physiology , Reaction Time/physiology , Adult , Electroencephalography , Electromyography , Female , Humans , Male , Young Adult
5.
Prog Brain Res ; 244: 101-114, 2019.
Article in English | MEDLINE | ID: mdl-30732833

ABSTRACT

In the study of the electrophysiological correlates of attention, a phasic change in alertness has been classically related to a negative frontal-central shift called Contingent Negative Variation (CNV). Studies investigating the effects of meditation on the CNV in participants reporting frequent transcendental experiences (TE) reported reduced CNV in choice reaction time task (CRT), and increased CNV in simple reaction time task (SRT), suggesting that meditation can induce a more balanced attentional state. In the current study, we tested whether a similar effect could be obtained in healthy non-meditators using a single session of a specifically structured sensorimotor training (Quadrato Motor Training-QMT). In addition, in contrast to previous studies, we further examined the P3 component, reflecting cognitive load and novelty detection. We found that similar to previous studies, following a QMT session, CNV amplitude reduced in CRT and increased in SRT. Conversely, the P3 amplitude increased in CRT and decreased in SRT. Taken together, these results support the idea that QMT has attentional benefits in normal healthy participants, similar to those observed in experienced meditators.


Subject(s)
Brain/physiology , Contingent Negative Variation/physiology , Event-Related Potentials, P300/physiology , Mindfulness/methods , Movement/physiology , Adult , Analysis of Variance , Choice Behavior/physiology , Electroencephalography , Female , Humans , Male , Reaction Time/physiology , Time Factors , Young Adult
6.
Pharmacopsychiatry ; 52(3): 126-133, 2019 Mar.
Article in English | MEDLINE | ID: mdl-29506304

ABSTRACT

INTRODUCTION: Cannabis use disorders (CUD) are highly prevalent among patients with schizophrenia (SCZ). Deficient mismatch negativity (MMN) generation is a characteristic finding in SCZ patients and cannabis users. This study therefore examined the effects of CUD on MMN generation in SCZ patients. METHODS: Twenty SCZ - CUD patients, 21 SCZ+CUD patients, and 20 healthy controls (HC) were included in this study. MMN to frequency and duration deviants was elicited within an auditory oddball paradigm and recorded by 32 channel EEG. RESULTS: As expected, SCZ - CUD patients showed reduced frontocentral MMN amplitudes to duration deviants compared to HC. Interestingly, SCZ+CUD patients demonstrated greater MMN amplitudes to duration deviants compared to SCZ - CUD patients at central electrodes with no differences compared to HC. DISCUSSION: These results demonstrate that comorbid cannabis use in SCZ patients might be associated with superior cognitive functioning. It can be assumed that the association between cannabis use and better cognitive performance may be due to a subgroup of cognitively less impaired SCZ patients characterized by lower genetic vulnerability for psychosis.


Subject(s)
Contingent Negative Variation/physiology , Evoked Potentials, Auditory/physiology , Marijuana Abuse/complications , Schizophrenia/complications , Acoustic Stimulation , Adult , Electroencephalography , Female , Humans , Male , Marijuana Abuse/epidemiology , Middle Aged , Psychiatric Status Rating Scales , Schizophrenia/epidemiology , Young Adult
7.
Neuropsychologia ; 117: 379-388, 2018 08.
Article in English | MEDLINE | ID: mdl-29981292

ABSTRACT

Auditory perceptual inference engages learning of complex statistical information about the environment. Inferences assist us to simplify perception highlighting what can be predicted on the basis of prior learning (through the formation of internal "prediction" models) and what might be new, potentially necessitating an investment of resources to remodel predictions. In the present study, we tested the hypothesis that sound sequences with multiple levels of predictability may rely on cognitive resources and be cognitively penetrable to a greater extent than was previously shown by studies presenting simpler sound sequences. Auditory-evoked potentials (AEPs) were recorded from 117 participants. All participants heard the exact same sound sequence but under different conditions: 51 while watching a DVD movie and 66 while performing a cognitively demanding task. Participants were asked to ignore the sounds and focus their attention on the movie/task. However, prior to commencing the experiment we manipulated what participants knew about the sound sequence by providing explicit sequence information to 15 and 34 of the participants in the DVD and cognitive-task conditions, respectively, and no information to the others. The results demonstrated that although local pattern violations elicited distinctive AEP responses (namely, mismatch negativity), the way the amplitude of this response was modulated by sequence learning over time was dependent upon both task and explicit sequence knowledge. The implications are discussed with reference to how the division of available attention resources between the primary task and concurrent sound impacts what is learned.


Subject(s)
Attention/physiology , Auditory Perception/physiology , Awareness , Cognition/physiology , Evoked Potentials, Auditory/physiology , Learning/physiology , Acoustic Stimulation , Adolescent , Adult , Contingent Negative Variation/physiology , Electroencephalography , Female , Humans , Male , Psychoacoustics , Young Adult
8.
Exp Brain Res ; 236(8): 2287-2297, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29860629

ABSTRACT

The current study investigated the effect of conscious intention to act on the Bereitschaftspotential. Situations in which the awareness of acting is minimally expressed were generated by asking 16 participants to press a button after performing a mental imagery task based on animal pictures (automatic condition). The affective responses induced by the pictures were controlled by selecting the animals according to different valences, threatening and neutral. The Bereitschaftspotential associated with the button presses was compared to the observed when similar movements were performed under the basic instructions of the self-paced movement paradigm (willed condition). Enhanced Bereitschaftspotential amplitudes were observed in the willed condition with respect to the automatic condition. This effect was manifested as a negative slope at medial frontocentral sites during the last 500 ms before movement onset. The valence of the pictures did not affect the motor preparatory potentials. The results suggest that significant part of the NS' subcomponent of the readiness potential is associated with the attention to-and, presumably, awareness of-intention to move, possibly reflecting cortical activation from supplementary motor areas. Secondarily, our findings supports that the feeling of threat does not influence the Bereitschaftspotential associated with automatic movements. Regarding methodological issues, the behavioural model of spontaneous voluntary movements proposed in automatic condition can benefit investigations on purely motor (or non-cognitive) subcomponents of the Bereitschaftspotential.


Subject(s)
Attention/physiology , Awareness/physiology , Cerebral Cortex/physiology , Consciousness/physiology , Contingent Negative Variation/physiology , Intention , Motor Activity/physiology , Pattern Recognition, Visual/physiology , Volition/physiology , Adult , Female , Humans , Male , Young Adult
9.
Neuropsychologia ; 117: 188-198, 2018 08.
Article in English | MEDLINE | ID: mdl-29885961

ABSTRACT

Consonant musical intervals tend to be more readily processed than dissonant intervals. In the present study, we explore the neural basis for this difference by registering how the brain responds after changes in consonance and dissonance, and how formal musical training modulates these responses. Event-related brain potentials (ERPs) were registered while participants were presented with sequences of consonant intervals interrupted by a dissonant interval, or sequences of dissonant intervals interrupted by a consonant interval. Participants were musicians and non-musicians. Our results show that brain responses triggered by changes in a consonant context differ from those triggered in a dissonant context. Changes in a sequence of consonant intervals are rapidly processed independently of musical expertise, as revealed by a change-related mismatch negativity (MMN, a component of the ERPs triggered by an odd stimulus in a sequence of stimuli) elicited in both musicians and non-musicians. In contrast, changes in a sequence of dissonant intervals elicited a late MMN only in participants with prolonged musical training. These different neural responses might form the basis for the processing advantages observed for consonance over dissonance and provide information about how formal musical training modulates them.


Subject(s)
Auditory Perception/physiology , Brain Mapping , Contingent Negative Variation/physiology , Evoked Potentials, Auditory/physiology , Music , Acoustic Stimulation/methods , Adolescent , Brain , Female , Humans , Male , Young Adult
10.
Neuropsychologia ; 117: 55-66, 2018 08.
Article in English | MEDLINE | ID: mdl-29768189

ABSTRACT

Tapping in synchrony to an isochronous rhythm involves several key functions of the sensorimotor system including timing, prediction and error correction. While auditory sensorimotor synchronization (SMS) has been well studied, much less is known about mechanisms involved in visual SMS. By comparing error correction in auditory and visual SMS, it can be determined if the neural mechanisms for detection and correction of synchronization errors are generalized or domain specific. To study this problem, we measured EEG while subjects tapped in synchrony to separate visual and auditory metronomes that both contained small temporal perturbations to induce errors. The metronomes had inter-onset intervals of 600 ms and the perturbations where of 4 kinds: ± 66 ms to induce period corrections, and ± 16 ms to induce phase corrections. We hypothesize that given the less precise nature of visual SMS, error correction to perturbed visual flashing rhythms will be more gradual than with the equivalent auditory perturbations. Additionally, we expect this more gradual error correction will be reflected in the visual evoked potentials. Our findings indicate that the visual system is only capable of more gradual phase corrections to even the larger induced errors. This is opposed to the swifter period correction of the auditory system to large induced errors. EEG data found the peak N1 auditory evoked potential is modulated by the size and direction of an induced error in line with previous research, while the P1 visual evoked potential was only effected by the large late-coming perturbations resulting in reduced peak latency. Looking at the error response EEG data, an Error Related Negativity (ERN) and related Error Positivity (pE) was found only in the auditory + 66 condition, while no ERN or pE were found in any of the visual perturbation conditions. In addition to the ERPs, we performed a dipole source localization and clustering analysis indicating that the anterior cingulate was active in the error detection of the perturbed stimulus for both auditory and visual conditions in addition to being involved in producing the ERN and pE induced by the auditory + 66 perturbation. Taken together, these results confirm that the visual system is less developed for synchronizing and error correction with flashing rhythms by its more gradual error correction. The reduced latency of the P1 to the visual + 66 suggests that the visual system can detect these errors, but that detection does not translate into any meaningful improvement in error correction. This indicates that the visual system is not as tightly coupled to the motor system as the auditory system is for SMS, suggesting the mechanisms of SMS are not completely domain general.


Subject(s)
Brain Mapping , Brain/physiology , Contingent Negative Variation/physiology , Electroencephalography Phase Synchronization/physiology , Evoked Potentials/physiology , Acoustic Stimulation , Adolescent , Adult , Analysis of Variance , Brain/diagnostic imaging , Electroencephalography , Female , Humans , Magnetic Resonance Imaging , Male , Photic Stimulation , Psychomotor Performance , Young Adult
11.
Neuroreport ; 29(6): 472-477, 2018 04 11.
Article in English | MEDLINE | ID: mdl-29578987

ABSTRACT

The aim of this study was to address the potential for the auditory mismatch negativity (aMMN) to be used in applied event-related potential (ERP) studies by determining whether the aMMN would be an attention-dependent ERP component and could be differently modulated across visual tasks or virtual reality (VR) stimuli with different visual properties and visual complexity levels. A total of 80 participants, aged 19-36 years, were assigned to either a reading-task (21 men and 19 women) or a VR-task (22 men and 18 women) group. Two visual-task groups of healthy young adults were matched in age, sex, and handedness. All participants were instructed to focus only on the given visual tasks and ignore auditory change detection. While participants in the reading-task group read text slides, those in the VR-task group viewed three 360° VR videos in a random order and rated how visually complex the given virtual environment was immediately after each VR video ended. Inconsistent with the finding of a partial significant difference in perceived visual complexity in terms of brightness of virtual environments, both visual properties of distance and brightness showed no significant differences in the modulation of aMMN amplitudes. A further analysis was carried out to compare elicited aMMN amplitudes of a typical MMN task and an applied VR task. No significant difference in the aMMN amplitudes was found across the two groups who completed visual tasks with different visual-task demands. In conclusion, the aMMN is a reliable ERP marker of preattentive cognitive processing for auditory deviance detection.


Subject(s)
Attention/physiology , Auditory Perception/physiology , Contingent Negative Variation/physiology , Evoked Potentials, Auditory/physiology , Acoustic Stimulation , Adult , Brain Mapping , Evoked Potentials, Visual/physiology , Female , Humans , Male , Photic Stimulation , Virtual Reality , Young Adult
12.
eNeuro ; 5(6)2018.
Article in English | MEDLINE | ID: mdl-30637328

ABSTRACT

Humans with absolute pitch (AP) are able to effortlessly name the pitch class of a sound without an external reference. The association of labels with pitches cannot be entirely suppressed even if it interferes with task demands. This suggests a high level of automaticity of pitch labeling in AP. The automatic nature of AP was further investigated in a study by Rogenmoser et al. (2015). Using a passive auditory oddball paradigm in combination with electroencephalography, they observed electrophysiological differences between musicians with and without AP in response to piano tones. Specifically, the AP musicians showed a smaller P3a, an event-related potential (ERP) component presumably reflecting early attentional processes. In contrast, they did not find group differences in the mismatch negativity (MMN), an ERP component associated with auditory memory processes. They concluded that early cognitive processes are facilitated in AP during passive listening and are more important for AP than the preceding sensory processes. In our direct replication study on a larger sample of musicians with (n = 54, 27 females, 27 males) and without (n = 50, 24 females, 26 males) AP, we successfully replicated the non-significant effects of AP on the MMN. However, we could not replicate the significant effects for the P3a. Additional Bayes factor analyses revealed moderate to strong evidence (Bayes factor > 3) for the null hypothesis for both MMN and P3a. Therefore, the results of this replication study do not support the postulated importance of cognitive facilitation in AP during passive tone listening.


Subject(s)
Brain Mapping , Contingent Negative Variation/physiology , Evoked Potentials, Auditory/physiology , Music , Pitch Perception/physiology , Acoustic Stimulation , Adolescent , Adult , Analysis of Variance , Attention , Bayes Theorem , Electroencephalography , Female , Humans , Male , Psychoacoustics , Reaction Time , Young Adult
13.
Schizophr Res ; 191: 5-9, 2018 01.
Article in English | MEDLINE | ID: mdl-28927552

ABSTRACT

BACKGROUND: Patients with schizophrenia (SZ) have impairments in processing auditory information that have been linked to deficits in cognitive and psychosocial functioning. Dysfunction in auditory sensory processing in SZ has been indexed by mismatch negativity (MMN), an event-related potential evoked by a rare, deviant stimulus embedded within a sequence of identical standard stimuli. Although MMN deficits in SZ have been studied extensively, relatively little is known about how these deficits relate to accurately identifying real-world, ecologically-salient sounds. METHODS: MMN was assessed in SZ patients (n=21) and non-psychiatric comparison subjects (NCS; n=16). Participants were also assessed in their ability to identify common environmental sounds using a subset of 80 sound clips from the International Affective Digitized Sounds 2nd Ed collection. RESULTS: SZ patients made significantly more errors in environmental sound identification (p<0.001, d=0.86) and showed significantly reduced MMN amplitude deficits in MMN compared to NCS (p<0.01, d=0.97). In SZ patients, MMN deficits were associated with significantly greater environmental sound identification errors (r=0.61, p<0.01). CONCLUSIONS: Impairments in early auditory information processing in schizophrenia account for significant proportions of variance in the ability to identify real-world, functionally relevant environmental sounds. This study supports the view that interventions targeting deficits in low-level auditory sensory processing may also impact more complex cognitive brain processes relevant to psychosocial disability.


Subject(s)
Contingent Negative Variation/physiology , Environment , Evoked Potentials, Auditory/physiology , Schizophrenia/physiopathology , Schizophrenic Psychology , Acoustic Stimulation , Adult , Arousal , Electroencephalography , Emotions/physiology , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Statistics as Topic
14.
Schizophr Res ; 193: 313-318, 2018 03.
Article in English | MEDLINE | ID: mdl-28760539

ABSTRACT

BACKGROUND: There is overlap between schizophrenia and bipolar disorder regarding genetic risk as well as neuropsychological and structural brain deficits. Finding common and distinct event-response potential (ERP) responses and connectivity patterns may offer potential biomarkers to distinguish the disorders. OBJECTIVE: To examine the neuronal auditory response elicited by a roving mismatch negativity (MMN) paradigm using magnetoencephalography (MEG). PARTICIPANTS: 15 Adolescents with schizophrenia (ASZ), 16 adolescents with bipolar disorder with psychosis (ABP), and 14 typically developing individuals (TD) METHODS: The data were analysed using time-series techniques and dynamic causal modelling (DCM). OUTCOME MEASURES: MEG difference wave (deviant - standard) at primary auditory (~90ms), MMN (~180ms) and long latency (~300ms). RESULTS: The amplitude of difference wave showed specific patterns at all latencies. Most notably, it was significantly reduced ABP compared to both controls and ASZ at early latencies. In contrast, the amplitude was significantly reduced in ASZ compared to both controls and ABP. The DCM analysis showed differential connectivity patterns in all three groups. Most notably, inter-hemispheric connections were strongly dominated by the right side in ASZ only. CONCLUSIONS: Dissociable patterns of the primary auditory response and MMN response indicate possible developmentally sensitive, but separate biomarkers for schizophrenia and bipolar disorder.


Subject(s)
Bipolar Disorder/physiopathology , Brain Mapping , Contingent Negative Variation/physiology , Evoked Potentials, Auditory/physiology , Magnetoencephalography , Psychotic Disorders/complications , Schizophrenia/complications , Acoustic Stimulation , Adolescent , Electroencephalography , Female , Humans , Male , Models, Neurological , Neuropsychological Tests , Psychiatric Status Rating Scales , Reaction Time/physiology
15.
Schizophr Res ; 191: 10-17, 2018 01.
Article in English | MEDLINE | ID: mdl-28779851

ABSTRACT

Deficits in mismatch negativity (MMN) generation are among the best replicated neurophysiological deficits in schizophrenia, with reduced amplitude reflecting impaired information processing at the level of supratemporal auditory cortex. Differential patterns of MMN dysfunction according to deviant types have been reported across studies, with some research groups showing impairment in duration MMN but not frequency MMN, and other research groups reporting both findings. We evaluate the hypothesis that recruitment setting, reflecting current functional status, might be an important determinant of the pattern of MMN dysfunction. Here, we evaluated patterns of MMN dysfunction, along with tone matching and neuropsychological performance in subjects drawn from 1) a predominant inpatient/residential care setting (Nathan Kline Institute) and 2) a predominant outpatient setting (Columbia University). As predicted, compared to healthy controls, deficits in duration MMN were observed across sites, whereas deficits in frequency MMN/tone matching were confined to the chronic inpatient setting. Within patients, the frequency MMN deficit was highly correlated with impairments in tone matching ability across sites (r=-0.52, p<0.0001), as well as impairments in verbal learning (r=-0.54, p<0.0001). Responses to standard stimuli in the MMN paradigm were assessed using measures of alpha evoked power and inter-trial coherence (ITC). While deficits in alpha ITC were observed across sites (both p<0.05), deficits in alpha power were observed at the inpatient (p=0.001) but not outpatient (p=0.2) site. Overall, these finding indicate that impairments of frequency MMN generation and response power to standard stimuli could be particularly linked to forms of schizophrenia that are associated with poor functional outcome.


Subject(s)
Contingent Negative Variation/physiology , Evoked Potentials, Auditory/physiology , Inpatients , Outpatients , Schizophrenia/physiopathology , Schizophrenic Psychology , Acoustic Stimulation , Adolescent , Adult , Analysis of Variance , Electroencephalography , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Young Adult
16.
Schizophr Res ; 191: 132-139, 2018 01.
Article in English | MEDLINE | ID: mdl-28450056

ABSTRACT

The event-related potential, mismatch negativity (MMN), has been touted as a robust and specific neurophysiological biomarker of schizophrenia. Earlier studies often included bipolar disorder (BD) as a clinical comparator and reported that MMN was significantly impaired only in schizophrenia. However, with the increasing number of MMN studies of BD (with larger sample sizes), the literature is now providing somewhat consistent evidence of this biomarker also being perturbed in BD, albeit to a lesser degree than that observed in schizophrenia. Indeed, two meta-analyses have now shown that the effect sizes in BD samples suggest a moderate impairment in MMN, compared to the large effect sizes shown in schizophrenia. Pharmacologically, MMN is an extremely useful non-invasive probe of glutamatergic (more specifically, N-methyl-d-aspartate [NMDA] receptor) disturbances and this system has been implicated in the pathophysiology of both schizophrenia and BD. Therefore, it may be best to conceptualize/utilize MMN as an index of a psychopathology that is shared across psychotic and related disorders, rather than being a diagnosis-specific biomarker. More research is needed, particularly longitudinal designs including studies that assess MMN over an individual's life course and then examine NMDA receptor expression/binding post-mortem. At this point and despite a disproportionate amount of research, the current evidence suggests that with respect to BD, MMN is a neurophysiological biomarker of intermediate effect. With replication and validation of this effect, MMN may prove to be an important indicator of a common psychopathology shared by a significant proportion of individuals with schizophrenia and bipolar spectrum illnesses.


Subject(s)
Bipolar Disorder/physiopathology , Contingent Negative Variation/physiology , Evoked Potentials, Auditory/physiology , Acoustic Stimulation , Electroencephalography , Humans , Neuropsychological Tests
17.
Schizophr Res ; 191: 51-60, 2018 01.
Article in English | MEDLINE | ID: mdl-28666633

ABSTRACT

Mismatch negativity (MMN) is among the best established biomarkers of cortical dysfunction in schizophrenia. MMN generators are localized primarily to primary and secondary auditory regions, and are known to reflect activity mediated by cortical N-methyl-d-aspartate-type glutamate receptors (NMDAR). Nevertheless, mechanisms underlying MMN generation at the local circuit level remain incompletely understood. This review synthesizes recent advances in circuit-level conceptualization of MMN based upon neuro-oscillatory findings. In the neuro-oscillatory (aka event-related spectral perturbation, ERSP) approach, responses to sensory stimuli are decomposed into underlying frequency bands prior to analysis. MMN reflects activity primarily in theta (4-7Hz) frequency band, which is thought to depend primarily upon interplay between cortical pyramidal neurons and somatostatin (SST)-type local circuit GABAergic interneurons. Schizophrenia-related deficits in theta generation are also observed not only in MMN, but also in other auditory and visual contexts. At the local circuit level, SST interneurons are known to maintain tonic inhibition over cortical pyramidal interneurons. SST interneurons, in turn, are inhibited by a class of interneurons expressing vasoactive intestinal polypeptide (VIP). In rodents, SST interneurons have been shown to respond differentially to deviant vs. standard stimuli, and inhibition of SST interneurons has been found to selectively inhibit deviance-related activity in rodent visual cortex. Here we propose that deficits in theta frequency generation, as exemplified by MMN, may contribute significantly to cortical dysfunction in schizophrenia, and may be tied to impaired interplay between cortical pyramidal neurons and local circuit SST-type GABAergic interneurons.


Subject(s)
Contingent Negative Variation/physiology , Evoked Potentials, Auditory/physiology , Schizophrenia/physiopathology , Theta Rhythm/physiology , Acoustic Stimulation , Electroencephalography , Humans , Interneurons/physiology , Nerve Tissue Proteins/metabolism , Schizophrenia/pathology
18.
Schizophr Res ; 191: 18-24, 2018 01.
Article in English | MEDLINE | ID: mdl-28506707

ABSTRACT

Mismatch negativity (MMN) is an event-related potential to stimulus change. MMN to infrequent deviant tones that differs in a simple physical parameter from repetitive standard tones is reduced in patients with long-term schizophrenia (Sz; d=~1). However, this simple MMN is not uniformly reduced at the first-episode of schizophrenia-spectrum psychosis (FESz; d<0.1 for pitch; <0.4 for duration). Deviant stimuli that violate pattern rules also evoke MMN. This complex MMN is evoked by deviations in the relation of sounds to each other. The simplest pattern involves tone pairs. Although the pitch of first tone in the pair varies, the second tone's pitch always follows a rule (e.g., always 3 semitones higher). We measured complex MMN to deviant tone pairs that descended in pitch among standard tone pairs that ascended in pitch, never before examined in Sz or in FESz. Experiment 1 showed significant reductions in complex MMN in 20 Sz compared to 22 matched controls. Experiment 2 replicated smaller complex MMN in a shorter protocol in 24 Sz compared to 21 matched controls, but showed no significant complex MMN reduction in 21 FESz compared to 21 matched controls. Although reduced in Sz, indicating deficits in generation of a simple acoustic pattern rule, the tone pair complex MMN was within normal limits in FESz. This suggests that more complex perceptual pattern analysis processes are, at least partially, still intact at the first break. Future work will determine at what point of pattern complexity subtle auditory perception pathophysiology will be revealed in FESz.


Subject(s)
Contingent Negative Variation/physiology , Evoked Potentials, Auditory/physiology , Psychotic Disorders/physiopathology , Schizophrenia/physiopathology , Acoustic Stimulation , Adult , Case-Control Studies , Electroencephalography , Female , Humans , Male , Psychiatric Status Rating Scales , Young Adult
19.
Schizophr Res ; 191: 140-147, 2018 01.
Article in English | MEDLINE | ID: mdl-28532686

ABSTRACT

Persistent auditory verbal hallucinations (AVH) in schizophrenia are increasingly tied to dysfunction at the level of auditory cortex. AVH may reflect in part misattribution of internally generated thoughts to external spatial locations. Here, we investigated the association between persistent AVH and spatial localization abilities assessed both behaviorally and by mismatch negativity (MMN) to location deviants. METHODS: Spatial- and tonal- discrimination abilities were assessed in patients (n=20) and controls (n=20) using free-field tones. MMN was assessed to spatial-location-, pitch- and duration-deviants. AVH and thought disorder were assessed using clinical evaluation. RESULTS: As predicted, patients showed significant reductions in behavioral spatial-discrimination (p<0.0001) and tone-matching (p<0.001) ability, along with impaired MMN generation to location (p<0.03) and pitch (p<0.05) deviants. Hallucinating (AVH+) and non-hallucinating (AVH-) subjects showed similar deficits in location MMN to left-hemifield stimuli (p<0.0001 vs. control). By contrast, AVH- patients differed significantly from controls (p=0.009) and AVH+ patients (p=0.018) for MMN to right-lateral hemifield (left auditory cortex) stimuli, whereas AVH+ patients showed paradoxically preserved MMN generation (p=0.99 vs. controls). Severity of thought disorder correlated with impaired spatial discrimination, especially to right-hemifield stimuli (p=0.013), but did not correlate significantly with MMN or tone matching deficits. CONCLUSION: These findings demonstrate a significant relationship between auditory cortical spatial localization abilities and AVH susceptibility, with relatively preserved function of left vs. right auditory cortex predisposing to more severe AVH, and support models that attribute persistent AVH to impaired source-monitoring. The findings suggest new approaches for therapeutic intervention for both AVH and thought disorder in schizophrenia.


Subject(s)
Contingent Negative Variation/physiology , Evoked Potentials, Auditory/physiology , Hallucinations/etiology , Schizophrenia/complications , Acoustic Stimulation , Adult , Analysis of Variance , Auditory Cortex/physiopathology , Auditory Perception , Brain Mapping , Electroencephalography , Female , Humans , Male , Middle Aged
20.
Schizophr Res ; 191: 123-131, 2018 01.
Article in English | MEDLINE | ID: mdl-28343741

ABSTRACT

Time, or more specifically temporal structure, is a critical variable in understanding how the auditory system uses acoustic patterns to predict input, and to filter events based on their relevance. A key index of this filtering process is the auditory evoked potential component known as mismatch negativity or MMN. In this paper we review findings of smaller MMN in schizophrenia through the lens of time as an influential contextual variable. More specifically, we review studies that show how MMN to a locally rare pattern-deviation is modulated by the longer-term context in which it occurs. Empirical data is presented from a non-clinical sample confirming that the absence of a stable higher-order structure to sound sequences alters the way MMN amplitude changes over time. This result is discussed in relation to how hierarchical pattern learning might enrich our understanding of how and why MMN amplitude modulation is disrupted in schizophrenia.


Subject(s)
Acoustic Stimulation/methods , Contingent Negative Variation/physiology , Evoked Potentials, Auditory/physiology , Analysis of Variance , Electroencephalography , Female , Humans , Male , Time Factors , Young Adult
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