Standard Tones Research Articles

Diminished neural resources allocation to time processing in Autism Spectrum Disorders.

BackgroundInterval timing, the ability to judge the duration of short events, has been shown to be compromised in Autism Spectrum Disorders (ASD). Timing abilities are ubiquitous and underlie behaviours as varied as sensory integration, motor coordination or communication. It has been suggested that atypical temporal processing in ASD could contribute to some of the disorder's symptoms, in particular motor clumsiness and difficulties in social interaction and communication. Recent behavioural investigations have suggested that interval timing in ASD is characterised by intact sensitivity but reduced precision in duration judgements.MethodsIn this study we investigated the processing of duration as compared to pitch in a group of high-functioning individuals with ASD using magnetoencephalography (MEG). 18 adolescents and adults with ASD and 18 age- and IQ-matched typically-developing control (TDC) individuals compared two consecutive tones according to their duration or pitch in separate experimental blocks. The analysis was carried out exclusively on physically identical stimuli (500 Hz tones lasting 600 ms), which served, according to instruction, as standard or probe in a Duration or Pitch task respectively.ResultsOur results suggest that compared to TDC individuals, individuals with ASD are less able to predict the duration of the standard tone accurately, affecting the sensitivity of the comparison process. In addition, contrary to TDC individuals who allocate resources at different times depending on the nature of the task (pitch or duration discrimination), individuals with ASD seem to engage less resources for the Duration task than for the Pitch task regardless of the context. Although individuals with ASD showed top-down adaptation to the context of the task, this neuronal strategy reflects a bias in the readiness to perform different types of tasks, and in particular a diminished allocation of resources to duration processing which could have cascading effect on learning and development of other cognitive functions.

P 102 Domain-specific effects of transcranial random noise stimulation (tRNS) on auditory feature processing

Theoretical background Decoding acoustic speech signals requires to parse the acoustic stream into linguistically meaningful units, and to extract stress and prosody. Accordingly, the temporal and spectral resolution of the auditory cortex is essential in successful speech processing ( Rosen, 1992 ). The reduced acuity in discriminating these features is considered as key factor in dyslexia ( Goswami, 2011 ) but is also a consequence of normal aging ( Walton, 2010 ). Transcranial random noise stimulation (tRNS), a non-invasive brain stimulation technique that applies weak currents at multiple frequencies, is assumed to modulate the excitability of neural assemblies and, in consequence, the reactivity of cortical structures. However, the effect of tRNS on the auditory system is yet unclear. The present study aimed to fill this gap by investigating the impact of tRNS on basic auditory feature processing. Considering the hemispheric specialization of the auditory system in analyzing theses features we hypothesized that a site-specific tRNS application leads to domain-specific changes in auditory features processing. In concrete, tRNS over the left auditory cortex (lAC) was hypothesized to affect the temporal domain while tRNS over the right auditory cortex (rAC) was assumed to modulate the spectral domain. Finally, we investigated whether tRNS over bilateral auditory cortex (bAC) leads to a modulation of both dimensions. Methods On four days 18 healthy, right-handed adults received 30 min. tRNS at an intensity of 1.5 mA either over the lAC, over the rAC, over bAC or sham stimulation while continuous EEG was recorded. The task consisted of the detection of a deviant tone in a sequence of three sine wave tones. While the duration of all tones and the pitch of the standard tones was kept stable, the inter-tone interval (temporal information) and the frequency in that the deviant tone differed from the standard tones (spectral information) was modulated. Results In result, we found that tRNS applied over the lAC and over bAC inferred with task performance. This effect was specifically modulated by the inter-tone interval between the tone triplets but not by the frequency of the deviant tone. On the electrophysiological level, this finding was paralleled by feature-specific brain response patterns in the alpha and the lower gamma band. Discussion Our findings demonstrate the functional relevance of the lAC in processing temporal features. Most importantly, we proved tRNS as a valid technique to modulate basic auditory perception. The current results stress the need for further investigations on the effect of tRNS in the auditory domain. Systematically assessing the most effective stimulation parameters provides the basis for the clinical application of tRNS in the context of speech and language disorders.

Delayed Mismatch Field Latencies in Autism Spectrum Disorder with Abnormal Auditory Sensitivity: A Magnetoencephalographic Study.

Although abnormal auditory sensitivity is the most common sensory impairment associated with autism spectrum disorder (ASD), the neurophysiological mechanisms remain unknown. In previous studies, we reported that this abnormal sensitivity in patients with ASD is associated with delayed and prolonged responses in the auditory cortex. In the present study, we investigated alterations in residual M100 and MMFs in children with ASD who experience abnormal auditory sensitivity. We used magnetoencephalography (MEG) to measure MMF elicited by an auditory oddball paradigm (standard tones: 300 Hz, deviant tones: 700 Hz) in 20 boys with ASD (11 with abnormal auditory sensitivity: mean age, 9.62 ± 1.82 years, 9 without: mean age, 9.07 ± 1.31 years) and 13 typically developing boys (mean age, 9.45 ± 1.51 years). We found that temporal and frontal residual M100/MMF latencies were significantly longer only in children with ASD who have abnormal auditory sensitivity. In addition, prolonged residual M100/MMF latencies were correlated with the severity of abnormal auditory sensitivity in temporal and frontal areas of both hemispheres. Therefore, our findings suggest that children with ASD and abnormal auditory sensitivity may have atypical neural networks in the primary auditory area, as well as in brain areas associated with attention switching and inhibitory control processing. This is the first report of an MEG study demonstrating altered MMFs to an auditory oddball paradigm in patients with ASD and abnormal auditory sensitivity. These findings contribute to knowledge of the mechanisms for abnormal auditory sensitivity in ASD, and may therefore facilitate development of novel clinical interventions.

The use of event-related potential (P300) and neuropsychological testing to evaluate cognitive impairment in mild traumatic brain injury patients

Background:The aim of the study is to compare the amplitude and latency of the P300 event-related potential (ERP) component between a control group and patients after mild traumatic brain injury (mTBI) during 1–7 days (short duration) and 2–3 months (long duration), and to compare the outcome of neuropsychological tests between the long duration postinjury and control study groups.Materials and Methods:We studied responses to auditory stimulation in two main and one subgroups, namely the control healthy group (19 patients, both ERP and neuropsychology test done), the mTBI 1 group (17 patients, only ERP done within 7 days after injury), and the mTBI 2 subgroup (the 17 mTBI 1 patients in whom a repeated ERP together with neuropsychological testing was done at 2–3 months postinjury). Auditory evoked responses were studied with two different stimuli (standard and target stimuli), where the P300 amplitude and latency were recorded from three midline sites and results were compared between the groups, as were the neuropsychological test results.Results:There was a significant prolongation of the target P300 latency values shown by the MBI 1 group measured at the central electrode when compared to the control group, which was also seen when the mTBI 1 and mTBI 2 groups were compared. The results of the P300 amplitude values measured at the frontal electrode showed the control group to have higher readings during the presentation of standard tones when compared to the mTBI 1 group. The mTBI 2 group performed better on some neuropsychological tests.Conclusion:The latency of P300 was significantly prolonged in early mTBI patients who improved over time, and the neuropsychological testing on mTBI 2 patients showed them to be comparable to the control group. The study indicates that ERP should be used as an additional modality of investigation in mTBI patients.

An EEG Brain–Computer Interface Approach for Classifying Vigilance States in Humans: A Gamma Band Focus Supports Low Misclassification Rates

ABSTRACTThis research investigated a brain–computer interface (BCI) for classifying vigilance states. A BCI approach based on event-related potential (ERP) and spectral features of electroencephalographic (EEG) data derived from an auditory oddball paradigm was employed. A 128-channel EEG system recorded potentials while participants simultaneously completed a prolonged visual match-to-sample task. It was hypothesized that better classification rates would be found for a group of “bored” participants, as compared to the not-bored participants. The best classification rates were found by extracting EEG features from gamma frequencies at middle and late latencies (for the standard tones). Critically, the BCI paradigm was most effective for the bored participants (mean misclassification rate = 13%), as compared to the not-bored participants (mean misclassification rate = 21%). These findings extend our knowledge of reliable latencies and spectral features of ERP data most salient to the classification of vigilance states.

Endocannabinoid Modulation of Stimulus-Specific Adaptation in Inferior Colliculus Neurons of the Rat

Cannabinoid receptors (CBRs) are widely distributed in the brain, including the inferior colliculus (IC). Here, we aim to study whether endocannabinoids influence a specific type of neuronal adaptation, namely, stimulus-specific adaptation (SSA) found in some IC neurons. SSA is important because it has been found as early as the level of the midbrain and therefore it may be a neuronal correlate of early indices of deviance detection. Furthermore, recent studies have demonstrated a direct link between SSA and MMN, that is widely used as an outcome measure in a variety of human neurodegenerative disorders. SSA is considered a form of short-term plasticity, and CBRs have been shown to play a role in short-term neural plasticity. Therefore, it is reasonable to hypothesize that endocannabinoids may play a role in the generation or modulation of SSA. We recorded single units in the IC under an oddball paradigm stimulation. The results demonstrate that cannabinoid agonists lead to a reduction in the neuronal adaptation. This change is due to a differential increase of the neuronal firing rate to the standard tone alone. Furthermore, we show that the effect is mediated by the cannabinoid receptor 1 (CBR1). Thus, cannabinoid agonists down-modulate SSA in IC neurons.

Music-space associations are grounded, embodied and situated: examination of cello experts and non-musicians in a standard tone discrimination task

In recent research, a systematic association of musical pitch with space has been described in the so-called Spatial-Pitch-Association-of-Response Codes-effect (SPARC). Typically, high pitch is associated with upper/right and low pitch with lower/left space. However, a theoretical classification of these associations regarding their experiential sources is difficult. Therefore, we applied a theoretical framework of numerical cognition classifying similar Space-Associated Response Codes (SARC) effects according to their groundedness, embodiedness and situatedness. We tested these attributes with a group of non-musicians and with a group of highly skilled cello players playing high tones with lower hand positions (i.e., reverse SPARC alignment) in a standard SPARC context of a piano and a reversed SPARC context of a cello. The results showed that SPARC is grounded, in general. However, for cello player SPARC is also situated and embodied. We conclude that groundedness, embodiedness and situatedness provide general characteristics of mapping cognitive representations to space.

MEG biomarker of Alzheimer's disease: Absence of a prefrontal generator during auditory sensory gating.

Magnetoencephalography (MEG), a direct measure of neuronal activity, is an underexplored tool in the search for biomarkers of Alzheimer's disease (AD). In this study, we used MEG source estimates of auditory gating generators, nonlinear correlations with neuropsychological results, and multivariate analyses to examine the sensitivity and specificity of gating topology modulation to detect AD. Our results demonstrated the use of MEG localization of a medial prefrontal (mPFC) gating generator as a discrete (binary) detector of AD at the individual level and resulted in recategorizing the participant categories in: (1) controls with mPFC generator localized in response to both the standard and deviant tones; (2) a possible preclinical stage of AD participants (a lower functioning group of controls) in which mPFC activation was localized to the deviant tone only; and (3) symptomatic AD in which mPFC activation was not localized to either the deviant or standard tones. This approach showed a large effect size (0.9) and high accuracy, sensitivity, and specificity (100%) in identifying symptomatic AD patients within a limited research sample. The present results demonstrate high potential of mPFC activation as a noninvasive biomarker of AD pathology during putative preclinical and clinical stages. Hum Brain Mapp 38:5180-5194, 2017. © 2017 Wiley Periodicals, Inc.

Pre-target neural oscillations predict variability in the detection of small pitch changes.

Pitch discrimination is important for language or music processing. Previous studies indicate that auditory perception depends on pre-target neural activity. However, so far the pre-target electrophysiological conditions which enable the detection of small pitch changes are not well studied, but might yield important insights into pitch-processing. We used magnetoencephalography (MEG) source imaging to reveal the pre-target effects of successful auditory detection of small pitch deviations from a sequence of standard tones. Participants heard a sequence of four pure tones and had to determine whether the last target tone was different or identical to the first three standard sounds. We found that successful pitch change detection could be predicted from the amplitude of theta (4–8 Hz) oscillatory activity in the right inferior frontal gyrus (IFG) as well as beta (12–30 Hz) oscillatory activity in the right auditory cortex. These findings confirm and extend evidence for the involvement of theta as well as beta-band activity in auditory perception.

Complex mismatch negativity to tone pair deviants in long-term schizophrenia and in the first-episode schizophrenia spectrum

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.

Acquiring research-grade ERPs on a shoestring budget: A comparison of a modified Emotiv and commercial SynAmps EEG system.

This study compared the performance of a low-cost wireless EEG system to a research-grade EEG system on an auditory oddball task designed to elicit N200 and P300 ERP components. Participants were 15 healthy adults (6 female) aged between 19 and 40 (M = 28.56; SD = 6.38). An auditory oddball task was presented comprising 1,200 presentations of a standard tone interspersed by 300 trials comprising a deviant tone. EEG was simultaneously recorded from a modified Emotiv EPOC and a NeuroScan SynAmps RT EEG system. The modifications made to the Emotiv system included attaching research grade electrodes to the Bluetooth transmitter. Additional modifications enabled the Emotiv system to connect to a portable impedance meter. The cost of these modifications and portable impedance meter approached the purchase value of the Emotiv system. Preliminary analyses revealed significantly more trials were rejected from data acquired by the modified Emotiv compared to the SynAmps system. However, the ERP waveforms captured by the Emotiv system were found to be highly similar to the corresponding waveform from the SynAmps system. The latency and peak amplitude of N200 and P300 components were also found to be similar between systems. Overall, the results indicate that, in the context of an oddball task, the ERP acquired by a low-cost wireless EEG system can be of comparable quality to research-grade EEG acquisition equipment.

Hearing Loss and Age-Induced Changes in the Central Auditory System Measured by the P3 Response to Small Changes in Frequency.

Recent behavioral studies have suggested that individuals with sloping audiograms exhibit localized improvements in frequency discrimination in the frequency region near the drop in hearing. Auditory-evoked potentials may provide evidence of such cortical plasticity and reorganization of frequency maps. The objective of this study was to evaluate electrophysiological evidence of cortical plasticity related to cortical frequency representation and discrimination abilities in older individuals with high-frequency sensorineural hearing loss (SNHL). It was hypothesized that the P3 response in this group would show evidence of physiological reorganization of frequency maps and enhanced neural representation at the edge of their high-frequency loss due to their restricted SNHL. The P3 auditory event-related potential in response to small frequency changes was recorded in a repeated measures design using an oddball paradigm that presented upward and downward frequency changes of 2%, 5%, and 20% to three groups of listeners. P3 recordings from a group of seven older individuals with a restricted sloping hearing loss >1000 or 2000 Hz was compared to two control groups of younger (n = 7) and older (n = 7) individuals with normal hearing/borderline normal hearing through 4000 Hz. The auditory P3 was recorded using an oddball paradigm (80%/20%) with the standard tone at the highest frequency of normal hearing in the hearing-impaired participants, also known as the edge frequency (EF). EFs were either 1000 or 2000 Hz for all participants. The target tones represented upward and downward frequency changes of 2%, 5%, and 20% from the standard tones of either 1000 or 2000 Hz. Waveforms were recorded using a two-channel clinical-evoked potential system. Latency and amplitude of the P300 peak were analyzed across groups for the three frequency conditions using repeated measures analysis of variance. The results of this study suggest that the P3 response can be elicited by frequency changes as small as 2-5%. P3 responses at the EF of hearing loss were present and larger in amplitude for more participants with a sloping hearing loss compared to age-matched normal-hearing peers tested at the same frequencies. As a result, the older participants with sloping hearing losses had P3 responses more similar to the younger normal-hearing participants than their age-matched peers with normal hearing. These preliminary results partially support the idea of enhanced cortical representation of frequency at the EF of localized SNHL in older adults that is not purely due to age.

Significance and Novelty effects in single-trial ERP components and autonomic responses

The phasic orienting reflex (OR) was investigated in two counterbalanced blocks of an auditory dishabituation paradigm differing in stimulus Significance (operationalised as tone counting). Twelve tones were presented at very long, randomly-varying interstimulus intervals (ISIs). Novelty and Significance were varied within subjects. Stimulus-response patterns were assessed to find ERP matches for autonomic measures. The phasic OR index was represented by the skin conductance response (SCR). SCR decremented over 10 standard trials, showed recovery on trial 11 (change trial), enhancement to re-presentation of the standard tone (trial 12: dishabituation), and a main effect of Significance over the first 10 trials – demonstrating the formal criteria for an OR index. The evoked cardiac response (HR) subcomponents ECR1 (deceleration) and ECR2 (acceleration) showed no trial effects, but ECR2 showed a Significance effect. Respiratory pause (RP) decreased linearly over trials, and showed recovery, but no dishabituation or Significance effect. Temporal PCA was applied to single-trial EOG-corrected data. Ten ERP components were extracted: P1, N1-3, N1-1, PN, P2, P3a, P3b, HabP3, a Frontal Slow Wave (FSW), and the Classic SW. The dependent measures showed 4 distinct patterns. Pattern 1: No trial or Significance effects (ECR1, P1, N1-3, P3a, FSW); Pattern 2: No trial effect but a Significance effect (ECR2, N1-1, P2); Pattern 3: Trial but not Significance effects (RP, PN, P3b, HabP3); Pattern 4: Both trial and Significance effects (SCR and Classic SW). The evidenced fractionation of autonomic and central measures is compatible with Preliminary Process Theory (PPT), contrary to the notion of a unitary OR.

Abnormal frontoparietal synaptic gain mediating the P300 in patients with psychotic disorder and their unaffected relatives.

The "dysconnection hypothesis" of psychosis suggests that a disruption of functional integration underlies cognitive deficits and clinical symptoms. Impairments in the P300 potential are well documented in psychosis. Intrinsic (self-)connectivity in a frontoparietal cortical hierarchy during a P300 experiment was investigated. Dynamic Causal Modeling was used to estimate how evoked activity results from the dynamics of coupled neural populations and how neural coupling changes with the experimental factors. Twenty-four patients with psychotic disorder, twenty-four unaffected relatives, and twenty-five controls underwent EEG recordings during an auditory oddball paradigm. Sixteen frontoparietal network models (including primary auditory, superior parietal, and superior frontal sources) were analyzed and an optimal model of neural coupling, explaining diagnosis and genetic risk effects, as well as their interactions with task condition were identified. The winning model included changes in connectivity at all three hierarchical levels. Patients showed decreased self-inhibition-that is, increased cortical excitability-in left superior frontal gyrus across task conditions, compared with unaffected participants. Relatives had similar increases in excitability in left superior frontal and right superior parietal sources, and a reversal of the normal synaptic gain changes in response to targets relative to standard tones. It was confirmed that both subjects with psychotic disorder and their relatives show a context-independent loss of synaptic gain control at the highest hierarchy levels. The relatives also showed abnormal gain modulation responses to task-relevant stimuli. These may be caused by NMDA-receptor and/or GABAergic pathologies that change the excitability of superficial pyramidal cells and may be a potential biological marker for psychosis. Hum Brain Mapp 38:3262-3276, 2017. © 2017 Wiley Periodicals, Inc.

Right hemisphere pitch-mismatch negativity reduction in patients with major depression: An MEG study

BackgroundThe mismatch negativity (MMN) component of the event-related potential and its magnetic counterpart, the MMNm, are generated by a mismatch between the physical features of a deviant stimulus and a neuronal sensory-memory trace produced by repetitive standard stimuli. Deficits in the MMN/MMNm have been reported in patients with major depression; however, the results are inconsistent. The present study investigated the pitch-MMNm in patients with major depression using whole-head 306-channel magnetoencephalography (MEG). MethodsTwenty patients with major depression and 36 healthy subjects participated in this study. Subjects were presented with two sequences of auditory stimuli. One consisted of 1000Hz standard signals (probability=90%) and 1200Hz deviant signals (probability=10%), while the other consisted of 1200Hz standard (90%) and 1000Hz deviant signals (10%). Event-related brain responses to standard tones were subtracted from responses to deviant tones. ResultsMajor depressive patients showed significantly reduced magnetic global field power (GFP) of MMNm in the right hemisphere (p=0.02), although no significant MMNm reduction was observed in the left hemisphere (p=0.81). Additionally, patients with major depression showed significantly earlier bilateral MMNm peak latencies (p=0.004). No significant associations were observed between MMNm variables and demographic data/clinical variables within the patients. LimitationsWe could not exclude the effects of antidepressants, mood stabilizers, or neuroleptics on the MMNm abnormalities found in patients with major depression. Sample size was also insufficient to permit subgroup analyses. ConclusionsPatients with major depression exhibited reduced GFP of MMNm in the right hemisphere. The present study suggested that patients with major depression may have right hemispheric dominant preattentive dysfunction.

Human centromedian-parafascicular complex signals sensory cues for goal-oriented behavior selection

Experimental research has shown that the centromedian-parafascicular complex (CM-Pf) of the intralaminar thalamus is activated in attentional orienting and processing of behaviorally relevant stimuli. These observations resulted in the hypothesis that the CM-Pf plays a pivotal role in goal-oriented behavior selection. We here set out to test this hypothesis with electrophysiological recordings from patients with electrodes implanted in CM-Pf for deep brain stimulation (DBS) treatment of chronic neuropathic pain. Six patients participated in (1) an auditory three-class oddball experiment, which required a button press to target tones, but not to standard and deviant tones and in (2) a multi-speaker experiment with a target word that required attention selection and a target image that required response selection. Subjects showed transient neural responses (8–15Hz) to the target tone and the target word. Two subjects additionally showed transient neural responses (15–25Hz) to the target image. All sensory target stimuli were related to an internal goal and required a behavior selection (attention selection, response selection). In group analyses, neural responses were greater to target tones than deviant and standard tones and to target words than other task-relevant words that did not require attention selection. The transient neural responses occurred after the target stimuli but prior to the overt behavioral response. Our results demonstrate that in human subjects the CM-Pf is involved in signaling sensory inputs related to goal-oriented selection of behavior.

SU66. Pilot Study on the Effects of Withania Somnifera on Electrophysiological Measures of Sensory and Cognitive Processing in Schizophrenia

Abstract Oxidative stress and neuroinflammation may contribute to decreased neuronal activity in schizophrenia by affecting the high metabolic demand parvalbumin-containing fast-spiking cortical interneurons. We measured the effects of the antioxidant and anti-inflammatory Ashwagandha (Withania Somnifera; WSE) on event-related potentials (ERPs). Eleven patients with long-term schizophrenia participated in a pilot double-blind adjunctive medication study: 6 took WSE, 5 placebo. Participants heard pitch (10%) and duration deviants (10%) among standard tones (80%) in a mismatch negativity (MMN) task while watching a silent movie. They also performed 2 auditory oddball tasks, either counting rare pitch deviants (15%) or ignoring sounds. For the oddball tasks, a 500-ms duration 40-Hz click train was presented between tones. ERPs were measured before administration of WSE or placebo (T1) and 3 months later (T2). Preliminary analyses indicated improvements in duration MMN with WSE ( = 1.28) but not with placebo ( = 0.27). In the oddball task, the WSE group showed a larger P3 from T1 to T2 (attend = 0.47; ignore = 0.69) compared to placebo (attend = 0.24; ignore = 0.29). Gamma-band steady-state potentials in the WSE group displayed greater attention-related amplitude increase at T2 ( = 0.59) than the placebo group ( = 0.07). WSE intake appears to recover some of the impaired early sensory/cognitive potentials in schizophrenia, possibly by reversing oxidative stress and neuroinflammation. These pilot data indicate further investigation into such adjunctive target pharmacotherapy is warranted.

SU72. Abnormal Frontal Synaptic Gain Mediating the P300 in Patients With Psychosis and Their Unaffected Relatives

Abstract Background: The “dysconnection hypothesis” of psychosis suggests that a disruption of functional integration underlies cognitive deficits and clinical symptoms. Impairments in the P300 potential are well documented in psychosis. We investigated intrinsic (self-)connectivity in a cortical hierarchy during a P300 experiment. We used Dynamic Causal Modeling to estimate how evoked activity results from the dynamics of coupled neural populations and how neural coupling changes with the experimental factors. Methods: Twenty-four patients with psychosis, 24 unaffected relatives, and 25 controls underwent EEG recordings during an auditory oddball paradigm. We analyzed 16 frontoparietal models (primary auditory, superior parietal, and superior frontal sources) and identified an optimal model of neural coupling, explaining diagnosis and genetic risk effects, as well as their interactions with task condition. Results: The winning model included changes in connectivity at all 3 hierarchical levels. Patients showed decreased self-inhibition (ie, increased cortical excitability) in left superior frontal gyrus across task conditions, compared to unaffected participants. Relatives had similar increases in excitability in left superior frontal and right superior parietal sources, and a reversal of the normal synaptic gain changes in response to targets, relative to standard tones. Conclusion: We confirmed that both subjects with psychosis and their relatives show a context-independent loss of synaptic gain control at the highest levels of the hierarchy. The relatives also showed abnormal gain modulation responses to task-relevant stimuli. These may be caused by NMDA-receptor and/or GABAergic pathologies that change the excitability of superficial pyramidal cells and may be a potential biological marker for psychosis.

SA73. Deficits in Attentional Modulation of Auditory Stimuli in First-Episode Schizophrenia

Abstract Background: Auditory deficits have been reported in schizophrenia patients, specifically when using passive tasks to look at mismatch negativity and active tasks to look at P3 suppression in event-related potentials. Attentional deficits have also been reported, so we created a task to determine whether these 2 symptoms were related. Methods: Thirteen first-episode schizophrenia participants and 11 matched healthy control participants heard sounds while watching a silent nature video. The task focuses on N1 auditory event-related potentials and how their size changes under different attention loads. Participants heard standard tones (1k Hz, 50 ms duration, 5 ms ramp) spaced 1050 ms to 1550 ms apart. In one condition, participants were told to ignore tones while in the other condition participants counted tones in groups of 7. Electroencephalography data were recorded from the subjects during the task, and the data were filtered between 0.5 Hz and 20 Hz. It was then processed using ICA to remove eye blinks, eye movements, and heartbeat components. The N1 size was measured using the area of the curve that occurred from 100 ms to 110 ms. Results: Both healthy participants and first episode participants produced an N1 to the tones. There was no main effect of attention or group (Ps > .1). There was a significant interaction effect between group membership and effect of attention (P = .029). The healthy subjects showed larger N1 in the attend condition compared with the ignore condition (P = .074). However, the first-episode subjects showed no significance between attend and ignore conditions (P > .1). In the attend condition, healthy controls N1 was significantly larger than first-episode patients’ (P = .03), but there was no group difference in the ignore condition (P > .1). Conclusion: Our results showed that healthy controls enhance their N1 response with attention, and this effect is not seen in the schizophrenia group. These findings suggest that the auditory deficits experienced by schizophrenia patients may not be the result of abnormalities in the auditory cortex, but abnormalities in the top-down modulation of attention. Clinically, this could result in a potential biomarker for the diagnosis of schizophrenia in high-risk individuals. Further examination of this connection could also lead to a better understanding of auditory neurophysiology in schizophrenia.

Impaired auditory-to-motor entrainment in Parkinson’s disease

Several electrophysiological studies suggest that Parkinson's disease (PD) patients have a reduced tendency to entrain to regular environmental patterns. Here we investigate whether this reduced entrainment concerns a generalized deficit or is confined to movement-related activity, leaving sensory entrainment intact. Magnetoencephalography was recorded during a rhythmic auditory target detection task in 14 PD patients and 14 control subjects. Participants were instructed to press a button when hearing a target tone amid an isochronous sequence of standard tones. The variable pitch of standard tones indicated the probability of the next tone to be a target. In addition, targets were occasionally omitted to evaluate entrainment uncontaminated by stimulus effects. Response times were not significantly different between groups and both groups benefited equally from the predictive value of standard tones. Analyses of oscillatory beta power over auditory cortices showed equal entrainment to the tones in both groups. By contrast, oscillatory beta power and event-related fields demonstrated a reduced engagement of motor cortical areas in PD patients, expressed in the modulation depth of beta power, in the response to omitted stimuli, and in an absent motor area P300 effect. Together, these results show equally strong entrainment of neural activity over sensory areas in controls and patients, but, in patients, a deficient translation of the adjustment to the task rhythm to motor circuits. We suggest that the reduced activation reflects not merely altered resonance to rhythmic external events, but a compromised recruitment of an endogenous response reflecting internal rhythm generation.NEW & NOTEWORTHY Previous studies suggest that motor cortical activity in PD patients has a reduced tendency to entrain to regular environmental patterns. This study demonstrates that the deficient entrainment in PD concerns the motor system only, by showing equally strong entrainment of neural activity over sensory areas in controls and patients but, in patients, a deficient translation of this adjustment to the task rhythm to motor circuits.