Recurrent Neural Network Model of Human Event-related Potentials in Response to Intensity Oddball Stimulation.

The mismatch negativity (MMN) component of the human event-related potential (ERP) is frequently interpreted as a sensory prediction-error signal. However, there is ambiguity concerning the neurophysiology underlying hypothetical prediction and prediction-error signalling components, and whether these can be dissociated from overlapping obligatory components of the ERP that are sensitive to physical properties of sounds. In the present study, a hierarchical recurrent neural network (RNN) was fitted to ERP data from 38 subjects. After training the model to reproduce ERP waveforms evoked by 80 dB standard and 70 dB deviant stimuli, it was used to simulate a response to 90 dB deviant stimuli. Internal states of the RNN effectively combined to generate synthetic ERPs, where individual hidden units are loosely analogous to population-level sources. Model behaviour was characterised using principal component analysis of stimulus condition, layer, and individual unit responses. Hidden units were categorised according to their temporal response fields, and statistically significant differences among stimulus conditions were observed for amplitudes of units peaking in the 0-75 ms (P50), 75-125 ms (N1), and 250-400 ms (N3) latency ranges, surprisingly not including the measurement window of MMN. The model demonstrated opposite polarity changes in MMN amplitude produced by falling (70 dB) and rising (90 dB) intensity deviant stimuli, consistent with loudness dependence of sensory ERP components. This modelling study suggests that loudness dependence is a principal driver of intensity MMN, and future studies ought to clarify the distinction between loudness dependence, adaptation and prediction-error signalling.

Auditory event-related potentials in separating patients with depressive disorders and non-depressed controls: A narrative review.

This narrative review brings together the findings regarding the differences in the auditory event-related potentials (ERPs) between patients with depressive disorder and non-depressed control subjects. These studies' results can inform us of the possible alterations in sensory-cognitive processing in depressive disorders and the potential of using these ERPs in clinical applications. Auditory P3, mismatch negativity (MMN) and loudness dependence of auditory evoked potentials (LDAEP) were the subjects of the investigation. A search in PubMed yielded 84 studies. The findings of the reviewed studies were not highly consistent, but some patterns could be identified. For auditory P3b, the common findings were attenuated amplitude and prolonged latency among depressed patients. Regarding auditory MMN, especially the amplitude of duration deviance MMN was commonly attenuated, and the amplitude of frequency deviance MMN was increased in depressed patients. In LDAEP studies, generally, no differences between depressed patients and non-depressed controls were reported, although some group differences concerning specific depression subtypes were found. This review posits that future research should investigate whether certain stimulus conditions are particularly efficient at separating depressed and non-depressed participant groups. Future studies should contrast responses in different subpopulations of depressed patients, as well as different clinical groups (e.g., depressive disorder and anxiety disorder patients), to investigate the specificity of the auditory ERP alterations for depressive disorders.

Preserved Serotonergic Activity in Early-Onset Parkinson's Disease.

BACKGROUND: Serotonergic dysfunction may play an important role in motor and nonmotor symptoms of Parkinson's disease (PD). The loudness dependence of auditory evoked potentials (LDAEP) has been used to evaluate serotonergic activity. Therefore, this study aimed to determine central serotonergic activity using LDAEP in de novo PD according to the age at onset and changes in serotonergic activity after dopaminergic treatment. METHODS: A total of 30 patients with unmedicated PD, 16 in the early-onset and 14 in the late-onset groups, were enrolled. All subjects underwent comprehensive neurological examination, laboratory tests, the Unified Parkinson's Disease Rating Scale, and LDAEP. The LDAEP was calculated as the slope of the two N1/P2 peaks measured at the Cz electrode, first at baseline conditions (pretreatment) and a second time after 12 weeks (post-treatment) following dopaminergic medications. RESULTS: The absolute values of pretreatment N1/P2 LDAEP (early-onset: late-onset, 0.99 ± 0.68: 1.62 ± 0.88, p = 0.035) and post-treatment N1 LDAEP (early-onset: late-onset, -0.61 ± 0.61: -1.26 ± 0.91, p = 0.03) were significantly lower in the early-onset group compared with those of the late-onset group. In addition, a higher value of pretreatment N1/P2 LDAEP was significantly correlated with the late-onset group (coefficient = 1.204, p = 0.044). The absolute value of the N1 LDAEP decreased after 12 weeks of taking dopaminergic medication (pretreatment: post-treatment, -1.457 ± 1.078: -0.904 ± 0.812, p = 0.0018). CONCLUSIONS: Based on the results of this study, LDAEP could be a marker for serotonergic neurotransmission in PD. Central serotonergic activity assessed by LDAEP may be more preserved in early-onset PD patients and can be altered with dopaminergic medication.

Tobacco use is associated with reduced amplitude and intensity dependence of the cortical auditory evoked N1-P2 component.

RATIONALE: Tobacco use is linked to cerebral atrophy and reduced cognitive performance in later life. However, smoking-related long-term effects on brain function remain largely uncertain. Previous studies suggest that nicotine affects serotonergic signaling, and the intensity dependence (alias loudness dependence) of the auditory evoked N1-P2 potential has been proposed as a marker of serotonergic neurotransmission. OBJECTIVE: In the present study, we assesed the effects of chronic smoking on amplitude and intensity dependence of the auditory evoked N1-P2 potential. METHODS: Subjects underwent a 15-min intensity dependence of auditory evoked potentials (IAEP) paradigm. From N = 1739 eligible subjects (40-79 years), we systematically matched current smokers, ex-smokers, and never-smokers by sex, age, alcohol and caffeine consumption, and socioeconomic status. Between-group differences and potential dose-dependencies were evaluated. RESULTS: Analyses revealed higher N1-P2 amplitudes and intensity dependencies in never-smokers relative to ex- and current smokers, with ex-smokers exhibiting intermediate intensity dependencies. Moreover, we observed pack years and number of cigarettes consumed per day to be inversely correlated with amplitudes in current smokers. CONCLUSIONS: According to the IAEP serotonin hypothesis, our results suggest serotonin activity to be highest in current smokers, intermediate in ex-smokers, and lowest in never-smokers. To our knowledge, the present study is the first providing evidence for a dose-dependent reduction in N1-P2 amplitudes. Further, we extend prior research by showing reduced amplitudes and intensity dependencies in ex-smokers even 25 years, on average, after cessation. While we can rule out several smoking-related confounders to bias observed associations, causal inferences remain to be established by future longitudinal studies.

Serotonin: from sensory processing to schizophrenia using an electrophysiological method.

Serotonin plays a major role in sensory processing especially with in the primary auditory cortex. The so-called loudness dependence of auditory evoked potentials is generated by pyramidal cells of the primary auditory cortex (LDAEP) which are modulated by serotonergic projection fibers to the main regulators of pyramidal cells, i.e. GABAergic interneurons. Therefore, there are a lot of preclinical as well as clinical proofs and hints that the LDAEP may serve as a valid indicator of synaptically released serotonin, although there are also data not supporting this relationship. This is further examplified by LDAEP data in patients with different states of schizophrenia, from prodromal to the chronic state. Hereby, a strong relationship was found between LDAEP, i.e. different serotonin levels, and the negative symptoms of these groups of patients with schizophrenia. This underlines the importance of LDAEP as indicator of central serotonergic neurotransmission and its high relevance for clinical psychiatry and psychopharmacology.

Spatiotemporal properties of auditory intensity processing in multisensor MEG.

Loudness dependence of auditory evoked potentials (LDAEP) evaluates loudness processing in the human auditory system and is often altered in patients with psychiatric disorders. Previous research has suggested that this measure may be used as an indicator of the central serotonergic system through the highly serotonergic innervation of the auditory cortex. However, differences among the commonly used analysis approaches (such as source analysis and single electrode estimation) may lead to different results. Putatively due to discrepancies of the underlying structures being measured. Therefore, it is important to learn more about how and where in the brain loudness variation is processed. We conducted a detailed investigation of the LDAEP generators and their temporal dynamics by means of multichannel magnetoencephalography (MEG). Evoked responses to brief tones of five different intensities were recorded from 19 healthy participants. We used magnetic field tomography in order to appropriately localize superficial as well as deep source generators of which we conducted a time series analysis. The results showed that apart from the auditory cortex other cortical sources exhibited activation during the N1/P2 time window. Analysis of time courses in the regions of interest revealed a sequential cortical activation from primary sensory areas, particularly the auditory and somatosensory cortex to posterior cingulate cortex (PCC) and to premotor cortex (PMC). The additional activation within the PCC and PMC has implications on the analysis approaches used in LDAEP research.