Loudness Dependence Research Articles

Electroconvulsive therapy modulates loudness dependence of auditory evoked potentials: a pilot MEG study.

Electroconvulsive therapy (ECT) remains a critical intervention for treatment-resistant depression (MDD), yet its neurobiological underpinnings are not fully understood. This pilot study aims to investigate changes in loudness dependence of auditory evoked potentials (LDAEP), a proposed biomarker of serotonergic activity, in patients undergoing ECT. High-resolution magnetoencephalography (MEG) was utilized to measure LDAEP in nine depressed patients receiving right unilateral ECT. We hypothesized that ECT would reduce the LDAEP slope, reflecting enhanced serotonergic neurotransmission. Depression severity and cognitive performance were assessed using the 24-item Hamilton Depression Rating Scale (HDRS24) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. Contrary to our hypothesis, findings indicated a significant increase in LDAEP post-ECT (t 8 = 3.17, p = .013). The increase in LDAEP was not associated with changes in depression severity or cognitive performance. The observed increase in LDAEP suggests a more complex interaction between ECT and neurobiological systems, rather than a direct reflection of serotonergic neurotransmission. Potential mechanisms for this increase include ECT's impact on serotonergic, dopaminergic, glutamatergic, and GABAergic receptor activity, neuroplasticity involving brain-derived neurotrophic factor (BDNF), and inflammatory modulators such as TNF-α. Our results highlight the multifaceted effects of ECT on brain function, necessitating further research to elucidate these interactions.

Electroconvulsive Therapy Modulates Loudness Dependence of Auditory Evoked Potentials: A Pilot MEG Study.

Electroconvulsive therapy (ECT) remains a critical intervention for treatment-resistant depression (MDD), yet its neurobiological underpinnings are not fully understood. This pilot study utilizes high-resolution magnetoencephalography (MEG) in nine depressed patients receiving right unilateral ECT, to investigate the changes in loudness dependence of auditory evoked potentials (LDAEP), a proposed biomarker of serotonergic activity, following ECT. We hypothesized that ECT would reduce the LDAEP slope, reflecting enhanced serotonergic neurotransmission. Contrary to this, our findings indicated a significant increase in LDAEP post-ECT ( t 8 = 3.17, p = .013). The increase in LDAEP was not associated with changes in depression severity or cognitive performance, as assessed by the Hamilton Depression Rating Scale (HAMD-24) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We discussed potential mechanisms for the observed increase, including ECT's impact on serotonergic, dopaminergic, glutamatergic, and GABAergic receptor activity, neuroplasticity involving brain-derived neurotrophic factor (BDNF), and inflammation modulators such as TNF- alpha . Our results suggest a complex interaction between ECT and these neurobiological systems, rather than a direct reflection of serotonergic neurotransmission.

Microbiome composition and central serotonergic activity in patients with depression and type 1 diabetes

The role of gut–brain axis functioning gains growing attention in research on the pathophysiology of major depressive disorders. Here, especially consequences of altered microbiota composition on tryptophan metabolism resulting in altered serotonergic neurotransmission in the central nervous system (CNS) have reached a central position. Previous research, however, mainly focused on either microbiota and peripheral serotonin levels or central serotonergic neurotransmission. The present study aimed to combine the analysis of microbiota composition and central serotonergic activity using a valid neurophysiological indicator. We recruited 19 adult patients with type 1 diabetes and depression (D + D; 7 males), 19 patients with type 1 diabetes (D-; 7 male), and 20 healthy participants (HC; 7 males). Next to the analysis of fecal microbiota regarding α- and β-diversity, the loudness dependence of auditory evoked potential (LDAEP) was investigated, a non-invasive measurement of central serotonergic activity. High α-diversity was associated with high LDAEP, i.e., low serotonergic activity, in patients with diabetes and additional depression. Furthermore, relative abundances of bacterial families belonging to Bacteroidetes, Proteobacteria and Firmicutes were shown to have an impact on central serotonergic activity. This finding was supported by a tendency indicating an association of central serotonergic activity with the Bacteroidetes–Firmicutes ratio in both patients’ groups. Together, this data suggests that the guts’ microbiota composition might play an important role in regulating the central serotonergic activity in the brain.

Machine learning-based classification using electroencephalographic multi-paradigms between drug-naïve patients with depression and healthy controls

BackgroundElectroencephalography (EEG) is a supplementary diagnostic tool in psychiatry but lacks practical usage. EEG has demonstrated inconsistent diagnostic ability because major depressive disorder (MDD) is a heterogeneous psychiatric disorder with complex pathologies. In clinical psychiatry, it is essential to detect these complexities using multiple EEG paradigms. Though the application of machine learning to EEG signals in psychiatry has increased, an improvement in its classification performance is still required clinically. We tested the classification performance of multiple EEG paradigms in drug-naïve patients with MDD and healthy controls (HCs). MethodsThirty-one drug-naïve patients with MDD and 31 HCs were recruited in this study. Resting-state EEG (REEG), the loudness dependence of auditory evoked potentials (LDAEP), and P300 were recorded for all participants. Linear discriminant analysis (LDA) and support vector machine (SVM) classifiers with t-test-based feature selection were used to classify patients and HCs. ResultsThe highest accuracy was 94.52 % when 14 selected features, including 12 P300 amplitudes (P300A) and two LDAEP features, were layered. The accuracy was 90.32 % when a SVM classifier for 30 selected features (14 P300A, 14 LDAEP, and 2 REEG) was layered in comparison to each REEG, P300A, and LDAEP, the best accuracies of which were 71.57 % (2-layered with LDA), 87.12 % (1-layered with LDA), and 83.87 % (6-layered with SVM), respectively. LimitationsThe present study was limited by small sample size and difference in formal education year. ConclusionsMultiple EEG paradigms are more beneficial than a single EEG paradigm for classifying drug-naïve patients with MDD and HCs.

Relationship between Loudness Dependence of Auditory-evoked Potentials and Suicidality.

: Serotonin concentration is associated with suicide in patients with major depressive disorder. Loudness dependence of auditory-evoked potentials (LDAEPs), a representative neurophysiological indicator, is related to serotonin activity. Therefore, this study aimed to investigate the relationship between LDAEPs and suicidal ideation, suicide attempts, and the severity of depression. : We evaluated the scalp N1, P2, and N1/P2 LDAEPs along with standardized low-resolution brain electromagnetic tomography (sLORETA)-localized N1, P2, and N1/P2 LDAEPs of 221 patients with major depressive disorder. The demographic and clinical data of the patients, including data on suicidal ideation and previous suicide attempts, were obtained from clinical interviews and medical records. The severity of depression was assessed using the Beck Depression Inventory and Hamilton Depression Rating Scale, whereas suicidal ideation was evaluated using the Beck Scale for Suicidal Ideation (BSS). : The total BSS score was associated with low N1/P2 LDAEP (p = 0.045), whereas P2 sLORETA-LDAEP was associated with lower previous suicide attempts (p = 0.043). In addition, suicide attempt was correlated with an elevated P2 left sLORETA-LDAEP (coefficient = 4.638, p = 0.038). : These findings suggest that suicidal ideation is associated with decreased LDAEP, whereas suicide attempt is associated with increased LDAEP.

Endocannabinergic modulation of central serotonergic activity in healthy human volunteers

BackgroundThe serotonergic and the endocannabinoid system are involved in the etiology of depression. Depressive patients exhibit low serotonergic activity and decreased level of the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2AG). Since the cannabinoid (CB) 1 receptor is activated by endogenous ligands such as AEA and 2AG, whose concentration are controlled by the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, respectively, we investigated the effects on serotonergic utilization. In this study, we investigated the impact of the rs1049353 single-nucleotide polymorphism (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the rs324420 SNP of the FAAH gene on the serotonergic and endocannabinoid system in 59 healthy volunteers.MethodsSerotonergic activity was measured by loudness dependence of auditory-evoked potentials (LDAEP). Plasma concentrations of AEA, 2AG and its inactive isomer 1AG were determined by mass spectrometry. Genotyping of two SNPs (rs1049353, rs344420) was conducted by polymerase chain reaction (PCR) and differential enzymatic analysis with the PCR restriction fragment length polymorphism method.ResultsGenotype distributions by serotonergic activity or endocannabinoid concentration showed no differences. However, after detailed consideration of the CNR1-A-allele-carriers, a reduced AEA (A-allele-carrier M = 0.66, SD = 0.24; GG genotype M = 0.72, SD = 0.24) and 2AG (A-allele-carriers M = 0.70, SD = 0.33; GG genotype M = 1.03, SD = 0.83) plasma concentration and an association between the serotonergic activity and the concentrations of AEA and 2AG has been observed.ConclusionsOur results suggest that carriers of the CNR1-A allele may be more susceptible to developing depression.

Association between the loudness dependence of auditory evoked potential, serotonergic neurotransmission and treatment outcome in patients with depression

Previous studies have suggested that the loudness dependence of auditory evoked potential (LDAEP) is associated with the effectiveness of antidepressant treatment in patients with major depressive disorders (MDD). Furthermore, both LDAEP and the cerebral serotonin 4 receptor (5-HT4R) density is inversely related to brain serotonin levels.We included 84 patients with MDD and 22 healthy controls to examined the association between LDAEP and treatment response and its association with cerebral 5-HT4R density. Participants underwent both EEG and 5-HT4R neuroimaging with [11C]SB207145 PET. Thirty-nine patients with MDD were re-examined after 8 weeks of treatment with selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitor (SSRI/SNRI).We found that the cortical source of LDAEP was higher in untreated patients with MDD compared to healthy controls (p=0.03). Prior to SSRI/SNRI treatment, subsequent treatment responders had a negative association between LDAEP and depressive symptoms and a positive association between scalp LDAEP and symptom improvement at week 8. This was not found in source LDAEP. In healthy controls, we found a positive correlation between both scalp and source LDAEP and cerebral 5-HT4R binding but that was not observed in patients with MDD. We did not see any changes in scalp and source LDAEP in response to SSRI/SNRI treatment.These results support a theoretical framework where both LDAEP and cerebral 5-HT4R are indices of cerebral 5-HT levels in healthy individuals while this association seems to be disrupted in MDD. The combination of the two biomarkers may be useful for stratifying patients with MDD.Clinical Trials Registration:https://clinicaltrials.gov/ct2/show/NCT02869035?draw=1Registration number: NCT0286903.

Relationships between fear of flying, loudness dependence of auditory evoked potentials and frontal alpha asymmetry

Previous research has suggested that fear of flying, which is defined as a situational, specific phobia, could overlap with depressive and anxiety disorders. Whether the neuronal dysfunctions including altered serotonergic activity in the brain and altered neural oscillations observed for depressive and anxiety disorders also overlap with alterations in fear of flying is unclear. Here, thirty-six participants with self-reported fear of flying (FF) and forty-one unaffected participants (NFF) were recruited. The participants completed the Beck Depression Inventory (BDI-II), the State-trait Anxiety Inventory (STAI) and the Fear of Flying Scale (FFS). EEG-recording was conducted during resting-state and during presentation of auditory stimuli with varying loudness levels for analysis of the Loudness Dependence of Auditory Evoked Potentials (LDAEP), which is suggested to be inversely related to central serotonergic activity. Participants with fear of flying did not differ from the control group with regard to BDI-II and STAI data. The LDAEP was higher over F4 electrode in the FF group compared to controls, whereas exploratory analysis suggest that differences between groups were conveyed by female participants. Moreover, the FF group showed relatively higher right frontal alpha activity compared to the control group, whereas no difference in frequency power (alpha, beta and theta) was observed. Thus, this study brought the first hint for reduced serotonergic activity in individuals with fear of flying and relatively higher right frontal activity. Thus, based on the preliminary findings, future research should aim to examine the boundaries with anxiety and depressive disorders and to clarify the distinct neural mechanisms.

Relationship of loudness-dependent auditory evoked potentials with change-related cortical responses

Previous studies have suggested that change-related cortical responses are phenomena similar to the onset response and could be applied to the loudness dependence of auditory evoked potential (LDAEP) paradigm. In the present study, we examined the relationship between LDAEP and the change-related response using electroencephalography findings in 50 healthy subjects. There were five conditions (55, 65, 75, 85, and 95 dB) for LDAEP and five similar conditions (abrupt sound pressure increase from 70 to 75, 80, 85, 90, and 95 dB) for the change-related response. Both the onset and abrupt sound pressure increase evoked a triphasic response with peaks at approximately 50 (P50), 100 (N100), and 200 (P200) ms. We calculated the peak-to-peak amplitudes for P50/N100 and N100/P200. Medians and slopes for P50/N100 and N100/P200 amplitudes were calculated and compared between the two measures. Results revealed a significant correlation for both the slope and median for P50/N100 (r = 0.36, 0.37, p = 1.0 × 10-2, 7.9 × 10-3), N100/P200 (r = 0.40, 0.34, p = 4.0 × 10-3, 1.6 × 10-2), and P50/N100/P200 (r = 0.36, 0.35, p = 1.0 × 10-2, 1.3 × 10-2). These results suggested that the change-related response and LDAEP shared generation mechanisms at least partially.

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.

The Loudness Dependence of Auditory Evoked Potentials is associated with the Symptom Severity and Treatment in Boys with Attention Deficit Hyperactivity Disorder.

ObjectiveThe loudness dependence of the auditory evoked potential (LDAEP) is associated with central serotonergic neurotransmission. Recent studies have proposed that LDAEP is also influenced by dopaminergic activity. Evidence shows attention deficit hyperactivity disorder (ADHD) symptoms are associated with dopamine dysfunction. This study aimed to evaluate the relation between ADHD symptoms and LDAEP, as well as medication-mediated changes of LDAEP.MethodsA total of 38 male children (6−12 years old) with ADHD were analyzed in this study. Symptom severity was assessed using the ADHD rating scale (ARS) and the continuous performance test. To determine LDAEP, the auditory event-related potential was evaluated before medication. Changes in LDAEP were measured after 12 weeks of treatment with methylphenidate.ResultsThe subjects had a mean age of 9.24 ± 1.74 years with an average IQ of 109.4 ± 13.8. Before pharmacological treatment with methylphenidate, LDAEP was positively associated with the ARS score after adjusting for age and IQ (r = 0.592, p = 0.005). LDAEP was correlated with inattention (r = 0.522, p = 0.015) and hyperactivity-impulsivity (r = 0.6, p = 0.004). However, the LDAEP of 15 subjects decreased following methylphenidate treatment (Z = −1.988, p = 0.047).ConclusionIn boys with ADHD, LDAEP appears to be associated with symptom severity. LDAEP showed a significant association with impulsivity and inattention. Importantly, LDAEP was shown to decrease after drug treatment. Our findings support the utility of LDAEP as a noninvasive and clinically useful method to assess symptom severity in children with ADHD.

Narcissism and central serotonergic neurotransmission in depression

Objectives Based on previous research, it has been proposed that the development of depressive disorders is related to altered functioning of the serotonergic systems as well as the personality style, including narcissism. However, it is unclear to date how personality style, especially narcissism, depressive disorders and serotonergic activity are related. Methods We included 74 patients with a depressive disorder (DP) and 74 healthy controls (HC) in the study. All participants completed the Personality Style and Disorder Inventory (PSDI) and the Beck Depression Inventory (BDI II). Moreover, we conducted EEG recordings for analysis of serotonergic neurotransmission by using the so-called intensity or loudness dependence of the auditory evoked potentials (LDAEP). Results Significantly higher LDAEP results emerged for the DP group compared to the HC group, which indicated lower serotonergic activity in the patient's group. In addition, the positive correlation between ambitious-narcissistic personality and LDAEP reached significance in depressive patients. Limitations There was only a monocentric cross-sectional study with only one scale having differences between the two groups due to age and education. Conclusions Our data supports the theory of lower serotonergic activity in patients with depressive disorders and further suggests that high narcissistic personality traits are related to lower serotonergic neurotransmission in patients.

Association between the loudness dependence of auditory evoked potentials and age in patients with schizophrenia and depression.

ObjectiveAlthough serotonergic dysfunction is significantly associated with major depressive disorder (MDD) and schizophrenia (SCZ), comparison of serotonergic dysfunction in both diseases has received little attention. Serotonin hypotheses have suggested diminished and elevated serotonin activity in MDD and SCZ, respectively. However, the foundations underlying these hypotheses are unclear regarding changes in serotonin neurotransmission in the aging brain. The loudness dependence of auditory evoked potentials (LDAEP) reflects serotonin neurotransmission. The present study compared the LDAEP between patients with SCZ or MDD and healthy controls (HCs). We further examined whether age was correlated with the LDAEP and clinical symptoms.MethodsThis prospective clinical study included 105 patients with SCZ (n = 54) or MDD (n = 51). Additionally, 35 HCs were recruited for this study. The LDAEP was measured on the midline channels via 62 electroencephalography channels.ResultsPatients with SCZ or MDD showed a significantly smaller mean LDAEP than those in HCs. The LDAEP was positively correlated with age in patients with SCZ or MDD.ConclusionsChanges in central serotonergic activity could be indicated by evaluating the LDAEP in patients with SCZ or MDD. Age-related reductions in serotonergic activity may be screened using the LDAEP in patients with SCZ or MDD.

Anxiolytic-Like Effects of Extremely Low Frequency Electric Field in Stressed Rats: Involvement of 5-HT2C Receptors

Background Possible modulatory effects of non-invasive brain stimulation have gained interest recently. In our study, the effect of low frequency electric fields (LF-EF) on stress-induced electrophysiological, behavioral changes and the possible involvement of serotonergic 5-HT2C receptors were investigated. Materials and Methods A total of 8 groups including the control groups were formed by applying LF-EF with or without a 5-HT2C receptor agonist to naïve or acute stress exposed rats to demonstrate the effects of LF-EF. LF-EF administration at 10 kV/m was started 30 minutes before acute stress application and lasted for 1 hour in total. Anxiety levels and social interaction were evaluated using the elevated plus maze test and social interaction test, respectively. Auditory evoked potentials (AEP) were recorded by using ascending loudness paradigms. Loudness dependence AEP (LDAEP) was calculated by using amplitude values to analyze serotonergic transmission. Serotonin and glucocorticoid levels were measured in the frontal cortex and hippocampus. Results It was observed that the applied LF-EF reduced the anxiety behavior, and attenuated the LDAEP responses in stress and/or 5-HT2C receptor agonist applied groups. In parallel, an increase in serotonin levels and a decrease in glucocorticoid levels were observed. However, LF-EF exposure was ineffective in impaired social interaction. Conclusions Our findings show that 10 kV/m LF-EF administration may modulate the neural network and physiological responses associated with mild acute stress. 5-HT2C receptor dependent functions are thought to play a role in the anxiolytic effect of LF-EF.

Investigation of the Serotonergic Activity and the Serotonin Content in Serum and Platelet, and the Possible Role of the Serotonin Transporter in Patients with Depression

According to the monoamine hypothesis, the development of depression is associated with dysfunctions of the serotonergic system. Alterations in the serotonin transporter gene (5-HTTLPR), the serotonergic activity in the brain, and the content of serotonin (5-HT) have been related to depression and were examined separately by previous studies. This study investigates these parameters in 89 depressed patients and 89 healthy participants. We investigated the serotonergic activity measured by the loudness dependence of auditory evoked potentials (LDAEP). In addition to the examination of the serotonin content (serum and platelet), enzyme-linked immunosorbent assays (ELISA) were used and 5-HTTLPR genotypes were analyzed. We observed a lower serotonin content in patients compared to healthy participants. Further, we noticed a correlation between anxiety and depression-associated symptoms with serotonergic activity. Patients treated with SSRI/SNRI showed decreased contents of serum serotonin compared to patients without any psychotropic medication or other psychotropic medications. Since the serotonergic activity, peripheral serotonin content, and 5-HTTLPR were unrelated, the results suggest independent alterations of central and peripheral serotonergic systems in depression. In line with this finding, serotonergic activity was related to anxiety and depression symptoms. Furthermore, the applied medication seems to influence serum serotonin content in patients with depression.

ELECTROPHYSIOLOGICAL CORRELATES OF SUICIDALITY

Suicidal risk assessment is still a major challenge not only in psychiatric practice. Clinical investigation of suicidality can be significantly improved by using standardized scales for assessing suicide risk. The choice of a method for assessing suicidality also has significant implications for the search of valid available biomarker of suicidal behavior, where a less complex suicidality assessment procedure yields inaccurate results. This article offers an overview and analyzes in detail clinical studies of suicidality by electrophysiological methods since 2005 to 5/2020, especially in connection with presumed pathophysiological mechanism of the "suicidal brain" and the chosen method of sucidality assessment. Electrophysiological methods such as quantitative electroencephalography indicators, event-related potential, loudness dependence of the auditory evoked potential, polysomnography and heart rate variability offer a robust battery of easily available methods for assessing impaired emotional regulation. Nowadays it is unfortunately very difficult to point out the optimal electrophysiological examination of suicidal behaviour because of conflicting conclusion of presented studies which have been probably caused by various suicidal risk assessments, not always available data on affecting medication prior to testing and small samples of suicidal participants among studies. The most consistent and hopeful results are presented by evaluation of theta power by quantitative electroencephalography, although there are also few conflicting conclusions. The authors of this paper believe that this article could be good starting point for further research of electrophysiological methods in the field of suicidality.

Serotonergic central tone in Parkinson’s disease with fatigue: Evidence from the loudness dependence of auditory evoked potentials (LDAEP)

Central fatigue in Parkinson’s disease (PD) is a common and disabling symptom that further worsens the patients’ quality of life. A deficit in the serotonergic system may be implicated in the occurrence of fatigue in patients with PD as well as in those with other chronic conditions characterized by fatigue. The loudness dependence of auditory evoked potentials (LDAEP) is a neurophysiological tool that has proved to be effective in measuring the serotonergic central function in vivo. The aim of the present study was to assess central serotonergic activity in PD patients and to explore its possible association with the presence of fatigue. LDAEP was recorded in 38 PD patients (26 without fatigue – PDnF and 12 with fatigue – PDF) and 34 healthy controls. A significant difference between parkinsonian patients and controls emerged, with patients displaying stronger LDAEP values (which reflect a lower serotonergic central tone) than controls. By contrast, no differences in LDAEP emerged between PDF and PDnF. Our electrophysiological data confirmed the presence of a deficit in serotonergic central transmission in PD. An association between this deficit and fatigue was not demonstrated. It is likely that an altered dopamine/serotonin balance, rather than a serotonin deficit alone, is involved in the genesis of central fatigue. This complex and multifaceted symptom is related above all to a dysfunction in the striato-thalamo-cortical loop that connects the neostriatum to the frontal lobe and is strongly affected by motivation.

The Assessments of Psychological Dynamics in Daily Life of Individual With Severe Motor and Intellectual Disabilities (SMID): Relationship Between the Inter-Stimulus Interval on Communications and the SMID’s Heart Rate

Central fatigue in Parkinson’s disease (PD) is a common and disabling symptom that further worsens the patients’ quality of life. A deficit in the serotonergic system may be implicated in the occurrence of fatigue in patients with PD as well as in those with other chronic conditions characterized by fatigue. The loudness dependence of auditory evoked potentials (LDAEP) is a neurophysiological tool that has proved to be effective in measuring the serotonergic central function in vivo. The aim of the present study was to assess central serotonergic activity in PD patients and to explore its possible association with the presence of fatigue. LDAEP was recorded in 38 PD patients (26 without fatigue – PDnF and 12 with fatigue – PDF) and 34 healthy controls. A significant difference between parkinsonian patients and controls emerged, with patients displaying stronger LDAEP values (which reflect a lower serotonergic central tone) than controls. By contrast, no differences in LDAEP emerged between PDF and PDnF. Our electrophysiological data confirmed the presence of a deficit in serotonergic central transmission in PD. An association between this deficit and fatigue was not demonstrated. It is likely that an altered dopamine/serotonin balance, rather than a serotonin deficit alone, is involved in the genesis of central fatigue. This complex and multifaceted symptom is related above all to a dysfunction in the striato-thalamo-cortical loop that connects the neostriatum to the frontal lobe and is strongly affected by motivation.

Relationship Between the Loudness Dependence of the Auditory Evoked Potential and the Severity of Suicidal Ideation in Patients with Major Depressive Disorder.

ObjectiveThe loudness dependence of the auditory evoked potential (LDAEP) is a reliable indicator that is inversely related to central serotonergic activity, and recent studies have suggested an association between LDAEP and suicidal ideation. This study investigated differences in LDAEP between patients with major depressive disorder and high suicidality and those with major depressive disorder and low suicidality compared to healthy controls.MethodsThis study included 67 participants 23 patients with major depressive disorder with high suicidality (9 males, mean age 29.3 ± 15.7 years, total score of SSI-BECK ≥ 15), 22 patients with major depressive disorder with low suicidality (9 males, mean age 42.2 ± 14.4 years, total score of SSI-BECK ≤ 14), and 22 healthy controls (11 males, mean age 31.6 ± 8.7 years). Participants completed the following assessments Patient Health Questionnaire-9, Beck Depression Inventory-II, Beck Scale for Suicidal ideation, State Anxiety Scale of the State-Trait Anxiety Inventory, Beck Anxiety Inventory, and LDAEP (measured at electrode Cz).ResultsThere were no sex-related differences among groups (p = 0.821). The high-suicidality group exhibited significantly higher LDAEP compared to the low-suicidality group (0.82 ± 0.79 vs. 0.26 ± 0.36, p = 0.014). No significant differences were found between the control and high-suicidality (p = 0.281) or the control and low-suicidality groups (p = 0.236).ConclusionLDAEP was applied to demonstrate the association between serotonergic activity and suicidal ideation and suicide risk in major depression and may be a candidate of biological marker for preventing suicide in this study.

Does the Loudness Dependence of Auditory Evoked Potential Predict Response to Selective Serotonin Reuptake Inhibitors?: A Meta-analysis.

ObjectiveLoudness of dependence of the auditory evoked potential (LDAEP) is an electroencephalogram-based measure that represents amplitude changes of auditory evoked potentials in primary auditory cortex. Several narrative reviews argued that pre-treatment LDAEP values predict responses to selective serotonin reuptake inhibitors (SSRIs). This study aims to quantify the overall relationship between baseline LDAEP values and treatment response to SSRIs in patients with depression and generalized anxiety disorders, evidenced by clinical symptoms reductions, across multiple studies.MethodsIn our meta-analysis, seven articles with a total sample of 241 patients were included.ResultsOur results showed that stronger baseline LDAEP values predicted favorable response to SSRIs for depression and anxiety, with a moderate effect size.ConclusionThe current results support the idea that LDAEP is a promising biomarker for SSRIs treatment prediction in patients with depression and generalized anxiety disorder.