Auditory target and novelty processing in patients with unilateral hippocampal sclerosis: A current-source density study

The capacity to respond to novel events is crucial for adapting to the constantly changing environment. Here, we recorded 29-channel Event Related Brain Potentials (ERPs) during an active auditory novelty oddball paradigm and used for the first time Current Source Density-transformed Event Related Brain Potentials and associated time-frequency spectra to study target and novelty processing in a group of epileptic patients with unilateral damage of the hippocampus (N = 18) and in healthy matched control participants (N = 18). Importantly, we used Voxel-Based Morphometry to ensure that our group of patients had a focal unilateral damage restricted to the hippocampus and especially its medial part. We found a clear deficit for target processing at the behavioral level. In addition, compared to controls, our group of patients presented (i) a reduction of theta event-related synchronization (ERS) for targets and (ii) a reduction and delayed P3a source accompanied by reduced theta and low-beta ERS and alpha event-related synchronization (ERD) for novel stimuli. These results suggest that the integrity of the hippocampus might be crucial for the functioning of the complex cortico-subcortical network involved in the detection of novel and target stimuli

The presence of anhedonia in individuals with subacute and chronic stroke: an exploratory cohort study

Background Anhedonia refers to the diminished capacity to experience pleasure. It has been described both as a symptom of depression and an enduring behavioral trait that contributes its development. Specifically, in stroke patients, anhedonia has been closely linked to depression, resulting in reduced sensitivity to everyday pleasures and intrinsic motivation to engage in rehabilitation programs and maintain a healthy active lifestyle. This condition may hinder patients' recovery, diminishing their autonomy, functioning, and quality of life.Objective We aimed to explore the prevalence and level of anhedonia and those variables that might be associated in patients with both ischemic and hemorrhagic stroke at subacute and chronic phases of the disease.Methods We conducted an exploratory cohort study with a sample of 125 patients with subacute and chronic stroke presenting upper-limb motor deficits. We measured participants' level of anhedonia with four items from the Beck Depression Inventory-II that describe the symptoms of this condition: loss of pleasure, loss of interest, loss of energy, and loss of interest in sex. We also collected demographic and clinical information and evaluated motor and cognitive functions as well as levels of depression, apathy, and various mood states. The results were compared to a sample of 71 healthy participants of similar age, sex, and level of education.Results Stroke patients demonstrated a significantly higher prevalence (18.5-19.7%) and level of anhedonia compared to the healthy controls (4.3%), regardless of stroke phase, level of motor impairment, and other clinical variables. Furthermore, post-stroke anhedonia was associated with lower levels of motivation and higher levels of negative mood states such as fatigue and anger in the long term. Importantly, anhedonia level was superior in stroke patients than in healthy controls while controlling for confounding effects of related emotional conditions.Conclusion This study provides novel evidence on the prevalence, level and factors related to anhedonia post-stroke. We emphasize the importance of assessing and treating anhedonia in this population, as well as conducting large-scale cohort and longitudinal studies to test its influence on long-term functional and emotional recovery

Preserved Error-Monitoring in Borderline Personality Disorder Patients with and without Non-Suicidal Self-Injury Behaviors

Background: The presence of non-suicidal self-injury acts in Borderline Personality Disorder (BPD) is very prevalent. These behaviors are a public health concern and have become a poorly understood phenomenon in the community. It has been proposed that the commission of non-suicidal self-injury might be related to a failure in the brain network regulating executive functions. Previous studies have shown that BPD patients present an impairment in their capacity to monitor actions and conflicts associated with the performance of certain actions, which suppose an important aspect of cognitive control. Method: We used Event Related Potentials to examine the behavioral and electrophysiological indexes associated with the error monitoring in two BPD outpatients groups (17 patients each) differentiated according to the presence or absence of non-suicidal self-injury behaviors. We also examined 17 age- and intelligence- matched healthy control participants. Results: The three groups did not show significant differences in event-related potentials associated with errors (Error-Related Negativity and Pe) nor in theta power increase following errors. Conclusions: This is the first study investigating the behavioral and electrophysiological error monitoring indexes in BPD patients characterized by their history of non-suicidal self-injury behaviors. Our results show that error monitoring is preserved in BPD patients and suggest that non-suicidal self-injury acts are not related to a dysfunction in the cognitive control mechanisms

Working memory updating training modulates a cascade of event-related potentials depending on task load

The brain mechanisms of working memory (WM) training in humans remain unclear. Here we examined how WM updating training modulates a cascade of event-related potentials (ERPs) elicited at different processing stages. We hypothesized that WM updating training results to decreases in the early responses reflecting stimulus selection and response preparation, and increases the late slow responses reflecting maintenance of to-be-remembered materials. Healthy adults were randomized to a WM updating group that trained an adaptive dual n-back task (n = 20), and an active control group that played a computer game (n = 20). Both groups performed three 25-min training sessions per week for five weeks. Pretest-posttest comparisons showed that the training group significantly improved their performance as compared to the active controls, but this was limited to the trained task. In line with our hypothesis, P2-N2-P3 complex showed changes from pre- to posttest. In the training group this was observed as decreased load-effect while in the control group there was an opposite pattern at some latencies. Slow waves elicited during the maintenance were decreased in the easy task and increased in the difficult task. Taken together, our findings suggest that the early and late ERPs are differentially affected by training. When task demands are high, training may lead to an improved ability to actively maintain several stimuli in memory, and when they are low, training results in more efficient processing and automatization.</p

Reward-based decision-making in mesial temporal lobe epilepsy patients with unilateral hippocampal sclerosis pre- and post-surgery

Background: Correct functioning of the reward processing system is critical for optimizing decision-making as well as preventing the development of addictions and/or neuropsychiatric symptoms such as depression, apathy, and anhedonia. Consequently, patients with mesial temporal lobe epilepsy due to unilateral hippocampal sclerosis (mTLE-UHS) represent an excellent opportunity to study the brain networks involved in this system. Objective: The aim of the current study was to evaluate decision-making and the electrophysiological correlates of feedback processing in a sample of mTLE-UHS patients, compared to healthy controls. In addition, we assessed the impact of mesial temporal lobe surgical resection on these processes, as well as general, neuropsychological functioning. Method: 17 mTLE-UHS patients and 17 matched healthy controls completed: [1] a computerized version of the Game of Dice Task, [2] a Standard Iowa Gambling Task, and [3] a modified ERP version of a probabilistic gambling task coupled with multichannel electroencephalography. Neuropsychological scores were also obtained both pre- and post-surgery. Results: Behavioral analyses showed a pattern of increased risk for the mTLE-UHS group in decision-making under ambiguity compared to the control group. A decrease in the amplitude of the Feedback Related Negativity (FRN), a weaker effect of valence on delta power, and a general reduction of delta and theta power in the mTLE-UHS group, as compared to the control group, were also found. The beta-gamma activity associated with the delivery of positive reward was similar in both groups. Behavioral performance and electrophysiological measures did not worsen post-surgery. Conclusions: Patients with mTLE-UHS showed impairments in decision-making under ambiguity, particularly when they had to make decisions based on the outcomes of their choices, but not in decision-making under risk. No group differences were observed in decision-making when feedbacks were random. These results might be explained by the abnormal feedback processing seen in the EEG activity of patients with mTLE-UHS, and by concomitant impairments in working memory, and memory. These impairments may be linked to the disruption of mesial temporal lobe networks. Finally, feedback processing and decision-making under ambiguity were already affected in mTLE-UHS patients pre-surgery and did not show evidence of clear worsening post-surgery

Preserved Error-Monitoring in Borderline Personality Disorder Patients with and without Non-Suicidal Self-Injury Behaviors

Background: The presence of non-suicidal self-injury acts in Borderline Personality Disorder (BPD) is very prevalent. These behaviors are a public health concern and have become a poorly understood phenomenon in the community. It has been proposed that the commission of non-suicidal self-injury might be related to a failure in the brain network regulating executive functions. Previous studies have shown that BPD patients present an impairment in their capacity to monitor actions and conflicts associated with the performance of certain actions, which suppose an important aspect of cognitive control. Method: We used Event Related Potentials to examine the behavioral and electrophysiological indexes associated with the error monitoring in two BPD outpatients groups (17 patients each) differentiated according to the presence or absence of non-suicidal self-injury behaviors. We also examined 17 age- and intelligence- matched healthy control participants. Results: The three groups did not show significant differences in event-related potentials associated with errors (Error-Related Negativity and Pe) nor in theta power increase following errors. Conclusions: This is the first study investigating the behavioral and electrophysiological error monitoring indexes in BPD patients characterized by their history of non-suicidal self-injury behaviors. Our results show that error monitoring is preserved in BPD patients and suggest that non-suicidal self-injury acts are not related to a dysfunction in the cognitive control mechanisms

Quantifying sensory thresholds along the migraine cycle: An exploratory longitudinal study

Allodynia; Osmophobia; PhonophobiaAlodínia; Osmofòbia; FonofòbiaAlodinia; Osmofobia; FonofobiaBackground To date, a number of studies on migraine have cross-sectionally evaluated sensory sensitivity with aversion thresholds/scores along the migraine cycle, reporting a decreased tolerance to sensory stimuli in different sensory modalities. Our hypothesis was that patients with migraine would exhibit heightened sensitivity to sound, light, touch and smell on days where they reported greater headache intensity. Methods This is an exploratory, longitudinal study, carried out over the course of 27 days. Aversion thresholds or scores to sound, light, touch and smell were quantified in six patients with migraine (11.33 ± 6.53 headache days/month). Results Patients reported an increased sensitivity to light (padj = 0.0297), touch (padj = 0.0077), and smell (padj = 0.0201) on days with higher headache intensity. However, a greater sensitivity to sound on days with higher headache intensity was only reported when anxiety levels were high (padj = 1.4e−06). Interestingly, variable levels of tolerance to bothersome light over time can also influence the correlation between light sensitivity and headache intensity (padj = 1.4e−06). Conclusions Based on the present findings, future longitudinal studies evaluating sensory threshold changes along the migraine cycle in patients with migraine should account for the increased tolerance to bothersome light over time as well as the effect of anxiety on auditory sensitivity.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: NI salary has been co-funded by the European Regional Development Fund (001-P-001682) under the framework of the FEDER Operative Programme for Catalunya 2014–2020, with €1,527,637.88. AMM salary has been partially financed by a predoctoral grant from the “Fundació Institut de Recerca Hospital Universitari Vall d’Hebron” (VHIR/BEQUESPREDOC/2020/MARTI). AVB salary has been partially financed by a Juan de la Cierva-Formación grant (FJC2018-036804-I) and Juan de la Cierva – Incorporación postdoctoral (IJC2020-043139-I) from the Spanish Ministry of Science and Innovation. EC salary has been funded by Río Hortega grant Acción Estratégica en Salud 2017–2020, instituto de Salud Carlos III (CM20/00217)

Exploring sensory sensitivity, cortical excitability, and habituation in episodic migraine, as a function of age and disease severity, using the pattern-reversal task

Cortical excitability; Migraine; Visual sensitivityExcitabilitat cortical; Migranya; Sensibilitat visualExcitabilidad cortical; Migraña; Sensibilidad visualBackground Migraine is a cyclic, neurosensory disorder characterized by recurrent headaches and altered sensory processing. The latter is manifested in hypersensitivity to visual stimuli, measured with questionnaires and sensory thresholds, as well as in abnormal cortical excitability and a lack of habituation, assessed with visual evoked potentials elicited by pattern-reversal stimulation. Here, the goal was to determine whether factors such as age and/or disease severity may exert a modulatory influence on sensory sensitivity, cortical excitability, and habituation. Methods Two similar experiments were carried out, the first comparing 24 young, episodic migraine patients and 28 healthy age- and gender-matched controls and the second 36 middle-aged, episodic migraine patients and 30 healthy age- and gender-matched controls. A neurologist confirmed the diagnoses. Migraine phases were obtained using eDiaries. Sensory sensitivity was assessed with the Sensory Perception Quotient and group comparisons were carried out. We obtained pattern-reversal visual evoked potentials and calculated the N1-P1 Peak-to-Peak amplitude. Two linear mixed-effects models were fitted to these data. The first model had Block (first block, last block) and Group (patients, controls) as fixed factors, whereas the second model had Trial (all trials) and Group as fixed factors. Participant was included as a random factor in both. N1-P1 first block amplitude was used to assess cortical excitability and habituation was defined as a decrease of N1-P1 amplitude across Blocks/Trials. Both experiments were performed interictally. Results The final samples consisted of 18 patients with episodic migraine and 27 headache-free controls (first experiment) and 19 patients and 29 controls (second experiment). In both experiments, patients reported increased visual hypersensitivity on the Sensory Perception Quotient as compared to controls. Regarding N1-P1 peak-to-peak data, there was no main effect of Group, indicating no differences in cortical excitability between groups. Finally, significant main effects of both Block and Trial were found indicating habituation in both groups, regardless of age and headache frequency. Conclusions The results of this study yielded evidence for significant hypersensitivity in patients but no significant differences in either habituation or cortical excitability, as compared to headache-free controls. Although the alterations in patients may be less pronounced than originally anticipated they demonstrate the need for the definition and standardization of optimal methodological parameters.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: AMM salary has been partially financed by a predoctoral grant from the “Fundacio Institut de Recerca Hospital Universitari Vall d’Hebron” (VHIR/BEQUESPREDOC/2020/MARTI). AVB salary has been partially financed by a Juan de la Cierva-Formacion grant (FJC2018-036804-I) and a Juan de la Cierva-Incorporación grant (IJC2020-043139-I) from the Spanish Ministry of Science and Innovation. XCC salary has been co-funded by the European Regional Development Fund (001-P-001682) under the framework of the FEDER Operative Programme for Catalunya 2014–2020, with 1,527,637.88 euros. EC salary has been funded by Rıo Hortega grant Accion Estrategica en Salud 2017–2020, Instituto de Salud Carlos III (CM20/00217). SSF has been supported by grants from the Ministerio de Ciencia e Innovación (PID2019-108531 GB-I00 AEI/FEDER) and AGAUR Generalitat de Catalunya (2021 SGR 00911). The project leading to these results has received funding from “la Caixa” Foundation under the project code “LCF/PR/PR16/51110005”

The influence of temporal unpredictability on the electrophysiological mechanisms of neural entrainment

Neural entrainment, or the synchronization of endogenous oscillations to exogenous rhythmic events, has been postulated as a powerful mechanism underlying stimulus prediction. Nevertheless, studies that have explored the benefits of neural entrainment on attention, perception, and other cognitive functions have received criticism, which could compromise their theoretical and clinical value. Therefore, the aim of the present study was [1] to confirm the presence of entrainment using a set of pre-established criteria and [2] to establish whether the reported behavioral benefits of entrainment remain when temporal predictability related to target appearance is reduced. To address these points, we adapted a previous neural entrainment paradigm to include: a variable entrainer length and increased target-absent trials, and instructing participants to respond only if they had detected a target, to avoid guessing. Thirty-six right-handed women took part in this study. Our results indicated a significant alignment of neural activity to the external periodicity as well as a persistence of phase alignment beyond the offset of the driving signal. This would appear to indicate that neural entrainment triggers preexisting endogenous oscillations, which cannot simply be explained as a succession of event-related potentials associated with the stimuli, expectation and/or motor response. However, we found no behavioral benefit for targets in-phase with entrainers, which would suggest that the effect of neural entrainment on overt behavior may be more limited than expected. These results help to clarify the mechanistic processes underlying neural entrainment and provide new insights on its applications.The project leading to these results has received funding from “la Caixa” Foundation under the project code LCF/PR/PR16/51110005 and has been co- funded with 50% by the European Regional Development Fund under the framework of the ERFD Operative Programme for Catalunya 2014– 2020, with a grant of 1.527.637,88€. AVB is supported by the Spanish MICINN Juan de la Cierva postdoctoral grant (FJC2018- 036804- I), and AMM by a predoctoral grant from the “Fundació Institut de Recerca Hospital Universitari Vall d'Hebron” (VHIR/BEQUESPREDOC/2020/MARTI). AVB and AMM have received a postdoctoral and a predoctoral contract re-spectively, from the “La Caixa” Foundation. SS- F is supported by grants from the Ministerio de Ciencia e Innovación (PID2019-108531GB-I00 AEI/FEDER) and AGAUR Generalitat de Catalunya (2017 SGR 1545). PPR has received honoraria as a consultant and speaker for Allergan, Almirall, Biohaven, Chiesi, Eli Lilly, Medscape, Neurodiem, Novartis, and Teva. Her research group has received research grants from Allergan, AGAUR, la Caixa foundation, Migraine Research Foundation, Instituto Investigación Carlos III, MICINN, PERIS; and has received funding for clinical trials from Alder, Electrocore, Eli Lilly, Novartis, and Teva

Auditory Target and Novelty Processing in Patients with Unilateral Hippocampal Sclerosis: A Current-Source Density Study

The capacity to respond to novel events is crucial for adapting to the constantly changing environment. Here, we recorded 29-channel Event Related Brain Potentials (ERPs) during an active auditory novelty oddball paradigm and used for the first time Current Source Density-transformed Event Related Brain Potentials and associated time-frequency spectra to study target and novelty processing in a group of epileptic patients with unilateral damage of the hippocampus (N = 18) and in healthy matched control participants (N = 18). Importantly, we used Voxel-Based Morphometry to ensure that our group of patients had a focal unilateral damage restricted to the hippocampus and especially its medial part. We found a clear deficit for target processing at the behavioral level. In addition, compared to controls, our group of patients presented (i) a reduction of theta event-related synchronization (ERS) for targets and (ii) a reduction and delayed P3a source accompanied by reduced theta and low-beta ERS and alpha event-related synchronization (ERD) for novel stimuli. These results suggest that the integrity of the hippocampus might be crucial for the functioning of the complex cortico-subcortical network involved in the detection of novel and target stimul