Dependency-like behaviors and pain coping styles in subjects with chronic migraine and medication overuse : Results from a 1-year follow-up study

Background: Even after successful detoxification, 20-40% of subjects presenting chronic migraine with symptomatic medication overuse (CMwMO) relapse into medication overuse within one year. In this restrospective analysis on subjects referred to our center for detoxification, we investigated whether personality traits, dependency-like behaviors and pain coping styles predicted those who relapsed into medication overuse within the 12\ua0months following the detoxification and those who did not.Methods: 63 patients with CMwMO were assessed for personality traits, mood and anxiety, pain coping styles and dependency-like behaviors prior-to and one year after a detoxification program.Results: Of the 42 subjects who attended 1-year follow-up interviews, 11 relapsed into medication overuse despite a temporary benefit from detoxification and did not show clinical or psychological improvement, instead reporting increased anxiety and unmodified perpetuation of severe dependency-like behaviors. In contrast, subjects who did not relapse into medication overuse had clinical improvements that generalized to untreated domains, including decreased depressive symptoms and dependency-like behaviors, although showing unmodified low internal control over pain.Conclusions: Subjects who did not fall into medication overuse throughout the 12\ua0months following the detoxification showed improved clinical, affective and dependence-related outcomes, but not pain coping strategies. Conversely, subjects who relapsed within one year into CMwMO continued to experience significant disability, pain intensity, and dependency-like behaviors. We believe that the persistence of maladaptive pain coping strategies and residual symptomatology increase the risk for recurrent relapses, against which pharmacological interventions are only partially effective. Further studies investigating predictors of relapse are needed to inform multi-disciplinary interventions for CMwMO

Psychiatric screening for migraine patients

Psychiatric disorders in migraine patients have a higher prevalence than general population. The presence of psychiatric comorbidities may influence the complexity of the migraine pictures and be related to medication overuse. Severely impaired chronic migraineurs presenting with medication overuse are a challenge for headache clinics. Psychiatric comorbities, such as dependency-like behaviors, anxiety and mood symptoms, might account for headache-related disability and recurrent relapses into medication overuse after a successful detoxification. Within a sample of 63 chronic migraineurs with medication overuse and severe disability, we investigated to which extent clinical severity, affective states and attitudes about medication impact the overall functioning at time of detoxification. To unravel whether some of these factors could predict their long-term outcome, we followed and retest them 1 year after withdrawal. We hypothesized that the detoxification would have led to a partial improvement and not modified the attitudes toward medication and dependence. Detoxification improves most of the clinical and affective measures, but does not free from significant levels of pain intensity and headache-related disability. The partial benefit from detoxification, the severity bias and the maladaptive cognitive profile led us to believe that subgroups of chronic-relapsing migraineurs deserve a multidisciplinary approach that addresses not only the reduction of clinical severity but also specific cognitive and behavioral impairments

INVESTIGATING THE NEUROPHYSIOLOGICAL EFFECTS OF OXYTOCIN ADMINISTRATION ON HEALTHY SUBJECTS AND INDIVIDUALS WITH SCHIZOPHRENIA USING MAGNETO-ENCEPHALOGRAPHY IMAGING.

INTRODUCTION Schizophrenia-spectrum disorders (SZ) are characterized by disturbances of early information processing across various sensory modalities that originate from disrupted spatial and temporal linkage in critical neural networks that include the limbic system and sensory cortices. These disturbances are known to underlie impairments in social cognition, i.e. the ability to understand the thoughts and behaviors of others, which is a critical skill for effectively navigating the social world. Patients with SZ have widespread social cognitive deficits that interfere with social relationships and impair occupational functioning. Current pharmacological treatments are ineffective in remediating social cognitive deficits and in regulating their neurophysiological underpinnings. The oxytocin (OT) system, which is critically involved in social behavior and cognition in mammals and is dysregulated in SZ, is a promising target. Intranasal administration of exogenous OT is well tolerated and improves social cognition in patients with SZ. Additionally, neuroimaging studies in healthy individuals suggest that OT improves information processing and social cognition by modulating regional activity within those neural networks that are impaired in SZ. While work on healthy individuals is promising, no studies investigated the effects induced by OT on spatiotemporal neural oscillatory patterns in patients with SZ. MATERIAL & METHODS. In this study, I used Magnetoencepholagraphy Imaging (MEG-I) to examine the effects of OT. I administered a single intranasal dose of OT (40 IU) or placebo (PL) in a randomized, doubleblind, counterbalanced order with a cross-over, within-subject design to 25 males with SZ and 25 matched healthy controls (HC). Participants\u2019 brain activity was recorded using MEG-I while they completed an auditory deviance task and a facial emotion processing task that robustly activate neural networks underlying information processing and social cognition. Change in auditory mismatch negativity induced by OT/PL in SZ and HC was assessed repeated measures ANOVA. Induced oscillatory activity in regions displaying early activation patterns was examined using adaptive spatial filtering techniques. Broadband activity estimated at each time point in a trial was averaged across trials, root-mean-square transformed, and z-normalized. Average amplitude from early time windows post-stimulus onset was calculated to assess early responses in the bilateral occipital face area (OFA) and the right amygdala. The Neurodynamic Utility Toolbox for MEG-I was used to conduct an exploratory time-frequency analysis of the neural sources during the processing of facial emotions. Task-induced neural oscillatory power changes were localized and examined after OT and PL administration. RESULTS. Compared to HC, SZ showed reduced amplitude of the mismatch negativity under PL. This impairment was normalized after OT administration. Under the effects of PL, the exploratory time-frequency analysis found differential early activations in SZ subjects relative to HC in several regions of interest, including the bilateral OFA and the right amygdala. In the OFA, SZ subjects showed impaired M100 responses that were normalized by OT, while HC showed no effects of OT on M100 response. In the right amygdala, SZ showed aberrant theta activity and impaired M100 under PL. These responses were normalized by OT. CONCLUSION. MEG-I analysis provided detailed measures of the location and time course of neural activations induced by OT. In SZ, OT remediated impaired facial emotion processing and auditory deviance processing, by normalizing the aberrant underlying early activation patterns. Future analyses will examine the neurophysiological effects of OT on late activation patterns in associative and cognitive control areas. This knowledge is critical to optimizing the use of OT as a treatment for social cognitive impairments in SZ and other neuropsychiatric illnesses

Predictors of response to cognitive remediation in patients with major psychotic disorders: a narrative review

Background: Cognitive impairments are prominent features of individuals diagnosed with major psychotic disorders (MPD), negatively affecting occupational and social functioning. Over the past few years, several cognitive remediation (CR) interventions have been developed, with different foundation principles, targets, and mechanisms of action. The vast majority consists of drill and practice approaches that are grounded in the principle of neuropsychology. More recently, neuroplasticity-based cognitive training (NBCT) has shown promise. While several CR approaches have shown moderate efficacy, improving both cognition and real-world functioning, there is considerable variability in individual treatment response. Studies that have investigated factors that predict CR outcome and can be used to guide treatment have historically grouped all CR approaches together. Here, we aim to explore common and distinct predictors of response to neuroplasticity-based and neuropsychology-based CR. Methods: an electronic database search on MEDLINE/PubMed was conducted in February 2020 to identify articles investigating predictors of response to CR. We limited our queries to peer-reviewed, English-language journal articles describing trials of CR for adults with MPD. Results: a total of 58 articles were examined, and 14 different categories of CR predictors were identified. CR predictors that most stood out were age, shorter illness duration, lower symptoms severity, lower antipsychotic medications, and the delivery of CR in combination with other treatments. Although results are still mixed, demographical variables appear to be far less important for NBCT than they are for other CR programs. Clinical and genetic variables \u2013 such as symptoms severity, lower antipsychotic dose, serum BDNF and serum D-serine \u2013 seem to influence more significantly NBCT than neuropsychology-based CR. Conclusions:Data on NBCT is relatively scarce, and further research is required to better understand which predictive factors uniquely pertain to it. The identification of predictors of response to CR will allow to implement a personalized medicine approach, in which each patient can receive a personalized cognitive remediation program according to their specific needs

Can neuroimaging-based biomarkers predict response to cognitive remediation in patients with psychosis? A state-of-the-art review

Background: Cognitive Remediation (CR) is designed to halt the pathological neural systems that characterize major psychotic disorders (MPD), and its main objective is to improve cognitive functioning. The magnitude of CR-induced cognitive gains greatly varies across patients with MPD, with up to 40% of patients not showing gains in global cognitive performance. This is likely due to the high degree of heterogeneity in neural activation patterns underlying cognitive endophenotypes, and to inter-individual differences in neuroplastic potential, cortical organization and interaction between brain systems in response to learning. Here, we review studies that used neuroimaging to investigate which biomarkers could potentially serve as predictors of treatment response to CR in MPD. Methods: This systematic review followed the PRISMA guidelines. An electronic database search (Embase, Elsevier; Scopus, PsycINFO, APA; PubMed, APA) was conducted in March 2021. peer-reviewed, English-language studies were included if they reported data for adults aged 18+ with MPD, reported findings from randomized controlled trials or single-arm trials of CR; and presented neuroimaging data. Results: Sixteen studies were included and eight neuroimaging-based biomarkers were identified. Auditory mismatch negativity (3 studies), auditory steady-state response (1), gray matter morphology (3), white matter microstructure (1), and task-based fMRI (7) can predict response to CR. Efference copy corollary/discharge, resting state, and thalamo-cortical connectivity (1) require further research prior to being implemented. Conclusions: Translational research on neuroimaging-based biomarkers can help elucidate the mechanisms by which CR influences the brain's functional architecture, better characterize psychotic subpopulations, and ultimately deliver CR that is optimized and personalized

Consultation-liaison psychiatry for patients with headaches

Screening of headache patients for psychiatric disorders is needed, because of the well-known high rates of comorbidity with depression and anxiety. Screening for both depression and anxiety is highly advisable in order to identify subjects who need psychiatric consultation and therapy. Screening tools for depression and anxiety range from informal questions to self-report instruments to structured interviews and the choice is up to the clinician and the setting of the clinical evaluation. Data on psychiatric disorders and medication overuse are till now not consistent. The treatment of mood and anxiety disorders in headache patients needs to take into account the possible drug interactions with headache therapies. The collaboration between neurologists and consultation-liaison psychiatrists helps the identification of headache patients who need a psychiatric therapeutic program and follow-up

The effects of cognitive remediation in patients with affective psychosis: A systematic review: Special Section on “Translational and Neuroscience Studies in Affective Disorders”. Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders

Background: Schizophrenia, schizoaffective disorder, and related illnesses are associated with significant impairment in cognitive functioning which is among the strongest predictors of disability and poor quality of life. Cognitive remediation (CR) was developed as a set of behavioral interventions directly targeting cognitive symptoms. Studies have shown that CR produces cognitive improvements in patients with schizophrenia and bipolar disorder that may be associated with improvements in functioning. However, the relative efficacy of CR across diagnoses has not been established. Indirect evidence suggests that CR is effective in patients with affective illness as well as patients with schizophrenia (SZ); however, the one study to evaluate the effects of diagnosis on outcomes directly in patients with SZ versus schizoaffective disorder (SZA) found no differences by diagnosis. Methods: In this systematic review, we evaluated cognitive and functional outcomes after CR in studies including patients with SZA, and examined specificity of training content to outcomes. Results: Sixteen studies met inclusion criteria: 10 studies that compared CR to a control condition (n = 779) and 6 comparative effectiveness studies. None of the studies explicitly compared patients by diagnosis. Studies included a mixture of patients with SZA or SZ. Of the CR versus control studies, effect sizes for cognitive outcomes were moderate-large (d =.36\u2013.94). Studies comparing CR paradigms targeting different cognitive domains showed specificity of training focus to outcomes. Five of studies reported significant functional improvement after CR as secondary outcomes. Conclusions: In this review, we found support for the use of CR paradigms in patients with affective psychosis, with evidence that reported treatment effects in mixed affective and non-affective samples are at or above the levels previously reported in SZ. However, lack of availability of data directly comparing patients by diagnosis or examining moderator or mediator effects of diagnosis or diagnosis-related patient characteristics limits our understanding of the relative efficacy of CR across patient group

Brain dysfunction underlying prolonged post-concussive syndrome : a systematic review

Background: One out of 4 patients who sustains a mild traumatic brain injury (mTBI) experiences persistent complaints, despite the absence of structural brain damage on conventional neuroimaging. Susceptibility to develop post concussive symptoms (PCS) is thought to originate from occult brain dysfunction. However, the influence of such neural changes on the development of persistent PCS is poorly characterized. Methods: In this article, we aim to integrate findings from longitudinal studies that investigated across the spectrum of neuroimaging modalities the changes within the first twelve months following a mTBI, with the goal of identifying possible predictors or biomarkers of persistent PCS. Results: Nine studies met inclusion criteria: 5 that used resting state functional MRI, 2 that used Diffusion Weighted Imaging, and 2 that used 1H-MR Spectroscopy. All studies indicate significant structural, functional and/or metabolic aberrations that occur in the acute and early subacute phases following a mTBI. However, in patients with persistent PCS, these mTBI-induced damages linger and relate to the severity of PCS. These biomarkers include: decreased diffusion along white matter fiber tracts, alteration of perfusion, disrupted metabolism, and reduced connectivity within several resting state networks. Additionally, in PCS patients, disruptions of brain function can manifest exclusively in the chronic phase. Conclusion: This review support the ongoing use of neuroimaging modalities to understand the brain changes that occur throughout the time course of mTBI. Based on the complexity of mTBI, however, more work is required to characterize injury and recovery mechanisms that could impact the emergence and persistence of PCS

Engagement with the auditory processing system during targeted auditory cognitive training mediates changes in cognitive outcomes in individuals with schizophrenia.

BACKGROUND: Individuals with schizophrenia who engage in targeted cognitive training (TCT) of the auditory system show generalized cognitive improvements. The high degree of variability in cognitive gains maybe due to individual differences in the level of engagement of the underlying neural system target. METHODS: 131 individuals with schizophrenia underwent 40 hours of TCT. We identified target engagement of auditory system processing efficiency by modeling subject-specific trajectories of auditory processing speed (APS) over time. Lowess analysis, mixed models repeated measures analysis, and latent growth curve modeling were used to examine whether APS trajectories were moderated by age and illness duration, and mediated improvements in cognitive outcome measures. RESULTS: We observed signifcant improvements in APS from baseline to 20 hours of training (initial change), followed by a flat APS trajectory (plateau) at subsequent time-points. Participants showed inter-individual variability in the steepness of the initial APS change and in the APS plateau achieved and sustained between 20–40 hours. We found that participants who achieved the fastest APS plateau, showed the greatest transfer effects to untrained cognitive domains. CONCLUSIONS: There is a significant association between an individual's ability to generate and sustain auditory processing efficiency and their degree of cognitive improvement after TCT, independent of baseline neurocognition. APS plateau may therefore represent a behavioral measure of target engagement mediating treatment response. Future studies should examine the optimal plateau of auditory processing efficiency required to induce significant cognitive improvements, in the context of inter-individual differences in neural plasticity and sensory system efficiency that characterize schizophrenia