The interplay between mentalization, personality traits and burnout in psychiatry training: Results from a large multicenter controlled study.

BACKGROUND: A better characterization of educational processes during psychiatry training is needed, both to foster personal resilience and occupational proficiency. METHODS: An adequate coverage of medical residents at the national level was reached (41.86% of the total reference population, 29 out of 36 training centers-80.55%). Controls were recruited among residents in other medical specialties. All participants were assessed by questionnaires to evaluate early life experiences, attachment style, personality traits, coping strategies, emotional competencies. A Structural Equation Model (SEM) framework was employed to investigate the interplay between individual factors. RESULTS: A total sample of 936 people was recruited (87.9% response-rate; 645 residents in psychiatry, 291 other medical residents). Psychiatry trainees reported a higher prevalence of adverse childhood experiences (emotional abuse, emotional neglect, physical neglect), greater attachment insecurity (anxious or avoidant) in comparison to other medical trainees. Psychiatry residents also reported higher social support-seeking as a coping strategy, lower problem-orientation, and lower transcendence. Lower neuroticism, higher openness to experience, and higher emotional awareness were also observed in psychiatry trainees. Psychiatry training was associated with a redefinition of conflict management skills as a function of seniority. The SEM model provided support for an interplay between early traumatic experiences, mentalization skills (coping strategies, emotion regulation), interpersonal competencies and occupational distress. CONCLUSIONS: The findings of the present study supported a theoretical model based on mentalization theory for the interactions between personal and relational competencies in psychiatry training, thus providing potential target of remodulation and redefinition of this specific process of education.

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment-resistant depression.

BACKGROUND: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD. OBJECTIVES: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch. METHODS: Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up. RESULTS: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch. CONCLUSIONS: Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment.

Investigating the Effectiveness and Tolerability of Intranasal Esketamine Among Older Adults With Treatment-Resistant Depression (TRD): A Post-hoc Analysis from the REAL-ESK Study Group.

INTRODUCTION: Treatment-resistant depression (TRD) is a serious and debilitating psychiatric disorder that frequently affects older patients. Esketamine nasal spray (ESK-NS) has recently been approved as a treatment for TRD, with multiple studies establishing its efficacy and tolerability. However, the real-world effectiveness, tolerability, and safety of this treatment in older adults is still unclear. OBJECTIVES: To evaluate the efficacy and tolerability of ESK-NS in older subjects with TRD. METHODS: This is a post-hoc analysis of the REAL-ESK study, a multicenter, retrospective, observational study. Participants here selected were 65 years or older at baseline. The Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A) were used to assess depressive and anxiety symptoms, respectively. Data were collected at three-time points: baseline, 1 month after the start of treatment (T1), and 3 months after treatment (T2). RESULTS: The sample included older adults with TRD (n = 30). MADRS and HAM-A values decreased significantly at T1 (T0 versus T1: pholm <0.001, Cohen's d = 0.840) and T2 follow-ups (T0 versus T2: pholm <0.001, Cohen's d = 1.419). At T2, 53.3% of subjects were responders (MADRS score reduced ≥50%), while 33.33% were in remission (MADRS<10). ESK-NS-related adverse effects were in order of frequency dizziness (50%), followed by dissociation (33.3%), sedation (30%), and hypertension (13.33%). Six out of 30 participants (20%) discontinued treatment. CONCLUSIONS: Our findings provide preliminary evidence of ESK-NS effectiveness in older adults with TRD, a highly debilitating depressive presentation. Furthermore, we observe high levels of treatment-emergent adverse events, which, in the majority of instances, did not require treatment suspension.

Sexual Dysfunctions and Problematic Sexuality in Personality Disorders and Pathological Personality Traits: A Systematic Review.

PURPOSE OF REVIEW: This aim of the present systematic literature review is to critically analyze problematic sexuality and sexual dysfunctions in personality disorders (PDs) and pathological personality traits. RECENT FINDINGS: An initial pool of 123 studies was found, out of which 17 met the selection criteria and were therefore included. Traumatic experiences as childhood sexual abuse and adverse childhood experiences characterize the relationship between sexual behavior and PDs. From this point of view, sexual compulsivity and sexual risk behaviors, typical of BPD and ASPD, respectively, are among the pathognomonic aspects of PDs and of pathological personality traits. A maladaptive personality functioning may manifest through a problematic sexuality and a sexual impairment. In this regard, traumatic life experiences may structure personality together with sexual functioning. Therefore, it would be useful to consider the relationship between trauma, sexuality, and personality in research and in the clinical setting.

Psychometric and factorial validity of the International Adjustment Disorder Questionnaire (IADQ) in an Italian sample: A validation and prevalence estimate study.

INTRODUCTION: Adjustment disorder (AjD) is a is a maladaptive emotional or behavioural reaction to a stressful event or change in a person's life. Compared to other previously validated tools, the International Adjustment Disorder Questionnaire (IADQ) stands out as one of the most reliable and handy one for AjD. Since no homologous instrument exists now, in this study, we aimed to validate an Italian version of the IADQ. METHODS: Twenty-one thousand two hundred and six subjects (80.4% females) during the initial stages of the SARS-CoV-2 pandemic were recruited. We conducted a confirmatory factor analysis (CFA), testing two latent models, a monofactorial and a bifactorial one. Concurrent validity by correlating the total and the two factors' scores with measures of depression, anxiety and post-traumatic stress was then estimated. We finally estimated the rates of AjD among the population, and a binary logistic regression was conducted to analyse the predictors of such disorder. RESULTS: CFA showed a bifactorial validity, with both excellent incremental and comparative fit indices. The IADQ scores correlated strongly with symptoms of depression, anxiety and stress. In the Italian sample, the prevalence of probable AjD was 8.23%. Female gender, being engaged, widowed and having COVID-19-related stressors resulted as significant independent risk factors for AjD. CONCLUSIONS: IADQ is an easy-to-use, brief and psychometrically sound self-report measure for AjD. Thus, it may be considered a reliable tool for both research and clinical settings. To the best of our knowledge, our study reported for the first time the prevalence of AjD during COVID-19 pandemic.

Factors associated with lifetime suicide attempts in bipolar disorder: results from an Italian nationwide study.

The purpose of the present study was to detect demographic and clinical factors associated with lifetime suicide attempts in Bipolar Disorder (BD). A total of 1673 bipolar patients from different psychiatric departments were compared according to the lifetime presence of suicide attempts on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (presence of suicide attempts) at the univariate analyses, preliminary multiple logistic regression analyses were realized. A final multivariable logistic regression was then performed, considering the presence of lifetime suicide attempts as the dependent variable and statistically significant demographic/clinical characteristics as independent variables. The final multivariable logistic regression analysis showed that an earlier age at first contact with psychiatric services (odds ratio [OR] = 0.97, p < 0.01), the presence of psychotic symptoms (OR = 1.56, p < 0.01) or hospitalizations (OR = 1.73, p < 0.01) in the last year, the attribution of symptoms to a psychiatric disorder (no versus yes: OR = 0.71, partly versus yes OR = 0.60, p < 0.01), and the administration of psychoeducation in the last year (OR = 1.49, p < 0.01) were all factors associated with lifetime suicide attempts in patients affected by BD. In addition, female patients resulted to have an increased association with life-long suicidal behavior compared to males (OR: 1.02, p < 0.01). Several clinical factors showed complex associations with lifetime suicide attempts in bipolar patients. These patients, therefore, require strict clinical monitoring for their predisposition to a less symptom stabilization. Future research will have to investigate the best management strategies to improve the prognosis of bipolar subjects presenting suicidal behavior.

Neural correlates of N-back task performance and proposal for corresponding neuromodulation targets in psychiatric and neurodevelopmental disorders.

AIM: Working memory (WM) deficit represents the most common cognitive impairment in psychiatric and neurodevelopmental disorders, making the identification of its neural substrates a crucial step towards the conceptualization of restorative interventions. We present a meta-analysis focusing on neural activations associated with the most commonly used task to measure WM, the N-back task, in patients with schizophrenia, depressive disorder, bipolar disorder, and attention-deficit/hyperactivity disorder. Showing qualitative similarities and differences in WM processing between patients and healthy controls, we propose possible targets for cognitive enhancement approaches. METHODS: Selected studies, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, were analyzed through the activation likelihood estimate statistical framework, with subsequent generation of disorder-specific N-back activation maps. RESULTS: Despite similar WM deficits shared across all disorders, results highlighted different brain activation patterns for each disorder compared with healthy controls. In general, results showed brain activity in frontal, parietal, subcortical, and cerebellar regions; however, reduced engagement of specific nodes of the fronto-parietal network emerged in patients compared with healthy controls. In particular, neither bipolar nor depressive disorders showed detectable activations in the dorsolateral prefrontal cortices, while their parietal activation patterns were lateralized to the left and right hemispheres, respectively. On the other hand, patients with attention-deficit/hyperactivity disorder showed a lack of activation in the left parietal lobe, whereas patients with schizophrenia showed lower activity over the left prefrontal cortex. CONCLUSION: These results, together with biophysical modeling, were then used to discuss the design of future disorder-specific cognitive enhancement interventions based on noninvasive brain stimulation.

A Hypothalamic Mechanism Regulates the Duration of a Migraine Attack: Insights from Microstructural and Temporal Complexity of Cortical Functional Networks Analysis.

The role of the hypothalamus and the limbic system at the onset of a migraine attack has recently received significant interest. We analyzed diffusion tensor imaging (DTI) parameters of the entire hypothalamus and its subregions in 15 patients during a spontaneous migraine attack and in 20 control subjects. We also estimated the non-linear measure resting-state functional MRI BOLD signal's complexity using Higuchi fractal dimension (FD) and correlated DTI/fMRI findings with patients' clinical characteristics. In comparison with healthy controls, patients had significantly altered diffusivity metrics within the hypothalamus, mainly in posterior ROIs, and higher FD values in the salience network (SN). We observed a positive correlation of the hypothalamic axial diffusivity with migraine severity and FD of SN. DTI metrics of bilateral anterior hypothalamus positively correlated with the mean attack duration. Our results show plastic structural changes in the hypothalamus related to the attacks severity and the functional connectivity of the SN involved in the multidimensional neurocognitive processing of pain. Plastic changes to the hypothalamus may play a role in modulating the duration of the attack.

Benefits of Sexual Activity on Psychological, Relational, and Sexual Health During the COVID-19 Breakout.

BACKGROUND: The COVID-19-related lockdown has profoundly changed human behaviors and habits, impairing general and psychological well-being. Along with psychosocial consequences, it is possible that sexual behavior was also affected. AIMS: With the present study, we evaluated the impact of the community-wide containment and consequent social distancing on the intrapsychic, relational, and sexual health through standardized psychometric tools. METHODS: A case-control study was performed through a web-based survey and comparing subjects of both genders with (group A, N = 2,608) and without (group B, N = 4,213) sexual activity during lockdown. The Welch and chi-square tests were used to assess differences between groups. Univariate analysis of covariance, logistic regression models, and structural equation modeling were performed to measure influence and mediation effects of sexual activity on psychological, relational, and sexual outcomes. OUTCOMES: Main outcome measures were General Anxiety Disorder-7 for anxiety, Patient Health Questionnaire-9 for depression, Dyadic Adjustment Scale for quality of relationship and a set of well-validated sexological inventories (International Index of Erectile Function, Female Sexual Function Index, and male-female versions of the Orgasmometer). RESULTS: Anxiety and depression scores were significantly lower in subjects sexually active during lockdown. Analysis of covariance identified gender, sexual activity, and living without partner during lockdown as significantly affecting anxiety and depression scores (P < .0001). Logistic regression models showed that lack of sexual activity during lockdown was associated with a significantly higher risk of developing anxiety and depression (OR: 1.32 [95% CI: 1.12 - 1.57, P < .001] and 1.34 [95% CI: 1.15 - 1.57, P < .0001], respectively). Structural equation modeling evidenced the protective role of sexual activity toward psychological distress (ßmales = -0.18 and ßfemales = -0.14), relational health (ßmales = 0.26 and ßfemales = 0.29) and sexual health, both directly (ßmales = 0.43 and ßfemales = 0.31), and indirectly (ßmales = 0.13 and ßfemales = 0.13). CLINICAL TRANSLATION: The demonstrated mutual influence of sexual health on psychological and relational health could direct the clinical community toward a reinterpretation of the relationship among these factors. STRENGTHS AND LIMITATIONS: Based on a large number of subjects and well-validated psychometric tools, this study elucidated the protective role of sexual activity for psychological distress, as well for relational and sexual health. Main limitations were the web-based characteristics of the protocol and the retrospective nature of prelockdown data on psychorelational and sexual health of subjects recruited. CONCLUSIONS: COVID-19 lockdown dramatically impacted on psychological, relational, and sexual health of the population. In this scenario, sexual activity played a protective effect, in both genders, on the quarantine-related plague of anxiety and mood disorders. Mollaioli D, Sansone A, Ciocca G, et al. Benefits of Sexual Activity on Psychological, Relational, and Sexual Health During the COVID-19 Breakout. J Sex Med 2021;18:35-49.

'Too many BeEPs in our teens!' Behavioral and emotional problems in a large group of Italian adolescents.

BACKGROUND: One in six adolescents suffers from mental health problems. Despite the presence of general information on Italian adolescents' mental health, researches conducted with standardized assessment tools are scarce in the literature. We evaluated the prevalence of self-reported behavioral and emotional problems in a group of Italian adolescents and examined their relation to socio-demographical variables. METHODS: This population-based sampling survey was conducted on high school students aged 14-18 from urban areas of Rome and Latina. Participants completed Youth Self-Report (YSR) and a socio-demographic schedule to collect information on age, gender, type of school attended, socio-economic status, urbanicity. RESULTS: Final sample consisted of 1400 adolescents (38.61% male, mean age 16 years, s.d. 1.42). Prevalence of Internalizing Problems, Externalizing Problems and Total Problems was 29.55%, 18.34% and 24.13%. In our multivariable model, Internalizing Symptoms were not explained by sociodemographic variables while Externalizing Symptoms were explained by Male Gender [OR = 1.53 (1.14-2.06)], older age [OR = 2.06 (1.52-2.79)] and attending a Technical and Professional Institute [OR = 2.15 (1.53-3.02)], with an adjusted R2 = 4.32%. Total Problems were explained by School Type [Technical and Professional Institutes and Art and Humanities v. Grammar and Science School; OR respectively 1.93 (1.40-2.67) and 1.64 (1.08-2.47)], adjusted R2 = 1.94. CONCLUSIONS: The study provides, for the first time, evidence of a great prevalence of self-reported behavioral and emotional problems in a large sample of Italian adolescents, highlighting the role of different socio-demographic variables as risk factors for externalizing behaviors. Our results emphasize the urgent need for implementing prevention programs on mental health in adolescence.

Haemodynamic activity characterization of resting state networks by fractal analysis and thalamocortical morphofunctional integrity in chronic migraine.

BACKGROUND: Chronic migraine (CM) can be associated with aberrant long-range connectivity of MRI-derived resting-state networks (RSNs). Here, we investigated how the fractal dimension (FD) of blood oxygenation level dependent (BOLD) activity may be used to estimate the complexity of RSNs, reflecting flexibility and/or efficiency in information processing in CM patients respect to healthy controls (HC). METHODS: Resting-state MRI data were collected from 20 untreated CM without history of medication overuse and 20 HC. On both groups, we estimated the Higuchi's FD. On the same subjects, fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from diffusion tensor imaging and correlated with the FD values. RESULTS: CM showed higher FD values within dorsal attention system (DAS) and the anterior part of default-mode network (DMN), and lower FD values within the posterior DMN compared to HC. Although FA and MD were within the range of normality, both correlated with the FD values of DAS. CONCLUSIONS: FD of DAS and DMN may reflect disruption of cognitive control of pain in CM. Since the normal microstructure of the thalamus and its positive connectivity with the cortical networking found in our CM patients reminds similar results obtained assessing the same structures but with the methods of neurophysiology, in episodic migraine during an attack, this may be yet another evidence in supporting CM as a never-ending migraine attack.

Thalamic morphometric changes induced by first-person action videogame training.

Cross-sectional data suggest videogaming as promoting modifications in perceptual and cognitive skills of players, as well as inducing structural brain changes. However, whether such changes are both possible after a systematic gaming exposure, and last beyond the training period, is not known. Here, we originally quantified immediate and long-lasting cognitive and morphometric impact of a systematic gaming experience on a first-person shooter (FPS) game. Thirty-five healthy participants, assigned to a videogaming and a control group, underwent a cognitive assessment and structural magnetic resonance imaging at baseline (T0), immediately post-gaming (T1) and after  3 months (T2). Enhancements of cognitive performance were found on perceptual and attentional measures at both T1 and T2. Morphometric analysis revealed immediate structural changes involving bilateral medial and posterior thalamic nuclei, as well as bilateral superior temporal gyrus, right precentral gyrus, and left middle occipital gyrus. Notably, significant changes in pulvinar volume were still present at T2, while a voxel-wise regression analysis also linked baseline pulvinar volume and individual changes in gaming performance. Present findings extend over the notion that videogame playing might impact cognitive and brain functioning in a beneficial way, originally showing long-term brain structural changes even months after gaming practice. The involvement of posterior thalamic structures highlights a potential link between FPS games and thalamo-cortical networks related to attention mechanisms and multisensory integration processing.

A ketogenic diet normalizes interictal cortical but not subcortical responsivity in migraineurs.

BACKGROUND: A short ketogenic diet (KD) treatment can prevent migraine attacks and correct excessive cortical response. Here, we aim to prove if the KD-related changes of cortical excitability are primarily due to cerebral cortex activity or are modulated by the brainstem. METHODS: Through the stimulation of the right supraorbital division of the trigeminal nerve, we concurrently interictally recorded the nociceptive blink reflex (nBR) and the pain-related evoked potentials (PREP) in 18 migraineurs patients without aura before and after 1-month on KD, while in metabolic ketosis. nBR and PREP reflect distinct brain structures activation: the brainstem and the cerebral cortex respectively. We estimated nBR R2 component area-under-the-curve as well as PREP amplitude habituation as the slope pof the linear regression between the 1st and the 2nd block of 5 averaged responses. RESULTS: Following 1-month on KD, the mean number of attacks and headache duration reduced significantly. Moreover, KD significantly normalized the interictal PREP habituation (pre: + 1.8, post: - 9.1, p = 0.012), while nBR deficit of habituation did not change. CONCLUSIONS: The positive clinical effects we observed in a population of migraineurs by a 1-month KD treatment coexists with a normalization at the cortical level, not in the brainstem, of the typical interictal deficit of habituation. These findings suggest that the cerebral cortex may be the primary site of KD-related modulation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03775252 (retrospectively registered, December 09, 2018).

Assessing Learning Needs and Career Attitudes of Italian Psychiatry Residents: Results from a National Survey Conducted by the Italian Society of Psychopathology Young Psychiatrists Section (SOPSI-GG).

OBJECTIVE: No data are available about learning needs and career attitudes of Italian Psychiatry Residents (IPRs). Authors aimed to assess such needs through a survey to generate insight for implementing educational programs close to IPRs' perceived learning needs. METHODS: A 54-item questionnaire was developed in order to investigate career information, educational preference and learning needs of IPRs. A sample of 298 IPRs participated to the survey and was divided into four subgroups according to their location (North, Centre, South and Islands). The subgroups were compared through ANOVA for age and chi-square tests for qualitative variables (including gender and all sub-items of the survey), with Bonferroni post-hoc analysis. RESULTS: IPRs were found to pursue, along with traditional and theoretical training, a quite practical approach, characterized by working groups, discussions on clinical cases and practical interactive sessions. The topics of major interest included: clinical psychiatry, psychopharmacology, psychiatric emergencies, communication and relationship skills (97%, 98.0%, 98.3% and 95.7% of the total sample, respectively). Indeed, a strong need for interaction with healthcare professionals emerged (97% of the total sample). North and Centre IPRs were more involved in Day Hospital activities than residents from South Italy and Islands (p<.001). South IPRs appeared to be more prone to invest for their education than residents from other areas (p<.01). CONCLUSION: Reported findings should be taken into account as a starting point for planning and developing future targeted packages of educational proposals for IPRs and they should stand as a useful pilot study for further investigation in the field.

Brain functional connectivity correlates of coping styles.

Coping abilities represent the individual set of mental and behavioral strategies adopted when facing stress or traumatic experiences. Coping styles related to avoidance have been linked to a disposition to develop psychiatric disorders such as PTSD, anxiety, and major depression, whereas problem-oriented coping skills have been positively correlated with well-being and high quality of life. Even though coping styles constitute an important determinant of resilience and can impact many aspects of everyday living, no study has investigated their brain functional connectivity underpinnings in humans. Here we analyzed both psychometric scores of coping and resting-state fMRI data from 102 healthy adult participants. Controlling for personality and problem-solving abilities, we identified significant links between the propensity to adopt different coping styles and the functional connectivity profiles of regions belonging to the default mode (DMN) and anterior salience (AS) networks-namely, the anterior cingulate cortex, left frontopolar cortex, and left angular gyrus. Also, a reduced negative correlation between AS and DMN nodes explained variability in one specific coping style, related to avoiding problems while focusing on the emotional component of the stressor at hand, instead of relying on cognitive resources. These results might be integrated with current neurophysiological models of resilience and individual responses to stress, in order to understand the propensity to develop clinical conditions (e.g., PTSD) and predict the outcomes of psychotherapeutic interventions.

Age of Insomnia Onset Correlates with a Reversal of Default Mode Network and Supplementary Motor Cortex Connectivity.

Insomnia might occur as result of increased cognitive and physiological arousal caused by acute or long acting stressors and associated cognitive rumination. This might lead to alterations in brain connectivity patterns as those captured by functional connectivity fMRI analysis, leading to potential insight about primary insomnia (PI) pathophysiology as well as the impact of long-term exposure to sleep deprivation. We investigated changes of voxel-wise connectivity patterns in a sample of 17 drug-naïve PI patients and 17 age-gender matched healthy controls, as well as the relationship between brain connectivity and age of onset, illness duration, and severity. Results showed a significant increase in resting-state functional connectivity of the bilateral visual cortex in PI patients, associated with decreased connectivity between the visual cortex and bilateral temporal pole. Regression with clinical scores originally unveiled a pattern of increased local connectivity as measured by intrinsic connectivity contrast (ICC), specifically resembling the default mode network (DMN). Additionally, age of onset was found to be correlated with the connectivity of supplementary motor area (SMA), and the strength of DMN←→SMA connectivity was significantly correlated with both age of onset (R2 = 41%) and disease duration (R2 = 21%). Chronic sleep deprivation, but most importantly early insomnia onset, seems to have a significant disruptive effect over the physiological negative correlation between DMN and SMA, a well-known fMRI marker of attention performance in humans. This suggests the need for more in-depth investigations on the prevention and treatment of connectivity changes and associated cognitive and psychological deficits in PI patients.

Impaired brainstem and thalamic high-frequency oscillatory EEG activity in migraine between attacks.

Introduction We investigated whether interictal thalamic dysfunction in migraine without aura (MO) patients is a primary determinant or the expression of its functional disconnection from proximal or distal areas along the somatosensory pathway. Methods Twenty MO patients and twenty healthy volunteers (HVs) underwent an electroencephalographic (EEG) recording during electrical stimulation of the median nerve at the wrist. We used the functional source separation algorithm to extract four functionally constrained nodes (brainstem, thalamus, primary sensory radial, and primary sensory motor tangential parietal sources) along the somatosensory pathway. Two digital filters (1-400 Hz and 450-750 Hz) were applied in order to extract low- (LFO) and high- frequency (HFO) oscillatory activity from the broadband signal. Results Compared to HVs, patients presented significantly lower brainstem (BS) and thalamic (Th) HFO activation bilaterally. No difference between the two cortical HFO as well as in LFO peak activations between the two groups was seen. The age of onset of the headache was positively correlated with HFO power in the right brainstem and thalamus. Conclusions This study provides evidence for complex dysfunction of brainstem and thalamocortical networks under the control of genetic factors that might act by modulating the severity of migraine phenotype.

Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study.

BACKGROUND: Here, we aim to identify cortical electrofunctional correlates of responsiveness to short-lasting preventiveintervention with ketogenic diet (KD) in migraine. METHODS: Eighteen interictal migraineurs underwent visual (VEPs) and median nerve somatosensory (SSEPs) evokedpotentials before and after 1 month of KD during ketogenesis. We measured VEPs N1-P1 and SSEPs N20-P25 amplitudes respectively in six and in two sequential blocks of 100 sweeps as well as habituation as theslope of the linear regression between block 1 to 6 for VEPs or between 1 to 2 for SSEPs. RESULTS: After 1-month of KD, a significant reduction in the mean attack frequency and duration was observed (all P< 0.001). The KD did not change the 1st SSEP and VEP block of responses, but significantly inducednormalization of the interictally reduced VEPs and SSEPs (all p < 0.01) habituation during the subsequentblocks. CONCLUSIONS: KD could restore normal EPs habituation curves during stimulus repetition without significantly changing theearly amplitude responses. Thus, we hypothesize that KD acts on habituation regulating the balancebetween excitation and inhibition at the cortical level.