Search

Abstract Objective Locomotion is an automated voluntary movement sustained by coordinated neural synchronization across a distributed brain network. The cerebral cortex is central for adapting the locomotion pattern to the environment and alterations of cortical network dynamics can lead to gait impairments. Gait problems are a common symptom with a still unclear pathophysiology and represent an unmet therapeutical need in Parkinson's disease. Little is known about the cortical network dynamics of locomotor control in these patients. Methods We studied the cortical basis of parkinsonian gait by combining metabolic brain imaging with high‐density EEG recordings and kinematic measurements performed at rest and during unperturbed overground walking. Results We found significant changes in functional connectivity between frontal, sensorimotor, and visuomotor cortical areas during walking as compared to resting. Specifically, hypokinetic gait was associated with poor information flow from the supplementary motor area (SMA) to precuneus and from calcarine to lingual gyrus, as well as high information flow from calcarine to cuneus. Interpretation Our findings support a role for visuomotor integration processes in PD‐related hypokinetic gait and suggest that reinforcing visual information may act as a compensatory strategy to allow SMA‐mediated feedforward locomotor control in PD.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Abstract Purpose Positron emission tomography (PET) with amyloid tracers (amy-PET) allows the quantification of pathological amyloid deposition in the brain tissues, including the white matter (WM). Here, we evaluate amy-PET uptake in WM lesions (WML) and in the normal-appearing WM (NAWM) of patients with Alzheimer’s disease (AD) and non-AD type of dementia. Methods Thirty-three cognitively impaired subjects underwent brain magnetic resonance imaging (MRI), Aβ1-42 (Aβ) determination in the cerebrospinal fluid (CSF) and amy-PET. Twenty-three patients exhibiting concordant results in both CSF analysis and amy-PET for cortical amyloid deposition were recruited and divided into two groups, amyloid positive (A+) and negative (A−). WML quantification and brain volumes’ segmentation were performed. Standardized uptake values ratios (SUVR) were calculated in the grey matter (GM), NAWM and WML on amy-PET coregistered to MRI images. Results A+ compared to A− showed a higher WML load (p = 0.049) alongside higher SUVR in all brain tissues (p

Study objectives: Sleep and circadian rhythms disorders are frequent in the acute stroke. Sleep modifications are likely to contribute to the development of stroke-related delirium, a common neuropsychiatric complication of acute stroke. This systematic review aimed to clarify the association between sleep modifications and the occurrence of delirium in patients with acute stroke. Methods: The current systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The search was performed on PubMed and Scopus databases. Only studies that provided data concerning sleep, or pre-existing sleep disorders, in acute stroke and performed a formal evaluation of delirium were included. Results: The literature search enabled the identification of 15 studies, which exhibited high heterogeneity in terms of study design, settings, sleep assessments, delirium measures, and types of sleep intervention. In the study quality assessment, the majority of the studies were rated as weak or moderate. In most of the cases, sleep was subjectively assessed by the patients or rated by clinicians. None of the studies performed polysomnography for the evaluation of sleep. Only four of the studies assessed the impact of a sleep intervention on delirium, suggesting the potentially protective role of sleep promotion in reducing the prevalence and severity of stroke-related delirium. Conclusions: The evidence arising from the present systematic review supports that sleep disruption is a potential promoting factor for stroke-related delirium. We suggest that a formal sleep assessment and sleep promotion should be included in routine stroke care.

Abstract Pathophysiological understanding of gait and balance disorders in Parkinson’s disease is insufficient and late recognition of fall risk limits efficacious follow‐up to prevent or delay falls. We show a distinctive reduction of glucose metabolism in the left posterior parietal cortex, with increased metabolic activity in the cerebellum, in parkinsonian patients 6–8 months before their first fall episode. Falls in Parkinson’s disease may arise from altered cortical processing of body spatial orientation, possibly predicted by abnormal cortical metabolism.

Abstract Objective To evaluate the ability of persons with metastatic cancer to self‐assess their medical decision‐making capacity (MDC). To investigate this, we compared an objective measure of MDC with self‐ratings and evaluated predictors of agreement. Methods Data were obtained from a cross‐sectional study of metastatic cancer patients at a large academic medical center. Across all standards of MDC, sensitivity, specificity, and reliability using Gwet's AC1 statistic were calculated using the objective measure as the gold standard. Logistic regression was used to evaluate predictors of agreement between the measures across all MDC standards. Results In those with brain metastases, high sensitivity (greater than 0.7), but low specificity was observed for all standards. Poor reliability was observed across all standards. Higher age resulted in higher odds of disagreement for Standard 3 (appreciation) (OR: 1.07, 95% CI: 1.00, 1.15) and Standard 4 (reasoning) (OR: 1.05, 95% CI: 1.00, 1.10). For Standard 3, chemotherapy use and brain metastases compared to other metastases resulted in higher odds of disagreement (Chemotherapy: OR: 5.62, 95% CI: 1.37, 23.09, Brain Metastases: OR: 5.93, 95% CI: 1.28, 27.55). For Standard 5 (understanding), no predictors were associated with disagreement. Conclusions For less cognitively complex standards (e.g., appreciation), self‐report may be more valid and reliable than more cognitively complex standards (e.g., reasoning or understanding). However, overall, MDC self‐report in the current sample is suboptimal. Thus, the need for detailed assessment of MDC, especially when patients are older or used chemotherapy, is indicated. Other studies should be conducted to assess MDC agreement longitudinally.

Mesenchymal stromal cells (MSCs) are multipotent cells with anti-inflammatory properties. Here we tested the safety of MSCs in patients with progressive supranuclear palsy (PSP; ClinicalTrials.gov: NCT01824121; Eudract No. 2011-004051-39). Seven patients were treated. To improve the safety, protocol adjustments were made during the performance of the study. The objectives of our work were: (1) to assess the safety of MSCs and (2) to identify critical issues in cell therapies for neurodegenerative diseases. Autologous MSCs from the bone marrow of PSP patients were administered through the internal carotid arteries. 1-year survival and number of severe adverse events were considered as safety endpoints. Clinical rating scales, neuropsychological assessments, gait and posture analysis, single-photon emission computed tomography, positron emission tomography, and brain magnetic resonance (BMR) were performed at different follow-up times. Peripheral blood levels of inflammatory cytokines were measured before and after cell infusion. Six of the seven treated patients were living 1 year after cell infusion. Asymptomatic spotty lesions were observed at BMR after 24 h in six of the seven treated patients. The last patient in the preliminary cohort (Case 5) exhibited transiently symptomatic BMR ischemic alterations. No severe adverse events were recorded in the last two treated patients. Interleukin-8 serum concentrations decreased in three patients (Case 2, 3, and 4). An adaptive study design, appropriate and up-to-date efficacy measures, adequate sample size estimation, and, possibly, the use of a cellular and/or allogeneic cell sources may help in performing phase II trials in the field.

Balance and gait impairments, and consequently, mobility restrictions and falls are common in Parkinson’s disease (PD). Various cognitive deficits are also common in PD and are associated with increased fall risk. These mobility and cognitive deficits are limiting factors in a person’s health, ability to perform activities of daily living, and overall quality of life. Community ambulation involves many dual-task (DT) conditions that require processing of several cognitive tasks while managing or reacting to sudden or unexpected balance challenges. DT training programs that can simultaneously target balance, gait, visuomotor, and cognitive functions are important to consider in rehabilitation and promotion of healthy active lives. In the proposed multi-center, randomized controlled trial (RCT), novel behavioral positron emission tomography (PET) brain imaging methods are used to evaluate the molecular basis and neural underpinnings of: (a) the decline of mobility function in PD, specifically, balance, gait, visuomotor, and cognitive function, and (b) the effects of an engaging, game-based DT treadmill walking program on mobility and cognitive functions. Both the interactive cognitive game tasks and treadmill walking require continuous visual attention, and share spatial processing functions, notably to minimize any balance disturbance or gait deviation/stumble. The ability to “walk and talk” normally includes activation of specific regions of the prefrontal cortex (PFC) and the basal ganglia (site of degeneration in PD). The PET imaging analysis and comparison with healthy age-matched controls will allow us to identify areas of abnormal, reduced activity levels, as well as areas of excessive activity (increased attentional resources) during DT-walking. We will then be able to identify areas of brain plasticity associated with improvements in mobility functions (balance, gait, and cognition) after intervention. We expect the gait-cognitive training effect to involve re-organization of PFC activity among other, yet to be identified brain regions. The DT mobility-training platform and behavioral PET brain imaging methods are directly applicable to other diseases that affect gait and cognition, e.g., cognitive vascular impairment, Alzheimer’s disease, as well as in aging.

Abstract Introduction Psychogenic nonepileptic seizures (PNES) are observable abrupt paroxysmal changes in behavior or consciousness that resemble epileptic seizures, but without concurrent electroencephalographic abnormalities. Methods In this manuscript, we reviewed literature concerning pediatric PNES and focused on those articles published in the last 10 years, in order to try to understand what the state of the art is at the moment, particularly as regards relationship and differential diagnosis with epilepsy. Results Psychogenic nonepileptic seizures have been extensively described in literature mainly in adults and less frequently in children. Despite the potential negative impact of a misdiagnosis (unnecessary investigations and antiepileptic drugs, structured pathological behavioral patterns), in literature there is little information regarding the real prevalence, clinical features, treatment, and outcome of PNES in children and adolescents. Conclusion Psychogenic nonepileptic seizures are common but frequently missed entity in pediatric population. Diagnosis could be difficult, especially in those children who have both epileptic and nonepileptic seizures; video EEG and home video can help clinicians in diagnosis. More studies are needed to better classify PNES in children and facilitate diagnosis and treatment.

Many cognitive functions face a decline in the healthy elderly. Within the cognitive domains, both attentional processes and executive functions are impaired with aging. Attention includes three attentional networks, i.e., alerting, orienting, and executive control, showing a hemispheric lateralized pattern in adults. This lateralized pattern could play a role in modulating the efficiency of attentional networks. For these reasons, it could be relevant to analyze the age-related change of the hemispheric specialization of attentional networks. This study aims to clarify this aspect with a lateralized version of the Attentional Network Test for Interaction (ANTI)-Fruit. One hundred seventy-one participants took part in this study. They were divided in three age groups: youth (N = 57; range: 20–30); adults (N = 57; range 31–64), and elderly/older people (N = 57; range: 65–87). The results confirmed the previous outcomes on the efficiency and interactions among attentional networks. Moreover, an age-related generalized slowness was evidenced. These findings also support the hypothesis of a hemispheric asymmetry reduction in elderly/older adults.

Francesco Precenzano,1,* Maria Ruberto,2,* Lucia Parisi,3 Margherita Salerno,4 Agata Maltese,3 Beatrice Gallai,5 Rosa Marotta,6 Serena Marianna Lavano,7 Francesco Lavano,6 Michele Roccella3 1Clinic of Child and Adolescent Neuropsychiatry, Headache Center for Children and Adolescent. Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania Luigi Vanvitelli, 2Department of Medical-Surgical and Dental Specialties, Università degli Studi della Campania Luigi Vanvitelli, Naples, 3Department of Psychological, Pedagogical and Educational Sciences, 4Sciences for Mother and Child Health Promotion, University of Palermo, Palermo, 5Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, 6Department of Medical and Surgery Sciences, 7Department of Health Sciences, University “Magna Graecia”, Catanzaro, Italy *These authors contributed equally to this work Abstract: Routinely in the clinical practice, children affected by migraine without aura (MwA) tend to exhibit severe and persistent difficulties within cognitive processes such as attention, memory, and visual–motor integration (VMI) skills. The aim of this study was to assess the visual–spatial and visual–motor abilities among a sample of children with MwA and the effects of a specific computerized training. The study population was composed of 84 patients affected by MwA (39 girls and 45 boys; mean age: 8.91±2.46 years), and they were randomly divided into two groups (group A and group B) comparable for age (P=0.581), gender (P=0.826), socioeconomic status (SES), migraine frequency (P=0.415), and intensity (P=0.323). At baseline (T0), the two groups were comparable for movement assessment battery for children (M-ABC) and VMI performances. After 6 months of treatment (T1), group A showed lower scores in the dexterity item of M-ABC test (P

Fragile X syndrome (FXS) is a genetic syndrome with intellectual disability due to the loss of expression of the FMR1 gene located on chromosome X (Xq27.3). This mutation can suppress the fragile X mental retardation protein (FMRP) with an impact on synaptic functioning and neuronal plasticity. Among associated sign and symptoms of this genetic condition, sleep disturbances have been already described, but few polysomnographic reports in pediatric age have been reported. This multicenter case-control study is aimed at assessing the sleep macrostructure and at analyzing the presence of EEG abnormalities in a cohort of FXS children. We enrolled children with FXS and, as controls, children with typical development. All subjects underwent at least 1 overnight polysomnographic recording (PSG). All recorded data obtained from patients and controls were compared. In children with FXS, all PSG-recorded parameters resulted pathological values compared to those obtained from controls, and in FXS children only, we recorded interictal epileptiform discharges (IEDs), as diffuse or focal spikes and sharp waves, usually singles or in brief runs with intermittent or occasional incidence. A possible link between IEDs and alterations in the circadian sleep-wake cycle may suggest a common dysregulation of the balance between inhibitory and excitatory pathways in these patients. The alteration in sleep pattern in children with FXS may negatively impact the neuropsychological and behavioral functioning, adding increasing burn of the disease on the overall management of these patients. In this regard, treating physicians have to early detect sleep disturbances in their patients for tailored management, in order to prevent adjunctive comorbidities.

Background. Developmental Language Disorder (DLD) is frequent in childhood and may have long-term sequelae. By employing an evidence-based approach, this scoping review aims at identifying (a) early predictors of DLD; (b) the optimal age range for the use of screening and diagnostic tools; (c) effective diagnostic tools in preschool children. Methods. We considered systematic reviews, meta-analyses, and primary observational studies with control groups on predictive, sensitivity and specificity values of screening and diagnostic tools and psycholinguistic measures for the assessment of DLD in preschool children. We identified 37 studies, consisting of 10 systematic reviews and 27 primary studies. Results. Delay in gesture production, receptive and/or expressive vocabulary, syntactic comprehension, or word combination up to 30 months emerged as early predictors of DLD, a family history of DLD appeared to be a major risk factor, and low socioeconomic status and environmental input were reported as risk factors with lower predictive power. Optimal time for screening is suggested between age 2 and 3, for diagnosis around age 4. Because of the high variability of sensitivity and specificity values, joint use of standardized and psycholinguistic measures is suggested to increase diagnostic accuracy. Conclusions. Monitoring risk situations and employing caregivers’ reports, clinical assessment and multiple linguistic measures are fundamental for an early identification of DLD and timely interventions.

Individuals with high anxiety preferentially focus attention on emotional information. The autonomic nervous system (ANS) plays an important role in modulating both anxiety and attentional processes. Despite many studies having evaluated attentional bias in anxious people, few of them have investigated the change blindness phenomenon associated with the attentional response toward salient stimuli, considering the role of the ANS. This study aimed to examine the role of heart rate variability (HRV) in trait anxiety and top-down and bottom-up attentional processes toward emotional stimuli. Seventy-five healthy university students were divided into high (N = 39) and low (N = 36) trait anxiety groups and completed a change detection flicker task with neutral, positive, and negative stimuli. The results evidenced a different attentional pattern between people with high and low anxiety considering both the two attentional processes and the valence of the stimuli. Specifically, individuals with high anxiety showed a bias in elaborating emotional stimuli related to their salience (i.e., negative stimuli were faster elaborated than neutral and positive stimuli when top-down attentional mechanisms were involved, while slower performances were highlighted considering bottom-up attentional mechanisms in response to emotional stimuli compared to neutral stimuli). Moreover, an association between HRV, trait anxiety levels, and change blindness phenomenon was confirmed. These results underline the role of HRV as a possible predictor of the alteration of attentional mechanism in anxiety.

Maria Esposito,1 Beatrice Gallai,2 Michele Roccella,3 Rosa Marotta,4 Francesco Lavano,4 Serena Marianna Lavano,4 Giovanni Mazzotta,5 Domenico Bove,6 Michele Sorrentino,1 Francesco Precenzano,1 Marco Carotenuto1 1Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Second University of Naples, Naples, Italy; 2Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, Italy; 3Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, Italy; 4Department of Psychiatry, “Magna Graecia” University of Catanzaro, Catanzaro, Italy; 5Unit of Child and Adolescent Neuropsychiatry, AUSL Umbria 2, Terni, Italy; 6Centro per la Diagnosi e Cura dei Disturbi dell’apprendimento e del Comportamento Associazione per la ricerca scientifica Fusis, Alvignano, Italy Introduction: Childhood obesity has become a worldwide epidemic in Western and in developing countries and has been accompanied by many serious and severe comorbidities, such as diabetes, hypertension, sleep apnea syndrome, depression, dyslipidemia, impaired glucose homeostasis, steatohepatitis, and intracranial hypertension, as well as medical concerns unique to youth, such as accelerated pubertal and skeletal development and orthopedic disorders. To date, no specific studies about the psychological assessment in pediatric obesity are present. Therefore, the aim of this study was to evaluate the putative relationship between psychological troubles and obesity in a sample of school-aged children. Materials and methods: The study population consists of 148 obese subjects (body mass index [BMI] >95th percentile) (69 males, mean age 8.9±1.23 years) consecutively referred from clinical pediatricians to the Child and Adolescent Neuropsychiatry department at the Second University of Naples. In all subjects, weight, height, and BMI z-score were evaluated. In order to assess the anxiety levels and the presence of depressive symptoms, the Children Depression Inventory (CDI) and the Italian Self-Administered Psychiatric Scales for Children and Adolescents (SAFA) were administered. The control group consisted of 273 healthy children (129 males and 144 females) (mean age 9.1±1.8 years), enrolled in schools within the Campania region of Italy. Results: No significant differences between the two study groups were found for age (8.9±1.23 years in the obese sample and 9.1±1.8 years in the control group) (P=0.228) or sex (ratio male/female: 69/79 in the obese group versus 129/144 in the control group) (P=0.983). Obviously, significant difference was found for the BMI z-score (2.46±0.31 in the obese group vs 0.73±0.51 in the control group) (P

Maria Esposito,1 Maria Ruberto,2 Francesca Gimigliano,1,2 Rosa Marotta,3 Beatrice Gallai,4 Lucia Parisi,5 Serena Marianna Lavano,3 Michele Roccella,5 Marco Carotenuto11Center for Childhood Headache, Child and Adolescent Neuropsychiatry Clinic, Department of Mental Health, Physical and Preventive Medicine, 2Department of Odonto-Stomathologic Disciplines, Pathology – Orthopedic Sciences, Second University of Naples, Naples, Italy; 3Department of Psychiatry, “Magna Graecia” University of Catanzaro, Catanzaro, Italy; 4Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, Italy; 5Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, ItalyBackground: Migraine without aura (MoA) is a painful syndrome, particularly in childhood; it is often accompanied by severe impairments, including emotional dysfunction, absenteeism from school, and poor academic performance, as well as issues relating to poor cognitive function, sleep habits, and motor coordination.Materials and methods: The study population consisted of 71 patients affected by MoA (32 females, 39 males) (mean age: 9.13±1.94 years); the control group consisted of 93 normally developing children (44 females, 49 males) (mean age: 8.97±2.03 years) recruited in the Campania school region. The entire population underwent a clinical evaluation to assess total intelligence quotient level, visual-motor integration (VMI) skills, and motor coordination performance, the later using the Movement Assessment Battery for Children (M-ABC). Children underwent training using the Wii-balance board and Nintendo Wii Fit Plus™ software (Nintendo Co, Ltd, Kyoto, Japan); training lasted for 12 weeks and consisted of three 30-minute sessions per week at their home.Results: The two starting populations (MoA and controls) were not significantly different for age (P=0.899) and sex (P=0.611). M-ABC and VMI performances at baseline (T0) were significantly different in dexterity, balance, and total score for M-ABC (P

Maria Esposito,1 Lucia Parisi,2 Beatrice Gallai,3 Rosa Marotta,4 Anna Di Dona,1 Serena Marianna Lavano,2 Michele Roccella,4 Marco Carotenuto11Center for Childhood Headache, Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Second University of Naples, Naples, Italy; 2Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, Italy; 3Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, Italy; 4Department of Psychiatry, The Magna Graecia University of Catanzaro, Catanzaro, ItalyBackground: In recent years, great attention has been given to the presence of psychological problems and psychiatric comorbidity that are also present in children affected by primary headaches. The relationship between pain and attachment has been identified, and it may be that pain perception may change in relation with specific attachment styles. The aim of the present study was to assess the prevalent attachment style and verify its putative relationship and correlation with the main characteristics of migraine attacks, in school-aged children affected by migraine without aura (MoA).Materials and methods: The study population consisted of 219 children (103 males, 116 females) aged between 6 and 11 years (mean 8.96 ± 2.14 years), consecutively referred for MoA compared with 381 healthy controls (174 males, 207 females; mean age 9.01 ± 1.75 years) randomly selected from schools. All the children were classified according to the attachment typologies of the Italian modified version of the Separation Anxiety Test; monthly headache frequency and mean headache duration were assessed from daily headache diaries kept by all the children. Headache intensity was assessed on a visual analogue scale. The chi-square test and t-test, where appropriate, were applied, and the Spearman rank correlation test was applied to explore the relationship between the types of attachment style and clinical aspects of MoA.Results: The MoA group showed a significantly higher prevalence of type A (avoidant) attachment (P

Maria Esposito,1 Francesca Gimigliano,1,2 Maria Ruberto,2 Rosa Marotta,3 Beatrice Gallai,4 Lucia Parisi,5 Serena Marianna Lavano,3 Giovanni Mazzotta,6 Michele Roccella,5 Marco Carotenuto1 1Center for Childhood Headache, Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Second University of Naples, Naples, Italy; 2Department of Odontostomathologic Disciplines, Head Pathology, Orthopedic Sciences, Second University of Naples, Italy; 3Department of Psychiatry, Magna Graecia University of Catanzaro, Catanzaro, Italy; 4Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, Italy; 5Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, Italy; 6Unit of Child and Adolescent Neuropsychiatry, AUSL Umbria, Terni, Italy Background: According to the Rome III criteria, encopresis without constipation was defined as nonretentive fecal soiling (FNRFS) with not yet well understood etiology. Treatment approaches reported in the literature with varying results include biofeedback, hypnosis, reflexology, and Internet-based educational programs. In developmental age, another behavioral treatment could be identified in the psychomotor approach, which is called psychomotricity in the European countries, or is also known as play therapy. The aim of the present study was to verify the safety and efficacy of play therapy plus toilet training in a small sample of prepubertal children affected by FNRFS. Materials and methods: Twenty-six patients (group 1; 16 males, mean age of 5.92 ± 0.84 years) underwent a psychomotor approach therapy program in association with toilet training for 6 months, and the other 26 subjects (group 2; 17 males, mean age of 5.76 ± 0.69) underwent the sole toilet training program for 6 months. During the observational time period (T0) and after 6 months (T1) of both treatments, the patients were evaluated for FNRFS frequency and for the behavioral assessment. Results: At T0, the FNRFS mean frequency per month for group 1 was 20.115 episodes/month (standard deviation [SD] ± 3.024) and for group 2 was 20.423 (SD ± 1.879) (P = 0.661). At T1 the mean frequency per month was 6.461 (SD ± 1.333) episodes/month and 12.038 (SD ± 1.341), respectively (P < 0.001). Moreover, the delta percent average of the frequency between T0 and T1 was 67.121 ± 8.527 for group 1 and 40.518 ± 9.259 for group 2 (P < 0.001). At T1, a significant improvement in scores on the behavioral scale was identified. Conclusion: Our preliminary results show the importance of a multidisciplinary approach, and suggest the positive effect of an additional psychomotor approach, as this holds a new and interesting rehabilitative purpose for children in a toilet training program, even if further research is necessary. Keyword: encopresis, psychomotricity, children, toilet training, rehabilitation

Maria Esposito,1 Michele Roccella,2 Beatrice Gallai,3 Lucia Parisi,2 Serena Marianna Lavano,4 Rosa Marotta,4 Marco Carotenuto1 1Center for Childhood Headache, Second University of Naples, Naples, Italy; 2Department of Psychology, University of Palermo, Palermo, Italy; 3Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, Italy; 4Department of Psychiatry, Magna Graecia University of Catanzaro, Catanzaro, Italy Background: Empirical evidence of the important role of the family in primary pediatric headache has grown significantly in the last few years, although the interconnections between the dysfunctional process and the family interaction are still unclear. Even though the role of parenting in childhood migraine is well known, no studies about the personality of parents of migraine children have been conducted. The aim of the present study was to assess, using an objective measure, the personality profile of mothers of children affected by migraine without aura (MoA). Materials and methods: A total of 269 mothers of MoA children (153 male, 116 female, aged between 6 and 12 years; mean 8.93 ± 3.57 years) were compared with the findings obtained from a sample of mothers of 587 healthy children (316 male, 271 female, mean age 8.74 ± 3.57 years) randomly selected from schools in the Campania, Umbria, Calabria, and Sicily regions. Each mother filled out the Minnesota Multiphasic Personality Inventory – second edition (MMPI-2), widely used to diagnose personality and psychological disorders. The t-test was used to compare age and MMPI-2 clinical basic and content scales between mothers of MoA and typical developing children, and Pearson’s correlation test was used to evaluate the relation between MMPI-2 scores of mothers of MoA children and frequency, intensity, and duration of migraine attacks of their children. Results: Mothers of MoA children showed significantly higher scores in the paranoia and social introversion clinical basic subscales, and in the anxiety, obsessiveness, depression, health concerns, bizarre mentation, cynicism, type A, low self-esteem, work interference, and negative treatment indicator clinical content subscales (P < 0.001 for all variables). Moreover, Pearson’s correlation analysis showed a significant relationship between MoA frequency of children and anxiety (r = 0.4903, P = 0.024) and low self-esteem (r = 0.5130, P = 0.017), while the MoA duration of children was related with hypochondriasis (r = 0.6155, P = 0.003), hysteria (r = 0.6235, P = 0.003), paranoia (r = 0.5102, P = 0.018), psychasthenia (r = 0.4806, P = 0.027), schizophrenia (r = 0.4350, P = 0.049), anxiety (r = 0.4332, P = 0.050), and health concerns (r = 0.7039, P < 0.001) MMPI-2 scores of their mothers. Conclusion: This could be considered a preliminary study that indicates the potential value of maternal personality assessment for better comprehension and clinical management of children affected by migraine, though further studies on the other primary headaches are necessary. Keywords: MMPI-2, childhood migraine, maternal personality

Maria Esposito,1 Lorenzo Antinolfi,1 Beatrice Gallai,2 Lucia Parisi,3 Michele Roccella,3 Rosa Marotta,4 Serena Marianna Lavano,4 Giovanni Mazzotta,5 Francesco Precenzano,1 Marco Carotenuto1 1Sleep Clinic for Developmental Age, Clinic of Child and Adolescent Neuropsychiatry, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy; 2Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, Italy; 3Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, Italy; 4Department of Psychiatry, Magna Graecia University of Catanzaro, Catanzaro, Italy; 5Unit of Child and Adolescent Neuropsychiatry, AUSL Umbria 2, Terni, Italy Introduction: The role of sleep in cognitive processes can be considered clear and well established. Different reports have disclosed the association between sleep and cognition in adults and in children, as well as the impact of disturbed sleep on various aspects of neuropsychological functioning and behavior in children and adolescents. Behavioral and cognitive dysfunctions can also be considered as related to alterations in the executive functions (EF) system. In particular, the EF concept refers to self-regulatory cognitive processes that are associated with monitoring and controlling both thought and goal directed behaviors. The aim of the present study is to assess the impact of the obstructive sleep apnea syndrome (OSAS) on EF in a large sample of school aged children. Materials and methods: The study population comprised 79 children (51 males and 28 females) aged 7–12 years (mean 9.14 ± 2.36 years) with OSAS and 92 healthy children (63 males and 29 females, mean age 9.08 ± 2.44 years). To identify the severity of OSAS, an overnight respiratory evaluation was performed. All subjects filled out the Italian version of the Modified Card Sorting Test to screen EFs. Moreover, to check the degree of subjective perceived daytime sleepiness, all subjects were administered the Pediatric Daytime Sleepiness Scale (PDSS). Results: No significant differences between the two study groups were found for age (P = 0.871), gender (P = 0.704), z-score of body mass index (P = 0.656), total intelligence quotient (P = 0.358), and PDSS scores (P = 0.232). The OSAS children showed a significantly higher rate of total errors (P < 0.001), perseverative errors (P < 0.001), nonperseverative errors (P < 0.001), percentage of total errors (P < 0.001), percentage of perseverative errors (P < 0.001), and percentage of nonperseverative errors (P< 0.001). On the other hand, OSAS children showed a significant reduction in the number of completed categories (P = 0.036), total correct sorts (P = 0.001), and categorizing efficiency (P < 0.001). The Pearson's correlation analysis revealed a significant positive relationship between all error parameters and apnea-hypopnea index, oxygen desaturation index, and percentage of mean desaturation of O2 with a specular negative relationship between the error parameters and the mean oxygen saturation values, such as a significant negative relationship between apnea-hypopnea index, oxygen desaturation index, percent of mean desaturation of O2, and the number of completed categories. Conclusion: Our study identified differences in the executive functioning of children affected by OSAS and is the first to identify a correlation between alteration in respiratory nocturnal parameters and EF that has not yet been reported in developmental age. These findings can be considered as the strength and novelty of the present report in a large pediatric population. Keywords: OSAS, polysomnography, executive functions, sleep, sleepiness, children

Maria Esposito,1 Beatrice Gallai,2 Lucia Parisi,3 Laura Castaldo,1 Rosa Marotta,4 Serena Marianna Lavano,4 Giovanni Mazzotta,5 Michele Roccella,3 Marco Carotenuto11Center for Childhood Headache, Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Second University of Naples, Naples, Italy; 2Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, Italy; 3Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, Italy; 4Department of Psychiatry, "Magna Graecia" University of Catanzaro, Catanzaro, Italy; 5Unit of Child and Adolescent Neuropsychiatry, AUSL Umbria 2, Terni, ItalyIntroduction: Self-esteem is related to the broadly understood concept of self-schemas and is a crucial mechanism for a correct psychological development in children and adolescents. The impact of the many psychological difficulties linked to the migraine without aura (MoA) and recurrent headache attacks, such as anger and separation anxiety, on self-esteem has not yet been well investigated. The aims of the present study were to assess self-esteem levels in an objective way and to verify their possible relationship and correlation with the frequency and intensity of migraine attacks, in a population of children and adolescents affected by MoA.Methods: The study population was comprised of 185 children (88 males [M], 97 females [F]) aged between 6 and 12 years (mean 9.04 ± 2.41 years) referred consecutively for MoA to the Center for Childhood Headache, Clinic of Child and Adolescent Neuropsychiatry, Second University of Naples and of 203 healthy controls (95 M, 108 F) with mean age 9.16 ± 2.37 years, recruited from schools in Campania. The monthly headache frequency and the mean headache duration were assessed from daily headache diaries kept by all the children, and MoA intensity was assessed on a VAS (visual analog scale). To further evaluate their level of self-concept, all subjects filled out the Multidimensional Self-Concept Scale (MSCS).Results: The two study groups were comparable for age (P = 0.621), sex (P = 0.960), and z-score BMI (P = 0.102). The MoA group showed a significant reduction in the MSCS total score (P < 0.001) and in the Social (P < 0.001), Affect (P < 0.001), Family (P < 0.001), and Physical (P < 0.001) domains of the MSCS compared with the control group. The Pearson's correlation analysis showed a significantly negative relationship between MoA clinical characteristics and MSCS scores, and similarly the frequency of attacks was significantly negatively related with the Social (r = −0.3176; P < 0.001), Competence (r = −0.2349; P = 0.001), Physical (r = −0.2378; P = 0.001), and total (r = −0.2825; P < 0.001) scores of the MSCS. On the other hand, the MoA duration was significantly negatively related with the Social (r = −0.1878; P = 0.01), Competence (r = −0.2270; P = 0.002), Physical (r = −0.1976; P = 0.007), and total (r = −0.1903; P = 0.009) scores of the MSCS.Conclusion: Our study first identified differences in self-esteem levels, with an objective tool, in children affected by MoA compared with controls, suggesting the need for evaluation of self-esteem for better psychological pediatric management of children with migraine.Keywords: children, self-esteem, MSCS

Maria Esposito,1 Rosa Marotta,2 Beatrice Gallai,3 Lucia Parisi,4 Giuseppina Patriciello,1 Serena Marianna Lavano,2 Giovanni Mazzotta,5 Michele Roccella,4 Marco Carotenuto11Center for Childhood Headache, Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Second University of Naples, Naples, Italy; 2Department of Psychiatry, "Magna Graecia" University of Catanzaro, Catanzaro, Italy; 3Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, Italy; 4Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, Italy; 5Unit of Child and Adolescent Neuropsychiatry, AUSL Umbria 2, Terni, ItalyBackground: Children with migraine seem to be more anxious, sensitive, deliberate, cautious, fearful, vulnerable to frustration, tidy, and less physically enduring than comparisons. To the best our knowledge no studies about the temperamental and the characterial dimension aspects in childhood migraine was conducted. Therefore, the aim of the present study was to describe the temperamental and character aspects in a sample of children affected by migraine without aura (MoA) and their relationship with clinical aspects of MoA such as frequency, duration, and severity of attacks.Materials and methods: In our study, 486 children affected by MoA (239 male, 247 female) aged 7–12 years, (mean 10.04 ± 2.53 years) and 518 typical developing children comparable for age (P = 0.227) and sex (P = 0.892) were enrolled to assess their temperamental characteristics. The mothers of all subjects filled out the Junior Temperament and Character Inventory: Parent Version.Results: Children affected by migraine show a higher prevalence of harm avoidance and persistence temperamental domains (P < 0.001) and significantly lower prevalence of the self-directedness character trait (P = 0.023) with respect to the comparisons, according to Cloninger's model. The Spearman rank correlation analysis shows a significant relationship between migraine characteristics and temperamental domains.Conclusion: The present study first identified differences in temperamental characteristics in children affected by MoA with respect to the comparisons, suggesting the need for this evaluation in order for better psychological pediatric management of children with migraine, with possible consequences and impact on the future outcomes of these subjects.Keywords: migraine without aura, children, temperament, JTCI

Maria Esposito,1 Beatrice Gallai,2 Lucia Parisi,3 Michele Roccella,3 Rosa Marotta,4 Serena Marianna Lavano,4 Giovanni Mazzotta,5 Giuseppina Patriciello,1 Francesco Precenzano,1 Marco Carotenuto1 1Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Second University of Naples, Italy; 2Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Italy; 3Child Neuropsychiatry, Department of Psychology, University of Palermo, Italy; 4Department of Psychiatry, "Magna Graecia" University of Catanzaro, Catanzaro, Italy; 5Unit of Child and Adolescent Neuropsychiatry, AUSL Umbria 2, Terni, Italy Background: Primary monosymptomatic nocturnal enuresis (PMNE) is a common problem in the developmental ages; it is the involuntary loss of urine during the night in children older than 5 years of age. Several clinical observations have suggested an association between bedwetting and developmental delays in motricity, language development, learning disability, physical growth, and skeletal maturation. The aim of the present study is to evaluate the prevalence of fine motor coordination and visuomotor integration abnormalities in prepubertal children with PMNE. Methods: The study population included 31 children (16 males, 15 females; mean age 8.14 years ± 1.36 years), and the control group comprised 61 typical developing children (32 males, 29 females; mean age 8.03 years ± 1.44 years). The whole population underwent a clinical evaluation to assess total intelligence quotient level, visuomotor integration (VMI) skills, and motor coordination performance (using the Movement Assessment Battery for Children, or M-ABC). Results: No significant differences between the two study groups were found for age (P = 0.725), gender (P = 0.886), z-body mass index (P = 0.149), or intellectual abilities (total intelligence quotient) (P = 0.163). The PMNE group showed a higher prevalence of borderline performance on M-ABC evaluation and in pathologic performance on VMI Total Task compared to controls (P < 0.001). No significant differences between the two study groups were found for pathologic performances on the M-ABC (P = 0.07), VMI Visual Task (P = 0.793), and VMI Motor Task (P = 0.213). Conclusion: Our findings pinpointed that PMNE should not be considered as a voiding disorder alone and, consequently, the children affected should be referred to specific rehabilitative programs that aim to improve motor coordination and visuomotor integration. Keywords: primary monosymptomatic nocturnal enuresis, visuomotor integration, childhood rehabilitation, VMI, M-ABC

Maria Esposito,1 Beatrice Gallai,2 Lucia Parisi,3 Michele Roccella,3 Rosa Marotta,4 Serena Marianna Lavano,4 Antonella Gritti,5 Giovanni Mazzotta,6 Marco Carotenuto11Center for Childhood Headache, Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical, and Preventive Medicine, Second University of Naples, Naples, 2Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, 3Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, 4Department of Psychiatry, "Magna Graecia" University of Catanzaro, Catanzaro, 5Suor Orsola Benincasa University, Naples, 6Unit of Child and Adolescent Neuropsychiatry, Azienda Sanitaria Locale 4, Terni, ItalyBackground: Migraine without aura is a primary headache which is frequent and disabling in the developmental age group. No reports are available concerning the prevalence and impact of migraine in children on the degree of stress experienced by parents. The aim of this study was to evaluate the prevalence of maternal stress in a large pediatric sample of individuals affected by migraine without aura.Methods: The study population consisted of 218 children (112 boys, 106 girls) of mean age 8.32 ± 2.06 (range 6–13) years suffering from migraine without aura and a control group of 405 typical developing children (207 boys, 198 girls) of mean age 8.54 ± 2.47 years. Mothers of children in each group answered the Parent Stress Index-Short Form (PSI-SF) questionnaire to assess parental stress levels.Results: The two groups were matched for age (P = 0.262), gender (P = 0.983), and body mass index adjusted for age (P = 0.106). Mothers of children with migraine without aura reported higher mean PSI-SF scores related to the Parental Distress domain (P < 0.001), Dysfunctional Parent-Child Interaction domain (P < 0.001), Difficult Child subscale (P < 0.001), and Total Stress domain than mothers of controls (P < 0.001). No differences between the two groups were found for Defensive Responding subscale scores.Conclusion: Our study may be the first to highlight the presence of high levels of stress in parents of children affected by migraine without aura.Keywords: parental stress, childhood migraine, migraine without aura, children

Maria Esposito,1 Beatrice Gallai,2 Lucia Parisi,3 Michele Roccella,3 Rosa Marotta,4 Serena Marianna Lavano,4 Giovanni Mazzotta,5 Marco Carotenuto11Center for Childhood Headache, Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Second University of Naples, Naples, Italy; 2Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, Italy; 3Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, Italy; 4Department of Psychiatry, “Magna Graecia” University of Catanzaro, Catanzaro, Italy; 5Unit of Child and Adolescent Neuropsychiatry, AUSL Umbria 2, Terni, ItalyIntroduction: Primary nocturnal enuresis (PNE) is a common problem in developmental age with an estimated overall prevalence ranging from 1.6% to 15%, and possible persistence during adolescence. There is a growing interest in the sleep habits of children affected by PNE, which is derived from the contradictory data present in clinical literature. The aim of the present study was to evaluate the presence of sleep disturbances in a population of children affected by PNE, and to identify whether PNE could be considered as a risk factor for sleep disturbances among children.Materials and methods: A total of 190 PNE children (97 males, 93 females) aged 7–15 years, (mean 9.64 ± 1.35 years), and 766 typically developing children matched for age (P = 0.131) and gender (P = 0.963) were enrolled. To evaluate the presence of sleep habits and disturbances, all of the subjects’ mothers filled out the Sleep Disturbances Scale for Children (SDSC), a questionnaire consisting of six subscales: Disorders in Initiating and Maintaining Sleep (DIMS), Sleep Breathing Disorders (SBD), Disorders of Arousal (DA), Sleep–Wake Transition Disorders (SWTD), Disorders of Excessive Somnolence (DOES), and Nocturnal Hyperhidrosis (SHY). The results were divided into “pathological” and “normal” scores using a cut-off value (pathological score = at least three episodes per week), according to the validation criteria of the test. Then, the Chi-square test was used to calculate the statistical difference and a univariate logistic regression analysis was applied to determine the role of PNE as a risk factor for the development of each category of sleep disorders and to calculate the odds ratio (OR).Results: PNE children show a higher prevalence of all sleep disturbances (41.03% DIMS; 85.12% SBD; 63.29% DA; 67.53% SWTD; 31.28% DOES; 37.92% SHY; 25.33% SDSC total score), and according to OR results (SDSC total score OR = 8.293, 95% confidence interval [CI] = 5.079–13.540; DIMS OR = 7.639, 95% CI = 5.192–11.238; SBD OR = 35.633, 95% CI = 22.717–55.893; DA OR = 13.734, 95% CI = 9.476–19.906; SWTD OR = 14.238, 95% CI = 9.829–20.625; DOES OR = 5.602, 95% CI = 3.721–8.432; SHY OR = 6.808, 95% CI = 4.608–10.059), PNE could be considered as a risk factor for the development of sleep disorders.Conclusion: Among PNE children, sleep could be strongly altered, thus helping to affirm the hypothesis that PNE tends to alter sleep architecture, or it could itself be the consequence of an abnormal sleep structure. The findings also point to the existence of a potential increase in the risk of developing sleep disorders in the presence of PNE.Keywords: primary nocturnal enuresis, SDSC, sleep

Maria Esposito,1 Antonio Pascotto,1 Beatrice Gallai,3 Lucia Parisi,2 Michele Roccella,2 Rosa Marotta,4 Serena Marianna Lavano,4 Antonella Gritti,5 Giovanni Mazzotta,6 Marco Carotenuto11Center for Childhood Headache, Clinic of Child and Adolescent Neuropsychiatry, Second University of Naples, Naples, 2Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, 3Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, 4Department of Psychiatry, “Magna Graecia” University of Catanzaro, Catanzaro, 5Suor Orsola Benincasa University, Napoli, 6Unit of Child and Adolescent Neuropsychiatry, Azienda Sanitaria Locale 4, Terni, ItalyBackground: The purpose of this study was to assess the cognitive functioning of children affected by headache, pinpointing the differences in intelligence style between subjects affected by migraine without aura and subjects with tension-type headache.Methods: The study population consisted of 147 children (mean age 10.82 ± 2.17 years) with headache, recruited from the Headache Center for Developmental Age, Child and Adolescent Neuropsychiatry Clinic, Second University of Naples. Cognitive profiling was performed using Weschler Intelligence Scale for Children Third Edition throughout the sample. According to the International Classification of Headache Disorders II criteria for pediatric age, subjects were divided into a migraine without aura group (n = 75; 43 boys, 32 girls) and a tension-type headache group (n = 72; 49 boys, 23 girls). The results were compared with the findings obtained from a sample of 137 healthy control subjects recruited from schools in the Campania region, matched for age and gender.Results: No difference in full intelligence quotient was found between the groups, but the children with tension-type headache had a lower verbal intelligence quotient and a higher performance intelligence quotient than the healthy controls and children with migraine. Factor analysis data showed that the children with migraine seemed to have lower perceptual organization than the children affected by tension-type headache.Conclusion: To our knowledge, studies on cognitive functioning in children affected by headache in the interictal phase are scarce, and our results suggest a new perspective in understanding of the neuropsychological aspects of young patients affected by headaches.Keywords: childhood headache, intelligence quotient, Weschler Intelligence Scale for Children Third Edition, intelligence, migraine

Marco Carotenuto,1 Maria Esposito,1 Lucia Parisi,2 Beatrice Gallai,3 Rosa Marotta,4 Antonio Pascotto,1 Michele Roccella21Sleep Clinic for Developmental Age, Clinic of Child and Adolescent Neuropsychiatry, Second University of Naples, Naples, Italy; 2Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, Italy; 3Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, 4Department of Psychiatry, "Magna Graecia" University of Catanzaro, Catanzaro, ItalyBackground: The relationship between sleep and mood regulation is well known, and some reports suggest a key role of sleep-related breathing disorders (SRBD) in the development of the symptomatology of depression, even if no conclusive data are actually found in the clinical literature. The aim of this study was to assess the relationship between SRBD and depressive symptoms in a population of school-aged children.Methods: The study population comprised 94 children affected by SRBD and 107 healthy children. To identify the severity of SRBD, an overnight respiratory evaluation was performed. All subjects filled out the Italian version of the Children Depression Inventory (CDI) to screen for the presence of depressive symptoms.Results: The group with SRBD showed higher CDI scores than the group without SRBD, with a positive correlation found between CDI scores, apnea-hypopnea index, and oxygen desaturation index values. Logistic regression showed that an apnea-hypopnea index ≥ 3 and an oxygen desaturation index ≥ 1 could be risk factors for development of depressive symptoms. According to receiver-operating characteristic curve analysis, the cutoff point for the apnea-hypopnea index that could cause a pathological CDI score (≥19) was >5.66, and the cutoff point for the oxygen desaturation index was >4.2. The limitations of this study are that our data are derived from one single psychometric test and not from a complete psychiatric evaluation, and our subjects came from a small group in southern Italy.Conclusion: Our results suggest the importance of mood assessment in children affected by SRBD.Keywords: depression, sleep-related breathing disorders, cardiorespiratory monitoring, children

Pathological gambling (PG) represents a behavioral side effect of dopamine replacement therapy in a minority of patients with Parkinson's disease (PD). Using striatal dopamine transporter (DAT) with single photon emission tomography we assessed presynaptic dopaminergic function in 8 PD patients with PG, 21 matched PD control subjects, and 14 healthy subjects. Statistical Parametric Mapping was applied for image analysis. The analysis of variance (ANOVA) revealed that the three groups differed in dorsal and ventral striata bilaterally. The post-hoc analysis displayed a reduced tracer binding in the ventral striatum of PD patients with PG compared to PD controls, possibly reflecting either a reduction of mesolimbic projections or, alternatively, a lower membrane DAT expression on presynaptic terminals. The latter hypothesis is most likely given that the functional reduction of presynaptic reuptake would be more consistent with the increased dopamine levels in the ventral striatum recently reported in PD gamblers.

Posterior Cortical Atrophy (PCA) is a rare clinical syndrome characterised by the predominance of higher-order visual disturbances such as optic ataxia, a characteristic of Balint’s syndrome. Deficits result from progressive neurodegeneration of occipito-temporal and occipito-parietal cortices. The current study sought to explore the visuomotor functioning of four individuals with PCA by testing their ability to reach out and grasp real objects under various viewing conditions. Experiment 1 had participants reach out and grasp simple, rectangular blocks under visually- and memory-guided conditions. Experiment 2 explored participants’ abilities to accurately reach for objects located in their visual periphery. This investigation revealed that PCA patients demonstrate many of the same deficits that have been previously reported in other individuals with optic ataxia, such as ‘magnetic misreaching’ – a pathological reaching bias towards the point of visual fixation when grasping peripheral targets. Unlike many other individuals with optic ataxia, however, the patients in the current study also show symptoms indicative of damage to the more perceptual stream of visual processing, including abolished grip scaling during memory-guided grasping and deficits in face and object identification. These investigations are the first to perform a quantitative analysis of the visuomotor deficits exhibited by patients with Posterior Cortical Atrophy. Critically, this study helps characterize common symptoms of PCA, a vital first step for generating effective diagnostic criteria and therapeutic strategies for this understudied neurodegenerative disorder.

Abstract Background According to the 2018 NIA-AA research framework, Alzheimer’s disease (AD) is not defined by the clinical consequences of the disease, but by its underlying pathology, measured by biomarkers. Evidence of both amyloid-β (Aβ) and phosphorylated tau protein (p-tau) deposition—assessed interchangeably with amyloid-positron emission tomography (PET) and/or cerebrospinal fluid (CSF) analysis—is needed to diagnose AD in a living person. Our aim was to test the new NIA-AA research framework in a large cohort of cognitively impaired patients to evaluate correspondence between the clinical syndromes and the underlying pathologic process testified by biomarkers. Methods We retrospectively analysed 628 subjects referred to our centre in suspicion of dementia, who underwent CSF analysis, together with neuropsychological assessment and neuroimaging, and were diagnosed with different neurodegenerative dementias according to current criteria, or as cognitively unimpaired. Subjects were classified considering CSF biomarkers, and the prevalence of normal, AD-continuum and non-AD profiles in each clinical syndrome was calculated. The positivity threshold of each CSF biomarker was first assessed by receiver operating characteristic analysis, using Aβ-positive/negative status as determined by amyloid-PET visual reads. The agreement between CSF and amyloid-PET data was also evaluated. Results Among patients with a clinical diagnosis of AD, 94.1% were in the AD-continuum, whereas 5.5% were classified as non-AD and 0.4% were normal. The AD-continuum profile was found also in 26.2% of frontotemporal dementia, 48.6% of Lewy body dementia, 25% of atypical parkinsonism and 44.7% of vascular dementia. Biomarkers’ profile did not differ in amnestic and not amnestic mild cognitive impairment. CSF Aβ levels and amyloid-PET tracer binding negatively correlated, and the concordance between the two Aβ biomarkers was 89%. Conclusions The examination of the 2018 NIA-AA research framework in our clinical setting revealed a good, but incomplete, correspondence between the clinical syndromes and the underlying pathologic process measured by CSF biomarkers. The AD-continuum profile resulted to be a sensitive, but non-specific biomarker with regard to the clinical AD diagnosis. CSF and PET Aβ biomarkers were found to be not perfectly interchangeable to quantify the Aβ burden, possibly because they measure different aspects of AD pathology.

Resting-state fMRI (rs-fMRI) is a widely used technique to investigate the residual brain functions of patients with Disorders of Consciousness (DoC). Nonetheless, it is unclear how the networks that are more associated with primary functions, such as the sensory–motor, medial/lateral visual and auditory networks, contribute to clinical assessment. In this study, we examined the rs-fMRI lower-order networks alongside their structural MRI data to clarify the corresponding association with clinical assessment. We studied 109 chronic patients with DoC and emerged from DoC with structural MRI and rs-fMRI: 65 in vegetative state/unresponsive wakefulness state (VS/UWS), 34 in minimally conscious state (MCS) and 10 with severe disability. rs-fMRI data were analyzed with independent component analyses and seed-based analyses, in relation to structural MRI and clinical data. The results showed that VS/UWS had fewer networks than MCS patients and the rs-fMRI activity in each network was decreased. Visual networks were correlated to the clinical status, and in cases where no clinical response occurred, rs-fMRI indicated distinctive networks conveying information in a similar way to other techniques. The information provided by single networks was limited, whereas the four networks together yielded better classification results, particularly when the model included rs-fMRI and structural MRI data (AUC = 0.80). Both quantitative and qualitative rs-fMRI analyses yielded converging results; vascular etiology might confound the results, and disease duration generally reduced the number of networks observed. The lower-order rs-fMRI networks could be used clinically to support and corroborate visual function assessments in DoC.

Classical studies have isolated a distributed network of temporal and frontal areas engaged in the neural representation of speech perception and production. With modern literature arguing against unique roles for these cortical regions, different theories have favored either neural code-sharing or cortical space-sharing, thus trying to explain the intertwined spatial and functional organization of motor and acoustic components across the fronto-temporal cortical network. In this context, the focus of attention has recently shifted toward specific model fitting, aimed at motor and/or acoustic space reconstruction in brain activity within the language network. Here, we tested a model based on acoustic properties (formants), and one based on motor properties (articulation parameters), where model-free decoding of evoked fMRI activity during perception, imagery, and production of vowels had been successful. Results revealed that phonological information organizes around formant structure during the perception of vowels; interestingly, such a model was reconstructed in a broad temporal region, outside of the primary auditory cortex, but also in the pars triangularis of the left inferior frontal gyrus. Conversely, articulatory features were not associated with brain activity in these regions. Overall, our results call for a degree of interdependence based on acoustic information, between the frontal and temporal ends of the language network.

Autism spectrum disorder (ASD) refers to complex neurobehavioral and neurodevelopmental conditions characterized by impaired social interaction and communication, restricted and repetitive patterns of behavior or interests, and altered sensory processing. Environmental, immunological, genetic, and epigenetic factors are implicated in the pathophysiology of autism and provoke the occurrence of neuroanatomical and neurochemical events relatively early in the development of the central nervous system. Many neurochemical pathways are involved in determining ASD; however, how these complex networks interact and cause the onset of the core symptoms of autism remains unclear. Further studies on neurochemical alterations in autism are necessary to clarify the early neurodevelopmental variations behind the enormous heterogeneity of autism spectrum disorder, and therefore lead to new approaches for the treatment and prevention of autism. In this review, we aim to delineate the state-of-the-art main research findings about the neurochemical alterations in autism etiology, and focuses on gamma aminobutyric acid (GABA) and glutamate, serotonin, dopamine, N-acetyl aspartate, oxytocin and arginine-vasopressin, melatonin, vitamin D, orexin, endogenous opioids, and acetylcholine. We also aim to suggest a possible related therapeutic approach that could improve the quality of ASD interventions. Over one hundred references were collected through electronic database searching in Medline and EMBASE (Ovid), Scopus (Elsevier), ERIC (Proquest), PubMed, and the Web of Science (ISI).

Functional movement disorders (FMD) are characterized by motor symptoms (e.g., tremor, gait disorder, and dystonia) that are not compatible with movement abnormalities related to a known organic cause. One key clinical feature of FMD is that motor symptoms are similar to voluntary movements but are subjectively experienced as involuntary by patients. This gap might be related to abnormal self-recognition of bodily action, which involves two main components: sense of agency and sense of body ownership. The aim of this study was to systematically investigate whether this function is altered in FMD, specifically focusing on the subjective feeling of agency, body ownership, and their interaction during normal voluntary movements. Patients with FMD (n = 21) and healthy controls (n = 21) underwent the moving Rubber Hand Illusion (mRHI), in which passive and active movements can differentially elicit agency, ownership or both. Explicit measures of agency and ownership were obtained via a questionnaire. Patients and controls showed a similar pattern of response: when the rubber hand was in a plausible posture, active movements elicited strong agency and ownership; implausible posture of the rubber hand abolished ownership but not agency; passive movements suppressed agency but not ownership. These findings suggest that explicit sense of agency and body ownership are preserved in FMD. The latter finding is shared by a previous study in FMD using a static version of the RHI, whereas the former appears to contrast with studies demonstrating altered implicit measures of agency (e.g., sensory attenuation). Our study extends previous findings by suggesting that in FMD: (i) the sense of body ownership is retained also when interacting with the motor system; (ii) the subjective experience of agency for voluntary tapping movements, as measured by means of mRHI, is preserved.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the substantia nigra. Our main objective was to determine the correspondence between changes in the substantia nigra, evident in neuromelanin and iron sensitive magnetic resonance imaging (MRI), and dopaminergic striatal innervation loss in patients with PD. Eighteen patients and eighteen healthy control subjects were included in the study. Using neuromelanin-MRI, we measured the volume of the substantia nigra and the contrast-to-noise-ratio between substantia nigra and a background region. The apparent transverse relaxation rate and magnetic susceptibility of the substantia nigra were calculated from dual-echo MRI. Striatal dopaminergic innervation was measured as density of dopamine transporter (DAT) by means of single-photon emission computed tomography and [123I] N-ω-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane. Patients showed a reduced volume of the substantia nigra and contrast-to-noise-ratio and both positively correlated with the corresponding striatal DAT density. The apparent transverse relaxation rate and magnetic susceptibility values of the substantia nigra did not differ between patients and healthy controls. The best predictor of DAT reduction was the volume of the substantia nigra. Clinical and imaging correlations were also investigated for the locus coeruleus. Our results suggest that neuromelanin-MRI can be used for quantifying substantia nigra pathology in PD where it closely correlates with dopaminergic striatal innervation loss. Longitudinal studies should further explore the role of Neuromelanin-MRI as an imaging biomarker of PD, especially for subjects at risk of developing the disease.

When viewing a face, healthy individuals focus more on the area containing the eyes and upper nose in order to retrieve important featural and configural information. In contrast, individuals with face blindness (prosopagnosia) tend to direct fixations towards individual facial features – particularly the mouth. Presented here is an examination of face perception deficits in individuals with Posterior Cortical Atrophy (PCA). PCA is a rare progressive neurodegenerative disorder that is characterized by atrophy in occipito-parietal and occipito-temporal cortices. PCA primarily affects higher visual processing, while memory, reasoning, and insight remain relatively intact. A common symptom of PCA is a decreased effective field of vision caused by the inability to ‘see the whole picture’. Individuals with PCA and healthy control participants completed a same/different discrimination task in which images of faces were presented as cue-target pairs. Eye-tracking equipment and a novel computer-based perceptual task – the Viewing Window paradigm – were used to investigate scan patterns when faces were presented in open view or through a restricted-view, respectively. In contrast to previous prosopagnosia research, individuals with PCA each produced unique scan paths that focused on non-diagnostically useful locations. This focus on non-diagnostically useful locations was also present when using a restricted viewing aperture, suggesting that individuals with PCA have difficulty processing the face at either the featural or configural level. In fact, it appears that the decreased effective field of view in PCA patients is so severe that it results in an extreme dependence on local processing, such that a feature-based approach is not even possible.