AGC1 Deficiency: Pathology and Molecular and Cellular Mechanisms of the Disease.

AGC1/Aralar/Slc25a12 is the mitochondrial carrier of aspartate-glutamate, the regulatory component of the NADH malate-aspartate shuttle (MAS) that transfers cytosolic redox power to neuronal mitochondria. The deficiency in AGC1/Aralar leads to the human rare disease named "early infantile epileptic encephalopathy 39" (EIEE 39, OMIM # 612949) characterized by epilepsy, hypotonia, arrested psychomotor neurodevelopment, hypo myelination and a drastic drop in brain aspartate (Asp) and N-acetylaspartate (NAA). Current evidence suggest that neurons are the main brain cell type expressing Aralar. However, paradoxically, glial functions such as myelin and Glutamine (Gln) synthesis are markedly impaired in AGC1 deficiency. Herein, we discuss the role of the AGC1/Aralar-MAS pathway in neuronal functions such as Asp and NAA synthesis, lactate use, respiration on glucose, glutamate (Glu) oxidation and other neurometabolic aspects. The possible mechanism triggering the pathophysiological findings in AGC1 deficiency, such as epilepsy and postnatal hypomyelination observed in humans and mice, are also included. Many of these mechanisms arise from findings in the aralar-KO mice model that extensively recapitulate the human disease including the astroglial failure to synthesize Gln and the dopamine (DA) mishandling in the nigrostriatal system. Epilepsy and DA mishandling are a direct consequence of the metabolic defect in neurons due to AGC1/Aralar deficiency. However, the deficits in myelin and Gln synthesis may be a consequence of neuronal affectation or a direct effect of AGC1/Aralar deficiency in glial cells. Further research is needed to clarify this question and delineate the transcellular metabolic fluxes that control brain functions. Finally, we discuss therapeutic approaches successfully used in AGC1-deficient patients and mice.

Improvement of psychomotor retardation after electroconvulsive therapy is related to decreased IL-6 levels.

BACKGROUND: Prior studies suggest that IL-6 may be involved in the pathophysiology of psychomotor symptoms in depression. Electroconvulsive therapy (ECT), as yet the most effective biological treatment of severe depression, is known to improve psychomotor functioning, while recent studies have shown a decrease in the elevated IL-6 levels of depressed patients following ECT. OBJECTIVES: This study investigates whether the improvement in psychomotor functions in patients with depression after ECT is related to changes in IL-6 levels. METHODS: Peripheral IL-6 was quantified and the severity of psychomotor agitation and retardation determined using the CORE assessment of psychomotor symptoms in 62 patients with a (unipolar or bipolar) depressive episode within one week before and within one week after their course of ECT. RESULTS: IL-6 levels had decreased significantly following ECT and both psychomotor retardation and agitation had improved. The decrease in IL-6 levels was related to the improvement of psychomotor retardation, with post-hoc analysis revealing that higher baseline IL-6 levels positively correlated with higher psychomotor retardation scores. CONCLUSION: With this study, we provide the first evidence that the improvement of psychomotor retardation after ECT for depression is related to the immunomodulatory properties of the treatment, most specifically the decrease in IL-6 levels.

Loss of Collapsin Response Mediator Protein 4 Attenuates 6-Hydroxydopamine-Induced Impairments in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by impaired motor symptoms induced by the degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNc). Many factors are speculated to operate in the mechanism of PD, including oxidative stress, mitochondrial dysfunction, abnormal protein handling, and PD induced apoptosis. Besides, researchers have recently shown that inflammatory secretions may engage neighboring cells such as astrocytes, which then induce autocrine and paracrine responses that amplify the inflammation, leading to neurodegeneration. In the present study, we analyzed the neuroprotective and anti-inflammatory effects of collapsin response mediator protein 4 (CRMP4) deletion in 6-hydroxydopamine (6-OHDA)-injected male mice, as well as its effects on motor impairments. Our findings indicated that the deletion of CRMP4 could maintain the TH-positive fibers in the striatum and the TH-positive cells in SNc, attenuate the inflammatory responses, and improve motor coordination and rotational behavior. Furthermore, based on our findings at the early time points, we hypothesized that primary differences between the Crmp4+/+ and Crmp4-/- mice may occur in microglia instead of neurons. Although further work should be carried out to clarify the specific role of CRMP4 in the pathogenesis of PD, our findings suggest that it could be a possible target for the treatment of PD.

Playback of 50-kHz ultrasonic vocalizations overcomes psychomotor deficits induced by sub-chronic haloperidol treatment in rats.

RATIONALE: In rodents, acute haloperidol treatment induces psychomotor impairments known as catalepsy, which models akinesia in humans and is characterized as an animal model of acute Parkinsonism, whereas sub-chronic haloperidol reduces exploratory behavior, which resembles bradykinesia. Haloperidol-induced catalepsy in rats can be ameliorated by playback of 50-kHz ultrasonic vocalizations (USV), an emotionally and motivationally relevant appetitive auditory stimulus, representing an animal model of paradoxical kinesia. In a condition like PD where patients suffer from chronic motor impairments, it is paramount to assess the long-term symptom relief in an animal model of Parkinsonism. OBJECTIVES: We investigated whether 50-kHz USV playback ameliorates psychomotor deficits induced by haloperidol in a sub-chronic dosing regimen. METHODS: In phase 1, distance traveled and number of rearing behavior were assessed in an activity chamber in order to investigate whether sub-chronic haloperidol treatment induced psychomotor impairments. In phase 2, we investigated whether 50-kHz USV playback could overcome these impairments by assessing exploratory behaviors and approach behavior towards the sound source in the 50-kHz USV radial maze playback paradigm. RESULTS: Sub-chronic haloperidol treatment led to psychomotor deficits since the distance traveled and number of rearing behavior were reduced as compared to saline control group or baseline. These psychomotor impairments were ameliorated during playback of 50-kHz USV, with haloperidol treated rats showing a clear social approach behavior towards the sound source exclusively during playback. CONCLUSIONS: This study provides evidence that 50-kHz USV playback induces paradoxical kinesia in rats exhibiting motor deficits after sub-chronic haloperidol, as we previously showed after acute haloperidol treatment.

Vitamin B12 deficiency as a cause of severe neurological symptoms in breast fed infant - a case report.

BACKGROUND: Vitamin B12 (cobalamin, cbl) deficiency in children is rare and may occurs in exclusively breast fed infants of mothers on vegetarian or vegan diet with lack of appropriate supplementation. The clinical manifestation of vitamin B12 deficiency include neurological disorders, megaloblastic anemia and failure to thrive. Routine and commonly used laboratory tests such as cell blood count (CBC) or serum vitamin B12 level are sufficient for appropriate diagnosis. Typical therapy is based on intramuscular cobalamin injections. Early diagnosis and early onset of treatment are crucial factors for long-term prognosis of patients as the duration of deficiency may be correlated with the development of long lasting changes in the nervous system. The purpose of this article is to present influence of maternal vitamin B12 deficiency as a cause of infant psychomotor retardation. CASE PRESENTATION: We report the case of a 7 months old girl whose parents sought medical advice due to pathological somnolence and developmental regression of their daughter with onset approximately 2 months prior to the visit. Following several diagnostic tests it was determined that the infant's symptoms were due to vitamin B12 deficiency which was secondary to the mother's latent Addison-Biermer disease. Apart from neurological symptoms the infant also showed megaloblastic anemia which is typical to cobalamin deficiencies. Intramuscular vitamin B12 supplementation resulted in instant improvement of the patient's general condition and blood morphology. Unfortunately, psychological examination indicated long-term psychomotor retardation due to delayed diagnosis of B12 deficiency. CONCLUSIONS: Vitamin B12 levels should be considered during differential diagnosis of neurological symptoms in exclusively breast-fed infants especially if they co-exist with megaloblastic anemia and psychomotor retardation.

Tools for the assessment of neuropsychomotor profile in the rehabilitation of children with central nervous system tumor: a systematic review.

OBJECTIVE: This study reviews the scientific literature to identify and describe which assessment tools (ATs) are used in pediatric oncology and neuro-oncology rehabilitation and which development neuropsychomotor (DNPM) ATs were built for children with central nervous system (CNS) tumors. METHODS: A systematic review was performed searching PubMed, CINAHL, PEDro, Science Direct, and Catalog of National Institute of Tumors databases and specialized journals. The search covered 7 years (2010-2017) and used relevant keywords in different combinations. A further search was carried out on DNPM rehabilitation manuals and academic thesis. RESULTS: The review retrieved 35 eligible articles containing 63 ATs. The most common ATs were the Behavioral Rating Inventory of Executive Function (BRIEF) and the Wechsler Intelligence Scale for Children (WISC). Most of the ATs covered a single area of child development among behavioral/psychological, cognitive, and motor areas. A total of 159 ATs were found in manuals and thesis, and only 17 of them were already identified in the journal search. None of the ATs identified in both searches had been specifically developed for children with CNS tumor. CONCLUSION: The results highlight the need to develop and validate a global multidimensional AT for children with CNS tumor, overcoming the fragmentation of the assessment procedures and promoting standardized rehabilitation protocols.

Management of Motor Features in Advanced Parkinson Disease.

Advanced Parkinson disease (PD) is characterized by the presence of motor fluctuations becoming the focus of treatment, prominent postural instability, significant disability despite levodopa therapy, and the presence of symptoms refractory to levodopa therapy. In this article, the authors review the motor manifestations of patients with advanced PD, as well as the most common pharmacologic and nonpharmacologic available therapies.

Multifactorial motor behavior assessment for real-time evaluation of emerging therapeutics to treat neurologic impairments.

Integrating multiple assessment parameters of motor behavior is critical for understanding neural activity dynamics during motor control in both intact and dysfunctional nervous systems. Here, we described a novel approach (termed Multifactorial Behavioral Assessment (MfBA)) to integrate, in real-time, electrophysiological and biomechanical properties of rodent spinal sensorimotor network activity with behavioral aspects of motor task performance. Specifically, the MfBA simultaneously records limb kinematics, multi-directional forces and electrophysiological metrics, such as high-fidelity chronic intramuscular electromyography synchronized in time to spinal stimulation in order to characterize spinal cord functional motor evoked potentials (fMEPs). Additionally, we designed the MfBA to incorporate a body weight support system to allow bipedal and quadrupedal stepping on a treadmill and in an open field environment to assess function in rodent models of neurologic disorders that impact motor activity. This novel approach was validated using, a neurologically intact cohort, a cohort with unilateral Parkinsonian motor deficits due to midbrain lesioning, and a cohort with complete hind limb paralysis due to T8 spinal cord transection. In the SCI cohort, lumbosacral epidural electrical stimulation (EES) was applied, with and without administration of the serotonergic agonist Quipazine, to enable hind limb motor functions following paralysis. The results presented herein demonstrate the MfBA is capable of integrating multiple metrics of motor activity in order to characterize relationships between EES inputs that modulate mono- and polysynaptic outputs from spinal circuitry which in turn, can be used to elucidate underlying electrophysiologic mechanisms of motor behavior. These results also demonstrate that proposed MfBA is an effective tool to integrate biomechanical and electrophysiology metrics, synchronized to therapeutic inputs such as EES or pharmacology, during body weight supported treadmill or open field motor activities, to target a high range of variations in motor behavior as a result of neurological deficit at the different levels of CNS.

Melancholia as Predictor of Electroconvulsive Therapy Outcome in Later Life.

OBJECTIVES: In clinical practice, particularly melancholic depression benefits from electroconvulsive therapy (ECT), albeit research melancholia criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM) is not conclusive. We compared clinical characteristics and ECT outcome of melancholic and nonmelancholic depression, here defined by psychomotor symptoms. METHODS: One hundred ten depressed older in-patients treated with ECT were included in the Mood Disorders in Elderly treated with ECT study. The CORE was used for the assessment of psychomotor symptoms, with a score of 8 or higher defining melancholic depression. Depression severity was measured before, during, and after ECT. Characteristics were compared across melancholic and nonmelancholic patients. Regression analysis was used to assess the relation between psychomotor symptoms and remission/response, and survival analysis was used to examine the difference in time. RESULTS: Patients with melancholic depression had higher severity, lower cognitive and overall functioning, and lower prevalence of cardiovascular disease. However, no significant relations were found between CORE scores and remission/response. Because psychotic symptoms are a positive predictor of ECT response and remission, we examined whether CORE score was a predictor of response in the nonpsychotic group (n = 49). In nonpsychotic patients, remission was 62%, and the association between CORE scores and remission almost reached significance (P = 0.057). DISCUSSION: Although melancholically and nonmelancholically depressed patients differed significantly on several clinical characteristics, ECT outcome did not differ. Analyses may be hampered by a high prevalence of psychotic features. In nonpsychotic patients, CORE scores neared significance as predictor of remission, suggesting that CORE scores might be a distinguishing characteristic of melancholia in nonpsychotic patients and a clinical useful predictor of ECT response.

Probabilistic sweet spots predict motor outcome for deep brain stimulation in Parkinson disease.

OBJECTIVE: To investigate whether functional sweet spots of deep brain stimulation (DBS) in the subthalamic nucleus (STN) can predict motor improvement in Parkinson disease (PD) patients. METHODS: Stimulation effects of 449 DBS settings in 21 PD patients were clinically and quantitatively assessed through standardized monopolar reviews and mapped into standard space. A sweet spot for best motor outcome was determined using voxelwise and nonparametric permutation statistics. Two independent cohorts were used to investigate whether stimulation overlap with the sweet spot could predict acute motor outcome (10 patients, 163 settings) and long-term overall Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) improvement (63 patients). RESULTS: Significant clusters for suppression of rigidity and akinesia, as well as for overall motor improvement, resided around the dorsolateral border of the STN. Overlap of the volume of tissue activated with the sweet spot for overall motor improvement explained R2 = 37% of the variance in acute motor improvement, more than triple what was explained by overlap with the STN (R2 = 9%) and its sensorimotor subpart (R2 = 10%). In the second independent cohort, sweet spot overlap explained R2 = 20% of the variance in long-term UPDRS-III improvement, which was equivalent to the variance explained by overlap with the STN (R2 = 21%) and sensorimotor STN (R2 = 19%). INTERPRETATION: This study is the first to predict clinical improvement of parkinsonian motor symptoms across cohorts based on local DBS effects only. The new approach revealed a distinct sweet spot for STN DBS in PD. Stimulation overlap with the sweet spot can predict short- and long-term motor outcome and may be used to guide DBS programming. ANN NEUROL 2019;86:527-538.

Can psychomotor disturbance predict ect outcome in depression?

Psychomotor symptoms are core features of melancholic depression. This study investigates whether psychomotor disturbance predicts the outcome of electroconvulsive therapy (ECT) and how the treatment modulates psychomotor disturbance. In 73 adults suffering from major depressive disorder psychomotor functioning was evaluated before, during and after ECT using the observer-rated CORE measure and objective measures including accelerometry and a drawing task. Regression models were fitted to assess the predictive value of melancholic depression (CORE ≥ 8) and the psychomotor variables on ECT outcome, while effects on psychomotor functioning were evaluated through linear mixed models. Patients with CORE-defined melancholic depression (n = 41) had a 4.9 times greater chance of reaching response than those (n = 24) with non-melancholic depression (Chi-Square = 7.5, P = 0.006). At baseline, both higher total CORE scores (AUC = 0.76; P = 0.001) and needing more cognitive (AUC = 0.78; P = 0.001) and motor time (AUC = 0.76; P = 0.003) on the drawing task corresponded to superior ECT outcomes, as did lower daytime activity levels (AUC = 0.76) although not significantly so after Bonferroni correction for multiple testing. A greater CORE-score reduction in the first week of ECT was associated with higher ECT effectiveness. ECT reduced CORE-assessed psychomotor symptoms and improved activity levels only in those patients showing the severer baseline retardation. Although the sample was relatively small, psychomotor symptoms were clearly associated with beneficial outcome of ECT in patients with major depression, indicating that monitoring psychomotor deficits can help personalise treatment.

Comparison of bilateral and unilateral upper limb training in people with stroke: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Bilateral upper limb training (BULT) and unilateral upper limb training (UULT) are two effective strategies for the recovery of upper limb motor function after stroke. This meta-analysis aimed to compare the improvements in motor impairment and functional performances of people with stroke after BULT and UULT. RESEARCH DESIGN AND METHODS: This systematic review and meta-analysis identified 21 randomized controlled trials (RCTs) met the eligibility criteria from CINAHL, Medline, Embase, Cochrane Library and PubMed. The outcome measures were the Fugl-Meyer Assessment of Upper Extremity (FMA-UE), Wolf Motor Function Test (WMFT), Action Research Arm Test (ARAT) and Box and Block Test (BBT), which are validated measures of upper limb function. RESULTS: Twenty-one studies involving 842 subjects with stroke were included. Compared with UULT, BULT yielded a significantly greater mean difference (MD) in the FMA-UE (MD = 2.21, 95% Confidence Interval (CI), 0.12 to 4.30, p = 0.04; I2 = 86%, p<0.001). However, a comparison of BULT and UULT yielded insignificant mean difference (MD) in terms of the time required to complete the WMFT (MD = 0.44; 95%CI, -2.22 to 3.10, p = 0.75; I2 = 55%, p = 0.06) and standard mean difference (SMD) in terms of the functional ability scores on the WMFT, ARAT and BBT (SMD = 0.25; 95%CI, -0.02 to 0.52, p = 0.07; I2 = 54%, p = 0.02). DISCUSSION AND IMPLICATIONS: Compared to UULT, BULT yielded superior improvements in the improving motor impairment of people with stroke, as measured by the FMA-UE. However, these strategies did not yield significant differences in terms of the functional performance of people with stroke, as measured by the WMFT, ARAT and BBT. More comparative studies of the effects of BULT and UULT are needed to increase the reliability of these conclusions.

Entrenamiento Neuromotor en pacientes ancianos pluripatológicos en las Unidades de Hospitalización a Domicilio: estudio piloto / Neuromotor Training in elderly multi-pathological patients in the Home Hospitalization Units: a pilot study / Treinamento neuromotor em pacientes idosos multipatológicos nas Unidades de Internação Domiciliar: estudo piloto

Introducción: El envejecimiento se acompaña de factores de riesgo cuya reducción mejora la supervivencia. La actividad física incide sobre ellos, lo que realza su papel preventivo y su valor como tratamiento no-farmacológico. Dada la escasez de programas de entrenamiento específicos para ancianos pluripatológicos, sobre todo durante el periodo de inicio de resolución de la actividad clínica de una enfermedad aguda, o de la exacerbación de una o varias de las enfermedades crónicas, el presente estudio piloto analiza la viabilidad y efectos de un programa corto de entrenamiento neuromotor en estos pacientes ingresados en UHD (Unidad de Hospitalización Domiciliaria). Método: 11 ancianos pluripatológicos (82,2±6,9 años, 8 hombres) completaron 4 semanas de entrenamiento funcional con orientación neuromuscular y cognitiva, con evaluación pre-post sobre capacidad funcional (equilibrio, marcha, fuerza de tren inferior y agilidad), composición corporal y calidad de vida -6 semanas, incluida la evaluación-. Se realizaron dos sesiones domiciliarias supervisadas y una tercera autónoma semanalmente. Resultados: Los ancianos mejoraron en equilibrio y marcha (Tinetti-total: 14,0±9,0 vs 17,9±7,3 puntos; p =0,007), fuerza (test sentarse y levantarse 30-s: 3,0±3,7 vs 4,1±4,1 reps.; p =0,034), agilidad (TUG-test categorizado; p =0,001) y peso (82,2±14,0 vs 79,2±13,9 kg; p =0,036), aunque no en calidad de vida relacionada con la salud (SF-36-v2: 32,9±7,8 vs 31,2±7,7 puntos; p =0,722). La presencia del técnico aumentó el cumplimiento un 20%. Conclusiones: El dinamismo de UHD es idóneo para implantar programas de actividad física especializada que frenen los efectos devastadores del binomio envejecimiento-inactividad. Una corta duración no les resta eficacia

Introduction: Aging is linked to a various risk factors whose reduction improves survival. Physical activity affects many of them, what enhances its preventive role and its value as a non-pharmacological treatment. Given the scarcity of specific training programs for elderly people with multiple pathologies, especially during the start period of resolution of the clinical activity of an acute disease, or the exacerbation of one or several of the chronic diseases, the present pilot study aims to analyze the feasibility and effects of a short neuromotor training program in these patients admitted to UHD (Home Hospitalization Unit). Methods: 11 elderly patients (82.2±6.9 years, 8 men; acute phase of disease) completed 4 weeks of a neuromuscular and cognitive orientated functional training program, with pre-post assessment of functional capacity (i.e. balance, gait speed, lower limb strength and agility), body composition and quality of life -6 weeks, including the evaluation-. There were 2 supervised sessions and a third autonomous session every week. Results: Significant improvements were found in balance and gait (Tinetti-total: 14.0±9.0 vs 17.9±7.3 points; p =0.007), strength (30-seconds Chair Stand Test: 3.0±3; p =0.001), agility (TUG-test categorized; p =0.001) and weight (82.2±14.0 vs. 79.2±13.9 kg; p =0.036), but not in health-related quality of life (SF-36-v2: 32.9±7.8 vs 31.2±7.7 points; p =0.722). The technician's presence increased adherence to the program by 20%. Conclusions: The dynamism of UHD is ideal for implementing specialized physical activity programs that counteract the devastating effects of the binomial aging-inactivity. A short duration does not reduce effectiveness

Introdução: O envelhecimento é acompanhado por fatores de risco cuja redução melhora a sobrevida. A atividade física os afeta, o que aumenta seu papel preventivo e seu valor como tratamento não farmacológico. Dada a escassez de programas específicos de treinamento para pacientes idosos, especialmente durante o período da iniciação da resolução da atividade clínica de uma doença aguda, ou da exacerbação de uma ou mais das doenças crônicas, o presente estudo piloto analisa a viabilidade e os efeitos de um programa curto de treinamento neuromotor nesses pacientes internados em UHD (Unidade de Internação Domiciliar). Método: 11 idosos com múltiplas patologias (82,2±6,9 anos, 8 homens, doença de fase aguda) completaram 4 semanas de treinamento funcional com orientação neuromuscular e cognitiva, com avaliação pré-pós de capacidade funcional (equilíbrio, marcha, menor força e agilidade do trem), composição corporal e qualidade de vida -6 semanas, incluindo avaliação-. Foram realizadas duas sessões domiciliares supervisionadas e uma sessão semanal autônoma. Resultados: Os idosos melhoraram em equilíbrio e marcha (Tinetti-total: 14,0±9,0 vs 17,9±7,3 pontos, p=0,007), força (teste de sentar e levantar 30-s: 3,0±3,7 vs 4,1±4,1 repetições, p=0,034), agilidade (teste categorizado pelo TUG, p=0,001) e peso (82,2±14,0 vs 79,2±13,9 kg; p=0,036), embora não na qualidade de vida relacionada à saúde (SF-36-v2: 32,9±7,8 vs 31,2±7,7 pontos, p=0,722). A presença do técnico aumentou a conformidade em 20%. Conclusões: O dinamismo da UHD é ideal para a implementação de programas especializados de atividade física que neutralizam os efeitos devastadores do binômio envelhecimento-inatividade. Uma curta duração não reduz a eficácia

Exercise Interventions in Children and Adolescents With ADHD: A Systematic Review.

OBJECTIVE: Exercise has attracted attention as a potential helpful intervention in children with ADHD. Effects are emphasized on cognition, social-emotional, and motor development. METHOD: A systematic literature search was conducted using the electronic databases Web of Science, PubMed, Scopus, and ERIC to analyze the efficacy of different types of exercise interventions in children and adolescents with ADHD. Seven studies examining the acute and 14 studies examining the long-term effects were included. RESULTS: The largest effects were reported for mixed exercise programs on ADHD symptomatology and fine motor precision. However, because of the large differences in the study designs, the comparability is limited. CONCLUSION: At this time, no evidence-based recommendation can be formulated regarding frequency, intensity, or duration of exercise. Nevertheless, some first trends regarding the effects of certain types of exercise can be identified. When focusing on long-term health benefits in children and adolescents with ADHD, qualitative exercise characteristics might play an important role.

Influence of age on ECT efficacy in depression and the mediating role of psychomotor retardation and psychotic features.

OBJECTIVE: To investigate whether older age predicts a higher efficacy of electroconvulsive therapy (ECT) in severely depressed patients. Also, to analyze whether psychomotor disturbance and/or psychotic features might explain the potential higher efficacy of ECT in older age. METHOD: A total of 96 patients with major depressive disorder treated with bilateral ECT were evaluated. The 17-item HAM-D and the MADRS were used to evaluate the efficacy of ECT and time to remission, respectively. Psychomotor disturbance was defined according the HAM-D. RESULTS: Middle-aged (MA; 50-70 years) and older-aged (OA; ≥70 years) patients had a non-significant larger symptom reduction compared with young-aged (YA; <50 years) patients. Medium effect size was found in favor of MA (d = 0.44) and small effect size in favor of OA (d = 0.30), when compared to YA. Patients with psychotic features and patients with psychomotor retardation had a significantly larger symptom reduction (p < 0.001 and p = 0.005, respectively; d = 0.88 and d = 0.66, respectively). The association between age and ECT efficacy is mediated by psychomotor retardation (p = 0.049) and in lesser extent by psychotic features (p = 0.071). CONCLUSION: The results show that psychomotor retardation and psychotic features are strong predictors of ECT efficacy and explain the association between age and ECT efficacy. Instead of focusing on the age of a patient, clinicians should focus on the presence of psychomotor disturbances and psychotic features of depression, when considering ECT treatment.

El grupo terapéutico con niños pequeños como tránsito entre familia y escuela: Experiencia grupal: historia de la construcción de un tren / Group therapy eith young children as a transition between family and school: Group experience: The history of building a train

En este artículo se reflexiona sobre los grupos terapéuticos en Atención Precoz. Se expone una experiencia grupal llevada a cabo en el CDIAP Equip40 con un grupo de niños pequeños conducido por una psicóloga y una fisioterapeuta. A través de viñetas clínicas, se describe el proceso terapéutico desde una mirada interdisciplinar y se muestran diferentes tipos de intervenciones

This article reflects on therapeutic groups in Early Years. It deals with a group experience carried out at the CDIAP Equip40 with a group of young children conducted by a psychologist and a physiotherapist. Through clinical vignettes, the therapeutic process is described from an interdisciplinary perspective and different types of interventions are shown

Utilization of Quantitative Susceptibility Mapping for Direct Targeting of the Subthalamic Nucleus During Deep Brain Stimulation Surgery.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN) has demonstrated efficacy in improving motor disability in Parkinson's disease. The recently developed quantitative susceptibility mapping (QSM) technique, which can accurately map iron deposits in deep brain nuclei, promises precise targeting of the STN. OBJECTIVE: To demonstrate the use of QSM to target STN effectively by correlating with classical physiological-based targeting measures in a prospective study. METHODS: The precision and accuracy of direct targeting with QSM was examined in a total of 25 Parkinson's disease patients between 2013 and 2015 at our institution. QSM was utilized as the primary magnetic resonance imaging (MRI) method to perform direct STN targeting on a stereotactic planning station utilizing computed tomography/MR fusion. Intraoperative microelectrode recordings (MER) were obtained to confirm appropriate trajectory through the sensorimotor STN. RESULTS: Estimations of STN thickness between the MER and QSM methods appeared to be correlated. Mean STN thickness was 5.3 mm. Kinesthetic responsive cells were found in > 90% of electrode runs. The mean radial error (±SEM) was 0.54 ± 0.1 mm. Satisfactory clinical response as determined by Unified Parkinson's Disease Rating Scale (UPDRS III) was seen at 12 mo after surgery. CONCLUSION: Direct targeting of the sensorimotor STN using QSM demonstrates MER correlation and can be safely used for deep brain stimulation lead placement with satisfactory clinical response. These results imply that targeting based on QSM signaling alone is sufficient to obtain reliable and reproducible outcomes in the absence of physiological recordings.

Sensorimotor learning and associated visual perception are intact but unrelated in autism spectrum disorder.

Humans show an astonishing capability to learn sensorimotor behaviours. However, data from sensorimotor learning experiments suggest the integration of efferent sensorimotor commands, afferent sensorimotor information, and visual consequences of a performed action during learning is different in autism, leading to atypical representation of internal action models. Here, we investigated the generalization of a sensorimotor internal action model formed during sensorimotor learning to a different, but associated, visual perception task. Although motor timing was generally less accurate in adults with autism, following practice with feedback both autistic adults, and controls, significantly improved performance of the movement sequence timing task by reducing timing error. In a subsequent perception task, both groups demonstrated similar temporal-discrimination accuracy (autism = 75%; control = 76%). Significant correlations between motor timing error, and temporal-discrimination during a perception task, was found for controls. No significant correlations were found for autistic adults. Our findings indicate that autistic adults demonstrated adaptation by reducing motor timing error through sensorimotor learning. However, the finding of significant correlations between motor timing error and temporal-discrimination accuracy in the control group only suggests sensorimotor processes underpinning internal action model formation operate differently in autism. Autism Res 2018, 11: 296-304. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We showed autistic adults learned a new motor skill, and visually judged moving objects, to a similar level of accuracy as a control group. Unlike the control group, there was no relationship between how well autistic adults learned the motor skill, and how well they judged objects. The lack of a relationship might be one of the reasons autistic adults interact differently in the social world.

A Smart Toy to Enhance the Decision-Making Process at Children's Psychomotor Delay Screenings: A Pilot Study.

BACKGROUND: EDUCERE ("Ubiquitous Detection Ecosystem to Care and Early Stimulation for Children with Developmental Disorders") is an ecosystem for ubiquitous detection, care, and early stimulation of children with developmental disorders. The objectives of this Spanish government-funded research and development project are to investigate, develop, and evaluate innovative solutions to detect changes in psychomotor development through the natural interaction of children with toys and everyday objects, and perform stimulation and early attention activities in real environments such as home and school. Thirty multidisciplinary professionals and three nursery schools worked in the EDUCERE project between 2014 and 2017 and they obtained satisfactory results. Related to EDUCERE, we found studies based on providing networks of connected smart objects and the interaction between toys and social networks. OBJECTIVE: This research includes the design, implementation, and validation of an EDUCERE smart toy aimed to automatically detect delays in psychomotor development. The results from initial tests led to enhancing the effectiveness of the original design and deployment. The smart toy, based on stackable cubes, has a data collector module and a smart system for detection of developmental delays, called the EDUCERE developmental delay screening system (DDSS). METHODS: The pilot study involved 65 toddlers aged between 23 and 37 months (mean=29.02, SD 3.81) who built a tower with five stackable cubes, designed by following the EDUCERE smart toy model. As toddlers made the tower, sensors in the cubes sent data to a collector module through a wireless connection. All trials were video-recorded for further analysis by child development experts. After watching the videos, experts scored the performance of the trials to compare and fine-tune the interpretation of the data automatically gathered by the toy-embedded sensors. RESULTS: Judges were highly reliable in an interrater agreement analysis (intraclass correlation 0.961, 95% CI 0.937-0.967), suggesting that the process was successful to separate different levels of performance. A factor analysis of collected data showed that three factors, trembling, speed, and accuracy, accounted for 76.79% of the total variance, but only two of them were predictors of performance in a regression analysis: accuracy (P=.001) and speed (P=.002). The other factor, trembling (P=.79), did not have a significant effect on this dependent variable. CONCLUSIONS: The EDUCERE DDSS is ready to use the regression equation obtained for the dependent variable "performance" as an algorithm for the automatic detection of psychomotor developmental delays. The results of the factor analysis are valuable to simplify the design of the smart toy by taking into account only the significant variables in the collector module. The fine-tuning of the toy process module will be carried out by following the specifications resulting from the analysis of the data to improve the efficiency and effectiveness of the product.