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Sensori-/psychomotor abnormalities refer to a wide range of disturbances in individual motor, affective and behavioral functions that are often observed in mental disorders. However, many of these studies have mainly used clinical rating scales, which can be potentially confounded by observer bias and are not able to detect subtle sensori-/psychomotor abnormalities. Yet, an innovative three-dimensional (3D) optical motion capturing technology (MoCap) can provide more objective and quantifiable data about movements and posture in psychiatric patients. To draw attention to recent rapid progress in the field, we performed a systematic review using PubMed, Medline, Embase, and Web of Science until May 01st 2024. We included 55 studies in the qualitative analysis and gait was the most examined movement. The identified studies suggested that sensori-/psychomotor abnormalities in neurodevelopmental, mood, schizophrenia spectrum and neurocognitive disorders are associated with alterations in spatiotemporal parameters (speed, step width, length and height; stance time, swing time, double limb support time, phases duration, adjusting sway, acceleration, etc.) during various movements such as walking, running, upper body, hand and head movements. Some studies highlighted the advantages of 3D optical MoCap systems over traditional rating scales and measurements such as actigraphy and ultrasound gait analyses. 3D optical MoCap systems are susceptible to detecting differences not only between patients with mental disorders and healthy persons but also among at-risk individuals exhibiting subtle sensori-/psychomotor abnormalities. Overall, 3D optical MoCap systems hold promise for objectively examining sensori-/psychomotor abnormalities, making them valuable tools for use in future clinical trials., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Psychomotor retardation (PMR) is a core feature of major depressive disorder (MDD), which is characterized by abnormalities in motor control and cognitive processes. PMR in MDD can predict a poor antidepressant response, suggesting that PMR may serve as a marker of the antidepressant response. However, the neuropathological relationship between treatment outcomes and PMR remains uncertain. Thus, this study examined electrophysiological biomarkers associated with poor antidepressant response in MDD., Methods: A total of 142 subjects were enrolled in this study, including 49 healthy controls (HCs) and 93 MDD patients. All participants performed a simple right-hand visuomotor task during magnetoencephalography (MEG) scanning. Patients who exhibited at least a 50 % reduction in disorder severity at the endpoint (>2 weeks) were considered to be responders. Motor-related beta desynchronization (MRBD) and inter- and intra-hemispheric functional connectivity were measured in the bilateral motor network., Results: An increased MRBD and decreased inter- and intra-hemispheric functional connectivity in the motor network during movement were observed in non-responders, relative to responders and HCs. This dysregulation predicted the potential antidepressant response., Conclusion: Abnormal local activity and functional connectivity in the motor network indicate poor psychomotor function, which might cause insensitivity to antidepressant treatment. This could be regarded as a potential neural mechanism for the prediction of a patient's treatment response., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Major depressive disorder (MDD) is characterized by psychomotor retardation whose underlying neural source remains unclear. Psychomotor retardation may either be related to a motor source like the motor cortex or, alternatively, to a psychomotor source with neural changes outside motor regions, like input regions such as visual cortex. These two alternative hypotheses in main (n = 41) and replication (n = 18) MDD samples using 7 Tesla MRI are investigated. Analyzing both global and local connectivity in primary motor cortex (BA4), motor network and middle temporal visual cortex complex (MT+), the main findings in MDD are: 1) Reduced local and global synchronization and increased local-to-global output in motor regions, which do not correlate with psychomotor retardation, though. 2) Reduced local-to-local BA4 - MT+ functional connectivity (FC) which correlates with psychomotor retardation. 3) Reduced global synchronization and increased local-to-global output in MT+ which relate to psychomotor retardation. 4) Reduced variability in the psychophysical measures of MT+ based motion perception which relates to psychomotor retardation. Together, it is shown that visual cortex MT+ and its relation to motor cortex play a key role in mediating psychomotor retardation. This supports psychomotor over motor hypothesis about the neural source of psychomotor retardation in MDD., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Psychomotor disturbance has been identified as a key feature of psychotic disorders, with motor signs observed in upwards of 66% of unmedicated, first-episode patients. Aberrations in the cerebellum have been directly linked to sensorimotor processing deficits including processing speed, which may underly psychomotor disturbance in psychosis, though these brain-behavior-symptom relationships are unclear, in part due to within-diagnosis heterogeneity across these levels of analysis. In 339 psychosis patients (242 schizophrenia-spectrum, 97 bipolar with psychotic features) and 217 controls, we evaluated the relationship between cerebellar grey matter volume in the Yeo sensorimotor network and psychomotor disturbance (mannerisms and posturing, retardation, excitement of the Positive and Negative Syndrome Scale [PANSS]), as mediated by processing speed (assessed via the SCIP). Models included intracranial volume, age, sex, and chlorpromazine equivalents as covariates. We observed significant mediation by processing speed, with a small positive effect of the cerebellum on processing speed (ß = 0.172, p = 0.029, d = 0.24) and a medium negative effect of processing speed on psychomotor disturbance (ß = -0.254, p < 0.001, d = 0.60), with acceptable specificity and sensitivity suggesting this model is robust against unmeasured confounding. The current findings suggest a critical role of cerebellar circuitry in a well-established sensorimotor aberration in psychosis (processing speed) and the presentation of related psychomotor phenotypes within psychosis. Establishing such relationships is critical for intervention research, such as TMS. Future work will employ more dimensional measures of psychomotor disturbance and cognitive processes to capture normative and aberrant brain-behavior-symptom relationships and may also determine the magnitude of these relationships within subtypes of psychosis (e.g., disorganized behavior, catatonia)., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Up to 70% of patients with major depressive disorder present with psychomotor disturbance (PmD), but at the present time understanding of its pathophysiology is limited. In this study, we capitalized on a large sample of patients to examine the neural correlates of PmD in depression. This study included 820 healthy participants and 699 patients with remitted (n = 402) or current (n = 297) depression. Patients were further categorized as having psychomotor retardation, agitation, or no PmD. We compared resting-state functional connectivity (ROI-to-ROI) between nodes of the cerebral motor network between the groups, including primary motor cortex, supplementary motor area, sensory cortex, superior parietal lobe, caudate, putamen, pallidum, thalamus, and cerebellum. Additionally, we examined network topology of the motor network using graph theory. Among the currently depressed 55% had PmD (15% agitation, 29% retardation, and 11% concurrent agitation and retardation), while 16% of the remitted patients had PmD (8% retardation and 8% agitation). When compared with controls, currently depressed patients with PmD showed higher thalamo-cortical and pallido-cortical connectivity, but no network topology alterations. Currently depressed patients with retardation only had higher thalamo-cortical connectivity, while those with agitation had predominant higher pallido-cortical connectivity. Currently depressed patients without PmD showed higher thalamo-cortical, pallido-cortical, and cortico-cortical connectivity, as well as altered network topology compared to healthy controls. Remitted patients with PmD showed no differences in single connections but altered network topology, while remitted patients without PmD did not differ from healthy controls in any measure. We found evidence for compensatory increased cortico-cortical resting-state functional connectivity that may prevent psychomotor disturbance in current depression, but may perturb network topology. Agitation and retardation show specific connectivity signatures. Motor network topology is slightly altered in remitted patients arguing for persistent changes in depression. These alterations in functional connectivity may be addressed with non-invasive brain stimulation., (© 2023. The Author(s).)

Autism is a neurodevelopmental disorder characterized by impaired social skills, motor and perceptual atypicalities. These difficulties were explained within the Bayesian framework as either reflecting oversensitivity to prediction errors or - just the opposite - slow updating of such errors. To test these opposing theories, we administer paced finger-tapping, a synchronization task that requires use of recent sensory information for fast error-correction. We use computational modelling to disentangle the contributions of error-correction from that of noise in keeping temporal intervals, and in executing motor responses. To assess the specificity of tapping characteristics to autism, we compare performance to both neurotypical individuals and individuals with dyslexia. Only the autism group shows poor sensorimotor synchronization. Trial-by-trial modelling reveals typical noise levels in interval representations and motor responses. However, rate of error correction is reduced in autism, impeding synchronization ability. These results provide evidence for slow updating of internal representations in autism., (© 2021. The Author(s).)

Objective: Schizencephaly is a rare congenital malformation that causes motor impairment. To determine the treatment strategy, each domain of the motor functions should be appropriately evaluated. We correlated a color map of diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS) with the hand function test (HFT) to identify the type of hand function that each test (DTI and TMS) reflects. Further, we attempted to demonstrate the motor neuron organization in schizencephaly., Method: This retrospective study was conducted on 12 patients with schizencephaly. TMS was conducted in the first dorsal interosseous (FDI), biceps (BB), and deltoid muscles of the upper extremity, and contralateral MEP (cMEP) and ipsilateral MEP (iMEP) were recorded. The HFT included the grip strength, box and block (B&B), and 9-hole peg test. The schizencephalic cleft was confirmed using magnetic resonance imaging, and the corticospinal tract (CST) was identified using the color map of DTI. The symmetry indices for the peduncle and CST at pons level were calculated as the ratios of the cross-sectional area of the less-affected side and that of the more-affected side., Result: In the more-affected hemisphere TMS, no iMEP was obtained. In the less-affected hemisphere TMS, the iMEP response was detected in 9 patients and cMEP in all patients, which was similar to the pattern observed in unilateral lesion. Paretic hand grip strength was strongly correlated with the presence of iMEP ( p = 0.044). The symmetry index of the color map of DTI was significantly correlated with the B&B ( p = 0.008, R 2 = 0.416), whereas the symmetry index of the peduncle was not correlated with all HFTs., Conclusion: In patients with schizencephaly, the iMEP response rate is correlated with the hand function related to strength, while the symmetricity of the CST by the color map of DTI is correlated with the hand function associated with dexterity. Additionally, we suggest the possible motor organization pattern of schizencephaly following interhemispheric competition., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2021 Ju-Yul Yoon et al.)

Background: Cervical dystonia (CD) is the most common form of focal dystonia with involuntary movements and postures of the head. The pathogenesis and neural mechanisms underlying CD have not been fully elucidated., Methods: Twenty-seven newly drug-naïve patients with CD and 21 healthy controls (HCs) were recruited with clinical assessment and resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Severity of CD was measured by Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui scores. Whole-brain voxel-wise intrinsic connectivity (IC) and seed-based functional connectivity (FC) analyses were performed for detection of changes in the CD group relative to HCs, controlling for age, gender, and global time series correlation, followed by correlation analyses of IC, seed-based FC and clinically relevant features, respectively., Results: In comparison with HCs, CD patients showed significantly increased IC measurement in the anterior part of the left supramarginal gyrus and extended to the inferior left postcentral gyrus (AL-SMG/IL-PCG). With this cluster as a seed, decreased FC was found in the right precentral and postcentral gyrus. Moreover, the regional IC value in the AL-SMG/IL-PCG was significantly positively correlated with TWSTRS-1 (severity) score, and significantly negatively correlated with the associated seed-based FC strength., Conclusions: Our results showed signs of both hyper- and hypo-connectivity in bilateral regions of the sensorimotor network related to CD. The imbalance of functional connectivity (both hyper- and hypo-) may hint both overloading and disrupted somatosensory or sensorimotor integration dysfunction within the sensorimotor network underlying the pathophysiology of CD, thus providing a network target for future therapies., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Premature babies are a special group at risk of persistent brain damage caused by diseases, the most serious of which are cerebral palsy(CP), autism spectrum disorders (ASD) and mental retardation, among others. These conditions may occur concurrently, but appear more often as separate disease syndromes in the same group of at-risk children. Long-term observation of psychomotor development by an interdisciplinary medical team closely cooperating with parents is necessary. It is important to detect the risk of developing these diseases as soon as possible in all development spheres., Material and Methods: The research was conducted to demonstrate the prognostic value of 'red flags' of developmental milestones and the ability to detect early signs of risk of developing CP and ASD in extremely premature babies. In this preliminary study, 42 preterm babies, born after less than 32 weeks pregnancy participated., Results: The occurrence of 'red flags'in the spheres: gross motor, fine motor and cognitive at 9 months was strongly associated with their presence at 24 months. The sensitivity and specificity were: gross motor - 0.91 (95% CI: 0.59, 1.00) and 0.94 (95% CI: 0.79, 0.99); fine motor - 0.83 (95% CI 0.36-1.00) and 1.00 (95% CI: 0.90-1.00); cognitive - 1.00 (0.40, 1.00) and 0.97 (0.86, 1.00). Other spheres had lower sensitivity but high specificity., Conclusions: The conclusion is that the 'red flags'at the 9 months milestones already predict the normal or developmental delay of premature babies, and predict the risk of CP and ASD. Due to the availability and lack of the need for specialized and costly training, it is worth considering their use in everyday life medical practice.

Hydrocephalus associated with long term spaceflight (HALS) for missions lasting over five months is well described but poorly understood. While structural changes of the brain due to microgravitational forces affecting the circulation of cerebrospinal fluid (CSF) have been described as one potential cause, we propose an alternative hypothesis based on dynamic disequilibrium of macromolecular transport across the blood brain barrier. We propose that factors altering physiology under conditions of spaceflight such as microgravity, hypercapnia, venous hypertension, medications, and dietary substances contribute to increased protein load in the ventricles and/or contribute to impairment of transport out of the ventricles that results in HALS. Individual variation in the genetic expression of efflux transporters (p-glycoprotein) has been shown to correlate with the presence and degree of hydrocephalus in animal studies. We describe the evidence behind this concept and propose how these factors can be studied in order to determine the underlying pathogenesis which is imperative in order to cure or prevent HALS., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Contrasting findings were reported in several animal models with a Shank3 mutation used to induce various autism spectrum disorder (ASD) symptoms. Here, we aimed at investigating behavioral, cellular, and molecular consequences of a C-terminal (frameshift in exon 21) deletion in Shank3 protein in mice, a mutation that is also found in clinical conditions and which results in loss of major isoforms of Shank3. A special focus was made on cerebellar related parameters., Methods: All three genotypes were analyzed [wild type (WT), heterozygote (Shank3+/ΔC) and homozygote (Shank3 ΔC/ΔC)] and males and females were separated into two distinct groups. Motor and social behavior, gait, Purkinje cells (PC) and glutamatergic protein levels were determined. Behavioral and cellular procedures used here were previously validated using two environmental animal models of ASD. ANOVA and post-hoc analysis were used for statistical analysis., Results: Shank3 ΔC/ΔC mice showed significant impairments in social novelty preference, stereotyped behavior and gait. These were accompanied by a decreased number of PC in restricted cerebellar sub-regions and decreased cerebellar expression of mGluR5. Females Shank3 ΔC/ΔC were less affected by the mutation than males. Shank3+/ΔC mice showed impairments only in social novelty preference, grooming, and decreased mGluR5 expression and that were to a much lesser extent than in Shank3 ΔC/ΔC mice., Limitations: As Shank3 mutation is a haploinsufficiency, it is of interest to emphasize that Shank3+/ΔC mice showed only mild to no deficiencies compared to Shank3 ΔC/ΔC., Conclusions: Our findings indicate that several behavioral, cellular, and molecular parameters are affected in this animal model. The reported deficits are more pronounced in males than in females. Additionally, male Shank3 ΔC/ΔC mice show more pronounced alterations than Shank3+/ΔC. Together with our previous findings in two environmental animal models of ASD, our studies indicate that gait dysfunction constitutes a robust set of motor ASD symptoms that may be considered for implementation in clinical settings as an early and quantitative diagnosis criteria.

Introduction: Falls among older people are a major health issue and the first cause of accidental death after 75 years of age. Post-fall syndrome (PFS) is commonly known and yet poorly studied., Objective: Identify risk factors for PFS and do a follow-up 1 year later., Methods: We included all patients over 70 years of age hospitalized after suffering a fall in a case-control study, and then followed them in a cohort study. PFS was retained in case of functional mobility decline (transferring, walking) occurring following a fall in the absence of an acute neurological, orthopedic or rheumatic pathology directly responsible for the decline. The data initially collected were: clinical (anamnestic, emergency and departmental/ward evolution, medical history, lifestyle, treatments, clinical examination items); and imaging if the patient had been subjected to brain imaging in the last 3 years prior to inclusion. Regarding the follow-up at 1 year, we collected from the general physician the occurrence and the characteristics of new falls, functional mobility assessment, hospitalization and death., Results: Inclusion took place from March 29, 2016 to June 7, 2016 and follow-up until June 30, 2017. We included 70 patients. A total of 29 patients exhibited a PFS (41.4 %). Risk factors for PFS included age, walking disorder prior to the fall, the use of a walking aid prior to the fall, no unaccompanied outdoor walk in the week before the fall, visual impairment making close reading impossible, stiffness in ankle dorsiflexion, grip strength and the fear of falling. Among patients with PFS, 52.9% could still perform a transfer at 1 year and 64.7% could still walk against 80.7% and 85.2%, respectively, for patients without PFS., Conclusion: The study showed the existence of body functions/structure impairments and activity limitations prior to the fall among patients exhibiting a PFS. This suggests the existence of a pre-fall syndrome, i.e., a psychomotor disadaptation syndrome existing prior to the fall. Among the 8 risk factors, fear of falling, vision impairment and muscle strength could be targeted for improvement. The diagnosis of PFS could be a marker of loss of functional mobility at 1 year., (© 2020 S. Karger AG, Basel.)

Autism spectrum disorder (ASD) and schizophrenia (SCZ) are neurodevelopmental disorders with partly overlapping clinical phenotypes including sensorimotor impairments. However, direct comparative studies on sensorimotor control across these two disorders are lacking. We set out to compare visuomotor upper limb impairment, quantitatively, in ASD and SCZ. Patients with ASD (N = 24) were compared to previously published data from healthy control participants (N = 24) and patients with SCZ (N = 24). All participants performed a visuomotor grip force-tracking task in single and dual-task conditions. The dual-task (high cognitive load) presented either visual distractors or required mental addition during grip force-tracking. Motor inhibition was measured by duration of force release and from principal component analysis (PCA) of the participant's force-trajectory. Common impairments in patients with ASD and SCZ included increased force-tracking error in single-task condition compared to controls, a further increase in error in dual-task conditions, and prolonged duration of force release. These three sensorimotor impairments were found in both patient groups. In contrast, distinct impairments in patients with ASD included greater error under high cognitive load and delayed onset of force release compared to SCZ. The PCA inhibition component was higher in ASD than SCZ and controls, correlated to duration of force release, and explained group differences in tracking error. In conclusion, sensorimotor impairments related to motor inhibition are common to ASD and SCZ, but more severe in ASD, consistent with enhanced neurodevelopmental load in ASD. Furthermore, impaired motor anticipation may represent a further specific impairment in ASD. Autism Res 2020, 13: 885-896. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism spectrum disorder (ASD) and schizophrenia (SCZ) are neurodevelopmental disorders with partly overlapping and partly distinct clinical symptoms. Sensorimotor impairments rank among these symptoms, but it is less clear whether they are shared or distinct. In this study, we showed using a grip force task that sensorimotor impairments related to motor inhibition are common to ASD and SCZ, but more severe in ASD. Impaired motor anticipation may represent a further specific impairment in ASD., (© 2020 International Society for Autism Research, Wiley Periodicals, Inc.)

Mucolipidosis type IV (MLIV) is an autosomal recessively inherited lysosomal storage disorder characterized by progressive psychomotor delay and retinal degeneration that is associated with biallelic variants in the MCOLN1 gene. The gene, which is expressed in late endosomes and lysosomes of various tissue cells, encodes the transient receptor potential channel mucolipin 1 consisting of six transmembrane domains. Here, we described 14-year follow-up observation of a 4-year-old Japanese male MLIV patient with a novel homozygous in-frame deletion variant p.(F313del), which was identified by whole-exome sequencing analysis. Neurological examination revealed progressive psychomotor delay, and atrophy of the corpus callosum and cerebellum was observed on brain magnetic resonance images. Ophthalmologically, corneal clouding has remained unchanged during the follow-up period, whereas optic nerve pallor and retinal degenerative changes exhibited progressive disease courses. Light-adapted electroretinography was non-recordable. Transmission electron microscopy of granulocytes revealed characteristic concentric multiple lamellar structures and an electron-dense inclusion in lysosomes. The in-frame deletion variant was located within the second transmembrane domain, which is of putative functional importance for channel properties., (© 2020 Wiley Periodicals, Inc.)

Case: We are reporting the third unrelated case of cerebral aspartate-glutamate carrier isoform 1 (AGC1) deficiency. Patient is a 21-month-old Yemeni male who presented with refractory seizure disorder and developmental arrest. Neuroimaging showed cerebral volume loss and diminished N-acetylaspartate (NAA) peak. Whole exome sequencing revealed a homozygous novel missense variant in the SLC25A12 gene. Patient's seizure frequency abated drastically following initiation of ketogenic diet., Discussion and Conclusion: Cerebral AGC1 deficiency results in dysfunction of mitochondrial malate aspartate shuttle, thereby prohibiting myelin synthesis. There are significant phenotypic commonalities between our patient and previously reported cases including intractable epilepsy, psychomotor delay, cerebral atrophy, and diminished NAA peak. Our report also provides evidence regarding beneficial effect of ketogenic diet in this rare neurometabolic epilepsy., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Finger tapping is sensitive to motor slowing and emerging symptoms in individuals at clinical high risk for psychosis (CHR). A sensitive, computerized finger tapping task would be beneficial in early psychosis screening batteries. The study included 41 CHR and 32 healthy volunteers, who completed a computerized finger tapping task and clinical interviews. This computerized finger tapping task was sensitive to slowing in the CHR group compared to healthy volunteers, and as expected negative but not positive symptoms related to motor slowing. Computerized finger tapping tasks may be an easily dispersible tool for early symptom detection battery relevant to emerging negative symptoms.

The majority of HIV + patients present with neuroendocrine dysfunction and ~50% experience co-morbid neurological symptoms including motor, affective, and cognitive dysfunction, collectively termed neuroHIV. In preclinical models, the neurotoxic HIV-1 regulatory protein, trans-activator of transcription (Tat), promotes neuroHIV pathology that can be exacerbated by opioids. We and others find gonadal steroids, estradiol (E 2 ) or progesterone (P 4 ), to rescue Tat-mediated pathology. However, the combined effects of Tat and opioids on neuroendocrine function and the subsequent ameliorative capacity of gonadal steroids are unknown. We found that conditional HIV-1 Tat expression in naturally-cycling transgenic mice dose-dependently potentiated oxycodone-mediated psychomotor behavior. Tat increased depression-like behavior in a tail-suspension test among proestrous mice, but decreased it among diestrous mice (who already demonstrated greater depression-like behavior); oxycodone reversed these effects. Combined Tat and oxycodone produced apparent behavioral disinhibition of anxiety-like responding which was greater on diestrus than on proestrus. These mice made more central entries in an open field, but spent less time there and demonstrated greater circulating corticosterone. Tat increased the E 2 :P 4 ratio of circulating steroids on diestrus and acute oxycodone attenuated this effect, but repeated oxycodone exacerbated it. Corticotropin-releasing factor was increased by Tat expression, acute oxycodone exposure, and was greater on diestrus compared to proestrus. In human neuroblastoma cells, Tat exerted neurotoxicity that was ameliorated by E 2 (1 or 10 nM) or P 4 (100, but not 10 nM) independent of oxycodone. Oxycodone decreased gene expression of estrogen and κ-opioid receptors. Thus, neuroendocrine function may be an important target for HIV-1 Tat/opioid interactions., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In 1874, Karl Kahlbaum described catatonia as an independent syndrome characterized by motor, affective, and behavioral anomalies. In the following years, various catatonia concepts were established with all sharing the prime focus on motor and behavioral symptoms while largely neglecting affective changes. In 21st century, catatonia is a well-characterized clinical syndrome. Yet, its neurobiological origin is still not clear because methodological shortcomings of hitherto studies had hampered this challenging effort. To fully capture the clinical picture of catatonia as emphasized by Karl Kahlbaum, 2 decades ago a new catatonia scale was developed (Northoff Catatonia Rating Scale [NCRS]). Since then, studies have used NCRS to allow for a more mechanistic insight of catatonia. Here, we undertook a systematic review searching for neuroimaging studies using motor/behavioral catatonia rating scales/criteria and NCRS published up to March 31, 2019. We included 19 neuroimaging studies. Studies using motor/behavioral catatonia rating scales/criteria depict cortical and subcortical motor regions mediated by dopamine as neuronal and biochemical substrates of catatonia. In contrast, studies relying on NCRS found rather aberrant higher-order frontoparietal networks which, biochemically, are insufficiently modulated by gamma-aminobutyric acid (GABA)-ergic and glutamatergic transmission. This is further supported by the high therapeutic efficacy of GABAergic agents in acute catatonia. In sum, this systematic review points out the difference between motor/behavioral and NCRS-based classification of catatonia on both neuronal and biochemical grounds. That highlights the importance of Kahlbaum's original truly psychomotor concept of catatonia for guiding both research and clinical diagnosis and therapy., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The Observable Movement Quality (OMQ) Scale measures generic movement quality. Each item of the OMQ Scale focuses on a different element; together, the 15 items assess the whole construct of movement quality., Objective: The aim of this study was to determine the construct validity of the OMQ Scale using 7 hypotheses defined to conform to the Consensus-Based Standards for the Selection of Health Measurement Instruments., Design: This was an exploratory validation study., Methods: A pediatric physical therapist assessed motor performance in 101 children using an age-specific motor test and the OMQ Scale. The direction, magnitude, and rationale for 7 hypotheses, which concerned relationships (n = 2), probability of low scores (n = 4), and difference between diagnosis subgroups (n = 1), were defined., Results: The results confirmed 6 of the 7 hypotheses, indicating sufficient construct validity. Significant positive relationships were found between OMQ Scale total scores and the severity of motor disabilities (r = 0.72) and z scores on motor tests (r = 0.60). Probabilities for low scores on OMQ Scale items-exceeding the chi-square critical value-were confirmed for children diagnosed with spasticity, psychomotor retardation, mitochondrial diseases, and ataxia; however, probabilities for low OMQ Scale item scores on strength regulation in children with ataxia were not confirmed. OMQ Scale total scores for children who were not ambulatory because of neurological conditions were significantly different from those for children who were not ambulatory because of fatigue (r = 0.66)., Limitations: The sample of children was based on theoretical assumptions about relevant variations in clinical representations; on the basis of the results, it appears that children with low strength regulation were underrepresented., Conclusion: The confirmation of nearly all hypotheses supported the validity of the OMQ Scale for measuring movement quality in clinical practice in addition to standardized age-adequate motor performance tests., (© 2019 American Physical Therapy Association.)

This study was conducted to investigate the effects of motor imagery (MI) and mirror therapy (MT) on upper extremity function according to the level of cognition in stroke patients. Twenty-four participants who were diagnosed with stroke were divided into a mild cognitive group (n = 12) and a severe cognitive group (n = 12). Then, the two groups were again divided into MI group (n = 6) and MT group (n = 6). The participants were evaluated for function of upper extremity using the Box and Block Test (BBT), the Jebsen-Taylor Hand Function Test (JTHFT), and Manual Function Test (MFT). There were significant differences between the two groups of cognitive function of mild level in the post-test of JTHFT (p < 0.05). In the MI group, significant differences were found in the pre- and post-test scores for all variance (p < 0.05). In the MT group, significant differences were found in the pre- and post-test scores for JTHFT and MFT (p < 0.05). There were significant differences between the two groups of cognitive function of severe level in the post-test of all variances (p < 0.05). Furthermore, in the MT group, significant differences were found in the pre- and post-test scores for all variances (P < 0.05). The results of this study suggest that applying MI to the mild cognitive group is effective and that applying MT to the severe cognitive group is effective.

Objective: In modern psychiatry, depression is diagnosed with the diagnostic criteria; however, the trajectory of each of the criterion symptoms is unknown. This study aims to examine this., Methods: We made repeated assessments of the nine diagnostic criterion symptoms with the Patient Health Questionnaire-9 (PHQ-9) among 2011 participants of a 25-week pragmatic randomised controlled trial of sertraline and/or mirtazapine for hitherto untreated major depressive episodes. The changes from baseline were estimated with the mixed-effects model with repeated measures. The time to disappearance of each symptom was modeled using the Kaplan-Meier survival analysis., Results: The total score on PHQ-9 was 18.5 (SD = 3.9, n = 2011) at baseline, which decreased to 15.3 (5.2, n = 2011) at week 1, to 11.5 (5.9, n = 1953) at week 3, to 7.8 (6.0, n = 1927) at week 9, and to 6.0 (5.9, n = 1910) at week 25. Suicidal ideas, psychomotor symptoms decreased rapidly, while anergia and sleep disturbance also decreased but only slowly. The survival analyses confirmed the primary analyses., Conclusions: Upon initiation of antidepressant treatment, patients with newly treated major depressive episodes can expect their suicidal ideas and psychomotor symptoms to disappear first but sleep disturbances and anergia to linger on., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

Posterior cortical atrophy (PCA) is a rare form of dementia primarily characterized by slowly progressing deterioration of visual processing corresponding to atrophy in the posterior parietal and occipital cortices with less prominent memory loss than are usually seen in other forms of dementia such as Alzheimer's Disease (AD). In the present case report, we describe longitudinal data over a period of 11 years regarding clinical and neuropsychological impairments and their relation to the location and extent of cortical changes related to higher order visual processing in a patient with posterior cortical atrophy. In our patient, visual processing deficits concerning space, motion and object perception emerged at the age of 50 and continued to worsen. By the age of 58, while the perception of contrast, color and figure-ground separation appeared undisturbed the patient exhibited pronounced dorsal- and ventral-related visual deficits, which continued to worsen with age. The patient's MRI scans over the course of the disease revealed increasing circumscribed and bilateral atrophy of the parietal and occipital cortices, with a right-sided predominance. The specific localization of cortical atrophy, the slow progression characterized by visual processing deficits and relatively preserved memory were the main criteria for the diagnosis of posterior cortical atrophy. The case report also highlights the importance of an early extensive neurological and neuropsychological evaluation of visual deficits that occur without the presence of ophthalmological disease.

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Psychomotor impairments in Autism Spectrum Disorders (ASD) have frequently been described in scientific literature. Such deficits impact upon the development of social motor function and interfere with the ability to adjust to everyday life. The inclusion of sensory-motor signs in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) confirms their importance in the diagnosis of ASD. Previous literature has shown the presence precocity of these signs, sometimes before the alteration of the social communication. To our knowledge, there are no existing clinical tools to measure sensory-psychomotor deficit, specifically in ASD. The current paper presents the construction and validation of a new scale, designed to evaluate sensory-psychomotor signs in Autism: 'the Sensory-psychomotor Particularities Scale in Autism' (SPSA)., Method: The scale is composed of 160 items describing common sensory-psychomotor signs in autism. These items are grouped into 20 variables: touch, nociception, vestibular sensitivity, proprioceptive sensitivity, vision, auditory, multimodality, tone, posture, balance, global coordination, manual dexterity, body schema, bodily self-consciousness, relational adjustment, emotional expression, use of objects, space, time and tonico-emotional regulation. For each item, the psychomotor therapist evaluated sensori-psychomotor signs according to a five-level Likert scale (0="the sign is never expressed by the person", 1="weakly expressed", 2="moderately expressed", 3="severely expressed" and 4="the sign is very characteristic of the person and very severely expressed"). This is completed by a family interview in order to assess the impact of these signs on everyday situations. The study included 111 children with autism. The presence of neurological and genetic diseases was exclusion criteria. For each child, a global developmental evaluation was carried out by an expert clinical team specializing in ASD. Standardized clinical tools were used: Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), Behavior Summarized Evaluation scale (BSE-R), Repeated and Restricted Behavior scale (RRB), Movement Assessment Battery for Children (M-ABC), Motor Development Rating scale (MDR), Sensory Profile (SP). Developmental quotients (DQ) were evaluated using various tests depending on age and ability., Results: Factor analysis produced three clinically relevant factors: F1: "sensory-emotional synchronization", F2: "multisensory integration" and F3: "motor skills": each containing a similar quantity of items. They account for roughly equal percentages of variance (18.9%, 18.0%, 16.8%, respectively). The factorial structure does not change if the 26 children with comorbid developmental coordination disorder are removed. The three factors show good internal consistency and excellent inter-rater reliability. F1 is comprised of 6 items: touch, nociception, proprioceptive sensitivity, vision, emotional expression and tonico-emotional regulation. This factor is significantly associated with items of the Sensory Profile (touch processing, poor registration, sensory seeking). F2 is comprised of 5 items: multimodality, bodily self-consciousness, relational adjustment, use of objects and space. This factor is associated with ADOS, BSE-R and RRB scores, and the item "touch processing" of the Sensory Profile. F3 is comprised of 4 items: tone, posture, global coordination, manual dexterity. This factor is associated with the M-ABC, the MDR and the item "low endurance" of the Sensory Profile., Conclusion: The SPSA is a relevant clinical tool to assess the severity of sensory-psychomotor clinical signs in order to describe the individual profiles of children with ASD. It represents a critical step in advancing knowledge of the complex and heterogeneous pattern of psychomotor development in autism. It could make a valuable contribution to the field, both in research and clinical practice., (Copyright © 2019 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Binge drinking (BD) is a common pattern of ethanol (EtOH) consumption by adolescents. The brain effects of the acute EtOH exposure are well-studied; however, the long-lasting cognitive and neurobehavioral consequences of BD during adolescence are only beginning to be elucidated. Environmental enrichment (EE) has long been known for its benefits on the brain and may serve as a potential supportive therapy following EtOH exposure. In this study, we hypothesized that EE may have potential benefits on the cognitive deficits associated with BD EtOH consumption. Four-week-old C57BL/6J male mice were exposed to EtOH following an intermittent 4-day drinking-in-the-dark procedure for 4 weeks. Then they were exposed to EE during EtOH withdrawal for 2 weeks followed by a behavioral battery of tests including novel object recognition, novel location, object-in-place, rotarod, beam walking balance, tail suspension, light-dark box and open field that were run during early adulthood. Young adult mice exposed to EE significantly recovered recognition, spatial and associative memory as well as motor coordination skills and balance that were significantly impaired after adolescent EtOH drinking with respect to controls. No significant permanent anxiety or depressive-like behaviors were observed. Taken together, an EE exerts positive effects on the long-term negative cognitive deficits as a result of EtOH consumption during adolescence., (© 2018 Society for the Study of Addiction.)

Objective: The aim of the study was to characterize subtle motor signs in children with moderate-severe traumatic brain injury in the chronic phase of injury., Design: Fourteen children with moderate (n = 6) or severe (n = 8) traumatic brain injury, ages 11-18 yrs, who had sustained their injury at least 1-yr before study participation (range 1-14 yrs since injury), and 14 matched typically developing controls were examined using the Physical and Neurological Examination of Subtle Signs (PANESS). To examine the neural correlates of subtle motor signs, measures of total cerebral volume and motor/premotor volume were derived from magnetic resonance imaging., Results: Children with traumatic brain injury had significantly poorer PANESS performance than controls on the total timed subscore, proximal overflow, and the PANESS total score. Participants with severe traumatic brain injury had greater proximal overflow than those with moderate injury, after controlling for age at injury. Across all participants, greater proximal overflow correlated with reduced total cerebral volume, whereas within the traumatic brain injury group, reduced motor/premotor volume correlated with lower PANESS total score., Conclusions: The study highlights the importance of examining subtle motor signs including overflow during clinical evaluation of chronic pediatric traumatic brain injury and establishes the clinical utility of the PANESS as a measure sensitive to chronic subtle motor signs in this population., To Claim Cme Credits: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Define subtle motor signs including motor overflow; (2) Identify subtle motor signs such as motor overflow during clinical evaluation of children with brain injury; and (3) Explain the relevance of examining subtle motor signs in chronic pediatric brain injury during clinical evaluations., Level: Advanced., Accreditation: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Aneurysmal subarachnoid hemorrhage (aSAH), characterized by the extravasation of blood into the subarachnoid space caused by an intracranial aneurysm rupture, may lead to neurocognitive impairments and permanent disability and usually carries poor outcome. Dental or gingiva-derived stem cells have been shown to contribute to immune modulation and neuroregeneration, but the underlying mechanisms are unclear. In the present study, we sought to investigate whether dental pulp stem cells (DPSCs) secrete certain factor(s) that can ameliorate the neural damage and other manifestations in a rat aSAH model. Twenty-four hours after the induction of aSAH, microthrombosis, cortical vasoconstriction, and the decrease in microcirculation and tissue oxygen pressure were detected. Intrathecal administration of DPSC-derived conditioned media (DPSC-CM) ameliorated aSAH-induced vasoconstriction, neuroinflammation, and improved the oxygenation in the injured brain. Rotarod test revealed that the aSAH-induced cognitive and motor impairments were significantly improved by this DPSC-CM administration. Cytokine array indicated the major constituent of DPSC-CM was predominantly insulin growth factor-1 (IGF-1). Immunohistochemistry staining of injured brain tissue revealed the robust increase in Iba1-positive cells that were also ameliorated by DPSC-CM administration. Antibody-mediated neutralization of IGF-1 moderately deteriorated the rescuing effect of DPSC-CM on microcirculation, Iba1-positive cells in the injured brain area, and the cognitive/motor impairments. Taken together, the DPSC-derived secretory factors showed prominent therapeutic potential for aSAH. This therapeutic efficacy may include improvement of microcirculation, alleviation of neuroinflammation, and microglial activation; partially through IGF-1-dependent mechanisms.

Objective: To clarify the clinical features of freezing of gait (FOG) in Parkinson's disease (PD) patients by classification into two groups: Clinically observed FOG (CFOG) and self-reported FOG (SFOG)., Methods: Two hundred twenty-nine PD patients were medically examined in an examination room as well as subjected to a New Freezing of Gait Questionnaire (NFOG-Q) and analysis of nonmotor symptoms including sleep, cognition, depression, and fatigue., Results: The prevalence of CFOG was 17.9%, while 53.7% of the patients without CFOG reported the presence of FOG via the NFOG-Q. Univariate analysis revealed that CFOG was associated with longer disease duration, motor dysfunction, sleepiness, fatigue, and cognitive dysfunction. These symptoms, excluding akinesia, apathy, rapid eye movement (REM) sleep Behavior Disorder, and cognitive dysfunction, were also associated with SFOG. Multivariate analysis revealed that long PD duration, postural instability, and gait difficulty (PIGD), along with fatigue, were independent factors for SFOG., Conclusions: SFOG and CFOG have many common clinical features. Although the clinical relevance of SFOG remains unclear, careful attention should be paid to related features in clinical practice., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Hypoxia exposure during high-altitude expedition cause psychomotor impairment. Neuroimaging studies indicated that the impairment may be significantly associated with neuron loss and decreased regional homogeneity (ReHo) in several brain regions, suggesting the neural functionality in these regions may be utilized to predict psychomotor impairment under exposure. In this study, 69 subjects come from Shaanxi-Tibet immigrant cohort. Reaction time (RT) tasks were performed to measure the subject's psychomotor function before and after 2-year high-altitude exposure. For each individual, the RT differences between pre-exposure and post-exposure were calculated, which were referred to as "targets" in model establishment. Rs-fMRI data were acquired at the same time with RT tasks. For each individual, the map of ReHo alteration was generated, from which the patterns would be recognized. A pattern recognition procedure was utilized to train and test the predictive models. Two different cross-validation strategies were utilized to evaluate the model performance: leave-one-out cross-validation and four-fold cross-validation. For the models displaying significant R 2 and MSE, weight maps were built. As a result, the predictive models were able to decode the changes of simple and recognition reaction time from the alterations of brain activation under the exposure. The regions with highest contributions to the predictions were bilateral putamen and bilateral pallidum, suggesting that predictions were mainly based on the patterns concentrated in these regions. This study was a proof of concept study designed to examine whether individual-level psychomotor impairment under high-altitude exposure could be predicted by a combination of pattern recognition approach and neuroimaging data.

Objective: To describe long-term neurological and functional outcomes for patients with penetrating spinal cord injury (PSCI) following surgical (SX) and nonsurgical (NSX) treatment. Methods: We identified all patients with PSCI in the Spinal Cord Injury Model Systems database from 1994-2015. Patients with PSCI were divided into surgical (SX) and nonsurgical (NSX) groups. Outcomes were measured using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and the Functional Independence Measure (FIM) motor scores. Outcomes were then analyzed separately for patients with complete and incomplete PSCI during acute hospitalization, SCI rehabilitation, and 1-year follow-up. Results: For patients with complete PSCI, acute hospital length of stay (LOS) was increased in the SX group (19 days vs 14 days; p < .0001) while median FIM motor scores were similar at 1-year follow-up (74 vs 75; p = .4). The percentage of patients with complete PSCI remained similar between groups at discharge from SCI rehabilitation (88% vs 88%; p = 0.5). For patients with incomplete PSCIs, acute hospital LOS was similar between groups (13 vs 11; p = .3) and no difference was observed in ASIA Impairment Scale improvement at discharge from rehabilitation (38% vs 37%; p = .9) or in FIM scores at 1 year (84 vs 85; p = .6). Conclusion: Surgery for patients with complete PSCI is associated with increased acute hospital LOS for complete PSCI and is not associated with improvement in neurological or functional outcomes in patients with either complete or incomplete PSCI., Competing Interests: Conflicts of Interest Drs. Roach and Chen report grant funding from NIDILRR. The other authors declare no conflicts of interest

Right before we move our eyes, visual performance and neural responses for the saccade target are enhanced. This effect, presaccadic attention, is considered to prioritize the saccade target and to enhance behavioral performance for the saccade target. Recent evidence has shown that presaccadic attention modulates the processing of feature information. Hitherto, it remains unknown whether presaccadic modulations on feature information are flexible, to improve performance for the task at hand, or automatic, so that they alter the featural representation similarly regardless of the task. Using a masking procedure, here we report that presaccadic attention can either improve or impair performance depending on the spatial frequency content of the visual input. These counterintuitive modulations were significant at a time window right before saccade onset. Furthermore, merely deploying covert attention within the same temporal interval without preparing a saccade did not affect performance. This study reveals that presaccadic attention not only prioritizes the saccade target, but also automatically modifies its featural representation.

Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and Genitopatellar syndrome (GTPTS) are very rare conditions caused by KAT6B truncating variants. Because of both syndromes often share common features the associated phenotypes are usually grouped under the term "KAT6B-related disorders." However, particular signs of each syndrome have been reported and their appearance seems to be dependent on where the KAT6B variant is located. Thus, whereas truncating variants associated with SBBYSS have their highest density in the distal part of exon 18, those resulting in GTPTS are distributed between the end of exon 17 and beginning of exon 18. Here, we reported two de novo heterozygous KAT6B truncating variants. The first variant (c.5802delA; p.A1935Pfs*16), identified in a boy with SSBYSS phenotype, resulting in the most distal KAT6B truncating variant reported up-to-date in the scientific literature. The second variant (c.3152delG; p.S1051Tfs*63), located in a region hitherto defined as specific of SBBYSS, seems to cause an overlapping SBBYSS/GTPTS phenotype. The clinical and genetic characterization of these patients could contribute to the understanding of the KAT6B-related disorders., (© 2018 Wiley Periodicals, Inc.)

Objectives: Melancholic depression is a type of depression which is closely related to biological variables than are other types of depression. Its clinical features can be assessed using six items on the Hamilton Depression Rating Scale (HAM-D 6 ). Previous studies have shown, using item response theory, that the symptom depressed mood is the least severe melancholic feature; work and activities, somatic symptoms and psychic anxiety are of moderate severity; and feelings of guilt and psychomotor retardation are the most severe. We aimed to evaluate whether the more severe melancholic signs or symptoms were associated with decreases in brain-derived neurotrophic factor (BDNF) levels., Methods: A total of 151 severely depressed inpatients had their BDNF levels analyzed by comparing those who presented with each HAM-D 6 melancholic feature to those for whom the HAM-D 6 feature was absent, using multiple linear regressions. The levels of BDNF of patients who presented with each melancholic feature were also compared with those of 100 healthy controls., Results: Depressed patients' median BDNF level was 44.06 ng/mL (interquartile range [IQR]: 33.99-62.4 ng/mL), and controls' median BDNF level was 65.22 ng/mL (IQR: 49.87-76.08 ng/mL) (P < .001). The presence of depressed mood, work and activities, somatic symptoms, psychic anxiety, and guilty feelings was not associated with BDNF levels. However, the presence of psychomotor retardation was associated with reduced BDNF (median reduction -10.07 ng/mL; 95% confidence interval [CI]: -19.43 to -0.71; P = .03)., Conclusions: To the best of our knowledge, this study is the first to associate BDNF levels with melancholic features in a sample of severely depressed inpatients. The main finding of this study was that severely depressed inpatients who presented the most severe melancholic feature, psychomotor retardation, had significantly reduced BDNF levels in the blood., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: Benign paroxysmal torticollis (BPT), benign paroxysmal vertigo (BPV), and benign tonic upward gaze (BTU) are characterized by transient and recurrent episodes of neurological manifestations. The purpose of this study was to analyse the clinical relationships between these syndromes, associated comorbidities, and genetic bases., Method: In this cross-sectional study, clinical data of patients with BPT, BPV, or BTU were collected with a focus on developmental achievements, learning abilities, and rehabilitation. Neuropsychological assessment and genetic testing were performed., Results: Fifty patients (median age at inclusion 6y) were enrolled. Psychomotor delay, abnormal neurological examination, and low or borderline IQ were found in 19%, 32%, and 26% of the patients respectively. Cognitive dysfunction was present in 27% of the patients. CACNA1A gene mutation was identified in eight families, and KCNA1 and FGF14 mutation in one family respectively. The identification of a CACNA1A mutation was significantly associated with BTU (p=0.03) and with cognitive dysfunction (p=0.01). Patients with BPV were less likely to have cognitive dysfunction., Interpretation: Children with BPT, BPV, or BTU are at high risk of impaired psychomotor and cognitive development. These syndromes should not be regarded as benign and should be considered as part of the spectrum of a neurodevelopmental disorder., What This Paper Adds Ok: Patients with benign paroxysmal torticollis (BPT), benign paroxysmal vertigo (BPV), and benign tonic upward gaze (BTU) have an increased risk of psychomotor delay. These patients also have an increased risk of abnormal neurological examination and cognitive dysfunction. Gene mutations, especially in CACNA1A, were identified in 21% of the families. BPT, BTU, and BPV should not be regarded as benign. BPT, BTU, and BPV should be considered as part of the spectrum of a neurodevelopmental disorder., (© 2018 Mac Keith Press.)

Purpose: The purpose of this longitudinal study was to examine the effect of time and sentence length on speech rate and its characteristics, articulation rate and pauses, within 2 groups of children with cerebral palsy (CP)., Method: Thirty-four children with CP, 18 with no speech motor involvement and 16 with speech motor involvement, produced sentences of varying lengths at 3 time points that were 1 year apart (mean age = 56 months at first time point). Dependent measures included speech rate, articulation rate, proportion of time spent pausing, and average number and duration of pauses., Results: There were no significant effects of time. For children with no speech motor involvement, speech rate increased with longer sentences due to increased articulation rate. For children with speech motor involvement, speech rate did not change with sentence length due to significant increases in the proportion of time spent pausing and average number of pauses in longer sentences., Conclusions: There were no significant age-related differences in speech rate in children with CP regardless of group membership. Sentence length differentially impacted speech rate and its characteristics in both groups of children with CP. This may be due to cognitive-linguistic and/or speech motor control factors.

Functional circuits of the human brain emerge and change dramatically over the second half of gestation. It is possible that variation in neural functional system connectivity in utero predicts individual differences in infant behavioral development, but this possibility has yet to be examined. The current study examines the association between fetal sensorimotor brain system functional connectivity and infant postnatal motor ability. Resting-state functional connectivity data was obtained in 96 healthy human fetuses during the second and third trimesters of pregnancy. Infant motor ability was measured 7 months after birth using the Bayley Scales of Infant Development. Increased connectivity between the emerging motor network and regions of the prefrontal cortex, temporal lobes, posterior cingulate, and supplementary motor regions was observed in infants that showed more mature motor functions. In addition, females demonstrated stronger fetal-brain to infant-behavior associations. These observations extend prior longitudinal research back into prenatal brain development and raise exciting new ideas about the advent of risk and the ontogeny of early sex differences.

Objective: Human aging is accompanied by a decrease in growth hormone secretion and serum insulin-like growth factor (IGF)-1 levels. Also, loss of muscle mass and strength and impairment of physical performance, ending in a state of frailty, are seen in elderly. We aimed to investigate whether handgrip strength, physical performance and recurrent falls are related to serum IGF-1 levels in community-dwelling elderly., Design: Observational cohort study (cross-sectional and prospective)., Methods: We studied the association between IGF-1 and handgrip strength, physical performance and falls in participants of the Longitudinal Aging Study Amsterdam. A total of 1292 participants were included (633 men, 659 women). Serum IGF-1 levels were divided into quartiles (IGF-1-Q1 to IGF-1-Q4). Data on falls were collected prospectively for a period of 3 years. All analyses were stratified for age and physical activity and adjusted for relevant confounders., Results: Men with a low physical activity score in IGF-1-Q1 and IGF-1-Q2 of the younger age group had a lower handgrip strength compared to IGF-1-Q4. In younger more active males in IGF-1-Q2 physical performance was worse. Recurrent fallers were less prevalent in older, low active males with low IGF-1 levels. In females, recurrent fallers were more prevalent in older, more active females in IGF-1-Q2. IGF-1 quartile may predict changes in handgrip strength and physical performance in men and women., Conclusions: Our results indicate that lower IGF-1 levels are associated with lower handgrip strength and worse physical performance, but less recurrent fallers especially in men. Associations were often more robust in IGF-1-Q2. Future studies on this topic are desirable., (© 2018 European Society of Endocrinology.)

We aimed to assess the brain signature of cognitive and behavioral impairment in C9orf72-negative non-demented ALS patients. The study included 50 amyotrophic lateral sclerosis (ALS) patients (out of 75 initially recruited) and 38 healthy controls. High-resolution T1-weighted and spin-echo diffusion tensor images were acquired in a 3T MRI scanner. The multi atlas-based analysis protocol and the FreeSurfer tool were employed for gray matter assessment, and fiber tractography for white matter evaluation. Cognitively impaired ALS patients (n = 12) had bilateral amygdalae and left thalamic volumetric reduction compared to non-impaired ALS patients. Behaviorally impaired ALS patients (n = 14) had lower fractional anisotropy (FA) at the fornix in comparison with healthy subjects. These parameters did correlate with cognitive/behavioral scores, but not with motor-functional parameters in the ALS cohort. We believe that basal ganglia and fornix damage might be related to cognitive and behavioral impairment across ALS-frontotemporal dementia continuum. Also, distinct anatomical areas seem to influence the behavioral and cognitive status of these individuals., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Functional connectivity differences between children with autism spectrum disorder (ASD) and typically developing children have been described in multiple datasets. However, few studies examine the task-related changes in connectivity in disorder-relevant behavioral paradigms. In this paper, we examined the task-related changes in functional connectivity using EEG and a movement-based paradigm that has behavioral relevance to ASD. Resting-state studies motivated our hypothesis that children with ASD would show a decreased magnitude of functional connectivity during the performance of a motor-control task. Contrary to our initial hypothesis, however, we observed that task-related modulation of functional connectivity in children with ASD was in the direction opposite to that of TDs. The task-related connectivity changes were correlated with clinical symptom scores. Our results suggest that children with ASD may have differences in cortical segregation/integration during the performance of a task, and that part of the differences in connectivity modulation may serve as a compensatory mechanism. Autism Res 2018, 11: 245-257. © 2017 International Society for Autism Research, Wiley Periodicals, Inc., Lay Summary: Decreased connectivity between brain regions is thought to cause the symptoms of autism. Because most of our knowledge comes from data in which children are at rest, we do not know how connectivity changes directly lead to autistic behaviors, such as impaired gestures. When typically developing children produced complex movements, connectivity decreased between brain regions. In children with autism, connectivity increased. It may be that behavior-related changes in brain connectivity are more important than absolute differences in connectivity in autism., (© 2017 International Society for Autism Research, Wiley Periodicals, Inc.)

Competing Interests: Conflicts of Interest: The authors have stated that they have no interests, which might be perceived as posing a conflict or bias.

KAT6B sequence variants have been identified in both patients with the Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and in the genitopatellar syndrome (GPS). In SBBYSS, they were reported to affect mostly exons 16-18 of KAT6B, and the predicted mechanism of pathogenesis was haploinsufficiency or a partial loss of protein function. Truncating variants in KAT6B leading to GPS appear to cluster within the proximal portion of exon 18, associated with a dominant-negative effect of the mutated protein, most likely. Although SBBYSS and GPS have been initially considered allelic disorders with distinctive genetic and clinical features, there is evidence that they represent two ends of a spectrum of conditions referable as KAT6B-related disorders. We detected a de novo truncating variant within exon 7 of KAT6B in a 8-year-old female who presented with mild intellectual disability, facial dysmorphisms highly consistent with SBBYSS, and skeletal anomalies including exostosis, that are usually considered component manifestations of GPS. Following the clinical diagnosis driven by the striking facial phenotype, we analyzed the KAT6B gene by NGS techniques. The present report highlights the pivotal role of clinical genetics in avoiding clear-cut genotype-phenotype categories in syndromic forms of intellectual disability. In addition, it further supports the evidence that a continuum exists within the clinical spectrum of KAT6B-associated disorders., (© 2017 Wiley Periodicals, Inc.)

Lowe syndrome (LS) is a very rare disorder of phosphatidylinositol metabolism, which manifests with a complex phenotype comprising a clinical triad encompassing major abnormalities of the eyes, the kidneys, and the central nervous system. We are reporting a 23-year-old Egyptian male with a severe phenotype of LS with a minimal kidney disease. Direct sequencing of the OCRL gene detected a p.His375Arg mutation in the catalytic domain of the protein. The patient suffered from bilateral congenital cataracts and glaucoma, striking growth deficiency, severe psychomotor disability, a severe osteopathy, and seizures, but only minimal renal dysfunction. Although the biological mechanisms underlying the pathophysiology of LS manifestations is yet unclear, it has been proposed that growth delay and osteopathy are linked to a renal dysfunction. This report, however, argues this association and suggests that kidney dysfunction may partially explain the growth deficiency and bone abnormalities, but other still undefined factors might have a potential impact., (© 2017 Wiley Periodicals, Inc.)

Objective: Infants ≤28 GA are at particular risk of psychomotor and neurological developmental disorder. They also remain at a higher risk of developing autism spectrum disorder (ASD), characterized by persistent deficits in communication/social interactions and restricted, repetitive behaviors, activities and interests. Monitoring their development by a team of specialists (a neurologist, psychologist, psychiatrist) allows us to make an early diagnosis and to implement appropriate therapy. Neuroimaging studies during the neonatal period may be helpful in clarifying diagnosis and prognosis. Objective: The aim of the study was to search for the interrelation between the results of neuroimaging and the neurological, psychological and psychiatric evaluation at the age of 2., Patients and Methods: Material and methods: Neonates born at ≤28 weeks between 01.06.2013 and 31.12.2015 and hospitalized at NICU were enrolled. We present the results of the first 12 children who have attained 2 years of corrected age and have undergone both neuroimaging, and neurological, psychological and psychiatric assessments. Transfontanel ultrasound was performed according to general standards, MRI between 38 and 42 weeks of corrected age. Neurological examination based on the Denver scale, ASD screening with use of the STAT test and psychological DSR assessment were performed at 2 years of corrected age., Results: Results: Median GA was 26 weeks and median weight 795 g. The ultrasound examination was normal in 9 cases (75%) and MRI in 4 (33%). Abnormalities in the cerebellum were the main additional information found in MRI as compared to US. Neurological examination was normal in 8 infants (67#37;), in 4 of whom neuroimaging was normal. In 4 (33%) infants the neurological examination was abnormal. Psychomotor development at an average level or above was found in seven (58#37;) children. In 4 of them neuroimaging was normal, whereas 3 had ventricular dilatation and haemorrhagic infarct. There were no abnormalities within the cerebellum in this group. In the remaining 5 children (42#37;) psychomotor development was rated as delayed. All of them had cerebellar haemorrhage. An increased risk of ASD was observed in 4 children who developed cerebellar hemorrhage., Conclusion: Conclusions: 1. The use of MRI at a term-equivalent age may contribute to the prognosis of neurodevelopmental outcomes in extremely premature infants, allowing risk stratification and thus enhancing early monitoring of a child's development and functional status 2. There is a clear tendency towards abnormal psychomotor development and positive screening for ASD to co-occur with abnormal MRI findings in the cerebellum.

Rett Syndrome (RTT), an autism-related disorder caused by mutation of the X-linked Methyl CpG-binding Protein 2 ( MECP2 ) gene, is characterized by severe cognitive and intellectual deficits. While cognitive deficits are well-documented in humans and rodent models, impairments of sensory, motor and metabolic functions also occur but remain poorly understood. To better understand non-cognitive deficits in RTT, we studied female rats heterozygous for Mecp2 mutation ( Mecp2 -/x ); unlike commonly used male Mecp2 -/y rodent models, this more closely approximates human RTT where males rarely survive. Mecp2 -/x rats showed rapid, progressive decline of motor coordination through six months of age as assessed by rotarod performance, accompanied by deficits in gait and posture. Mecp2 -/x rats were hyper-responsive to noxious pressure and cold, but showed visceral hyposensitivity when tested by colorectal distension. Mecp2 -/x rats ate less, drank more, and had more body fat resulting in increased weight gain. Our findings reveal an array of progressive non-cognitive deficits in this rat model that are likely to contribute to the compromised quality of life that characterizes RTT., Competing Interests: The authors declare no conflict of interest.

The article provides an overview of modern physiological evidence to support the hypothesis on cortico limbic sys tem dysfunction due to the hippocampal neurogenesis impairment as a basis of the brain interhemispheric asym metry and neurocognitive deficit after radiation exposure. The importance of the research of both evoked poten tials and fields as a highly sensitive and informative method is emphasized.Particular attention is paid to cerebral sensor systems dysfunction as a typical effect of ionizing radiation. Changes in functioning of the central parts of sensory analyzers of different modalities as well as the violation of brain integrative information processes under the influence of small doses of ionizing radiation can be critical when determining the radiation risks of space flight. The possible long term prospects for manned flights into space, including to Mars, given the effects identified are discussed. Potential risks to the central nervous system during space travel comprise cognitive functions impairment, including the volume of short term memory short ening, impaired motor functions, behavioral changes that could affect human performance and health. The remote risks for CNS are considered to be the following possible neuropsychiatric disorders: accelerated brain aging, Alzheimer's disease and other types of dementia. The new radiocerebral dose dependent effect, when applied cog nitive auditory evoked potentials P300 technique with a possible threshold dose of 0.05 Gy, manifesting in a form of disruption of information processing in the Wernicke's area is under discussion. In order to identify neurophys iological biological markers of ionizing radiation further international researches with adequate dosimetry support are necessary., (K. Loganovsky, K. Kuts.)

Differentiation of melancholic (MEL) and non-melancholic (N-MEL) depression results from subjective assessment of psychomotor disturbance, which obscures their accurate diagnosis. CORE instrument assigned participants with severe or refractory depression to MEL or N-MEL group. Participants underwent 7 days of actigraphy. Data was fitted to a cosinusoidal curve corresponding to a 24-h rhythm. Nocturnal activity was significantly higher in N-MEL. ROC curve shows that average night activity discriminate participants with 71% sensitivity and 100% specificity (area under the curve = 0.84). Actigraphy contribute to the objective differentiation of depression subtypes, and have implications for research on their neurobiology and clinical management., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: There are few reports pertaining to Asian patients with neonatal diabetes mellitus (NDM) caused by activating mutations in the ATP-sensitive potassium channel genes (KATP-NDM)., Objectives: To elucidate the characteristics of Japanese patients with KATP-NDM., Methods: By the amplification and direct sequencing of all exons and exon-intron boundaries of the KCNJ11 and ABCC8 genes, 25 patients with KATP-NDM were identified from a total of 70 patients with NDM. Clinical data were collected from the medical charts., Results: Sixteen patients had mutations in KCNJ11 and nine in ABCC8. Eight novel mutations were identified; two in KCNJ11 (V64M, R201G) and six in ABCC8 (R216C, G832C, F1176L, A1263V, I196N, T229N). Interestingly, V64M caused DEND (developmental delay, epilepsy, neonatal diabetes) syndrome in our patient, while mutation of the same residue (V64G) had been reported to cause congenital hyperinsulinism. Mutations in ABCC8 were associated with TNDM (4/9) or isolated PNDM (5/9), whereas those in KCNJ11 were associated with more severe phenotypes, including DEND (3/16), iDEND (intermediate DEND, 4/16), or isolated PNDM (6/16). Switching from insulin to glibenclamide monotherapy was successful in 87.5% of the patients. Neurological improvement was observed in two patients, one with DEND (T293N) and one with iDEND (R50P) syndrome. Three others with iDEND mutations (R201C, G53D, and V59M) remained neurologically normal at 5, 1, and 4 years of age, respectively, with early introduction of sulfonylurea., Conclusion: Overall, clinical presentation of KATP-NDM in Japanese patients was similar to those of other populations. Early introduction of sulfonylurea appeared beneficial in ameliorating neurological symptoms., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chromosomal rearrangements involving 17q23 have been described rarely. Deletions at 17q23.1q23.2 have been reported in individuals with developmental delay and growth retardation, whereas duplications at 17q23.1q23.2 appear to segregate with clubfoot. Dosage alterations in the TBX2 and TBX4 genes, located in 17q23.2, have been proposed to be responsible for the phenotypes observed in individuals with 17q23.1q23.2 deletions and duplications. In this report, we present the clinical phenotype of a child with a previously unreported de novo duplication at 17q23.2q23.3 located distal to the TBX2 and TBX4 region., Case Presentation: We report a 7.5-year-old boy with speech and language disorder, learning difficulties, incoordination, fine motor skill impairment, infrequent seizures with abnormal EEG, and behavior disturbances (mild self-inflicted injuries, hyperactivity-inattention, and stereotyped hand movements). Chromosomal microarray revealed a 2-Mb duplication of chromosome 17q23.2q23.3. Both parents did not have the duplication indicating that this duplication is de novo in the child., Conclusions: The duplicated region encompasses 16 genes. It is possible that increased dosage of one or more genes in this region is responsible for the observed phenotype. The TANC2 gene is one of the genes in the duplicated region.It encodes a member of the TANC (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing) family which includes TANC1 and TANC2. These proteins are highly expressed in brain and play major roles in synapsis regulation. Hence, it is suggestive that TANC2 is the likely candidate gene responsible for the observed phenotype as an increased TANC2 dosage can potentially alter synapsis, resulting in neuronal dysfunction and the neurobehavioral phenotype observed in this child with 17q23.2q23.3 duplication.