Marc T. Pisansky

Continuous Three-Dimensional Control of a Virtual Helicopter Using a Motor Imagery Based Brain-Computer Interface

Brain-computer interfaces (BCIs) allow a user to interact with a computer system using thought. However, only recently have devices capable of providing sophisticated multi-dimensional control been achieved non-invasively. A major goal for non-invasive BCI systems has been to provide continuous, intuitive, and accurate control, while retaining a high level of user autonomy. By employing electroencephalography (EEG) to record and decode sensorimotor rhythms (SMRs) induced from motor imaginations, a consistent, user-specific control signal may be characterized. Utilizing a novel method of interactive and continuous control, we trained three normal subjects to modulate their SMRs to achieve three-dimensional movement of a virtual helicopter that is fast, accurate, and continuous. In this system, the virtual helicopters forward-backward translation and elevation controls were actuated through the modulation of sensorimotor rhythms that were converted to forces applied to the virtual helicopter at every simulation time step, and the helicopters angle of left or right rotation was linearly mapped, with higher resolution, from sensorimotor rhythms associated with other motor imaginations. These different resolutions of control allow for interplay between general intent actuation and fine control as is seen in the gross and fine movements of the arm and hand. Subjects controlled the helicopter with the goal of flying through rings (targets) randomly positioned and oriented in a three-dimensional space. The subjects flew through rings continuously, acquiring as many as 11 consecutive rings within a five-minute period. In total, the study group successfully acquired over 85% of presented targets. These results affirm the effective, three-dimensional control of our motor imagery based BCI system, and suggest its potential applications in biological navigation, neuroprosthetics, and other applications.

Iron deficiency with or without anemia impairs prepulse inhibition of the startle reflex.

Iron deficiency (ID) during early life causes long‐lasting detrimental cognitive sequelae, many of which are linked to alterations in hippocampus function, dopamine synthesis, and the modulation of dopaminergic circuitry by the hippocampus. These same features have been implicated in the origins of schizophrenia, a neuropsychiatric disorder with significant cognitive impairments. Deficits in sensorimotor gating represent a reliable endophenotype of schizophrenia that can be measured by prepulse inhibition (PPI) of the acoustic startle reflex. Using two rodent model systems, we investigated the influence of early‐life ID on PPI in adulthood. To isolate the role of hippocampal iron in PPI, our mouse model utilized a timed (embryonic day 18.5), hippocampus‐specific knockout of Slc11a2, a gene coding an important regulator of cellular iron uptake, the divalent metal transport type 1 protein (DMT‐1). Our second model used a classic rat dietary‐based global ID during gestation, a condition that closely mimics human gestational ID anemia (IDA). Both models exhibited impaired PPI in adulthood. Furthermore, our DMT‐1 knockout model displayed reduced long‐term potentiation (LTP) and elevated paired‐pulse facilitation (PPF), electrophysiological results consistent with previous findings in the IDA rat model. These results, in combination with previous findings demonstrating impaired hippocampus functioning and altered dopaminergic and glutamatergic neurotransmission, suggest that iron availability within the hippocampus is critical for the neurodevelopmental processes underlying sensorimotor gating. Ultimately, evidence of reduced PPI in both of our models may offer insights into the roles of fetal ID and the hippocampus in the pathophysiology of schizophrenia.

What's New in the Diagnosis and Treatment of Peripheral Nerve Entrapment Neuropathies

Entrapment neuropathies can be common conditions with the potential to cause significant disability. Correct diagnosis is essential for proper management. This article is a review of recent developments related to diagnosis and treatment of various common and uncommon nerve entrapment disorders. When combined with classical peripheral nerve examination techniques, innovations in imaging modalities have led to more reliable diagnoses. Moreover, innovations in conservative and surgical techniques have been controversial as to their effects on patient outcome, but randomized controlled trials have provided important information regarding common operative techniques. Treatment strategies for painful peripheral neuropathies are also reviewed.

Oxytocin enhances observational fear in mice

Empathy is fundamental to human relations, but its neural substrates remain largely unknown. Here we characterize the involvement of oxytocin in the capacity of mice to display emotional state-matching, an empathy-like behavior. When exposed to a familiar conspecific demonstrator in distress, an observer mouse becomes fearful, as indicated by a tendency to freeze and subsequent efforts to escape. Both intranasal oxytocin administration and chemogenetic stimulation of oxytocin neurons render males sensitive to the distress of an unfamiliar mouse. Acute intranasal oxytocin penetrates the brain and enhances cellular activity within the anterior cingulate cortex, whereas chronic administration produces long-term facilitation of observational fear and downregulates oxytocin receptor expression in the amygdala. None of these manipulations affect fear acquired as a result of direct experience with the stressor. Hence, these results implicate oxytocin in observational fear in mice (rather than fear itself) and provide new avenues for examining the neural substrates of empathy.Oxytocin modulates social behaviours in mammals. Here the authors demonstrate that observational fear, a measure of empathy-like behaviour in rodents, is modulated by oxytocin.

Prenatal Choline Supplementation Diminishes Early-Life Iron Deficiency–Induced Reprogramming of Molecular Networks Associated with Behavioral Abnormalities in the Adult Rat Hippocampus

BACKGROUND Early-life iron deficiency is a common nutrient deficiency worldwide. Maternal iron deficiency increases the risk of schizophrenia and autism in the offspring. Postnatal iron deficiency in young children results in cognitive and socioemotional abnormalities in adulthood despite iron treatment. The rat model of diet-induced fetal-neonatal iron deficiency recapitulates the observed neurobehavioral deficits. OBJECTIVES We sought to establish molecular underpinnings for the persistent psychopathologic effects of early-life iron deficiency by determining whether it permanently reprograms the hippocampal transcriptome. We also assessed the effects of maternal dietary choline supplementation on the offsprings hippocampal transcriptome to identify pathways through which choline mitigates the emergence of long-term cognitive deficits. METHODS Male rat pups were made iron deficient (ID) by providing pregnant and nursing dams an ID diet (4 g Fe/kg) from gestational day (G) 2 through postnatal day (PND) 7 and an iron-sufficient (IS) diet (200 g Fe/kg) thereafter. Control pups were provided IS diet throughout. Choline (5 g/kg) was given to half the pregnant dams in each group from G11 to G18. PND65 hippocampal transcriptomes were assayed by next generation sequencing (NGS) and analyzed with the use of knowledge-based Ingenuity Pathway Analysis. Real-time polymerase chain reaction was performed to validate a subset of altered genes. RESULTS Formerly ID rats had altered hippocampal expression of 619 from >10,000 gene loci sequenced by NGS, many of which map onto molecular networks implicated in psychological disorders, including anxiety, autism, and schizophrenia. There were significant interactions between iron status and prenatal choline treatment in influencing gene expression. Choline supplementation reduced the effects of iron deficiency, including those on gene networks associated with autism and schizophrenia. CONCLUSIONS Fetal-neonatal iron deficiency reprograms molecular networks associated with the pathogenesis of neurologic and psychological disorders in adult rats. The positive response to prenatal choline represents a potential adjunctive therapeutic supplement to the high-risk group.

Forebrain-specific loss of BMPRII in mice reduces anxiety and increases object exploration

To investigate the role of Bone Morphogenic Protein Receptor Type II (BMPRII) in learning, memory, and exploratory behavior in mice, a tissue-specific knockout of BMPRII in the post-natal hippocampus and forebrain was generated. We found that BMPRII mutant mice had normal spatial learning and memory in the Morris water maze, but showed significantly reduced swimming speeds with increased floating behavior. Further analysis using the Porsolt Swim Test to investigate behavioral despair did not reveal any differences in immobility between mutants and controls. In the Elevated Plus Maze, BMPRII mutants and Smad4 mutants showed reduced anxiety, while in exploratory tests, BMPRII mutants showed more interest in object exploration. These results suggest that loss of BMPRII in the mouse hippocampus and forebrain does not disrupt spatial learning and memory encoding, but instead impacts exploratory and anxiety-related behaviors.

Mice lacking the chromodomain helicase DNA-binding 5 chromatin remodeler display autism-like characteristics

Although autism spectrum disorders (ASDs) share a core set of nosological features, they exhibit substantial genetic heterogeneity. A parsimonious hypothesis posits that dysregulated epigenetic mechanisms represent common pathways in the etiology of ASDs. To investigate this hypothesis, we generated a novel mouse model resulting from brain-specific deletion of chromodomain helicase DNA-binding 5 (Chd5), a chromatin remodeling protein known to regulate neuronal differentiation and a member of a gene family strongly implicated in ASDs. RNA sequencing of Chd5−/− mouse forebrain tissue revealed a preponderance of changes in expression of genes important in cellular development and signaling, sociocommunicative behavior and ASDs. Pyramidal neurons cultured from Chd5−/− cortex displayed alterations in dendritic morphology. Paralleling ASD nosology, Chd5−/− mice exhibited abnormal sociocommunicative behavior and a strong preference for familiarity. Chd5−/− mice further showed deficits in responding to the distress of a conspecific, a mouse homolog of empathy. Thus, dysregulated chromatin remodeling produces a pattern of transcriptional, neuronal and behavioral effects consistent with the presentation of ASDs.

Social Endophenotypes in Mouse Models of Psychiatric Disease

Psychiatric diseases encompass some of the most complex and debilitating afflictions known to man. Common to several of these diseases, namely autism spectrum disorders (ASDs) and schizophrenia, are impairments in socio-communicative behavior. These impairments have been proposed as candidate endophenotypes of disease processes, being present in prodromal and active stages of disease, as well as in undiagnosed relatives. The genetic bases for these diseases and associated socio-communicative endophenotypes make them highly amenable to study using mouse models. In this review, socio-communicative endophenotypes of two psychiatric diseases—ASDs and schizophrenia—are discussed and translated to measurable behavior in mice. Social interaction and ultrasonic vocalization behavioral paradigms serve as reliable methods for assessing social and communicative functioning in mice, respectively. Several of these paradigms will be overviewed alongside evidence of abnormalities in genetic mouse models of psychiatric disease.