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To competently navigate the world, individuals must flexibly balance distinct aspects of social gaze, orienting toward others and inhibiting orienting responses, depending on the context. These behaviors are often disrupted amongst patient populations treated with serotonergic drugs. However, those in the field lack a clear understanding of how the serotonergic system mediates social orienting and inhibiting behaviors. Here, we tested how increasing central concentrations of serotonin with the direct precursor 5-hydroxytryptophan (5-HTP) would modulate the ability of rhesus macaques (both sexes) to use eye movements to flexibly orient to, or inhibit orienting to, faces. Systemic administrations of 5-HTP effectively increased central serotonin levels and impaired flexible orientation and inhibition. Critically, 5-HTP selectively impaired the ability of monkeys to inhibit orienting to face images, whereas it similarly impaired orienting to face and control images. 5-HTP also caused monkeys to perseverate on their gaze responses, making them worse at flexibly switching between orienting and inhibiting behaviors. Furthermore, the effects of 5-HTP on performance correlated with a constriction of the pupil, an increased time to initiate trials, and an increased reaction time, suggesting that the disruptive effects of 5-HTP on social gaze behaviors are likely driven by a downregulation of arousal and motivational states. Together, these findings provide causal evidence for a modulatory relationship between 5-HTP and social gaze behaviors in nonhuman primates and offer translational insights for the role of the serotonergic system in social gaze. SIGNIFICANCE STATEMENT Behavioral changes arising from pharmacological agents that target serotonergic functions are complex and difficult to predict. Here, we examined the causal impacts of administering the direct precursor of serotonin, 5-HTP, on orienting and inhibiting social gaze in nonhuman primates. 5-HTP increased central concentrations of serotonin and selectively impaired the ability of monkeys to inhibit orienting to faces while similarly impairing the ability of monkeys to orient to face and control images. These behavioral gaze impairments were systematically associated with a downregulation of arousal and motivational states, indexed by pupil constriction, increased time to initiate trials, and increased reaction time. These findings provide a causal link between 5-HTP and social gaze behaviors in nonhuman primates and provide translational insights about serotonergic interventions., (Copyright © 2022 the authors.)

The superior colliculus (SC) is the midbrain center for integrating visual and multimodal sensory information. Neurons in the SC exhibit direction and orientation selectivity. Recent studies reported that neurons with similar preferences formed clusters in the mouse SC (Ahmadlou and Heimel, 2015; Feinberg and Meister, 2015; de Malmazet et al., 2018; Li et al., 2020). However, it remains controversial as to how these clusters are organized within the SC (Inayat et al., 2015; Chen et al., 2021). Here, we found that different brain states (i.e., awake or anesthetized with isoflurane) changed the selectivity of individual SC neurons and organizations of the neuronal population in both male and female mice. Using two-photon Ca 2+ imaging, we examined both individual neuronal responses and the spatial patterns of their population responses. Under isoflurane anesthesia, orientation selectivity increased and a larger number of orientation-selective cells were observed when compared with the awake condition, whereas the proportions of direction-selective cells were similar in both conditions. Furthermore, direction- and orientation-selective cells located at closer positions showed more similar preferences, and cluster-like spatial patterns were enhanced. Inhibitory responses of direction-selective neurons were also reduced under isoflurane anesthesia. Thus, the changes in the spatial organization of response patterns were considered to be because of changes in the balance of excitation and inhibition, with excitation dominance, in the local circuits. These results provide new insights into the possibility that the functional organization of feature selectivity in the brain is affected by brain state. SIGNIFICANCE STATEMENT Recent large-scale recording studies are changing our view of visual maps in the superior colliculus (SC), including findings of cluster-like localizations of direction- and orientation-selective neurons. However, results from several laboratories are conflicting regarding the presence of cluster-like organization. Here, we demonstrated that light isoflurane anesthesia affected the direction- and orientation-tuning properties in the mouse superficial SC and that their cluster-like localization pattern was enhanced by the anesthesia. Furthermore, the effect of anesthesia on direction selectivity appeared to be different in the excitatory and inhibitory populations in the SC. Our results suggest that the functional organization of direction and orientation selectivity might be regulated by the excitation-inhibition balance that depends on the brain state., (Copyright © 2022 the authors.)

Alzheimer's disease (AD) is a profoundly debilitating neurodegenerative disorder characterized most notably by progressive cognitive decline, but also agitation and behavioral disturbances that are extremely disruptive to patient and caregiver. Current pharmacological treatments for these symptoms have limited efficacy and significant side effects. We have recently reported the discovery of Compound 24, an M4 positive allosteric modulator (PAM) that is potent, highly selective, and devoid of cholinergic-like side effects in rats. In order to further evaluate the translatability of the effects of compound 24 in primates, here we describe the effect of Compound 24 on three behavioral and cognition assays in rhesus monkeys, the stimulant induced motor activity (SIMA) assay, the object retrieval detour task (ORD), and the visuo-spatial paired-associates learning (vsPAL) task. As far as we know, this is the first such characterization of an M4 PAM in non-human primate. Compound 24 and the clinical standard olanzapine attenuated amphetamine induced hyperactivity to a similar degree. In addition, Compound 24 demonstrated procognitive effects in scopolamine-impaired ORD and vsPAL, and these effects were of similar magnitude to donepezil. These findings suggest that M4 PAMs may be beneficial to diseases such as Alzheimer's disease and schizophrenia, which are marked by behavioral disturbances as well as deficits in cognitive function., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Gaze direction is an important cue of the eye region. Previous studies have revealed that oxytocin (OXT) increases orienting to the eye region of face. However, little has been known about the effect of OXT in men and women on the perception of gaze direction particularly when associated with different emotions., Objectives: We investigated how oxytocin would affect gaze direction judgments for threatening, angry, and neutral facial expressions and whether this effect would be modulated by observers' sex., Methods: We used the cone of direct gaze (CoDG) task. Participants were required to judge the gaze direction of face between directed and averted gaze., Results: Results showed opposing sex-dependent effects of OXT such that OXT, as compared with placebo, tended to decrease the CoDG in men but increase it in women. The CoDG was marginally wider in men than in women in the placebo condition, and however, this difference was abolished following OXT treatment. We also found that the perception of gaze direction varied as a function of emotional expression such that the CoDG for angry and neutral faces was wider than that for fearful faces and the CoDG for angry faces was marginally wider than that for neutral ones. However, there was no significant interaction between treatment and facial expression., Conclusions: Our findings provide the first evidence for sex-dependent effects of OXT on gaze direction perception, suggesting that OXT attenuates the self-referential judgment of gaze directions of others in men and enhances it in women despite differentiated emotions of faces.

Even though previously described iron-containing structures in the upper beak of pigeons were almost certainly macrophages, not magnetosensitive neurons, behavioural and neurobiological evidence still supports the involvement of the ophthalmic branch of the trigeminal nerve (V1) in magnetoreception. In previous behavioural studies, inactivation of putative V1-associated magnetoreceptors involved either application of the surface anaesthetic lidocaine to the upper beak or sectioning of V1. Here, we compared the effects of lidocaine treatment, V1 ablations and sham ablations on magnetic field-driven neuronal activation in V1-recipient brain regions in European robins. V1 sectioning led to significantly fewer Egr-1-expressing neurons in the trigeminal brainstem than in the sham-ablated birds, whereas lidocaine treatment had no effect on neuronal activation. Furthermore, Prussian blue staining showed that nearly all iron-containing cells in the subepidermal layer of the upper beak are nucleated and are thus not part of the trigeminal nerve, and iron-containing cells appeared in highly variable numbers at inconsistent locations between individual robins and showed no systematic colocalization with a neuronal marker. Our data suggest that lidocaine treatment has been a nocebo to the birds and a placebo for the experimenters. Currently, the nature and location of any V1-associated magnetosensor remains elusive., (© 2018 The Author(s).)

Introduction: Prenatal nicotine exposure (PNE) from maternal cigarette smoking is linked to developmental deficits, including impaired auditory processing, language, generalized intelligence, attention, and sleep. Fetal brain undergoes massive growth, organization, and connectivity during gestation, making it particularly vulnerable to neurotoxic insult. Nicotine binds to nicotinic acetylcholine receptors, which are extensively involved in growth, connectivity, and function of developing neural circuitry and neurotransmitter systems. Thus, PNE may have long-term impact on neurobehavioral development. The purpose of this study was to compare the auditory K-complex, an event-related potential reflective of auditory gating, sleep preservation and memory consolidation during sleep, in infants with and without PNE and to relate these neural correlates to neurobehavioral development., Methods: We compared brain responses to an auditory paired-click paradigm in 3- to 5-month-old infants during Stage 2 sleep, when the K-complex is best observed. We measured component amplitude and delta activity during the K-complex., Results: Infants with PNE demonstrated significantly smaller amplitude of the N550 component and reduced delta-band power within elicited K-complexes compared to nonexposed infants and also were less likely to orient with a head turn to a novel auditory stimulus (bell ring) when awake., Conclusions: PNE may impair auditory sensory gating, which may contribute to disrupted sleep and to reduced auditory discrimination and learning, attention re-orienting, and/or arousal during wakefulness reported in other studies., Implications: Links between PNE and reduced K-complex amplitude and delta power may represent altered cholinergic and GABAergic synaptic programming and possibly reflect early neural bases for PNE-linked disruptions in sleep quality and auditory processing. These may pose significant disadvantage for language acquisition, attention, and social interaction necessary for academic and social success.

Distractibility can be defined as an attention deficit where orientation toward irrelevant targets cannot be inhibited. There is now mounting evidence that the superior colliculus is a key neural correlate of distractibility, with increased collicular-activity resulting in heightened distractibility. Heightened distractibility is reduced by amphetamine, which acutely suppresses collicular responsiveness. However, when amphetamine is used to treat distractibility, it is given chronically, yet no data exist on whether chronic amphetamine treatment affects the colliculus. Here, the effect of chronic amphetamine treatment was assessed in healthy hooded lister rats on two collicular dependent behaviours following a twenty-eight day treatment period: i) orienting to visual stimuli, and ii) height-dependent modulation of air-righting. We found no significant impact of amphetamine treatment on visual orienting despite showing dose-dependent decreases in orienting to repeated stimuli. However, we did find that treatment with amphetamine significantly reduced the ability to modulate righting according to the height the animal is dropped from - a function known to be dependent on the colliculus. We suggest that the results are in line with previous research showing acute amphetamine suppresses collicular activity and we speculate that the psychostimulant may increase receptive field size, altering time-to-impact calculations carried out by the colliculus during air-righting., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to develop and introduce new method to quantify motor functions of the upper extremity., Methods: The movement was recorded using a three-dimensional motion capture system, and the movement trajectory was analyzed using newly developed two indices, which measure precise repeatability and directional smoothness. Our target task was shoulder flexion repeated ten times. We applied our method to a healthy adult without and with a weight, simulating muscle impairment. We also applied our method to assess the efficacy of a drug therapy for amelioration of motor functions in a non-ambulatory patient with spinal muscular atrophy. Movement trajectories before and after thyrotropin-releasing hormone therapy were analyzed., Results: In the healthy adult, we found the values of both indices increased significantly when holding a weight so that the weight-induced deterioration in motor function was successfully detected. From the efficacy assessment of drug therapy in the patient, the directional smoothness index successfully detected improvements in motor function, which were also clinically observed by the patient's doctors., Conclusion: We have developed a new quantitative evaluation method of motor functions of the upper extremity. Clinical usability of this method is also greatly enhanced by reducing the required number of body-attached markers to only one. This simple but universal approach to quantify motor functions will provide additional insights into the clinical phenotypes of various neuromuscular diseases and developmental disorders., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Chemotherapy in childhood can result in long-term neurophysiological side-effects, which could extend to visual processing, specifically the degree to which a person relies on vision to determine vertical and horizontal (visual dependency). We investigated whether adults treated with chemotherapy in childhood experience elevated visual dependency compared to controls and whether any difference is associated with the age at which subjects were treated. Visual dependency was measured in 23 subjects (mean age 25.3 years) treated in childhood with chemotherapy (CTS) for malignant, solid, non-CNS tumors. We also stratified CTS into two groups: those treated before 12 years of age and those treated from 12 years of age and older. Results were compared to 25 healthy, age-matched controls. The subjective visual horizontal (SVH) and vertical (SVV) orientations was recorded by having subjects position an illuminated rod to their perceived horizontal and vertical with and without a surrounding frame tilted clockwise and counter-clockwise 20° from vertical. There was no significant difference in rod accuracy between any CTS groups and controls without a frame. However, when assessing visual dependency using a frame, CTS in general (p = 0.006) and especially CTS treated before 12 years of age (p = 0.001) tilted the rod significantly further in the direction of the frame compared to controls. Our findings suggest that chemotherapy treatment before 12 years of age is associated with elevated visual dependency compared to controls, implying a visual bias during spatial activities. Clinicians should be aware of symptoms such as visual vertigo in adults treated with chemotherapy in childhood.

An 89-year-old woman with Alzheimer's dementia was admitted because of altered orientation, aggressiveness and inability to take care of herself at home. Her patient history indicated that 14 days ago the battery of the pacemaker had be renewed. During that time the patient suffered from psychomotor alterations. Therefore, melperone had been initiated. Inspection of the urine and laboratory findings pointed towards an acute exacerbation of acute intermittent porphyria as a possible cause of the delirium. After discontinuation of melperone with additional parenteral therapy with physiological fluids, the signs of delirium significantly improved.

Background: Caffeine is a widely used dietary stimulant that can reverse the effects of fatigue on cognitive, motor and oculomotor function. However, few studies have examined the effect of caffeine on the oculomotor system when homeostasis has not been disrupted by physical fatigue. This study examined the influence of a moderate dose of caffeine on oculomotor control and visual perception in participants who were not fatigued., Methods: Within a placebo-controlled crossover design, 13 healthy adults ingested caffeine (5 mg·kg -1 body mass) and were tested over 3 h. Eye movements, including saccades, smooth pursuit and optokinetic nystagmus, were measured using infrared oculography., Results: Caffeine was associated with higher peak saccade velocities (472 ± 60° s -1 ) compared to placebo (455 ± 62° s -1 ). Quick phases of optokinetic nystagmus were also significantly faster with caffeine, whereas pursuit eye movements were unchanged. Non-oculomotor perceptual tasks (global motion and global orientation processing) were unaffected by caffeine., Conclusions: These results show that oculomotor control is modulated by a moderate dose of caffeine in unfatigued humans. These effects are detectable in the kinematics of rapid eye movements, whereas pursuit eye movements and visual perception are unaffected. Oculomotor functions may be sensitive to changes in central catecholamines mediated via caffeine's action as an adenosine antagonist, even when participants are not fatigued.

Rationale: The cognitive deficits observed in young binge drinkers have been largely documented during the last decade. Yet, these earlier studies have mainly focused on high-level cognitive abilities (particularly memory and executive functions), and uncertainty thus still abounds regarding the integrity of less complex cognitive processes in binge drinking. This is particularly true for attentional abilities, which play a crucial role in behavior regulation and are impaired in other alcohol-related disorders., Objectives and Methods: To specify the attentional deficits associated with binge drinking, two groups of university students (40 binge drinkers and 40 matched controls) performed the Attention Network Task, a theoretically grounded test assessing three independent attentional networks: alerting, orienting, and executive control., Results: Binge drinkers displayed preserved orienting performance but impaired alerting and executive control. Binge drinking is thus not related to a general attentional impairment but rather to specific impairments of the alerting and executive control networks., Conclusions: These results underline that, beyond the already explored high-level deficits, binge drinking is also related to impairments for attentional abilities. In view of the role played by attentional impairments in alcohol dependence, the present data also suggest that rehabilitation programs should be developed to improve attentional abilities at the early stages of alcohol-related disorders.

Introduction: Alzheimer’s disease is one of the most prevalent neurodegenerative dementia in developed world. This fact, coupled with the lack cure, makes new no pharmacological therapeutic strategies such as nutrient management to investigate. In this regard, it stresses the possible influence of coconut oil as alternative energy source capable of stopping the progressively neuronal death that occurs in this disease. Objectives: To assess the cognitive impact of coconut oil in Alzheimer’s patients, and specifically in orientation, language-building, fixing, calculation-concentration and memory areas. Methods: Prospective, longitudinal, qualitative, analytical and experimental study through a clinical trial where 44 patients with Alzheimer’s in region of Ribera (Valencia), of which half was selected to receive during 21 days, 40 ml coconut oil daily divided between breakfast (20 ml) and food (20 ml). Before and after administration of the oil, they were evaluated through cognitive test Mini-Mental State Examination to determine possible changes. Results: It was observed in patients who received coconut oil, that cognitive improvement after completion of the intervention, statistically significant improved in the orientation and language-construction areas. Conclusions: Coconut oil appears to improve cognitive abilities of Alzheimer’s patients, with different intensity depending on the cognitive area.

Introduction and Rationale: Given baseline-dependent effects of nicotine on other forms of attention, there is reason to believe that inconsistent findings for the effects of nicotine on attentional orienting may be partly due to individual differences in baseline (abstinence state) functioning. Individuals with low baseline attention may benefit more from nicotine replacement., Method: The effects of nicotine as a function of baseline performance (bottom, middle, and top third of mean reaction times during placebo) were assessed in 52 habitual abstinent smokers (26 females/26 males) utilizing an arrow-cued covert orienting of attention task., Results: Compared to a placebo patch, a 14mg nicotine patch produced faster overall reaction times (RTs). In addition, individuals with slower RTs during the placebo condition benefitted more from nicotine on cued trials than did those who had shorter (faster) RTs during placebo. Nicotine also enhanced the validity effect (shorter RTs to validly vs. invalidly cued targets), but this nicotine benefit did not differ as a function of overall placebo-baseline performance., Conclusions: These findings support the view that nicotine enhances cued spatial attentional orienting in individuals who have slower RTs during placebo (nicotine-free) conditions; however, baseline-dependent effects may not generalize to all aspects of spatial attention. These findings are consistent with findings indicating that nicotine's effects vary as a function of task parameters rather than simple RT speeding or cognitive enhancement., Competing Interests: The authors have no conflicts of interest with the submitted work., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The capability of memantine, a noncompetitive antagonist of the NMDA receptors, to prevent impairments of cognitive functions in rats was investigated in the lithium-pilocarpine model of epilepsy. After status epilepticus, rats exhibited impaired exploratory behavior and spatial memory, and a decline of extinction of orienting behavior. Memantine administration prevented these disturbances. Thus, the blockade of the NMDA receptors immediately after status epilepticus allowed prevention of the development of the possible cognitive impairments.

Objective: The study investigated whether baseline plasma oxytocin (OXT) concentrations might moderate the effects of nasally administered OXT on social orienting., Methods: Thirty-one males with Autism spectrum disorder (ASD) and thirty healthy males participated in a double-blind placebo-controlled crossover trial. After administration of the compound, participants were viewing pictures from the International Affective Picture System that represented a systematic variation of pleasant, unpleasant and neutral scenes with and without humans. The outcome measures were a cardiac evoked response (ECR) and a cortical evoked long latency parietal positivity (LPP)., Results: Males with ASD had significantly higher plasma baseline levels than the controls. In the absence of general treatment effects, higher baseline concentrations were found to be associated with larger treatment effects, particularly in the group of males with ASD. Higher post-treatment plasma OXT concentrations were found to be associated with smaller treatment effects and larger orienting responses in the placebo situation in the group of controls., Conclusions: We interpret our findings as suggesting that it is the central availability of OXT determining how much of the nasally administered OXT will become centrally absorbed and how much of it will become released into the bloodstream.

The discovery of shared behavioral processes across phyla is a significant step in the establishment of a comparative study of behavior. We use immobility as an origin and reference for the measurement of fly locomotor behavior; speed, walking direction and trunk orientation as the degrees of freedom shaping this behavior; and cocaine as the parameter inducing progressive transitions in and out of immobility. We characterize and quantify the generative rules that shape Drosophila locomotor behavior, bringing about a gradual buildup of kinematic degrees of freedom during the transition from immobility to normal behavior, and the opposite narrowing down into immobility. Transitions into immobility unfold via sequential enhancement and then elimination of translation, curvature and finally rotation. Transitions out of immobility unfold by progressive addition of these degrees of freedom in the opposite order. The same generative rules have been found in vertebrate locomotor behavior in several contexts (pharmacological manipulations, ontogeny, social interactions) involving transitions in-and-out of immobility. Recent claims for deep homology between arthropod central complex and vertebrate basal ganglia provide an opportunity to examine whether the rules we report also share common descent. Our approach prompts the discovery of behavioral homologies, contributing to the elusive problem of behavioral evolution.

Plants damaged by herbivores emit volatile organic compounds (VOCs) that are used by parasitoids for host location. In nature, however, plants are exposed to multiple abiotic and biotic stresses of varying intensities, which may affect tritrophic interactions. Here, we studied the effects of ozone exposure and feeding by Pieris brassicae larvae on the VOCs emitted by Brassica nigra and the effects on oriented flight of the parasitoid Cotesia glomerata. We also investigated the oriented flight of C. glomerata in a wind-tunnel with elevated ozone levels. Herbivore-feeding induced the emission of several VOCs, while ozone alone had no significant effect. However, exposure to 120 ppb ozone, followed by 24 hr of herbivore-feeding, induced higher emissions of all VOCs as compared to herbivore-feeding alone. In accordance, herbivore-damaged plants elicited more oriented flights than undamaged plants, whereas plants exposed to 120 ppb ozone and 24 hr of herbivore-feeding elicited more oriented flights than plants subjected to herbivore-feeding alone. Ozone enrichment of the wind-tunnel air appeared to negatively affect orientation of parasitoids at 70 ppb, but not at 120 ppb. These results suggest that the combination of ozone and P. brassicae-feeding modulates VOC emissions, which significantly influence foraging efficiency of C. glomerata.

Motor function and motor excitability can be modulated by changes of somatosensory input. Here, we performed a randomized single-blind trial to investigate behavioral and neurophysiological changes during temporary deafferentation of left upper arm and forearm in 31 right-handed healthy adults. Lidocaine cream was used to anesthetize the skin from wrist to shoulder, sparing the hand. As control condition, on a different day, a neutral cream was applied to the same skin area. The sequence (first Lidocaine, then placebo or vice versa) was randomized. Behavioral measures included the Grating Orientation Task, the Von Frey hair testing and the Nine-hole-peg-test. Transcranial magnetic stimulation was used to investigate short-interval intracortical inhibition, stimulus response curves, motor evoked potential amplitudes during pre-innervation and the cortical silent period (CSP). Recordings were obtained from left first dorsal interosseous muscle and from left flexor carpi radialis muscle. During deafferentation, the threshold of touch measured at the forearm was significantly worse. Other behavioral treatment-related changes were not found. The CSP showed a significant interaction between treatment and time in first dorsal interosseous muscle. CSP duration was longer during Lidocaine application and shorter during placebo exposure. We conclude that, in healthy subjects, temporary cutaneous deafferentation of upper and lower arm may have minor effects on motor inhibition, but not on sensory or motor function for the adjacent non-anesthetized hand.

Orientation selectivity (OS) is a prominent and well studied feature of early visual processing in mammals, but recent work has highlighted the possibility that parallel OS circuits might exist in multiple brain locations. Although both classic and modern work has identified an OS mechanism in selective wiring from lateral geniculate nucleus (LGN) to primary visual cortex, OS responses have now been found upstream of cortex in mouse LGN and superior colliculus, suggesting a possible origin in the retina. Indeed, retinal OS responses have been reported for decades in rabbit and more recently in mouse. However, we still know very little about the properties and mechanisms of retinal OS in the mouse, including whether there is a distinct OS ganglion cell type, which orientations are represented, and what are the synaptic mechanisms of retinal OS. We have identified two novel types of OS ganglion cells in the mouse retina that are highly selective for horizontal and vertical cardinal orientations. Reconstructions of the dendritic trees of these OS ganglion cells and measurements of their synaptic conductances offer insights into the mechanism of the OS computation at the earliest stage of the visual system., Significance Statement: Orientation selectivity (OS) is one of the most well studied computations in the brain and has become a prominent model system in various areas of sensory neuroscience. Although the cortical mechanism of OS suggested by Hubel and Wiesel (1962) has been investigated intensely, other OS cells exist upstream of cortex as early as the retina and the mechanisms of OS in subcortical regions are much less well understood. We identified two ON retinal ganglion cells (RGCs) in mouse that compute OS along the horizontal (nasal-temporal) and vertical (dorsoventral) axes of visual space. We show the relationship between dendritic morphology and OS for each RGC type and reveal new synaptic mechanisms of OS computation in the retina., (Copyright © 2016 the authors 0270-6474/16/363208-14$15.00/0.)

The basic behavioral activity of nonlinear rats was evaluated from the sum of crossed peripheral and central squares and peripheral and central rearing postures in the open fi eld test. This index was low (<20 episodes), intermediate (20-29 episodes), or high (>30 episodes). Male rats with high score of orientation and exploratory activity were characterized by higher indexes of total heart rate variability than rats with low or intermediate activity. Specimens with a greater contribution of VLF waves into the total power spectrum of heart rate variability were shown to dominate among the rats with high behavioral activity. Our results are consistent with the notions of a suprasegmental nature of VLF waves.

Objective: The study investigated the effects of nasally administered oxytocin on neurophysiological orienting to empathy-evoking pictures in normally intelligent male adults with and without an autism spectrum disorder (ASD). It further investigated whether these effects might be moderated by the individual's approach and avoidance tendencies., Methods: All subjects participated in a randomised double-blind placebo controlled crossover trial where either oxytocin (OXT) or placebo was administered preceding the viewing of affective pictures.The pictures, selected from the International Affective Picture System (IAPS), represented a systematic variation of pleasant, unpleasant and neutral scenes with and without humans. Both cardiac (ECR) and cortical (LPP) evoked orienting responses were measured and both were enhanced for the pictures with humans, in particular for the unpleasant ones., Results: No significant group differences were found, nor were there any treatment effects. Moderator analysis, however, demonstrated that OXT did enhance orienting to affective pictures with humansin male adults with ASD who are easily distressed when seeing others in stressful situations and in healthy males who are highly sensitive to anticipated punishment and criticism or have a low drive for goal achievement., Conclusion: Individual differences in stress-related avoidance tendencies should be taken into account when considering OXT as a treatment of social deficiencies in autism., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The orienting attention network is responsible for prioritizing sensory input through overt or covert shifts of attention among targets. The ability to disengage attention is essential for the proper functioning of this network. In addition to its importance for proper orienting, deficits in disengagement have been recently implicated in autism disorders. Despite its importance, the neural mechanisms underlying disengagement processing are still poorly understood. In this study, the involvement of the superior colliculus (SC) in disengagement was investigated in unrestrained rats that had been trained in a two-alternative light-guided spatial choice task. At each trial, the rats had to choose one of two paths, leading either to a large or a small reward, based on 1 (single-cue) or 2 (double-cue) lights. The task consisted of serial trials with single- and/or double-cue lights, and rats could acquire a large reward if the rats chose infrequent lights when infrequent cue lights were presented after preceding frequent cue lights. Experiment 1 included trials with either single- or double-cue lights, and infrequent trials with double-cue lights required both attentional disengagement and shift of attention from preceding frequent single-cue lights, while experiment 2 included only trials with single-cue lights requiring shifts of attention but not attentional disengagement. The results indicated that temporary inactivation of the SC by muscimol injections selectively impaired performance on trials requiring disengagement. No impairment was observed on the other trials, in which attention disengagement was not required. The results provide the first evidence that the SC is necessary for attentional disengagement., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Neglect is a neuropsychological disorder characterized by the failure to report or respond to stimuli presented to the side of the body opposite a brain lesion and occurs in approximately 40% of right hemisphere strokes. The need for effective therapies to treat neglect in humans has led to the development of a rodent model. Unilateral destruction of medial agranular cortex (AGm), which is part of a cortical network for directed attention, produces severe multimodal neglect with deficits similar to those seen in humans. Amphetamines have previously been investigated for inducing plasticity and recovery of function following brain damage. Amphetamine treatment has been shown to produce recovery from visual, frontal, and sensorimotor cortex damage in animals and this recovery may be the result of axonal growth originating from the opposite, unlesioned hemisphere. The purpose of this study was to investigate whether amphetamine treatment would induce recovery from neglect produced by unilateral AGm destruction, the time frame in which amphetamine must be administered in order to be effective, and the permanence of recovery following treatment. The results indicated that subjects injected with 2mg/kg of d-amphetamine on days 0, 2, and 5 recovered in significantly fewer days than saline-treated controls, even when administration was delayed by 2 and 7 days. Additionally, these studies indicated that recovery persisted for at least 60 days suggesting that recovery is likely to be long term., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Attentional deficits are prominent in the cognitive profile of patients with schizophrenia. However, it remains unclear whether treatment with clozapine, an atypical antipsychotic and first-line intervention used to reduce positive and negative symptoms of psychosis, improves the attentional functions. We used the revised attention network test to measure alerting, orienting, and executive control of attention both pre- and post-treatment with clozapine in patients with schizophrenia (n=32) and compared performance to healthy controls (n=32). Results revealed that there were deficits in all three attentional functions pre-treatment, and while clozapine improved the orienting function in patients with schizophrenia, there was no evidence for improvement in the alerting and executive control of attention. The enhancement of the orienting function by clozapine may increase the ability of patients with schizophrenia to orient towards objects and thoughts of interest., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the structure of the dendritic arbor and the pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and inhibition arising from the OFF pathway converge to generate a quasi-linear integration of visual signals in the receptive field center. This serves to suppress responses to high spatial frequencies, thereby improving sensitivity to larger objects and enhancing orientation selectivity. Inhibition also regulates the magnitude and time course of excitatory inputs to this PAC through serial inhibitory connections onto the presynaptic terminals of ON bipolar cells. This presynaptic inhibition is driven by graded potentials within local microcircuits, similar in extent to the size of single bipolar cell receptive fields. Additional presynaptic inhibition is generated by spiking amacrine cells on a larger spatial scale covering several hundred microns. The orientation selectivity of this PAC may be a substrate for the inhibition that mediates orientation selectivity in some types of ganglion cells. Significance statement: The retina comprises numerous excitatory and inhibitory circuits that encode specific features in the visual scene, such as orientation, contrast, or motion. Here, we identify a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation, a feature selectivity that is primarily due to the elongated shape of the dendritic arbor. Integration of convergent excitatory and inhibitory inputs from the ON and OFF visual pathways suppress responses to small objects and fine textures, thus enhancing selectivity for larger objects. Feedback inhibition regulates the strength and speed of excitation on both local and wide-field spatial scales. This study demonstrates how different synaptic inputs are regulated to tune a neuron to respond to specific features in the visual scene., (Copyright © 2015 the authors 0270-6474/15/3513336-15$15.00/0.)

Background: Plants under herbivore attack release volatiles that attract natural enemies, and herbivores in turn avoid such plants. Whilst herbivore-induced plant volatile blends appeared to reduce the attractiveness of host plants to herbivores, the volatiles that are key in this process and particularly the way in which deterrence is coded in the olfactory system are largely unknown. Here we demonstrate that herbivore-induced cotton volatiles suppress orientation of the moth Spodoptera littoralis to host plants and mates., Results: We found that (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), an induced volatile, is key in herbivore deterrence: DMNT suppressed plant odour- and pheromone-induced behaviours. We then dissected the neurophysiological basis of this interaction. DMNT-responding glomeruli were also activated by other plant compounds, suggesting that S. littoralis possesses no segregated olfactory circuit dedicated exclusively to DMNT. Instead, DMNT suppressed responses to the main pheromone component, (Z)-9-(E)-11-tetradecenyl acetate, and primarily to (Z)-3-hexenyl acetate, a host plant attractant., Conclusion: Our study shows that olfactory sensory inhibition, which has previously been reported without reference to an animal's ecology, can be at the core of coding of ecologically relevant odours. As DMNT attracts natural enemies and deters herbivores, it may be useful in the development or enhancement of push-pull strategies for sustainable agriculture.

To study rapid sensorimotor remapping, we developed a method to train rats in a behavior in which subjects are cued, on each trial, to apply a sensorimotor association to orient either toward a visual target ("Pro") or away from it, toward its reverse ("Anti"). Multiple behavioral asymmetries suggested that Anti behavior is cognitively demanding while Pro is easier to learn and perform. This is consistent with a prominent hypothesis in the primate literature that Anti requires prefrontal cortex (PFC), whereas Pro could be mediated by midbrain superior colliculus (SC). Pharmacological inactivation of rat medial PFC supported its expected role in Anti. Remarkably, bilateral SC inactivation substantially impaired Anti while leaving Pro essentially intact. Moreover, SC inactivation eliminated the performance cost of switching from Anti to Pro tasks. Our results establish a rodent model of single-trial sensorimotor remapping and suggest a critical role for SC in the cognitively demanding Anti task., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Psocids have emerged as worldwide pests of stored commodities during the past two decades, and are difficult to control with conventional management tactics such as chemical insecticides. Therefore, it is necessary to investigate alternative management strategies, such as the use of attractants for monitoring and controlling psocids, which can be incorporated into integrated pest management programs for psocids. Using a two-choice pitfall test, we studied the response of adults of different ages and sexes of Liposcelis entomophila (Enderlein) (Psocoptera: Liposcelididae), Liposcelis paeta Pearman, Liposcelis decolor (Pearman), Liposcelis brunnea Motschulsky, Liposcelis corrodens (Heymons), and Lepinotus reticulatus Enderlein (Psocoptera: Trogiidae) to volatiles from different potential attractants including grains, grain-based oils, brewer's yeast, wheat germ, and commercially available kairomone lures. For all species tested, sex and age did not have a major influence on response to the different potential attractants. Brewer's yeast most consistently elicited the strongest response for psocids, but this response frequently was not different from that to wheat germ and wheat germ oil. The percentage response to brewer's yeast varied among the psocid species tested: L. decolor (73-78%), L. entomophila (62-73%), L. brunnea (64-68%), L. paeta (42-57%), Lep. reticulatus (40%), and L. corrodens (15-19%). Two psocids species (L. corrodens and Lep. reticulatus) had low responses to all the potential attractants evaluated compared with the other four species. These results show there is high potential for using these attractants in a psocid-monitoring program., (Published by Oxford University Press on behalf of Entomological Society of America 2015. This work is written by US Government employees and is in the public domain in the US.)

Spontaneously hypertensive rats (SHRs), a commonly used animal model of attention-deficit/hyperactivity disorder, exhibit little habituation of the orienting response to repeated presentations of a nonreinforced visual stimulus. However, SHRs that have access to a running wheel for 5, 10, or 21 days exhibit robust habituation that is indistinguishable from normo-active rats. Two days of exercise, in comparison, is not sufficient to affect habituation. Here we tested the hypothesis that the effect of exercise on orienting behavior in SHRs is mediated by changes in noradrenergic function. In Experiment 1, we found that 5, 10, or 21 days of access to a running wheel, but not 2 days, significantly reduced levels of the norepinephrine transporter in medial prefrontal cortex. In Experiment 2, we tested for a causal relationship between changes in noradrenergic function and orienting behavior by blocking noradrenergic receptors during exercise. Rats that received propranolol (beta adrenergic/noradrenergic receptor blocker) during 10 days of exercise failed to exhibit an exercise-induced reduction in orienting behavior. The results inform a growing literature regarding the effects of exercise on behavior and the potential use of exercise as a treatment for mental disorders., ((c) 2015 APA, all rights reserved).)

Rationale: The standards of care for Alzheimer's disease, acetylcholinesterase inhibitors such as donepezil (Aricept®), are dose-limited due to adverse side-effects. These adverse events lead to significant patient non-compliance, constraining the dose and magnitude of efficacy that can be achieved. Non-selective muscarinic receptor orthosteric agonists such as Xanomeline have been shown to be effective in treating symptoms as well, but were also poorly tolerated. Therefore, there is an unmet medical need for a symptomatic treatment that improves symptoms and is better tolerated., Methods: We compared donepezil, xanomeline, and the novel selective muscarinic 1 receptor positive allosteric modulator PQCA in combination with donepezil in the object retrieval detour (ORD) cognition test in rhesus macaque. Gastrointestinal (GI) side effects (salivation and feces output) were then assessed with all compounds to determine therapeutic window., Results: All three compounds significantly reduced a scopolamine-induced deficit in ORD. Consistent with what is observed clinically in patients, both donepezil and xanomeline produced significant GI effects in rhesus at doses equal to or less than a fivefold margin from the minimum effective dose that improves cognition. In stark contrast, PQCA produced no GI side effects when tested at the same dose range., Conclusions: These data suggest M1 positive allosteric modulators have the potential to improve cognition in Alzheimer's disease with a greater therapeutic margin than the current standard of care, addressing an important unmet medical need.

The widely observed between-subject variability in cognitive responses to coffee may have a genetic basis. We evaluated cognitive responses to caffeine throughout three complex cognitive tasks assessing different subdomains of attention, namely Alerting and Orienting (Categorical Search Task) and Executive Control (Stroop Task and Eriksen Flanker Task). We explored whether they are influenced by gene variants affecting adenosine metabolism or catecholamine receptors. We recruited 106 healthy male subjects who were administered, in a double-blind design, 40mL of either a decaffeinated coffee preparation plus 3mg/kg caffeine (caf) or the corresponding vehicle (decaf). The protocol was repeated 24h later with the alternative preparation. Cognitive tasks were performed between 30min and 2h after caf or decaf administration. Each subject underwent ambulatory blood pressure monitoring for 2h. Blood samples were collected for genetic evaluations and for plasma caffeine and catecholamines measures. We found a significant reduction of reaction times in two of the cognitive tasks (Categorical Search Task and Stroop Task) after caf compared with decaf, indicating that caffeine, on average, improved the attention level in the domains under investigation. We also found, however, a great inter-individual variability in the cognitive performance responses to caffeine. In exploring genetic sources for such variability, we found a relation between polymorphisms of adenosine A2A and the caffeine effects on the attentional domains of Orienting and Executive control. In conclusion, variability in the attentional response to coffee may be partly explained by genetic polymorphisms of adenosine and adrenergic receptors., (Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.)

The influence of salt concentration in the seawater on solar orientation in Talitrus saltator and Talorchestia ugolinii was studied in a confined environment (transparent plexiglass bowls). Sodium and calcium concentrations strongly affect both sea-land orientation and the sun compass mechanism in T.saltator, whereas the behaviour of T. ugolinii is less influenced. The absence of Na(+) does not influence the sun compass mechanism, but causes an inversion in the mean direction of orientation in T. saltator. In T. ugolinii, there was no influence on the compass mechanism for solar orientation and no inversion in the directional choice. In the absence of Ca(2+), a photonegative tendency was observed for T saltator together with marked reduction in the capacity to go in any direction. However, the effect of Ca(2+) absence on the orientation capacity of T. saltator is reversible and the orientation capacity can be reduced in a few minutes. The different behaviour of the two species of sandhoppers is discussed.

Head Direction (HD) cells of the rodent Papez circuit are thought to reflect the spatial orientation of the animal. Because NMDA transmission is important for spatial behavior, we sought to determine the effects of NMDA blockade on the basic directional signal carried by HD cells and on experience-dependent modification of this system. In Experiment 1, HD cells were recorded from the anterior dorsal thalamus in female Long-Evans rats while they foraged in a familiar enclosure following administration of the NMDA antagonist CPP or saline. While the drug produced a significant decrease in peak firing rates, it failed to affect the overall directional specificity and landmark control of HD cells. Experiment 2 took place over 2 days and assessed whether the NMDA antagonist would interfere with the stabilization of the HD network in a novel environment. On Day 1 the animal was administered CPP or saline and placed in a novel enclosure to allow the stabilization of the HD signal relative to the new environmental landmarks. On Day 2 the animal was returned to the formerly novel enclosure to determine if the enclosure specific direction-dependent activity established on Day 1 was maintained. In contrast to HD cells from control animals, cells from animals receiving CPP during the initial exposure to the novel enclosure did not maintain the same direction-dependent activity relative to the enclosure in the subsequent drug-free exposure. These findings demonstrate that plasticity in the HD system is dependent on NMDA transmission similar to many other forms of spatial learning., ((PsycINFO Database Record (c) 2015 APA, all rights reserved).)

A discrete cue associated with intravenous injections of cocaine acquires greater control over motivated behavior in some rats ('sign-trackers', STs) than others ('goal-trackers', GTs). It is not known, however, if such variation generalizes to cues associated with other drugs. We asked, therefore, whether a discrete cue (a light) associated with the intravenous administration of an opioid drug (the short-acting mu receptor agonist, remifentanil) acquires incentive motivational properties differently in STs and GTs, as indicated by tests of Pavlovian conditioned approach and conditioned reinforcement. Consistent with studies using cocaine, STs approached a classically conditioned opioid cue more readily than GTs, and in a test of conditioned reinforcement worked more avidly to get it. Interestingly, STs and GTs did not differ in the acquisition of a conditioned orienting response. In addition, the performance of conditioned approach behavior, but not conditioned orientation, was attenuated by pretreatment with the dopamine receptor antagonist, flupenthixol, into the core of the nucleus accumbens. Lastly, food and opioid cues engaged similar amygdalo-striatal-thalamic circuitry to a much greater extent in STs than GTs, as indicated by Fos expression. Taken together, these data demonstrate that, similar to food and cocaine cues: (1) a discrete opioid cue attains greater incentive motivational value in STs than GTs; (2) the attribution of incentive motivational properties to an opioid cue is dopamine dependent; and (3) an opioid cue engages the so-called 'motive circuit' only if it is imbued with incentive salience.

Anesthesia affects brain activity at the molecular, neuronal and network level, but it is not well-understood how tuning properties of sensory neurons and network connectivity change under its influence. Using in vivo two-photon calcium imaging we matched neuron identity across episodes of wakefulness and anesthesia in the same mouse and recorded spontaneous and visually evoked activity patterns of neuronal ensembles in these two states. Correlations in spontaneous patterns of calcium activity between pairs of neurons were increased under anesthesia. While orientation selectivity remained unaffected by anesthesia, this treatment reduced direction selectivity, which was attributable to an increased response to the null-direction. As compared to anesthesia, populations of V1 neurons coded more mutual information on opposite stimulus directions during wakefulness, whereas information on stimulus orientation differences was lower. Increases in correlations of calcium activity during visual stimulation were correlated with poorer population coding, which raised the hypothesis that the anesthesia-induced increase in correlations may be causal to degrading directional coding. Visual stimulation under anesthesia, however, decorrelated ongoing activity patterns to a level comparable to wakefulness. Because visual stimulation thus appears to 'break' the strength of pairwise correlations normally found in spontaneous activity under anesthesia, the changes in correlational structure cannot explain the awake-anesthesia difference in direction coding. The population-wide decrease in coding for stimulus direction thus occurs independently of anesthesia-induced increments in correlations of spontaneous activity.

We explored how lateral line cues interact with visual cues to mediate flow sensing behaviors in the nocturnal developing frog, Xenopus laevis, by exposing animals to current flows under different lighting conditions and after exposure to the ototoxin gentamicin. Under dark conditions, Xenopus tadpoles move downstream at the onset of current flow, then turn, and orient toward the direction of the flow with high accuracy. Postmetamorphic froglets also exhibit positive rheotaxis but with less accuracy and longer latency. The addition of discrete light cues to an otherwise dark environment disrupts rheotaxis and positioning. Orientation is less accurate, latency to orient is longer, and animals do not move as far downstream in the presence of light. Compared with untreated tadpoles tested in the dark, tadpoles exposed to gentamicin show less accurate rheotaxis with longer latency and do not move as far downstream in response to flow. These effects are compounded by the presence of light cues. The disruptive effects of light on flow sensing in Xenopus emphasize the disturbances to natural behaviors that may be produced by anthropogenic illumination in nocturnal habitats.

Objective: Pharmacologic ototoxicity is well described in the medical literature, yet efficient screening models are lacking. Aurelia aurita ephyrae, transparent jellyfish with identifiable hair cells, could be an effective model. Structural changes readily manifest behaviorally, and hair cells are easily stained and observed. We treated ephyrae with various gentamicin concentrations, evaluated its motility, and quantified its hair cell loss., Study Design: Baseline pulsing per minute (P), swimming (S), and orientation (O) values were recorded from cultured ephyrae. Ephyrae were transferred into test tubes containing artificial seawater (ASW), gentamicin, or penicillin. P, S, and O were scored at 0, 24, and 48 hours. Ephyrae were formalin fixed, phalloidin stained, and imaged with confocal microscopy, and hair cells were then counted., Results: P was impaired by gentamicin in a dose-dependent fashion, whereas ASW controls maintained baseline P, S, and O values. Impairment of S and O occurred with 3.5 mmol/L gentamicin at 24 hours. For six experiments each using 40 ephyrae, at 24 hours, average P was reduced from 75.2 in ASW to 28.8, 12.3, and 1.9 for 1, 2, and 3.5 mmol/L gentamicin, respectively (p < 0.05 for all cases). Hair cell loss at 24 and 48 hours was significant (32% and 48% reduction compared with control, p < 0.05) and correlated with motility deficits. Deficits from penicillin exposure were not statistically significant., Conclusion: The ephyra model demonstrated functional and histologic gentamicin-mediated impairments, showing promise as a screening tool for ototoxic agents. The changes in ephyra motility after gentamicin exposure correlated significantly with hair cell loss.

Context: Panax ginseng and Gingko biloba are commonly used herbal supplements in the United States that have been reported to increase alertness and cognitive function., Objective: The objective of this study was to investigate the effects of these specific herbals on driving performance., Materials and Methods: 30 volunteers were tested using the STISIM3® Driving Simulator (Systems Technology Inc., Hawthorne, CA, USA) in this double-blind, placebo-controlled study. The subjects were randomized into 3 groups of 10 subjects per group. After 10-min of simulated driving, subjects received either ginseng (1200 mg), Gingko (240 mg), or placebo administered orally. The test herbals and placebo were randomized and administered by a research assistant outside of the study to maintain blinding. One hour following administration of the herbals or placebo, the subjects completed an additional 10-min of simulated driving. Standard driving parameters were studied including reaction time, standard deviation of lateral positioning, and divided attention. Data collected for the divided attention parameter included time to response and number of correct responses. The data was analyzed with repeated-measures analysis of variance (ANOVA) and Kruskal-Wallis test using SPSS 22 (IBM, Armonk, NY, USA)., Results: There was no difference in reaction time or standard deviation of lateral positioning for both the ginseng and Ginkgo arms. For the divided attention parameter, the response time in the Ginkgo arm decreased from 2.9 to 2.5 s. The ginseng arm also decreased from 3.2 to 2.4 s. None of these values were statistically significant when between group differences were analyzed., Discussion and Conclusion: The data suggests there was no statistically significant difference between ginseng, Ginkgo or placebo on driving performance. We postulate this is due to the relatively small numbers in our study. Further study with a larger sample size may be needed in order to elucidate more fully the effects of Ginkgo and ginseng on driving ability.

The neural representation of directional heading is conveyed by head direction (HD) cells located in an ascending circuit that includes projections from the lateral mammillary nuclei (LMN) to the anterodorsal thalamus (ADN) to the postsubiculum (PoS). The PoS provides return projections to LMN and ADN and is responsible for the landmark control of HD cells in ADN. However, the functional role of the PoS projection to LMN has not been tested. The present study recorded HD cells from LMN after bilateral PoS lesions to determine whether the PoS provides landmark control to LMN HD cells. After the lesion and implantation of electrodes, HD cell activity was recorded while rats navigated within a cylindrical arena containing a single visual landmark or while they navigated between familiar and novel arenas of a dual-chamber apparatus. PoS lesions disrupted the landmark control of HD cells and also disrupted the stability of the preferred firing direction of the cells in darkness. Furthermore, PoS lesions impaired the stable HD cell representation maintained by path integration mechanisms when the rat walked between familiar and novel arenas. These results suggest that visual information first gains control of the HD cell signal in the LMN, presumably via the direct PoS → LMN projection. This visual landmark information then controls HD cells throughout the HD cell circuit., (Copyright © 2015 the authors 0270-6474/15/351354-14$15.00/0.)

The saccadic eye movements declining given the development of Parkinson's disease (PD) still deserves thorough analysis. Recent studies confirmed that PD patients show poor saccadic control in visuomotor tasks. The purpose of this study was to investigate the dynamics of saccades parameters at the development of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. The gradual decline of saccadic control was studied in two monkeys that executed the visuomotor task with low doses of MPTP being injected at a prolonged period of time. The experiment included investigating the horizontal, vertical, oblique visually guided saccades as well as the corrective saccades triggered by stimuli onset in various loci within a two-dimensional visual field in the Gap-Step-Overlap paradigm. Our study revealed that the execution of visually guided saccades with small amplitude and corrective saccades changed dramatically with MPTP-model progressing. These changes are also confirmed statistically at the presymptomatic stage of MPTP syndrome. Not only our study gives a robust report of PD dynamics development and saccadic control but the obtained data could also be helpful in developing methods for the early diagnosis of PD., (© The Author(s) 2015.)

In moths, which include many agricultural pest species, males are attracted by female-emitted sex pheromones. Although integrated pest management strategies are increasingly developed, most insect pest treatments rely on widespread use of neurotoxic chemicals, including neonicotinoid insecticides. Residual accumulation of low concentrations of these insecticides in the environment is known to be harmful to beneficial insects such as honey bees. This environmental stress probably acts as an "info-disruptor" by modifying the chemical communication system, and therefore decreases chances of reproduction in target insects that largely rely on olfactory communication. However, low doses of pollutants could on the contrary induce adaptive processes in the olfactory pathway, thus enhancing reproduction. Here we tested the effects of acute oral treatments with different low doses of the neonicotinoid clothianidin on the behavioral responses to sex pheromone in the moth Agrotis ipsilon using wind tunnel experiments. We show that low doses of clothianidin induce a biphasic effect on pheromone-guided behavior. Surprisingly, we found a hormetic-like effect, improving orientation behavior at the LD20 dose corresponding to 10 ng clothianidin. On the contrary, a negative effect, disturbing orientation behavior, was elicited by a treatment with a dose below the LD0 dose corresponding to 0.25 ng clothianidin. No clothianidin effect was observed on behavioral responses to plant odor. Our results indicate that risk assessment has to include unexpected effects of residues on the life history traits of pest insects, which could then lead to their adaptation to environmental stress.

This study determined the duration of exercise and amount of methylphenidate that is needed to affect attentional function and social behavior in spontaneously hypertensive rats (SHR), a commonly used animal model of Attention-Deficit/Hyperactivity Disorder (ADHD). Attention was assessed by measuring the orienting response to repeated presentations of a nonreinforced visual cue. Social behavior was examined by allowing rats to freely explore a large arena containing an unfamiliar conspecific rat. Consistent with their hyper-responsive phenotype, nonexercising SHRs exhibited a high level of orienting behavior and little habituation, as well as hyper-social behavior compared with normo-active rats. Exercise or methylphenidate decreased orienting behavior and social behavior in a dose-dependent fashion. In addition, we found an additive effect of combining doses of exercise and methylphenidate that alone were ineffective in altering behavior. These data indicate that physical exercise and methylphenidate can reduce hyper-responsiveness to irrelevant stimuli and reduce hyper-social behavior in SHR. Moreover, subthreshold doses of methylphenidate can be used in combination with moderate amounts of exercise to reduce distractibility, supporting the notion that exercise may be useful as an adjunctive or replacement therapy in ADHD.

The ability to integrate local orientation information into a global form percept was investigated in long-term ecstasy users. Evidence suggests that ecstasy disrupts the serotonin system, with the visual areas of the brain being particularly susceptible. Previous research has found altered orientation processing in the primary visual area (V1) of users, thought to be due to disrupted serotonin-mediated lateral inhibition. The current study aimed to investigate whether orientation deficits extend to higher visual areas involved in global form processing. Forty-five participants completed a psychophysical (Glass pattern) study allowing an investigation into the mechanisms underlying global form processing and sensitivity to changes in the offset of the stimuli (jitter). A subgroup of polydrug-ecstasy users (n=6) with high ecstasy use had significantly higher thresholds for the detection of Glass patterns than controls (n=21, p=0.039) after Bonferroni correction. There was also a significant interaction between jitter level and drug-group, with polydrug-ecstasy users showing reduced sensitivity to alterations in jitter level (p=0.003). These results extend previous research, suggesting disrupted global form processing and reduced sensitivity to orientation jitter with ecstasy use. Further research is needed to investigate this finding in a larger sample of heavy ecstasy users and to differentiate the effects of other drugs., (© The Author(s) 2014.)

Pediatric AIDS caused by human immunodeficiency virus type 1 (HIV-1) remains one of the leading worldwide causes of childhood morbidity and mortality. HIV-1 proteins, such as Tat and gp120, are believed to play a crucial role in the neurotoxicity of pediatric HIV-1 infection. Detrimental effects on development, behavior, and neuroanatomy follow neonatal exposure to the HIV-1 viral toxins Tat1-72 and gp120. The present study investigated the neurobehavioral effects induced by the HIV-1 neurotoxic protein Tat1-86, which encodes the first and second exons of the Tat protein. In addition, the potential effects of HIV-1 toxic proteins Tat1-86 and gp120 on inflammatory pathways were examined in neonatal brains. Vehicle, 25 μg Tat1-86 or 100 ng gp120 was injected into the hippocampus of male Sprague-Dawley pups on postnatal day 1 (PD1). Tat1-86 induced developmental neurotoxic effects, as witnessed by delays in eye opening, delays in early reflex development and alterations in prepulse inhibition (PPI) and between-session habituation of locomotor activity. Overall, the neurotoxic profile of Tat1-86 appeared more profound in the developing nervous system in vivo relative to that seen with the first exon encoded Tat1-72 (Fitting et al., 2008b), as noted on measures of eye opening, righting reflex, and PPI. Neither the direct PD1 CNS injection of the viral HIV-1 protein variant Tat1-86, nor the HIV-1 envelope protein gp120, at doses sufficient to induce neurotoxicity, necessarily induced significant expression of the inflammatory cytokine IL-1β or inflammatory factors NF-κβ and I-κβ. The findings agree well with clinical observations that indicate delays in developmental milestones of pediatric HIV-1 patients, and suggest that activation of inflammatory pathways is not an obligatory response to viral protein-induced neurotoxicity that is detectable with behavioral assessments. Moreover, the amino acids encoded by the second tat exon may have unique actions on the developing hippocampus., (Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.)

Head direction (HD) cells, found in the rodent Papez circuit, are thought to form the neural circuitry responsible for directional orientation. Because NMDA transmission has been implicated in spatial tasks requiring directional orientation, we sought to determine if the NMDA antagonist dizocilpine (MK-801) would disrupt the directional signal carried by the HD network. Anterior thalamic HD cells were isolated in female Long-Evans rats and initially monitored for baseline directional activity while the animals foraged in a familiar enclosure. The animals were then administered MK-801 at a dose of .05 mg/kg or 0.1 mg/kg, or isotonic saline, and cells were re-examined for changes in directional specificity and landmark control. While the cells showed no changes in directional specificity and landmark control following administration of saline or the lower dose of MK-801, the higher dose of MK-801 caused a dramatic attenuation of the directional signal, characterized by decreases in peak firing rates, signal to noise, and directional information content. While the greatly attenuated directional specificity of cells in the high dose condition usually remained stable relative to the landmarks within the recording enclosure, a few cells in this condition exhibited unstable preferred directions within and between recording sessions. Our results are discussed relative to the possibility that the findings explain the effects of MK-801 on the acquisition and performance of spatial tasks., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The effectiveness of distractor-filtering is a potentially important determinant of working memory capacity (WMC). However, a distinction between the contributions of distractor-filtering at WM encoding as opposed to filtering during maintenance has not been made and the assumption is that these rely on the same mechanism. Within 2 experiments, 1 conducted in the laboratory with 21 participants, and the other played as a game on smartphones (n = 3,247) we measure WMC without distractors, and present distractors during encoding or during the delay period of a WM task to determine performance associated with distraction at encoding and during maintenance. Despite differences in experimental setting and paradigm design between the 2 studies, we show a unique contribution to WMC from both encoding and delay distractor performance in both experiments, while controlling for performance in the absence of distraction. Thus, within 2 separate experiments, 1 involving an extremely large cohort of 3,247 participants, we show a dissociation between encoding and delay distractor-filtering, indicating that separate mechanisms may contribute to WMC., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)

Psychostimulants containing methylphenidate (MPH) are increasingly being used both on and off-label to enhance learning and memory. Still, almost no studies have investigated MPH's ability to specifically improve spatial or long-term memory. Here we examined the effect of training with 1 or 10mg/kg MPH on hidden platform learning in the Morris water maze. 10mg/kg MPH improved memory acquisition and retention, while 1mg/kg MPH improved memory retention. Taken together with prior evidence that low, clinically relevant, doses of MPH (0.01-1mg/kg MPH) enhance fear memory we conclude that MPH broadly enhances memory., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The psocid, Liposcelis bostrychophila Badonnel (Psocoptera: Liposcelididae), can cause significant damage to stored commodities, and its pest status in the United States has been increasing over the last decade. Because L. bostrychophila is difficult to control with conventional methods, it is critical to explore alternative approaches such as the use of attractants that can be incorporated into integrated pest management programs for monitoring psocids. The orientation response of several L. bostrychophila life stages (first and second instars, third and fourth instars, 0- to 7-d-old adults, 21- to 28-d-old adults, and adults of mixed ages) to a range of potential attractants (including whole and cracked grains, grain-based oils, wheat germ, brewer's yeast, and commercially available kairomone lures) was studied using a two-choice pitfall test to identify candidates for further development as lures in traps. Among the potential attractants evaluated, the strongest response by all stages of L. bostrychophila was to brewer's yeast. Other materials for which there was consistently a strong response were psocid diet, wheat germ, and wheat germ oil. These results show the potential for developing monitoring tools for integrated pest management programs for L. bostrychophila and other psocid species.