Cerebellar contributions to visuomotor adaptation and motor sequence learning: an ALE meta-analysis

Cerebellar contributions to motor learning are well-documented. For example, under some conditions, patients with cerebellar damage are impaired at visuomotor adaptation and at acquiring new action sequences. Moreover, cerebellar activation has been observed in functional MRI (fMRI) investigations of various motor learning tasks. The early phases of motor learning are cognitively demanding, relying on processes such as working memory, which have been linked to the cerebellum as well. Here, we investigated cerebellar contributions to motor learning using activation likelihood estimation (ALE) meta-analysis. This allowed us to determine, across studies and tasks, whether or not the location of cerebellar activation is constant across differing motor learning tasks, and whether or not cerebellar activation in early learning overlaps with that observed for working memory. We found that different regions of the anterior cerebellum are engaged for implicit and explicit sequence learning and visuomotor adaptation, providing additional evidence for the modularity of cerebellar function. Furthermore, we found that lobule VI of the cerebellum, which has been implicated in working memory, is activated during the early stages of explicit motor sequence learning. This provides evidence for a potential role for the cerebellum in the cognitive processing associated with motor learning. However, though lobule VI was activated across both early explicit sequence learning and working memory studies, there was no spatial overlap between these two regions. Together, our results support the idea of modularity in the formation of internal representations of new motor tasks in the cerebellum, and highlight the cognitive processing relied upon during the early phases of motor skill learning

Toxicty of a Serotonin-derived Neuromelanin

Neuroscience - Vision and Functional Brain Imaging Poster SessionIntroduction: POCD (Postoperative Cognitive Dysfunction) is associated with increased mortality and disability and may develop as a consequence of lipid peroxidative byproducts (i.e. acrolein), which accumulate with aging. We previously showed that sevoflurane sequesters acrolein, which promotes the formation of a novel species of neuromelanin (NM) that may play a role in POCD. In this current study, we examined the properties of NM and hypothesized that this novel serotonin-derived melanoid (SDM) product may be neurotoxic. Methods: SDM was produced at the interface of an upper aqueous phase containing serotonin and a lower sevoflurane phase containing acrolein. Uni-lamellar vesicles (ULVs) of dioleoyl-phosphatidylcholine were made using an extrusion technique. The interaction of SDM with ULVs was examined using two lipid membrane probes: diphenyl-hexatriene (DPH) and merocyanine (MC). Vesicle disruption was investigated by monitoring the leakage of dye from calcein-loaded ULVs. Absorbance spectra of SDM were also examined. Statistical analysis involved linear regression and unpaired Student t-tests (p<0.05). Results: We observed that SDM decreased DPH fluorescence anisotropy and increased the temperature-dependent change in anisotropy of DPH. SDM increased the ratio of absorbance (570nm/530nm) of MC-bound ULVs. Using calcein-loaded ULVs, SDM increased detergent-mediated calcein leakage. The intense absorbance band below 250nm of SDM was dramatically altered in the presence of ULVs, yielding three well-resolved peaks from a single broad band. Conclusion: From these data we conclude that SDM has the potential of being neurotoxic. Discussion: This study further characterizes SDM as an important species of NM. SDM disorganized the acyl chains and the phospholipid head groups of ULVs. The electronic structure of SDM was dramatically altered upon interaction with ULVs. We also observed that SDM enhanced detergent-mediated leakage of loaded ULVs, suggesting that SDM may be neurotoxic. We propose that inhalational agents that sequester acrolein [3], may promote the production of certain species of NM that deplete local serotonin and enhance neuronal vulnerability

Developmental Exposure of Rats to Chlorpyrifos Elicits Sex-Selective Hyperlipidemia and Hyperinsulinemia in Adulthood

Developmental exposure to chlorpyrifos alters cell signaling both in the brain and in peripheral tissues, affecting the responses to a variety of neurotransmitters and hormones. We administered 1 mg/kg/day chlorpyrifos to rats on postnatal days 1–4, a regimen below the threshold for systemic toxicity. When tested in adulthood, chlorpyrifos-exposed animals displayed elevations in plasma cholesterol and triglycerides, without underlying alterations in nonesterified free fatty acids and glycerol. This effect was restricted to males. Similarly, in the postprandial state, male rats showed hyperinsulinemia in the face of normal circulating glucose levels but demonstrated appropriate reduction of circulating insulin concentrations after fasting. These outcomes and sex selectivity resemble earlier findings at the cellular level, which identified hepatic hyperresponsiveness to gluconeogenic inputs from β-adrenoceptors or glucagon receptors. Our results thus indicate that apparently subtoxic neonatal chlorpyrifos exposure, devoid of effects on viability or growth but within the parameters of human fetal or neonatal exposures, produce a metabolic pattern for plasma lipids and insulin that resembles the major adult risk factors for atherosclerosis and type 2 diabetes mellitus

Impulsivity in Parkinson’s disease is associated with alterations in affective and sensorimotor striatal networks

A subset of patients with Parkinson’s disease (PD) experiences problems with impulse control, characterized by a loss of voluntary control over impulses, drives, or temptations regarding excessive hedonic behavior. The present study aimed to better understand the neural basis of such impulse control disorders (ICDs) in PD. We collected resting-state functional connectivity and structural MRI data from 21 PD patients with ICDs and 30 patients without such disorders. To assess impulsivity, all patients completed the Barratt Impulsiveness Scale and performed an information-gathering task. MRI results demonstrated substantial differences in neural characteristics between PD patients with and without ICDs. Results showed that impulsivity was linked to alterations in affective basal ganglia circuitries. Specifically, reduced frontal–striatal connectivity and GPe volume were associated with more impulsivity. We suggest that these changes affect decision making and result in a preference for risky or inappropriate actions. Results further showed that impulsivity was linked to alterations in sensorimotor striatal networks. Enhanced connectivity within this network and larger putamen volume were associated with more impulsivity. We propose that these changes affect sensorimotor processing such that patients have a greater propensity to act. Our findings suggest that the two mechanisms jointly contribute to impulsive behaviors in PD

Patterns of Transfer of Adaptation Among Body Segments

Two experiments were conducted in order to determine the patterns of transfer of visuomotor adaptation between arm and head pointing. An altered gain of display of pointing movements was used to induce a conflict between visual and somatosensory representations. Two subject groups participated in Experiment One: group 1 adapted shoulder pointing movements, and group 2 adapted wrist pointing movements to a 0.5 gain of display. Following the adaptation regimen, subjects performed a transfer test in which the shoulder group performed wrist movements and the wrist group performed shoulder movements. The results demonstrated that both groups displayed typical adaptation curves, initially undershooting the target followed by a return to baseline performance. Transfer tests revealed that both groups had high transfer of the acquired adaptation to the other joint. Experiment Two followed a similar design except that group 1 adapted head pointing movements and group 2 adapted arm pointing movements. The arm adaptation had high transfer to head pointing while the head adaptation had very little transfer to arm pointing. These results imply that, while the arm segments may share a common target representation for goal-directed actions, individual but functionally dependent target representations may exist for the control of head and arm movements

Performance Benefits Associated with Context-Dependent Arm Pointing Adaptation

Our previous work has demonstrated that head orientation can be used as a contextual cue to switch between mUltiple adaptive states. Subjects were assigned to one of three groups: the head orientation group tilted the head towards the right shoulder when drawing under a 0.5 gain of display and towards the left shoulder when drawing under a 1.5 gain of display; the target orientation group had the home & target positions rotated counterclockwise when drawing under the 0.5 gain and clockwise for the l.5 gain; the arm posture group changed the elbow angle of the arm they were not drawing with from full flexion to full extension with 0.5 and l.5 gain display changes. The head orientation cue was effectively associated with the multiple gains, in comparison to the control conditions. The purpose of the current investigation was to determine whether this context-dependent adaptation results in any savings in terms of performance measures such as movement duration and movement smoothness when subjects switch between multiple adaptive states. Subjects in the head adaptation group demonstrated reduced movement duration and increased movement smoothness (measured via normalized j erk scores) in comparison to the two control groups when switching between the 0.5 and 1.5 gain. of display. This work has demonstrated not only that subjects can acquire context-dependent adaptation, but also that it results in a significant savings of performance upon transfer between adaptive state

The local electronic structure of alpha-Li3N

New theoretical and experimental investigation of the occupied and unoccupied local electronic density of states (DOS) are reported for alpha-Li3N. Band structure and density functional theory calculations confirm the absence of covalent bonding character. However, real-space full-multiple-scattering (RSFMS) calculations of the occupied local DOS finds less extreme nominal valences than have previously been proposed. Nonresonant inelastic x-ray scattering (NRIXS), RSFMS calculations, and calculations based on the Bethe-Salpeter equation are used to characterize the unoccupied electronic final states local to both the Li and N sites. There is good agreement between experiment and theory. Throughout the Li 1s near-edge region, both experiment and theory find strong similarities in the s- and p-type components of the unoccupied local final density of states projected onto an orbital angular momentum basis (l-DOS). An unexpected, significant correspondence exists between the near-edge spectra for the Li 1s and N 1s initial states. We argue that both spectra are sampling essentially the same final density of states due to the combination of long core-hole lifetimes, long photoelectron lifetimes, and the fact that orbital angular momentum is the same for all relevant initial states. Such considerations may be generically applicable for low atomic number compounds.Comment: 34 pages, 7 figures, 1 tabl

Context-Dependent Arm Pointing Adaptation

We sought to determine the effectiveness of head posture as a contextual cue to facilitate adaptive transitions in manual control during visuomotor distortions. Subjects performed arm pointing movements by drawing on a digitizing tablet, with targets and movement trajectories displayed in real time on a computer monitor. Adaptation was induced by presenting the trajectories in an altered gain format on the monitor. The subjects were shown visual displays of their movements that corresponded to either 0.5 or 1.5 scaling of the movements made. Subjects were assigned to three groups: the head orientation group tilted the head towards the right shoulder when drawing under a 0.5 gain of display and towards the left shoulder when drawing under a 1.5 gain of display, the target orientation group had the home & target positions rotated counterclockwise when drawing under the 0.5 gain and clockwise for the 1.5 gain, the arm posture group changed the elbow angle of the arm they were not drawing with from full flexion to full extension with 0.5 and 1.5 gain display changes. To determine if contextual cues were associated with display alternations, the gain changes were returned to the standard (1.0) display. Aftereffects were assessed to determine the efficacy of the head orientation contextual cue. . compared to the two control cues. The head orientation cue was effectively associated with the multiple gains. The target orientation cue also demonstrated some effectiveness while the.arm posture cue did not. The results demonstrate that contextual cues can be used to switch between multiple adaptive states. These data provide support for the idea that static head orientation information is a crucial component to the arm adaptation process. These data further define the functional linkage between head posture and arm pointing movements