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Experimental conditions are the subsets of an experiment that define the relevant experimental manipulation.
In the Cognitive Atlas, we define a contrast as any function over experimental conditions. The simplest contrast is the indicator value for a specific condition; more complex contrasts include linear or nonlinear functions of the indicator across different experimental conditions.
An indicator is a specific quantitative or qualitative variable that is recorded for analysis. These may include behavioral variables (such as response time, accuracy, or other measures of performance) or physiological variables (including genetics, psychophysiology, or brain imaging data).
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2013-01-16 CTorgerson: Added supporting citation.
2013-01-16 CTorgerson: Added supporting citation.
2013-01-16 CTorgerson: Added contrast for Motor Screening Task
2013-01-16 CTorgerson: Added indicator for Motor Screening Task
2013-01-16 CTorgerson: Added indicator for Motor Screening Task
2013-01-16 CTorgerson: Added term Motor Screening Task to the Atlas.
2013-01-16 CTorgerson: Added definition for Motor Screening Task to the Atlas.
Stip E, Sepehry AA, Prouteau A, Briand C, Nicole L, Lalonde P, Lesage A
Brain and cognition (Brain Cogn)
Citation added by CTorgerson about one year ago
Open Abstract | Citation Profile
Nature.com Literature MatchesMatches have been found on Nature.com for Motor Screening Task:
http://dx.doi.org/10.1038/npp.2011.292 [view abstract]
http://dx.doi.org/10.1038/npp.2011.291 [view abstract]
http://dx.doi.org/10.1038/npp.2012.221 [view abstract]
http://dx.doi.org/10.1038/npp.2012.220 [view abstract]
Julia M Lappin, Suzanne J Reeves, Mitul A Mehta, Alice Egerton, Mark Coulson, Paul M Grasby
Journal of Cerebral Blood Flow & Metabolism (2008)
http://dx.doi.org/10.1038/jcbfm.2008.146 [view abstract]
Striatal dopamine (DA) release has been shown during behavioural tasks, but the relative contribution of motor, reward, and cognitive components is unclear. Dopamine release was quantified using [11C]-raclopride in two studies using a triple-scan approach, comprising active task, motor control, and rest. In the first, bolus radiotracer was delivered during a sequential motor learning paradigm; in the second, a spatial planning task, bolus plus constant infusion was applied. [11C]-raclopride binding potentials (BPNDs) in striatal functional subdivisions were compared across conditions. [11C]-raclopride BPND was significantly reduced in active task compared with rest in both the sensorimotor and associative striatum in both studies, because of differences between rest and motor control conditions. In both regions, the motor control BPND fell between the rest and active task in the planning study, but the difference between motor control and active task conditions was not significant. No such changes were observed in the limbic striatum. Using rigorous methodology, this study validates earlier evidence that striatal DA release occurs during behavioural challenges. Increased DA release during movement was reliably detected in the sensorimotor and associative striatum, supporting use of the functional subdivision model in humans. No additional DA release was observed specific to the cognitive component of either task.
Maryam M Shanechi, Rollin C Hu, Marissa Powers, Gregory W Wornell, Emery N Brown, Ziv M Williams
Nature Neuroscience (2012)
http://dx.doi.org/10.1038/nn.3250 [view abstract]
Although brain-machine interfaces (BMIs) have focused largely on performing single-targeted movements, many natural tasks involve planning a complete sequence of such movements before execution. For these tasks, a BMI that can concurrently decode the full planned sequence before its execution may also consider the higher-level goal of the task to reformulate and perform it more effectively. Using population-wide modeling, we discovered two distinct subpopulations of neurons in the rhesus monkey premotor cortex that allow two planned targets of a sequential movement to be simultaneously held in working memory without degradation. Such marked stability occurred because each subpopulation encoded either only currently held or only newly added target information irrespective of the exact sequence. On the basis of these findings, we developed a BMI that concurrently decodes a full motor sequence in advance of movement and can then accurately execute it as desired.
Gioele Gavazzi, Ambra Bisio, Thierry Pozzo
Scientific Reports (2013)
http://dx.doi.org/10.1038/srep01168 [view abstract]
Several studies have shown that the observation of a rapidly moving stimulus dilates our perception of time. However, this effect appears to be at odds with the fact that our interactions both with environment and with each other are temporally accurate. This work exploits this paradox to investigate whether the temporal accuracy of visual motion uses motor representations of actions. To this aim, the stimuli were a dot moving with kinematics belonging or not to the human motor repertoire and displayed at different velocities. Participants had to replicate its duration with two tasks differing in the underlying motor plan. Results show that independently of the task's motor plan, the temporal accuracy and precision depend on the correspondence between the stimulus' kinematics and the observer's motor competencies. Our data suggest that the temporal mechanism of visual motion exploits a temporal visuomotor representation tuned by the motor knowledge of human actions.
Daniel M. Wolpert, Jörn Diedrichsen, J. Randall Flanagan
Nature Reviews Neuroscience (2011)
http://dx.doi.org/10.1038/nrn3112 [view abstract]
The exploits of Martina Navratilova and Roger Federer represent the pinnacle of motor learning. However, when considering the range and complexity of the processes that are involved in motor learning, even the mere mortals among us exhibit abilities that are impressive. We exercise these abilities when taking up new activities — whether it is snowboarding or ballroom dancing — but also engage in substantial motor learning on a daily basis as we adapt to changes in our environment, manipulate new objects and refine existing skills. Here we review recent research in human motor learning with an emphasis on the computational mechanisms that are involved.
Simon P. Brooks, Stephen B. Dunnett
Nature Reviews Neuroscience (2009)
http://dx.doi.org/10.1038/nrn2652 [view abstract]
The characterization of mouse models of human disease is essential for understanding the underlying pathophysiology and developing new therapeutics. Many diseases are often associated with more than one model, and so there is a need to determine which model most closely represents the disease state or is most suited to the therapeutic approach under investigation. In the case of neurological disease, motor tests provide a good read-out of neurological function. This overview of available motor tasks aims to aid researchers in making the correct choice of test when attempting to tease out a transgenic phenotype or when assessing the recovery of motor function following therapeutic intervention.
Michael W Cole, Jeremy R Reynolds, Jonathan D Power, Grega Repovs, Alan Anticevic, Todd S Braver
Nature Neuroscience (2013)
http://dx.doi.org/10.1038/nn.3470 [view abstract]
Extensive evidence suggests that the human ability to adaptively implement a wide variety of tasks is preferentially a result of the operation of a fronto-parietal brain network (FPN). We hypothesized that this network's adaptability is made possible by flexible hubs: brain regions that rapidly update their pattern of global functional connectivity according to task demands. Using recent advances in characterizing brain network organization and dynamics, we identified mechanisms consistent with the flexible hub theory. We found that the FPN's brain-wide functional connectivity pattern shifted more than those of other networks across a variety of task states and that these connectivity patterns could be used to identify the current task. Furthermore, these patterns were consistent across practiced and novel tasks, suggesting that reuse of flexible hub connectivity patterns facilitates adaptive (novel) task performance. Together, these findings support a central role for fronto-parietal flexible hubs in cognitive control and adaptive implementation of task demands.
Johannes G Ramaekers, Gerhold Kauert, Peter van Ruitenbeek, Eef L Theunissen, Erhard Schneider, Manfred R Moeller
http://dx.doi.org/10.1038/sj.npp.1301068 [view abstract]
Human performance studies have usually relied on low-potency marijuana (4% THC) for determining THC-induced impairment. The present study was designed to assess the effects of high-potency marijuana (13% THC) on human performance. In all, 20 recreational users of marijuana participated in a double-blind, placebo controlled, three way cross-over study. The treatments consisted of single doses of 0, 250, and 500 μg/kg THC. Performance tests were conducted at regular intervals between 15 min and 6 h postsmoking and included measures of motor control (Critical tracking task), executive function (Tower of London) motor impulsivity (Stop signal task), and risk taking (Iowa gambling task). THC significantly impaired performance in the Critical tracking task and decreased the number of correct decisions in the Tower of London task. In addition, THC significantly increased stop reaction time and the proportions of commission and omission errors in the Stop signal task. THC-induced impairments lasted up to 6 h postsmoking as indicated by the absence of a THC × Time after smoking interaction. Effect sizes for performance impairments produced by THC 250 μg/kg were relatively low but generally increased by a factor of two in case of THC 500 μg/kg. These data suggest that high potency marijuana consistently impairs executive function and motor control. Use of higher doses of THC in controlled studies may offer a reliable indication of THC induced impairment as compared to lower doses of THC that have traditionally been used in performance studies.
http://dx.doi.org/10.1038/npp.2012.218 [view abstract]
http://dx.doi.org/10.1038/npp.2011.293 [view abstract]
G. Ganesh, R. Osu, E. Naito
Scientific Reports (2013)
http://dx.doi.org/10.1038/srep02648 [view abstract]
Our brain is known to automatically optimize effort expenditure during motor coordination, such that for example, during bimanual braking of a bicycle, a well-oiled brake will automatically be used more than a corroded, heavy brake. But how does our brain infer the effort expenditure? All previous motor coordination models have believed that the effort in a task is known precisely to our brain, solely from the motor commands it generates. Here we show that this belief is incorrect. Through experiments and simulation we exhibit that in addition to the motor commands, the returning haptic signals play a crucial role in the inference of the effort during a force sharing task. Our results thus elucidate a previously unknown sensory-motor association that has major ramifications for our understanding of motor coordination and provides new insights into how sensory modifications due to ergonomics, stroke and disease can affect motor coordination in humans.
Johannes G Ramaekers, Kim P C Kuypers
http://dx.doi.org/10.1038/sj.npp.1300894 [view abstract]
The use of 3,4-methylenedioxymethamphetamine (MDMA) has frequently been associated with increased levels of impulsivity during abstinence. The effects of MDMA on measures of impulsivity, however, have not yet been studied during intoxication. The present study was designed to assess the acute effects of MDMA and alcohol, alone and in combination, on behavioral measures of impulsivity and risk-taking behavior. A total of 18 recreational users of MDMA entered a double-blind placebo-controlled six-way crossover study. The treatments consisted of MDMA 0, 75, and 100 mg with and without alcohol. Alcohol dosing was designed to achieve a peak blood alcohol concentration (BAC) of about 0.06 g/dl during laboratory testing. Laboratory tests of impulsivity were conducted between 1.5 and 2 h post-MDMA and included a stop-signal task, a go/no-go task, and the Iowa gambling task. MDMA decreased stop reaction time in the stop-signal task indicating increased impulse control. Alcohol increased the proportion of commission errors in the stop-signal task and the go/no-go task. Signal detection analyses of alcohol-induced commission errors indicated that this effect may reflect impairment of perceptual or attentive processing rather than an increase of motor impulsivity per se. Performance in the Iowa gambling task was not affected by MDMA and alcohol, but there was a nonsignificant tendency towards improvement following alcohol intake. None of the behavioral measures of impulsivity showed a MDMA × alcohol interaction effect. The lack of interaction indicated that the CNS stimulant effects of MDMA were never sufficient to overcome alcohol-induced impairment of impulse control or risk-taking behavior.
Alexa E Horner, Christopher J Heath, Martha Hvoslef-Eide, Brianne A Kent, Chi Hun Kim, Simon R O Nilsson, Johan Alsiö, Charlotte A Oomen, Andrew Holmes, Lisa M Saksida, Timothy J Bussey
Nature Protocols (2013)
http://dx.doi.org/10.1038/nprot.2013.122 [view abstract]
An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive rather than aversive reinforcement), has high translational potential and lends itself to a high degree of standardization and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.g., Alzheimer's disease, schizophrenia, Huntington's disease, frontotemporal dementia), as well as the characterization of the role of select brain regions, neurotransmitter systems and genes in rodents. This protocol describes how to perform four touchscreen assays of learning and memory: visual discrimination, object-location paired-associates learning, visuomotor conditional learning and autoshaping. It is accompanied by two further protocols (also published in this issue) that use the touchscreen platform to assess executive function, working memory and pattern separation.
http://dx.doi.org/10.1038/npp.2013.278 [view abstract]
Monday, December 09, 2013 1. Mini-Panel Neuronal Immaturity in Schizophrenia 1.1 GABA Signaling in Postmortem Human Brain and Schizophrenia: A Question of Immaturity?
http://dx.doi.org/10.1038/npp.2012.219 [view abstract]
Nitzan Censor, Dov Sagi, Leonardo G. Cohen
Nature Reviews Neuroscience (2012)
http://dx.doi.org/10.1038/nrn3315 [view abstract]
The adult mammalian brain has a remarkable capacity to learn in both the perceptual and motor domains through the formation and consolidation of memories. Such practice-enabled procedural learning results in perceptual and motor skill improvements. Here, we examine evidence supporting the notion that perceptual and motor learning in humans exhibit analogous properties, including similarities in temporal dynamics and the interactions between primary cortical and higher-order brain areas. These similarities may point to the existence of a common general mechanism for learning in humans.
Kevin D'Ostilio, Julien Cremers, Valérie Delvaux, Bernard Sadzot, Gaëtan Garraux
Scientific Reports (2013)
http://dx.doi.org/10.1038/srep02095 [view abstract]
While it is increasingly recognized that voluntary movements are produced by an interaction between conscious and unconscious processes, the role of the latter in Parkinson's disease has received little attention to date. Here, we administered a subliminal masked prime task to 15 Parkinson's disease patients and 15 age-matched healthy elderly subjects. Compatibility effects were examined by manipulating the direction of the arrows and the interstimuli interval. Analysis of the positive compatibility effect revealed performance differences between the most and the least affected hand in Parkinson's disease patients. Additionally, patients did not show the same tendency toward a negative compatibility effect as compared to elderly controls. These novel findings provide evidence supporting the role of basal ganglia circuits in controlling the balance between automatic motor response facilitation and inhibition.
Javier Quintana, Tom Davidson, Edward Kovalik, Stephen R Marder, John C Mazziotta
http://dx.doi.org/10.1016/S0893-133X(01)00304-9 [view abstract]
When primates passively observe other subjects perform specific gestures or actions, premotor and motor cortical areas involved in the internal representation and actual execution of those actions exhibit neuronal activation. This mirror mechanism matches observation, representation, and execution, facilitating internal motor rehearsal, imitation, recognition of actions by others and their meanings, and social learning. Schizophrenic patients have deficits in processing affect displayed by other people's faces, which likely relates to the poor social adaptation and functioning seen in the condition. We hypothesized that, when correctly performing working-memory tasks requiring facial affect processing, schizophrenic patients would show relative increased activity in brain areas involved in social learning and in the internal representation of facial expressions when compared to controls. We used functional magnetic resonance imaging in schizophrenic patients and normal controls to detect relative changes of blood flow in cortical areas related to the representation of facial expressions while the subjects performed simple working-memory tasks with facial emotion diagrams or color circles as cues. We found that, when the task cues were facial expressions in contrast to color circles, the schizophrenic group exhibited increased activation of the face movement areas in motor and pre-motor cortex.
Paul Cisek, John F. Kalaska
http://dx.doi.org/10.1038/nature03005 [view abstract]
Behavioural and imaging studies suggest that when humans mentally rehearse a familiar action they execute some of the same neural operations used during overt motor performance. Similarly, neural activation is present during action observation in many of the same brain regions normally used for performance, including premotor cortex. Here we present behavioural evidence that monkeys also engage in mental rehearsal during the observation of sensory events associated with a well-learned motor task. Furthermore, most task-related neurons in dorsal premotor cortex exhibit the same activity patterns during observation as during performance, even during an instructed-delay period before any actual observed motion. This activity might be a single-neuron correlate of covert mental rehearsal.
Charlotte A Oomen, Martha Hvoslef-Eide, Christopher J Heath, Adam C Mar, Alexa E Horner, Timothy J Bussey, Lisa M Saksida
Nature Protocols (2013)
http://dx.doi.org/10.1038/nprot.2013.124 [view abstract]
The automated touchscreen operant chamber for rats and mice allows for the assessment of multiple cognitive domains within the same testing environment. This protocol presents the location discrimination (LD) task and the trial-unique delayed nonmatching-to-location (TUNL) task, which both assess memory for location. During these tasks, animals are trained to a predefined criterion during ∼20–40 daily sessions. In LD sessions, touching the same location on the screen is rewarded on consecutive trials, followed by a reversal of location-reward contingencies. TUNL, a working memory task, requires animals to 'nonmatch' to a sample location after a delay. In both the LD and TUNL tasks, spatial similarity can be varied, allowing assessment of pattern separation ability, a function that is thought to be performed by the dentate gyrus (DG). These tasks are therefore particularly useful in animal models of hippocampal, and specifically DG, function, but they additionally permit discernment of changes in pattern separation from those in working memory.
Abdallah Hadj Tahar, Pierre J Blanchet, Julien Doyon
http://dx.doi.org/10.1038/sj.npp.1300317 [view abstract]
NMDA receptor antagonists impair learning and memory in animal models, presumably by inhibiting long-term potentiation in the motor cortex. Human studies are limited and restricted by the paucity of safe NMDA antagonists. Here, we investigated the contribution of glutamatergic neurotransmission to the capacity of acquiring motor-adaptation learning in humans. In a double-blind design, 200 mg of amantadine (a low-affinity NMDA receptor channel blocker) or a matching placebo were given orally to groups of 14 and 13 human healthy young volunteers, respectively. Blood samples were collected 3 h after treatment to assay plasma concentrations, and the subjects were then tested using a motor-adaptation paradigm consisting of an eight-target-pointing task. To rule out drug-related generalized impairments such sedation, tests measuring motor dexterity and attention were also administered pre- and post-treatment. Comparison of the mean performance levels on the motor-adaptation task revealed that subjects in the amantadine group performed at a lower level than those in the placebo group, but this difference did not reach significance. Interestingly, however, despite plasma amantadine concentrations being relatively low, ranging from 2.09 to 4.74 μM (mean=3.3 μM), they nevertheless correlated negatively with motor learning. Furthermore, when the amantadine group was divided into low-performance and high-performance subgroups, subjects in the former subgroup displayed mean amantadine concentrations 36% higher than the latter subgroup, and performed significantly worser than the placebo group. No change in performance was found on the motor-dexterity and attention tests. Altogether, our results lend support to the hypothesis that normal NMDA receptor function is necessary for the acquisition of motor adaptation.
Annik Hauri-Hohl, Nicole Dusoczky, Anastasia Dimitropoulos, Russia Ha-Vinh Leuchter, Luciano Molinari, Jon Caflisch, Oskar G Jenni, Beatrice Latal
Pediatric Research (2011)
http://dx.doi.org/10.1203/PDR.0b013e3182321128 [view abstract]
Congenital hypothyroidism (CH) can lead to intellectual deficits despite early high-dose treatment. Our study aimed to determine whether motor impairments can occur despite early high-dose treatment. Sixty-three children with CH and early (median age of onset of treatment 9 d), high-dose treatment (median starting dose of levothyroxine 14.7 μg/kg/d) were tested with the Zurich Neuromotor Assessment (ZNA) at a median age of 13.8 y (range 7.0–14.2 y). Median z-scores in the children with CH were −0.95 in the pure and −0.56 in the adaptive fine motor component, significantly lower than in the ZNA test norms (p < 0.001 and p = 0.01, respectively). The 26 children with athyreosis were more affected than the 33 children with dysgenesis, particularly in the pure motor (−1.55 versus −0.76, p = 0.03), adaptive fine motor (−1.31 versus 0.13, p < 0.01), and static balance task (−0.47 versus 0.67, p = 0.01). Boys performed worse than girls. Older age at onset of treatment was related to poorer adaptive fine motor performance. Movement quality (assessed by associated movements) was not affected. We conclude that severe CH can cause neuromotor deficits persisting into adolescence. These deficits cannot completely be reversed by postnatal treatment, but earlier age at treatment may reduce the degree of impairment.
Adam C Mar, Alexa E Horner, Simon R O Nilsson, Johan Alsiö, Brianne A Kent, Chi Hun Kim, Andrew Holmes, Lisa M Saksida, Timothy J Bussey
Nature Protocols (2013)
http://dx.doi.org/10.1038/nprot.2013.123 [view abstract]
This protocol details a subset of assays developed within the touchscreen platform to measure various aspects of executive function in rodents. Three main procedures are included: extinction, measuring the rate and extent of curtailing a response that was previously, but is no longer, associated with reward; reversal learning, measuring the rate and extent of switching a response toward a visual stimulus that was previously not, but has become, associated with reward (and away from a visual stimulus that was previously, but is no longer, rewarded); and the 5-choice serial reaction time (5-CSRT) task, gauging the ability to selectively detect and appropriately respond to briefly presented, spatially unpredictable visual stimuli. These protocols were designed to assess both complementary and overlapping constructs including selective and divided visual attention, inhibitory control, flexibility, impulsivity and compulsivity. The procedures comprise part of a wider touchscreen test battery assessing cognition in rodents with high potential for translation to human studies.
Monique Ernst, Karen Bolla, Maria Mouratidis, Carlo Contoreggi, John A Matochik, V Kurian, Jean-Lud Cadet, Alane S Kimes, Edythe D London
http://dx.doi.org/10.1016/S0893-133X(01)00414-6 [view abstract]
As decision-making is central to motivated behavior, understanding its neural substrates can help elucidate the deficits that characterize various maladaptive behaviors. Twenty healthy adults performed a risk-taking task during positron emission tomography with 15O-labeled water. The task, a computerized card game, tests the ability to weigh short-term rewards against long-term losses. A control task matched all components of the risk-taking task except for decision-making and the difference between responses to contingent and non-contingent reward and punishment. Decision-making (2 runs of the active task minus 2 runs of the control task) activated orbital and dorsolateral prefrontal cortex, anterior cingulate, insula, inferior parietal cortex and thalamus predominantly on the right side, and cerebellum predominantly on the left side. In an exploratory analysis, guessing (run 1 minus run 2 of the active task) accompanied activation of sensory-motor associative areas, and amygdala on the left side, whereas informed decision-making (run 2 minus run 1) activated areas that subserve memory (hippocampus, posterior cingulate) and motor control (striatum, cerebellum). The findings provide a framework for future investigations of decision-making in maladaptive behaviors.
Kielan Yarrow, Peter Brown, John W. Krakauer
Nature Reviews Neuroscience (2009)
http://dx.doi.org/10.1038/nrn2672 [view abstract]
Events like the World Championships in athletics and the Olympic Games raise the public profile of competitive sports. They may also leave us wondering what sets the competitors in these events apart from those of us who simply watch. Here we attempt to link neural and cognitive processes that have been found to be important for elite performance with computational and physiological theories inspired by much simpler laboratory tasks. In this way we hope to inspire neuroscientists to consider how their basic research might help to explain sporting skill at the highest levels of performance.
H Booth, L A Harvey, S Denis, D Barratt, G T Allison, R D Adams
Spinal Cord (2013)
http://dx.doi.org/10.1038/sc.2013.100 [view abstract]
Clinometrics study. To devise a way of capturing the unbiased perspectives of people living with a spinal cord injury (SCI) in assessments of mobility. SCI unit and community. Three groups of raters used the Global Impression of Change Scale (GICS) to rate change in mobility of a cohort of patients with a recent SCI. The three groups of raters were as follows: 10 people with a recent SCI, 10 people with an established SCI and 10 physiotherapists. The ratings were done after viewing 51 pairs of videos depicting one of three motor tasks: sitting unsupported, transferring and walking. Each pair of videos showed the same person performing the same motor task on two occasions. The videos were taken between 1 h and 5 months apart and presented side by side, randomly left or right, on the screen. Raters were asked to score the amount of change in performance between the two videos on a 7-point Global Impression of Change Scale (GICS). Intra-rater reliability for the three motor tasks and three groups of raters was determined using intra-class correlation coefficients. People with an SCI were reliable at rating change in patients’ abilities to transfer and walk with ICC’s ranging from 0.66 to 0.81 (95% Confidence interval bounds ranging from 0.51 to 0.94). Physiotherapists were consistently but only marginally more reliable at rating than people with an SCI. Videos and the GICS may provide a way of using the unbiased perspectives of people living with spinal cord injury in assessments of mobility.
To devise a way of capturing the unbiased perspectives of people living with a spinal cord injury (SCI) in assessments of mobility.Setting:
SCI unit and community.Methods:
Three groups of raters used the Global Impression of Change Scale (GICS) to rate change in mobility of a cohort of patients with a recent SCI. The three groups of raters were as follows: 10 people with a recent SCI, 10 people with an established SCI and 10 physiotherapists. The ratings were done after viewing 51 pairs of videos depicting one of three motor tasks: sitting unsupported, transferring and walking. Each pair of videos showed the same person performing the same motor task on two occasions. The videos were taken between 1 h and 5 months apart and presented side by side, randomly left or right, on the screen. Raters were asked to score the amount of change in performance between the two videos on a 7-point Global Impression of Change Scale (GICS). Intra-rater reliability for the three motor tasks and three groups of raters was determined using intra-class correlation coefficients.Results:
People with an SCI were reliable at rating change in patients’ abilities to transfer and walk with ICC’s ranging from 0.66 to 0.81 (95% Confidence interval bounds ranging from 0.51 to 0.94). Physiotherapists were consistently but only marginally more reliable at rating than people with an SCI.Conclusions:
Videos and the GICS may provide a way of using the unbiased perspectives of people living with spinal cord injury in assessments of mobility.
Jennifer McDonald, Laura Schleifer, Jerry B Richards, Harriet de Wit
http://dx.doi.org/10.1038/sj.npp.1300176 [view abstract]
This study investigated the acute effects of Δ9-tetrahydrocannabinol (THC) on four behavioral measures of impulsivity in recreational marijuana users. Although impulsive behavior has been studied using several different measures of impulsivity, few studies have utilized more than one of these measures on a single cohort. In this study, 37 healthy men and women participated in three sessions, in which they received capsules containing placebo, 7.5, or 15 mg THC in randomized order under double-blind conditions. Subjects were tested on the following four tasks: the Stop task, which measures the ability to inhibit a prepotent motor response; a Go/no-go task; a Delay discounting task, which measures the value of delayed or uncertain reinforcers; and a time estimation task, which measures alterations in time perception through a time reproduction procedure. Subjects also completed mood questionnaires and general measures of performance. THC produced its expected effects on subjective measures including increases in ARCI euphoria and marijuana scales. THC increased impulsive responding on the Stop task but did not affect performance on either the Go/no-go or Delay or Probability discounting tasks. On the time reproduction task, THC increased estimates of the duration of short intervals while not affecting estimates of longer intervals. There were no significant correlations between the four tasks either before or after drug administration. These results suggest that THC may increase certain forms of impulsive behavior while not affecting other impulsive behaviors. The dissociations between the four measures of impulsivity suggest that impulsivity is an assemblage of distinct components rather than a unitary process.
A. M. Barrett, Kelly M. Goedert, Julia C. Basso
Nature Reviews Neurology (2012)
http://dx.doi.org/10.1038/nrneurol.2012.170 [view abstract]
Spatial neglect increases hospital morbidity and costs in around 50% of the 795,000 people per year in the USA who survive stroke, and an urgent need exists to reduce the care burden of this condition. However, effective acute treatment for neglect has been elusive. In this article, we review 48 studies of a treatment of intense neuroscience interest: prism adaptation training. Due to its effects on spatial motor 'aiming', prism adaptation training may act to reduce neglect-related disability. However, research failed, first, to suggest methods to identify the 50–75% of patients who respond to treatment; second, to measure short-term and long-term outcomes in both mechanism-specific and functionally valid ways; third, to confirm treatment utility during the critical first 8 weeks poststroke; and last, to base treatment protocols on systematic dose–response data. Thus, considerable investment in prism adaptation research has not yet touched the fundamentals needed for clinical implementation. We suggest improved standards and better spatial motor models for further research, so as to clarify when, how and for whom prism adaptation should be applied.
Matthew F. S. Rushworth, Amanda Ellison, Vincent Walsh
Nature Neuroscience (2001)
http://dx.doi.org/10.1038/88492 [view abstract]
It is widely agreed that the right posterior parietal cortex has a preeminent role in visuospatial and orienting attention. A number of lines of evidence suggest that although orienting and the preparation of oculomotor responses are dissociable from each other, the two are intimately related. If this is true, then it should be possible to identify other attentional mechanisms tied to other response modalities. We used repetitive transcranial magnetic stimulation (rTMS) to demonstrate the existence of a distinct anterior parietal mechanism of motor attention. The critical area for motor attention is anterior to the one concerned with orienting, and it is lateralized to the left hemisphere in humans.
Daniel Waldvogel, Peter van Gelderen, Wolf Muellbacher, Ulf Ziemann, Ilka Immisch, Mark Hallett
http://dx.doi.org/10.1038/35023171 [view abstract]
By using the (14C)2-deoxyglucose method, inhibition has been shown to be a metabolically active process at the level of the synapse. This is supported by recent results from magnetic resonance spectroscopy that related the changes in neuroenergetics occurring with functional activation to neurotransmitter cycling. However, inhibitory synapses are less numerous and strategically better located than excitatory synapses, indicating that inhibition may be more efficient, and therefore less energy-consuming, than excitation. Here we test this hypothesis using event-related functional magnetic resonance imaging in volunteers whose motor cortex was inhibited during the no-go condition of a go/no-go task, as demonstrated by transcranial magnetic stimulation. Unlike excitation, inhibition evoked no measurable change in the blood-oxygenation-level-dependent signal in the motor cortex, indicating that inhibition is less metabolically demanding. Therefore, the ‘activation’ seen in functional imaging studies probably results from excitation rather than inhibition.
Björn Rasch, Steffen Gais, Jan Born
http://dx.doi.org/10.1038/npp.2009.6 [view abstract]
Rapid eye movement (REM) sleep has been considered important for the consolidation of memories, particularly of procedural skills. REM sleep, in contrast to slow-wave sleep (SWS), is hallmarked by the high, wake-like activity of the neurotransmitter acetylcholine (ACh), which promotes certain synaptic plastic processes underlying the formation of memories. Here, we show in healthy young men that off-line consolidation of a motor skill during a period of late sleep with high amounts of REM sleep depends essentially on high cholinergic activity. After a 3-h sleep period during the early night to satisfy the need for SWS, subjects learned a procedural finger sequence tapping task and a declarative word-pair learning task. After learning, they received either placebo or a combination of the muscarinic receptor antagonist scopolamine (4 μg/kg bodyweight, intravenously) and the nicotinic receptor antagonist mecamylamine (5 mg, orally), and then slept for another 3 h, ie, the late nocturnal sleep period, which is dominated by REM sleep. Retrieval was tested the following evening. Combined cholinergic receptor blockade significantly impaired motor skill consolidation, whereas word-pair memory remained unaffected. Additional data show that the impairing effect of cholinergic receptor blockade is specific to sleep-dependent consolidation of motor skill and does not occur during a wake-retention interval. Taken together, these results identify high cholinergic activity during late, REM sleep-rich sleep as an essential factor promoting sleep-dependent consolidation of motor skills.
G Bush, L M Shin, J Holmes, B R Rosen, B A Vogt
Molecular Psychiatry (2002)
http://dx.doi.org/10.1038/sj.mp.4001217 [view abstract]
Dorsal anterior cingulate cortex (dACC) plays critical roles in cognitive processing, but group-averaging techniques have generally been required to obtain significant dACC activation in functional neuroimaging studies. Development of a task that reliably and robustly activates dACC within individuals is needed to improve imaging studies of neuropsychiatric disorders and localization of dACC in normal volunteers. By combining sources of cognitive interference (Stroop, Eriksen and Simon) with factors known to increase dACC activity, the Multi-Source Interference Task (MSIT) maximally taxes dACC, making it possible to reliably activate dACC within individuals using functional magnetic resonance imaging (fMRI). In this study, eight normal adult volunteers performed the MSIT during fMRI. We compared fMRI responses and performance data between interference and control trials. Significant dACC activation (P<1.7×10−4) was observed in all eight individuals and in the group-averaged fMRI data. In addition to dACC activation, group data also showed activation of presumably networked regions including dorsolateral prefrontal, premotor, and parietal cortices. The MSIT's reaction time interference effect (overall mean 312±61 ms) was up to 10 times greater than that of its component predecessors and temporally stable over hundreds of trials. The robustness, reliability and stability of the neuroimaging and performance data should make the MSIT a useful task with which to study normal human cognition and psychiatric pathophysiology.
Julie Dumas, Catherine Hancur-Bucci, Magdalena Naylor, Cynthia Sites, Paul Newhouse
http://dx.doi.org/10.1038/sj.npp.1301042 [view abstract]
Estrogen has been shown to interact with the cholinergic system and influence cognition in animal models. This study investigated the interaction of estrogen and cholinergic system functioning and the effects of this interaction on cognitive task performance in healthy older women. Fifteen post-menopausal women were randomly and blindly placed on 1 mg of 17-β estradiol or placebo for 3 months after which they participated in five anticholinergic challenge sessions, where they were administered one of two doses of the antimuscarinic drug scopolamine (SCOP) or the antinicotinic drug mecamylamine (MECA) or placebo. After the first challenge phase, they were crossed over to the other hormone treatment for another 3 months and repeated the challenges. Performance in multiple domains of cognition was assessed during anticholinergic drug challenge, including attention and verbal and nonverbal learning and memory. Results showed that estrogen pretreatment attenuated the anticholinergic drug-induced impairments on tests of attention and tasks with speed components. This study is the first to demonstrate the interaction of estrogen and the cholinergic system and the effects on cognitive performance in humans. The results suggest that estrogen status may affect cholinergic system tone and may be important for cholinergic system integrity.
Sandra Chanraud, Anne-Lise Pitel, Torsten Rohlfing, Adolf Pfefferbaum, Edith V Sullivan
http://dx.doi.org/10.1038/npp.2010.56 [view abstract]
Controversy exists regarding the role of cerebellar systems in cognition and whether working memory compromise commonly marking alcoholism can be explained by compromise of nodes of corticocerebellar circuitry. We tested 17 alcoholics and 31 age-matched controls with dual-task, working memory paradigms. Interference tasks competed with verbal and spatial working memory tasks using low (three item) or high (six item) memory loads. Participants also underwent structural MRI to obtain volumes of nodes of the frontocerebellar system. On the verbal working memory task, both groups performed equally. On the spatial working memory with the high-load task, the alcoholic group was disproportionately more affected by the arithmetic distractor than were controls. In alcoholics, volumes of the left thalamus and left cerebellar Crus I volumes were more robust predictors of performance in the spatial working memory task with the arithmetic distractor than the left frontal superior cortex. In controls, volumes of the right middle frontal gyrus and right cerebellar Crus I were independent predictors over the left cerebellar Crus I, left thalamus, right superior parietal cortex, or left middle frontal gyrus of spatial working memory performance with tracking interference. The brain–behavior correlations suggest that alcoholics and controls relied on the integrity of certain nodes of corticocerebellar systems to perform these verbal and spatial working memory tasks, but that the specific pattern of relationships differed by group. The resulting brain structure–function patterns provide correlational support that components of this corticocerebellar system not typically related to normal performance in dual-task conditions may be available to augment otherwise dampened performance by alcoholics.
P Jäkälä, M Riekkinen, J Sirviö, E Koivisto, P Riekkinen
http://dx.doi.org/10.1016/S0893-133X(99)00048-2 [view abstract]
The present study compares the effects of two α2-adrenoceptor agonists, clonidine (0.5, 2, and 5 μg/kg, p.o.), and guanfacine (7 and 29 μg/kg, p.o.), in young healthy volunteers on attentional performance. A placebo-controlled double-blind cross-over design (one drug dose/group) was employed. Neither of the drugs affected measures of motor performance or performance at easy levels in an attentional test. However, at the most difficult level in the attentional test, the highest dose of clonidine (5 μg/kg), but not guanfacine, decreased the number of correct responses and increased reaction latency. Clonidine 5 and guanfacine 29 μg/kg equally increased subjective feelings of sedation and reduced systolic and diastolic blood pressures. Thus, the effects of the drugs on attentional performance could be dissociated from their sedative effects. The results demonstrate that clonidine, but not guanfacine, disrupts performance in an attentional task requiring effortful processing, while leaving performance intact in tests requiring more automatic processing. The lower α2A- vs. α2C-adrenoceptor selectivity ratio of clonidine and the affinity for α1-adrenoceptors of clonidine may be responsible for the different action of these drugs on attention.
Haiyan Wu, Xiaoqin Mai, Honghong Tang, Yue Ge, Yue-Jia Luo, Chao Liu
Scientific Reports (2013)
http://dx.doi.org/10.1038/srep02049 [view abstract]
The embodied view of language processing holds that language comprehension involves the recruitment of sensorimotor information, as evidenced by the somatotopic representation of action verbs in the motor system. However, this review has not yet been examined in logographic scripts such as Chinese, in which action verbs can provide explicit linguistic cues to the effectors (arm, leg, mouth) that conduct the action (hit, jump, drink). We compared the somatotopic representation of Chinese verbs that contain such effector cues and those that do not. The results showed that uncued verbs elicited similar somatotopic representation in the motor and premotor cortex as found in alphabetic scripts. However, effector-cued verbs demonstrated an inverse somatotopic pattern by showing reduced activation in corresponding motor areas, despite that effector-cued verbs actually are rated higher in imageability than uncued verbs. Our results support the universality of somatotopic representation of action verbs in the motor system.
Giacomo Rizzolatti, Leonardo Fogassi, Vittorio Gallese
Nature Reviews Neuroscience (2001)
http://dx.doi.org/10.1038/35090060 [view abstract]
What are the neural bases of action understanding? Although this capacity could merely involve visual analysis of the action, it has been argued that we actually map this visual information onto its motor representation in our nervous system. Here we discuss evidence for the existence of a system, the 'mirror system', that seems to serve this mapping function in primates and humans, and explore its implications for the understanding and imitation of action.
Ranulfo Romo, Emilio Salinas
Nature Reviews Neuroscience (2003)
http://dx.doi.org/10.1038/nrn1058 [view abstract]
Recent studies combining psychophysical and neurophysiological experiments in behaving monkeys have provided new insights into how several cortical areas integrate efforts to solve a vibrotactile discrimination task. In particular, these studies have addressed how neural codes are related to perception, working memory and decision making in this model. The primary somatosensory cortex drives higher cortical areas where past and current sensory information are combined, such that a comparison of the two evolves into a behavioural decision. These and other observations in visual tasks indicate that decisions emerge from highly-distributed processes in which the details of a scheduled motor plan are gradually specified by sensory information.
R. J. Seitz, C. Bohm, T. Greitz, P. E. Roland, L. Eriksson, G. Blomqvist, G. Rosenqvist, B. Nordell
Journal of Cerebral Blood Flow & Metabolism (1990)
http://dx.doi.org/10.1038/jcbfm.1990.87 [view abstract]
Summary: The computerized brain atlas programme (CBA) provides a powerful tool for the anatomical analysis of functional images obtained with positron emission tomography (PET). With a repertoire of simple transformations, the data base of the CBA is first adapted to the anatomy of the subject's brain represented as a set of magnetic resonance (MR) or computed tomography (CT) images. After this, it is possible to spatially standardize (reformat) any set of tomographic images related to the subject, PET images, as well as CT and MR images, by applying the inverse atlas transformations. From these reformatted images, statistical images, such as average images and associated error images corresponding to different groups of subjects, may be produced. In all these images, anatomical structures can be localized using the atlas data base and the functional values can be evaluated quantitatively. The purpose of this study was to determine the spatial and quantitative accuracy and precision of the calculated regional mean values. Therefore, the CBA was applied to regional CBF (rCBF) measurements with [11C]fluoromethane and PET on 26 healthy male volunteers during rest and during three different physiological stimulation tasks. First, the spatial accuracy and precision of the reformation process were determined by measuring the spread of defined anatomical structures in the reformatted MR images of the subjects. Second, the mean global CBF and the mean rCBF in the average PET images were compared with the global CBF and rCBF in the original PET images. Our results demonstrate that the reformation process accurately transformed the individual brains of the subjects into the standard brain anatomy of the CBA. The precision of the reformation process had an SD of ~1 mm for the lateral dislocation of midline structures and —2-3 mm for the dislocation of the inner and outer brain surfaces. The quantitative rCBF values of the original PET images were accurately represented in the reformatted PET images. Moreover, this study shows that the application of the CBA improves the analysis of functional PET images: (a) The average PET images had a low background noise [0.4 ml/100 g/min ± 0.7 (SD)] compared to the mean rCBF changes specifically induced by physiological stimulation, (b) The reformatted PET images had a voxel volume of 10.9 mm3. Owing to this high sampling resolution, it was possible to differentiate the mean rCBF changes in adjacent activated fields such as the left motor hand area from the sensory hand area and the left premotor cortex, (c) By calculating the relation of the mean rCBF change to the SEM of the mean rCBF change on a pixel-by-pixel basis, areas with significant rCBF changes could be determined. By use of the CBA, it was found that there was a high intersubject consistency in location of stimulation-induced rCBF changes. Furthermore, the rCBF changes in specifically stimulated areas were of similar magnitude among the subjects. It was shown that the stimulation-induced mean rCBF increases may be accompanied by mean rCBF decreases in other areas.
Reto Huber, M Felice Ghilardi, Marcello Massimini, Fabio Ferrarelli, Brady A Riedner, Michael J Peterson, Giulio Tononi
Nature Neuroscience (2006)
http://dx.doi.org/10.1038/nn1758 [view abstract]
Sleep slow wave activity (SWA) is thought to reflect sleep need, increasing after wakefulness and decreasing after sleep. We showed recently that a learning task involving a circumscribed brain region produces a local increase in sleep SWA. We hypothesized that increases in cortical SWA reflect synaptic potentiation triggered by learning. To further investigate the link between synaptic plasticity and sleep, we asked whether a procedure leading to synaptic depression would cause instead a decrease in sleep SWA. We show here that if a subject's arm is immobilized during the day, motor performance deteriorates and both somatosensory and motor evoked potentials decrease over contralateral sensorimotor cortex, indicative of local synaptic depression. Notably, during subsequent sleep, SWA over the same cortical area is markedly reduced. Thus, cortical plasticity is linked to local sleep regulation without learning in the classical sense. Moreover, when synaptic strength is reduced, local sleep need is also reduced.
Jeffrey A Kleim, Erin D Kleim, Steven C Cramer
Nature Protocols (2007)
http://dx.doi.org/10.1038/nprot.2007.206 [view abstract]
Measuring changes in the characteristics of corticospinal output has become a critical part of assessing the impact of motor experience on cortical organization in both the intact and injured human brain. In this protocol we describe a method for systematically assessing training-induced changes in corticospinal output that integrates volumetric anatomical MRI with transcranial magnetic stimulation (TMS). A TMS coil is sited to a target grid superimposed onto a 3D MRI of cortex using a stereotaxic neuronavigation system. Subjects are then required to exercise the first dorsal interosseus (FDI) muscle on two different tasks for a total of 30 min. The protocol allows for reliably and repeatedly detecting changes in corticospinal output to FDI muscle in response to brief periods of motor training.
Stéphane Thobois, Gary R Hotton, Serge Pinto, Leonora Wilkinson, Patricia Limousin-Dowsey, David J Brooks, Marjan Jahanshahi
Journal of Cerebral Blood Flow & Metabolism (2006)
http://dx.doi.org/10.1038/sj.jcbfm.9600425 [view abstract]
To investigate the effects of bilateral subthalamic nucleus (STN) stimulation on patterns of brain activation during random number generation (RNG), a task that requires suppression of habitual counting and response selection under competition. We used H215O positron emission tomography to investigate the changes of regional cerebral blood flow (rCBF) induced by bilateral STN stimulation during a RNG task, in six patients with Parkinson's disease. Paced RNG at 1 Hz was compared with a control counting task. Both tasks were performed off medication with deep brain stimulation on and off. Subthalamic nucleus stimulation had a negative effect on performance of fast-paced RNG, leading to reduced randomness and increased habitual counting. Subthalamic nucleus stimulation also induced a reduction of rCBF in the left dorsal frontal gyrus, inferior frontal gyrus, dorsolateral prefrontal cortex, posterior and right anterior cingulate, and an increase of rCBF in the right internal globus pallidum (GPi) during RNG. Stimulation of the STN significantly altered pallidal coupling with frontal and temporal areas compared with when the stimulators were off. In conclusion, during RNG: (i) STN stimulation activates its output neurons to the GPi; (ii) STN stimulation induces increased inhibition of a prefrontal–cingulate network. This is the first direct evidence that STN stimulation significantly alters pallidal coupling with prefrontal, cingulate, and temporal cortices during performance of a task that requires response selection under competition.
Elke Wezenberg, Robert Jan Verkes, Ge S F Ruigt, Wouter Hulstijn, Bernard G C Sabbe
http://dx.doi.org/10.1038/sj.npp.1301257 [view abstract]
Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place 1 h after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning and picture memory), working and short-term memory (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the continuous trail making test (CTMT). Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. Furthermore, it tended to decrease the number of switching errors in the CTMT. Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. The positive results on short-term memory and the favorable trends in the trail making test (CTMT) are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia.
Jonathan L Brigman, Rachel A Daut, Tara Wright, Ozge Gunduz-Cinar, Carolyn Graybeal, Margaret I Davis, Zhihong Jiang, Lisa M Saksida, Seiichiro Jinde, Matthew Pease, Timothy J Bussey, David M Lovinger, Kazu Nakazawa, Andrew Holmes
Nature Neuroscience (2013)
http://dx.doi.org/10.1038/nn.3457 [view abstract]
A choice that reliably produces a preferred outcome can be automated to liberate cognitive resources for other tasks. Should an outcome become less desirable, behavior must adapt in parallel or it becomes perseverative. Corticostriatal systems are known to mediate choice learning and flexibility, but the molecular mechanisms of these processes are not well understood. We integrated mouse behavioral, immunocytochemical, in vivo electrophysiological, genetic and pharmacological approaches to study choice. We found that the dorsal striatum (DS) was increasingly activated with choice learning, whereas reversal of learned choice engaged prefrontal regions. In vivo, DS neurons showed activity associated with reward anticipation and receipt that emerged with learning and relearning. Corticostriatal or striatal deletion of Grin2b (encoding the NMDA-type glutamate receptor subunit GluN2B) or DS-restricted GluN2B antagonism impaired choice learning, whereas cortical Grin2b deletion or OFC GluN2B antagonism impaired shifting. Our convergent data demonstrate how corticostriatal GluN2B circuits govern the ability to learn and shift choice behavior.
Tom A Schweizer, Muriel Vogel-Sprott, James Danckert, Eric A Roy, Amanda Skakum, Carole E Broderick
http://dx.doi.org/10.1038/sj.npp.1300941 [view abstract]
Numerous studies have investigated the effects of alcohol on motor processes during rising and declining blood alcohol concentrations (BAC), however, relatively little research has examined the alcohol-induced impairment of cognitive performance on the two limbs of the BAC curve. This experiment administered a neuropsychological test battery to assess the degree to which rising and declining BACs during an acute dose of alcohol impair nine cognitive processes within an individual. In all, 20 healthy male social drinkers (university students) were assigned to one of two groups (n=10) who received a beverage containing either 0.0 g/kg (placebo) or 0.65 g/kg alcohol and performed the test battery when BAC was increasing and was decreasing. Comparisons of alcohol and placebo groups revealed impairment (slower response and/or increased errors) in seven of the cognitive processes: long-term verbal memory; information processing; declarative memory; inhibitory control; short-term visual memory; long-term visual memory, and visual-spatial working memory. However, some processes were impaired only during rising BACs whereas the impairment of others during declining BACs was evident only by an increase in errors. These results show cognitive tasks performed by an individual are not similarly affected by rising and declining BACs, and call attention to the importance of assessing both speed and accuracy on both limbs of the BAC curve. The particular cognitive processes differentially affected by rising vs declining BACs raised the possibility that acute alcohol intoxication may impair one cerebral hemisphere to a greater degree than the other, and this could be explored by neuroimaging techniques.
Christopher D Verrico, Shijing Liu, Elizabeth J Bitler, Hong Gu, Allan R Sampson, Charles W Bradberry, David A Lewis
http://dx.doi.org/10.1038/npp.2011.321 [view abstract]
Among adolescents, the perception that cannabis can cause harm has decreased and use has increased. However, in rodents, cannabinoid administration during adolescence induces working memory (WM) deficits that are more severe than if the same exposure occurs during adulthood. As both object and spatial WM mature in a protracted manner, although apparently along different trajectories, adolescent cannabis users may be more susceptible to impairments in one type of WM. Here, we evaluate the acute effects of a range of doses (30–240 μg/kg) of intravenous Δ9-tetrahydrocannabinol (THC) administration on the performance of spatial and object WM tasks in adolescent rhesus monkeys. Accuracy on the object WM task was not significantly affected by any dose of THC. In contrast, THC administration impaired accuracy on the spatial WM task in a delay- and dose-dependent manner. Importantly, the THC-induced spatial WM deficits were not because of motor or motivational impairments. These data support the idea that immature cognitive functions are more sensitive to the acute effects of THC.
Suzanne Vrshek-Schallhorn, Dustin Wahlstrom, Kelly Benolkin, Tonya White, Monica Luciana
http://dx.doi.org/10.1038/sj.npp.1301172 [view abstract]
Acute phenylalanine/tyrosine depletion (ATPD) has been used to transiently lower central nervous system dopamine activity in animals and humans. Findings suggest that ATPD may impact dopamine transmission in limbic and striatal regions. Impact on cognitive functions has varied across studies, although several recent reports suggest that affective processing in the context of a go/no-go response control task may be impaired during ATPD. In this study, response control under affective vs nonaffective conditions was examined in healthy individuals who underwent either ATPD or a balanced condition in a between-subjects design. Effects of ATPD were validated through its effects on serum prolactin secretion. ATPD resulted in significantly increased prolactin levels relative to the balanced mixture. Although there were no differences in self-reported mood between the groups, individuals in the ATPD condition demonstrated diminished sensitivity to positively valenced words and seemingly enhanced sensitivity to negatively valenced words in an affective go/no-go task. They also showed difficulties in modulating ongoing behavior in a nonaffective go/no-go task when responses had to be intermittently inhibited then immediately restarted. Basic motor functions were not impacted. Findings are discussed in relation to dopamine's role in switching signals within neural networks that are important for response modulation and affective control.
Johannes G Ramaekers, Kim P C Kuypers, Marleen Wingen, Armin Heinecke, Elia Formisano
http://dx.doi.org/10.1038/npp.2008.219 [view abstract]
Prospective memory refers to the realization of delayed intentions. Several studies have shown that 3,4-methylenedioxy-methamphetamine (MDMA) users perform worse on measures of prospective memory as compared to nondrug users. Interpretation of these data may be limited because of polydrug use, psychosocial stressors, and increased psychopathology that have been reported in MDMA users. This study was designed to directly assess the pharmacological effect of MDMA on prospective memory and brain activity in a double-blind, placebo-controlled, cross-over study. Twelve recreational MDMA users received MDMA 75 mg and placebo and performed an objective prospective memory task during functional imaging. During prospective memory task performance subjects were engaged in a foreground task that consisted of a simple reaction time to visual stimuli (Go trials) and a prospective task of withholding a response during trials that were part of a dynamic memory set (No go trials). Behavioral data showed that a single dose of MDMA increased prospective memory failures in the No go trials, and that number of prospective memory failures was positively correlated to MDMA concentration in plasma. Functional imaging showed that MDMA decreased BOLD activation during Go trials in the thalamus (left), putamen (left), precuneus (left), and the inferior parietal lobules (bilateral), as compared to placebo. During No go trials, MDMA reduced BOLD deactivation in the inferior parietal lobules (bilateral), as compared to placebo. It is concluded that the loss of deactivation in inferior parietal lobules may account for increments in memory failures observed during MDMA intoxication.
Matteo Pardini, Laura Bonzano, Luca Roccatagliata, Giovanni L. Mancardi, Marco Bove
Scientific Reports (2013)
http://dx.doi.org/10.1038/srep02001 [view abstract]
Subjective fatigue is a typical symptom in Multiple Sclerosis (MS) even in the earliest stages of the disease. The relationship between persistent fatigue and motor task performance is still unclear. Aim of this study was to better investigate this relationship at both the motor behavioral and neuroanatomical levels. Towards this goal, we combined a quantitative evaluation of an undemanding finger motor task with concurrent brain functional magnetic resonance imaging (fMRI) in a group of MS patients with minimal disability but reporting persistent subjective fatigue. We found an unexpected significant positive correlation between persistent subjective fatigue and task-related temporal accuracy, revealing a “fatigue-motor performance paradox”. fMRI analysis indicated that this association is potentially mediated by cerebellar and orbitofrontal cortex activity, suggesting a role of these regions in developing subjective fatigue. Our data point to a possible adaptive role for fatigue as the subjective correlate of increased resource demand for motor activities.
Hiroshi Ito, Masanobu Ibaraki, Iwao Kanno, Hiroshi Fukuda, Shuichi Miura
Journal of Cerebral Blood Flow & Metabolism (2005)
http://dx.doi.org/10.1038/sj.jcbfm.9600030 [view abstract]
The discrepancy between the increases in cerebral blood flow (CBF) and CMRO2 during neural activation causes an increase in venous blood oxygenation and, therefore, a decrease in paramagnetic deoxyhemoglobin concentration in venous blood. This can be detected by functional magnetic resonance imaging (fMRI) as blood oxygenation level-dependent (BOLD) contrast. In the present study, changes in the cerebral oxygen extraction fraction (OEF) that corresponds to the ratio of CMRO2 to CBF, and in the BOLD signal during neural activation, were measured by both positron emission tomography (PET) and fMRI in the same human subjects. C15O, 15O2, and H215O PET studies were performed in each subject at rest (baseline) and during performance of a right-hand motor task. Functional magnetic resonance imaging studies were then performed to measure the BOLD signal under the two conditions. During performance of the motor task, a significant increase in CBF and a significant decrease in OEF were observed in the left precentral gyrus, left superior frontal gyrus, right precentral gyrus, right cingulate gyrus, and right cerebellum. A significant positive correlation was observed between changes in the CBF and the BOLD signal, and a significant negative correlation was observed between changes in the OEF and the BOLD signal. This supports the assumption on which BOLD contrast studies during neural activation are based.
Rony Paz, Thomas Boraud, Chen Natan, Hagai Bergman, Eilon Vaadia
Nature Neuroscience (2003)
http://dx.doi.org/10.1038/nn1097 [view abstract]
In humans, learning to produce correct visually guided movements to adapt to new sensorimotor conditions requires the formation of an internal model that represents the new transformation between visual input and the required motor command. When the new environment requires adaptation to directional errors, learning generalizes poorly to untrained locations and directions, indicating that such learning is local. Here we replicated these behavioral findings in rhesus monkeys using a visuomotor rotation task and simultaneously recorded neuronal activity. Specific changes in activity were observed only in a subpopulation of cells in the motor cortex with directional properties corresponding to the locally learned rotation. These changes adhered to the dynamics of behavior during learning and persisted between learning and relearning of the same rotation. These findings suggest a neural mechanism for the locality of newly acquired sensorimotor tasks and provide electrophysiological evidence for their retention in working memory.