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Agingisassociatedwithchangesinthecentralnervoussystemandleadsto reducedlifequality.Here,weinvestigatedtheage-relateddifferencesinthe CNSunderlyingmotorperformancedeficitsusingmagneticresonancespectroscopyanddiffusionMRI.MRSmeasuredN-acetylaspartate(NAA),choline(Cho), andcreatine(Cr)concentrationsinthesensorimotorandoccipitalcortex, whereasdMRIquantifiedapparentfiberdensity(FD)inthesamevoxelstoevaluatewhitemattermicrostructuralorganization.WefoundthatagingwasassociatedwithincreasedreactiontimeandreducedFDandNAAconcentrationinthe sensorimotorvoxel.BothFDandNAAmediatedtheassociationbetweenage andreactiontime.TheNAAconcentrationwasfoundtomediatetheassociation betweenageandFDinthesensorimotorvoxel.Weproposethattheage-related decreaseinNAAconcentrationmayresultinreducedaxonalfiberdensityinthe sensorimotorcortexwhichmayultimatelyaccountfortheresponseslownessof olderparticipants. Wethankallparticipantsfortakingpartinthisstudy,PaulMeugensfortaskdeviceconstruction,andRene´ Clerckxforprogrammingthebehavioraltask.ThisworkwassupportedbytheResearchFoundationFlanders(G089818N,K174216N),theExcellenceSciencegrant(EOS,30446199,MEMODYN),andtheKU LeuvenResearchFund(C16/15/070).

Currently, the assessment of the neurobehavioral consequences of repeated cannabis use is restricted to studies in which brain function of chronic cannabis users is compared to that of non-cannabis using controls. The assumption of such studies is that changes in brain function of chronic users are caused by repeated and prolonged exposure to acute cannabis intoxication. However, differences in brain function between chronic cannabis users and non-users might also arise from confounding factors such as polydrug use, alcohol use, withdrawal, economic status, or lifestyle conditions. We propose a methodology that highlights the relevance of acute Δ

Being exposed to acute stress may cause people to behave more habitual, which purportedly is associated stress-induced increased dopamine release. In contrast, experimental rises in systemic dopamine levels have been shown to increase goal-directed behaviour and, thus, decrease habitual control. Whether experimentally increased dopamine functioning can modulate stress-induced reductions in goal-directed behaviour and its neural substrates, is currently unknown. To assess whether increased dopamine functioning reduces stress effects on goal-directed behaviour, 100 participants were recruited who were randomly assigned to one of four conditions in a 2x2 between participants design. Participants underwent a stress induction protocol (Maastricht Acute Stress Test; MAST) or a control procedure and received methylphenidate (40 mg, oral) or placebo. In a well-established instrumental learning paradigm, participants were trained to learn stimulus-response-outcome associations, after which rewards were selectively devalued and participants’ goal-directed behaviour was assessed at peak cortisol/methylphenidate concentrations in a magnetic resonance imaging scanner to assess brain activation. The MAST effectively increased physiological measures of stress (salivary cortisol, blood pressure) and subjective stress. Methylphenidate also increased cortisol levels over time. While stress selectively reduced goal-directed behaviour, this effect was not modulated by methylphenidate. However, methylphenidate modulated stress effects on activation in paracingulate, orbitofrontal cortex, and anterior cingulate associated with expected value representation in goal-directed behaviour. Our neuroimaging data suggest increased dopamine levels reverse stress-induced changes in brain activation associated with goal-directed behaviour. These effects may be relevant for preventing stress-induced relapse in addictive behaviour.

Contract grant sponsor: Research Fund of KU Leuven, Belgium; Contract grant number: OT/11/071; Contract grant sponsor: Flanders Fund for Scientific Research; Contract grant numbers: G0721.12 and G0708.14; Contract grant sponsor: Inter-university Attraction Poles Program of the Belgian Federal Government; Contract grant number: Grant P7/11; Contract grant sponsor: Research Foundation-Flanders (FWO); Contract grant sponsor: VIDI Grant from the Netherlands Organization for Scientific Research (NWO); Contract grant number: 639.072.411.

There is a convergence in the literature toward a critical role for the basal ganglia in action selection. However, which substructures within the basal ganglia fulfill this role is still unclear. Here we used shape analyses of structural magnetic resonance imaging data to determine the extent to which basal ganglia structures predict performance in easy and complex multilimb reaction-time tasks in young and old adults. Results revealed that inward deformation (i.e., local atrophy) of the nucleus accumbens and caudate were predictive of longer action selection times in complex conditions, but not in easy conditions. Additionally, when assessing the relation between behavioral performance and the shape of the left nucleus accumbens in the two age groups separately, we found a significant performance–structure association in old, but not young adults. This result suggests that the relevance of the nucleus accumbens for the process of action selection increases with age. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.

Background and PurposeCognitive deficits including impaired working memory are a hallmark feature of schizophrenia. Changes in prefrontal cortex function modulated by dopamine D1 receptors, play a potentially important role in the pathology underlying such deficits. However, pharmacological interventions that selectively engage the D1 receptor are severely restricted for research in humans. The present study is a proof-of-principle for enhancing cognitive performance and associated brain activation via indirect D1 stimulation. Here, we combine the non-selective dopamine agonist L-dopa with the D2-antagonist haloperidol, theoretically producing increased stimulation at the D1 receptor.Experimental ApproachFourteen healthy volunteers received placebo or combined carbidopa (125 mg, 100mg L-dopa) plus haloperidol (2 mg) orally on two separate occasions according to a within-subjects cross-over design. Drug-induced differences in brain activity were assessed during an N-back working memory task in a 3T magnetic resonance imaging environment.Key ResultsDrug treatment was associated with a reduction in activity in a large number of brain areas, most prominently occipital/temporal brain areas during 2-back performance, which may be due to the effects of haloperidol specifically. Drug treatment was also associated with greater functional connectivity within parts of the salience network during all N-back trials.Conclusion and ImplicationsThis preliminary study provides initial evidence for combined L-dopa/haloperidol modulation in cognition-related brain areas and networks, which is relevant for the treatment of cognitive impairments in mental illness.

The histaminergic involvement in selective processes underlying its role in human sensori-motor performance is largely unknown. Recently, selective effects of central H₁-inverse agonism on sensory visual processes were observed in electrophysiological--but not behavioral data; a discrepancy suggested to result from speeded response-choice related processes. This study attempts to establish the effects on visual processes and identify putative compensatory mechanisms related to increased visual and response-choice task demands by assessing H₁-inverse agonism induced changes in blood oxygenation level dependent (BOLD) response. Twelve participants received oral doses of dexchlorpheniramine 4 mg, lorazepam 1 mg, and placebo in a three-way crossover designed study. Brain activity was assessed for choice reaction time task performance in a 3 T magnetic resonance scanner 2 h after drug administration. Participants responded with their left or right hand and index or middle finger as indicated by the laterality of stimulus presentation and identity of the stimulus, respectively. Stimuli were intact or visually degraded and responses were compatible or incompatible with the laterality of stimulus presentation. Both dexchlorpheniramine and lorazepam affected the BOLD response in the occipital cortex indicating affected visual information processing. Dexchlorpheniramine decreased BOLD response in the dorsal precuneus and left precentral gyrus as part of a motor network, which however might not be interpreted as a compensatory mechanism, but may be the upstream consequence of impaired visual processing.

There is a convergence in the literature toward a critical role for the basal ganglia in action selection. However, which substructures within the basal ganglia fulfill this role is still unclear. Here we used shape analyses of structural magnetic resonance imaging data to determine the extent to which basal ganglia structures predict performance in easy and complex multilimb reaction‐time tasks in young and old adults. Results revealed that inward deformation (i.e., local atrophy) of the nucleus accumbens and caudate were predictive of longer action selection times in complex conditions, but not in easy conditions. Additionally, when assessing the relation between behavioral performance and the shape of the left nucleus accumbens in the two age groups separately, we found a significant performance–structure association in old, but not young adults. This result suggests that the relevance of the nucleus accumbens for the process of action selection increases with age. Hum Brain Mapp 37:4629–4639, 2016. © 2016 Wiley Periodicals, Inc.

Declines in both cortical grey matter and bimanual coordination performance are evident in healthy ageing. However, the relationship between ageing, bimanual performance, and grey matter loss remains unclear, particularly across the whole adult lifespan. Therefore, participants (N = 93, range 20-80 years) performed a complex Bimanual Tracking Task, and structural brain images were obtained using magnetic resonance imaging. Analyses revealed that age correlated negatively with task performance. Voxel-based morphometry analysis revealed that age was associated with grey matter declines in task-relevant cortical areas and that grey matter in these areas was negatively associated with task performance. However, no evidence for a mediating effect of grey matter in age-related bimanual performance decline was observed. We propose a new hypothesis that functional compensation may account for the observed absence of mediation, which is in line with the observed pattern of increased inter-individual variance in performance with age.

Rationale Alprazolam extended-release (XR) is approved for the treatment of panic disorder. This sustained formulation is absorbed in a delayed manner and is therefore expected to produce fewer and less severe side effects than its immediate release equivalent (alprazolam IR). The effect of alprazolam XR on potentially dangerous daily activities, such as driving a car, is expected to be less as compared to alprazolam IR. Objectives The present study was designed to compare the effects of alprazolam XR (1 mg) and alprazolam IR (1 mg) on actual driving ability and cognitive function. Method Eighteen healthy volunteers (aged 20-45 years) participated in a double-blind, placebo-controlled, three-way crossover study. At 4 h post-dose, subjects performed a standardized driving test on a primary highway in normal traffic. Cognitive and psychomotor tests were assessed 1, 2.5, and 5.5 h post-dose. Memory functioning was measured only 1 h after administration. Results Both formulations severely impaired driving performance between 4 and 5 h after administration. The magnitude of impairment in the driving test observed with alprazolam XR was about half that observed with alprazolam IR. Laboratory test results were in line with the driving data. Conclusions The acute impairing effects of alprazolam XR 1 mg on driving and psychomotor functions were generally less, as compared to its immediate-release equivalent, but still of sufficient magnitude to increase the risk of becoming involved in traffic accidents.

Successfully switching between tasks is critical in many daily activities. Age‐related slowing of this switching behavior has been documented extensively, but the underlying neural mechanisms remain unclear. Here, we investigated the contribution of brain white matter changes associated with myelin alterations to age‐related slowing of switching performance. Diffusion tensor imaging derived radial diffusivity (RD) and magnetization transfer imaging derived magnetization transfer ratio (MTR) were selected as myelin sensitive measures. These metrics were studied in relation to mixing cost (i.e., the increase in reaction time during task blocks that require task switching) on a local‐global switching task in young (n = 24) and older (n = 22) adults. Results showed that higher age was associated with widespread increases in RD and decreases in MTR, indicative of white matter deterioration, possibly due to demyelination. Older adults also showed a higher mixing cost, implying slowing of switching performance. Finally, mediation analyses demonstrated that decreases in MTR of the bilateral superior corona radiata contributed to the observed slowing of switching performance with increasing age. These findings provide evidence for a role of cortico‐subcortical white matter changes in task switching performance deterioration with healthy aging. Hum Brain Mapp 37:4084–4098, 2016. © 2016 Wiley Periodicals, Inc.

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 microg/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 x Time after smoking interaction. Effect sizes for performance impairments produced by THC 250 microg/kg were relatively low but generally increased by a factor of two in case of THC 500 microg/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.

Introduction Les correlats cerebraux de la stabilite posturale ont ete largement etudies. Cependant, au regard des resultats, l’ensemble du cerveau semble contribuer a cette performance. Dans cet ensemble, nous avons cherche a determiner quelles structures cerebrales jouaient un role plus preponderant que les autres pour nous maintenir debout. Materiel et methodes Des adultes jeunes et âges ont realise des tâches posturales statiques et dynamiques sur une plateforme de force qui oscillait autour d’un axe transversal a differentes frequences et amplitudes. Le deplacement du centre des pressions etait utilise comme variable dependante et les indicateurs cerebraux resultants de differents types d’analyses d’imagerie structurelle etaient utilises comme predicteurs dans des modeles lineaires mixtes. Resultats Les resultats montrent que parmi toutes les regions qui liees au controle de la posture, le tronc cerebral est le plus fort predicteur de la stabilite posturale. Specifiquement, un plus petit volume etait associe a une moins bonne stabilite. Inversement, un plus petit volume des ganglions de la base etait associe a une meilleure stabilite posturale. Discussion–conclusion Ces resultats soulignent le role fondamental du tronc cerebral dans le controle de la stabilite posturale alors que de plus grandes ressources neurales au niveau des ganglions de la base pourraient etre associees a une vigueur de mouvement plus importante provoquant des ajustements posturaux exageres.

The histaminergic involvement in selective processes underlying its role in human sensori‐motor performance is largely unknown. Recently, selective effects of central H(1)‐inverse agonism on sensory visual processes were observed in electrophysiological—but not behavioral data; a discrepancy suggested to result from speeded response‐choice related processes. This study attempts to establish the effects on visual processes and identify putative compensatory mechanisms related to increased visual and response‐choice task demands by assessing H(1)‐inverse agonism induced changes in blood oxygenation level dependent (BOLD) response. Twelve participants received oral doses of dexchlorpheniramine 4 mg, lorazepam 1 mg, and placebo in a three‐way crossover designed study. Brain activity was assessed for choice reaction time task performance in a 3 T magnetic resonance scanner 2 h after drug administration. Participants responded with their left or right hand and index or middle finger as indicated by the laterality of stimulus presentation and identity of the stimulus, respectively. Stimuli were intact or visually degraded and responses were compatible or incompatible with the laterality of stimulus presentation. Both dexchlorpheniramine and lorazepam affected the BOLD response in the occipital cortex indicating affected visual information processing. Dexchlorpheniramine decreased BOLD response in the dorsal precuneus and left precentral gyrus as part of a motor network, which however might not be interpreted as a compensatory mechanism, but may be the upstream consequence of impaired visual processing. Hum Brain Mapp 35:3095–3106, 2014. © 2013 Wiley Periodicals, Inc.