Peter van Ruitenbeek

High-Potency Marijuana Impairs Executive Function and Inhibitory Motor Control

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.

Individual differences in brainstem and basal ganglia structure predict postural control and balance loss in young and older adults

It remains unclear which specific brain regions are the most critical for human postural control and balance, and whether they mediate the effect of age. Here, associations between postural performance and corticosubcortical brain regions were examined in young and older adults using multiple structural imaging and linear mixed models. Results showed that of the regions involved in posture, the brainstem was the strongest predictor of postural control and balance: lower brainstem volume predicted larger center of pressure deviation and higher odds of balance loss. Analyses of white and gray matter in the brainstem showed that the pedunculopontine nucleus area appeared to be critical for postural control in both young and older adults. In addition, the brainstem mediated the effect of age on postural control, underscoring the brainstems fundamental role in aging. Conversely, lower basal ganglia volume predicted better postural performance, suggesting an association between greater neural resources in the basal ganglia and greater movement vigor, resulting in exaggerated postural adjustments. Finally, results showed that practice, shorter height and heavier weight (i.e., higher body mass index), higher total physical activity, and larger ankle active (but not passive) range of motion were predictive of more stable posture, irrespective of age.

Subcortical volumetric changes across the adult lifespan: Subregional thalamic atrophy accounts for age-related sensorimotor performance declines

Even though declines in sensorimotor performance during healthy aging have been documented extensively, its underlying neural mechanisms remain unclear. Here, we explored whether age-related subcortical atrophy plays a role in sensorimotor performance declines, and particularly during bimanual manipulative performance (Purdue Pegboard Test). The thalamus, putamen, caudate and pallidum of 91 participants across the adult lifespan (ages 20-79 years) were automatically segmented. In addition to studying age-related changes in the global volume of each subcortical structure, local deformations within these structures, indicative of subregional volume changes, were assessed by means of recently developed shape analyses. Results showed widespread age-related global and subregional atrophy, as well as some notable subregional expansion. Even though global atrophy failed to explain the observed performance declines with aging, shape analyses indicated that atrophy in left and right thalamic subregions, specifically subserving connectivity with the premotor, primary motor and somatosensory cortical areas, mediated the relation between aging and performance decline. It is concluded that subregional volume assessment by means of shape analyses offers a sensitive tool with high anatomical resolution in the search for specific age-related associations between brain structure and behavior.

Whole-brain grey matter density predicts balance stability irrespective of age and protects older adults from falling

Functional and structural imaging studies have demonstrated the involvement of the brain in balance control. Nevertheless, how decisive grey matter density and white matter microstructural organisation are in predicting balance stability, and especially when linked to the effects of ageing, remains unclear. Standing balance was tested on a platform moving at different frequencies and amplitudes in 30 young and 30 older adults, with eyes open and with eyes closed. Centre of pressure variance was used as an indicator of balance instability. The mean density of grey matter and mean white matter microstructural organisation were measured using voxel-based morphometry and diffusion tensor imaging, respectively. Mixed-effects models were built to analyse the extent to which age, grey matter density, and white matter microstructural organisation predicted balance instability. Results showed that both grey matter density and age independently predicted balance instability. These predictions were reinforced when the level of difficulty of the conditions increased. Furthermore, grey matter predicted balance instability beyond age and at least as consistently as age across conditions. In other words, for balance stability, the level of whole-brain grey matter density is at least as decisive as being young or old. Finally, brain grey matter appeared to be protective against falls in older adults as age increased the probability of losing balance in older adults with low, but not moderate or high grey matter density. No such results were observed for white matter microstructural organisation, thereby reinforcing the specificity of our grey matter findings.

Nucleus accumbens and caudate atrophy predicts longer action selection times in young and old adults

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.

Alterations in brain white matter contributing to age-related slowing of task switching performance: The role of radial diffusivity and magnetization transfer ratio

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.

Antihistamine induced blood oxygenation level dependent response changes related to visual processes during sensori‐motor performance

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. Hum Brain Mapp 35:3095–3106, 2014.