Catherine Orr

Neuropsychosocial profiles of current and future adolescent alcohol misusers

A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.

Magical ideation and its relation to lateral preference

Schizophrenia and schizotypal personality have been linked to sinistrality as well as ambidextrality. The current study clarifies the relation between laterality and schizotypal personality by administering a battery of laterality questionnaires to measure hand, eye, ear, and foot preference in a group of 933 university students. To determine whether the relationship between schizotypy and laterality is limited to self-report measures, performance asymmetries between the hands were measured with tapping rate. There was no difference between dextrals and sinistrals in schizotypal personality, as indexed by the Magical Ideation (MI) scale. MI was higher, however, for individuals with a weak preference for either hand or eye compared to those with a strong dominance. In addition, individuals inconsistent in their lateral preference across modalities showed higher MI scores. Performance asymmetries had no effect on MI scores. This lack of effect was attributed to the inability of performance measures, such as tapping rate, to identify ambidextrals. The results support research linking schizotypal personality to ambidextrality and weak cerebral dominance and demonstrate that the association extends to modalities other than hand preference.

Altered resting-state connectivity in adolescent cannabis users

Abstract Background: Cannabis is the most commonly used illicit drug in adolescence. Heavy use is associated with deficits on a broad range of cognitive functions and heavy use during adolescence may impact development of gray and white matter. Objectives: To examine differences in intrinsic brain activity and connectivity associated with cannabis dependence in adolescence using whole-brain voxelwise approaches. Methods: Adolescents admitted to a drug-treatment facility for cannabis dependence (n = 17) and age-matched controls (n = 18) were compared on a measure of oscillations in the low-frequency blood oxygen level-dependent signal at rest (the fractional amplitude of low-frequency fluctuations fALFF, 0.01–0.1 Hz) and interhemispheric resting-state functional connectivity (RSFC) using voxel-mirrored homotopic connectivity. Results: The cannabis-dependent population showed increased fALFF activity compared to the control group in right hemisphere regions including the superior parietal gyrus, superior frontal gyrus, inferior frontal gyrus, inferior semilunar lobe of the cerebellum and the inferior temporal gyrus. Post-hoc analyses revealed stronger intra-hemispheric functional connectivity between these functionally defined regions of interest (ROIs) in the cannabis-dependent population than in the controls. Reduced interhemispheric connectivity was observed in the cannabis users compared to controls in the pyramis of the cerebellum and the superior frontal gyrus. Controls showed reduced interhemispheric connectivity compared to users in the supramarginal gyrus. Conclusions: The reduced interhemispheric RSFC in adolescent cannabis users complements previous reports of white matter deficits associated with cannabis use. The evidence of elevated connectivity within the right hemisphere may reflect a compensatory mechanism. Combined, the results suggest that altered intrinsic connectivity may be characteristic of adolescent cannabis dependence.

A new means of measuring index/ring finger (2D:4D) ratio and its association with gender and hand preference

Relative finger length can predict a persons gender or their hand preference. We measured finger length using a new “tubes” test, which required participants to slide a clear plastic tube over their fingers and read the length from an attached mm scale. Data collected from 600 students demonstrated that the right fingers are longer than the left for dextrals, but not for non-dextrals. Examination of the relative length of the index and ring fingers revealed a clear gender effect. There was also an effect of hand preference on index/ring finger ratio whereby non-dextrals showed a more masculine pattern compared to dextrals. For non-dextrals, prenatal exposure to high testosterone levels may have caused both a shift away from dextrality and a more masculine pattern of finger ratio. In the second experiment, finger length was measured by the tubes test and by photocopying the hands in 124 undergraduates. The tubes test yielded a longer estimate of ring finger length compared to the photocopy method. Despite this, there was a strong correlation between the tests and both showed an association with gender. Finally, test–retest scores for 45 participants showed a high level of reliability for absolute and relative finger measures. We conclude that the tubes technique provides an effective and easy-to-use means of measuring finger length, which can be administered in a classroom setting.

Error-related anterior cingulate cortex activity and the prediction of conscious error awareness

Research examining the neural mechanisms associated with error awareness has consistently identified dorsal anterior cingulate cortex (ACC) activity as necessary but not predictive of conscious error detection. Two recent studies (Steinhauser and Yeung, 2010; Wessel et al., 2011) have found a contrary pattern of greater dorsal ACC (dACC) activity [in the form of the error-related negativity (ERN)] during detected errors, but suggested that the greater activity may instead reflect task influences (e.g., response conflict, error probability) and or individual variability (e.g., statistical power). We re-analyzed fMRI BOLD data from 56 healthy participants who had previously been administered the Error Awareness Task (EAT), a motor Go/No-go response inhibition task in which subjects make errors of commission of which they are aware (Aware errors), or unaware (Unaware errors). Consistent with previous data, the activity in a number of cortical regions was predictive of error awareness, including bilateral inferior parietal and insula cortices, however, in contrast to previous studies, including our own smaller sample studies using the same task, error-related dACC activity was significantly greater during aware errors when compared to unaware errors. While the significantly faster RT for aware errors (compared to unaware) was consistent with the hypothesis of higher response conflict increasing ACC activity, we could find no relationship between dACC activity and the error RT difference. The data suggests that error awareness is associated with error-related dACC activity but that the role of this activity is probably best understood in relation to the activity in other regions. Activity in the dACC may be important to conscious error detection, but it remains unclear what task and individual factors influence error awareness.

Rightward collisions and their association with pseudoneglect

Whereas right parietal damage can result in left hemineglect, the general population shows a subtle neglect of the right hemispace-known as pseudoneglect. A recent study has demonstrated that people collide to the right more often and attributed this bias to pseudoneglect. [Nicholls, M. E. R., Loftus, A., Meyer, K., & Mattingley, J.B. (2007). Things that go bump in the right: The effect of unimanual activity on rightward collisions. Neuropsychologia, 45, 1122-1126]. Nicholls examined the effect of unimanual activation by requiring participants to fire projectiles at a target whilst walking and found that the rightward bias was exaggerated or reversed when the left and right hands were active, respectively. However, the act of aiming at a target may have inadvertently biased walking trajectory to the right. The current study addressed this issue by requiring participants (n=149) to walk through a narrow doorway three times whilst entering text into a phone using the (a) left, (b) right or (c) both hands. Despite the fact that entering text into a phone should produce no rightward bias, participants bumped to the right more often. Unlike previous research, no effect of unimanual activation was observed. This lack of effect was attributed to the smaller hand movements for entering numbers compared to firing a toy gun. Finally, this study showed an association for the first time between biases in observable bumping and line bisection performance-suggesting that unilateral bumping is related to pseudoneglect.

The nature and contribution of space- and object-based attentional biases to free-viewing perceptual asymmetries

Two experiments investigated the contribution of space- and object-based coordinates to previously reported leftward perceptual biases (pseudoneglect) at various locations across visual space. Neurologically intact participants (n=34 and 27) made luminance discriminations between two left/right mirror-reversed luminance gradients (greyscales task), which were variously displaced around the midline in the participants’ left and right hemispaces. The orientations of the stimuli were manipulated so that object- and space-based coordinates were congruent or incongruent. Experiment 1 confirmed the presence of a leftward object-based perceptual bias. The bias was moderated, however, by overattention to the more central stimulus. This central spatial effect could have resulted from the use of task-specific strategies, which were controlled by presenting the stimuli sequentially in Experiment 2. The findings of Experiment 1, a leftward object-based bias and a central spatial bias, were replicated. Overall, the results indicate a leftward object-based bias and a central spatial bias, both of which are relevant for the allocation of attention. The results are discussed with reference to a variety of models of the distribution of attention across space.

Neuroimaging Biomarkers of a History of Concussion Observed in Asymptomatic Young Athletes

Participation in contact sports places athletes at elevated risk for repeated head injuries and is associated with negative mental health outcomes later in life. The current study identified changes observable on neuroimaging that persisted beyond the apparent resolution of acute symptoms of concussion. Sixteen young adult ice hockey players with a remote history of concussion but no subjective complaints were compared against 13 of their teammates with no history of concussion. Participants completed a detailed phenotypic assessment and a neuroimaging battery including diffusion kurtosis imaging and resting-state functional magnetic resonance imaging. Athletes with a history of concussion performed no differently from those without on phenotypic assessment, but showed significantly elevated fractional anisotropy (FA) in the left genu and anterior corona radiata relative to those without. Post hoc analyses revealed that elevated FA was associated with increased microstructural complexity perpendicular to the primary axon (radial kurtosis). Athletes with concussion history also showed significant differences in the organization of the default mode network (DMN) characterized by stronger temporal coherence in posterior DMN, decreased temporal coherence in anterior DMN, and increased functional connectivity outside the DMN. In the absence of deficits on detailed phenotypic assessment, athletes with a history of concussion displayed changes to the microstructural architecture of the cerebral white matter and to the functional connectivity of the brain at rest. Some of these changes are consistent with those previously associated with persisting deficits and complaints, but we also report novel, complementary changes that possibly represent compensatory mechanisms.

Brain Regions Related to Impulsivity Mediate the Effects of Early Adversity on Antisocial Behavior.

BACKGROUND Individual differences in impulsivity and early adversity are known to be strong predictors of adolescent antisocial behavior. However, the neurobiological bases of impulsivity and their relation to antisocial behavior and adversity are poorly understood. METHODS Impulsivity was estimated with a temporal discounting task. Voxel-based morphometry was used to determine the brain structural correlates of temporal discounting in a large cohort (n = 1830) of 14- to 15-year-old children. Mediation analysis was then used to determine whether the volumes of brain regions associated with temporal discounting mediate the relation between adverse life events (e.g., family conflict, serious accidents) and antisocial behaviors (e.g., precocious sexual activity, bullying, illicit substance use). RESULTS Greater temporal discounting (more impulsivity) was associated with 1) lower volume in frontomedial cortex and bilateral insula and 2) greater volume in a subcortical region encompassing the ventral striatum, hypothalamus and anterior thalamus. The volume ratio between these cortical and subcortical regions was found to partially mediate the relation between adverse life events and antisocial behavior. CONCLUSIONS Temporal discounting is related to regions of the brain involved in reward processing and interoception. The results support a developmental imbalance model of impulsivity and are consistent with the idea that negative environmental factors can alter the developing brain in ways that promote antisocial behavior.

Near, yet so far: The effect of pictorial cues on spatial attention

Distinct cognitive and neural mechanisms underlie perception and action in near (within-reach) and far (outside-reach) space. Objects in far space can be brought into the brains near-space through tool-use. We determined whether a near object can be pushed into far space by changing the pictorial context in which it occurs. Participants (n = 372) made relative length judgements for lines presented in near space, but superimposed over photographs of near and far objects. The left segment of the line was overestimated in the baseline and near-context conditions whereas the right was overestimated in the far-context. The change from leftward to rightward overestimation is the same when lines are physically shifted from near to far space. Because participants did not have to do anything in relation to the photograph, the results suggest that simply viewing images with a near/far context can cause a shift of attention along the distal/proximal axis, which may reflect differential activation of the ventral/dorsal visual streams.