Michael J. Wesley

Chimpanzees (Pan troglodytes) are predominantly right-handed: replication in three populations of apes.

Population-level right-handedness has historically been considered a hallmark of human evolution. Even though recent studies in chimpanzees (Pan troglodytes) have demonstrated population-level right-handedness for certain behaviors, some have questioned the validity and consistency of these findings by arguing that reported laterality effects are specific to certain colonies of apes and to those chimpanzees reared by humans. The authors report evidence of population-level right-handedness in 3 separate colonies of chimpanzees. Moreover, handedness in the 3 colonies was unrelated to the proportion of subjects that were raised by humans. This is the strongest evidence to date that population-level handedness is evident in chimpanzees and is not an artifact of human rearing.

Remember the Future II: Meta-analyses and Functional Overlap of Working Memory and Delay Discounting

Previously we showed that working memory training decreased the discounting of future rewards in stimulant addicts without affecting a go/no-go task. While a relationship between delay discounting and working memory is consistent with other studies, the unique brain regions of plausible causality between these two abilities have yet to be determined. Activation likelihood estimation meta-analyses were performed on foci from studies of delay discounting (DD = 449), working memory (WM = 452), finger tapping (finger tapping = 450), and response inhibition (RI = 450). Activity maps from relatively less (finger tapping) and more (RI) demanding executive tasks were contrasted with maps of DD and WM. Overlap analysis identified unique functional coincidence between DD and WM. The anterior cingulate cortex was engaged by all tasks. Finger tapping largely engaged motor-related brain areas. In addition to motor-related areas, RI engaged frontal brain regions. The right lateral prefrontal cortex was engaged by RI, DD, and WM and was contrasted out of overlap maps. A functional cluster in the posterior portion of the left lateral prefrontal cortex emerged as the largest location of unique overlap between DD and WM. A portion of the left lateral prefrontal cortex is a unique location where delay discounting and working memory processes overlap in the brain. This area, therefore, represents a therapeutic target for improving behaviors that rely on the integration of the recent past with the foreseeable future.

Poor decision-making by chronic marijuana users is associated with decreased functional responsiveness to negative consequences

Chronic marijuana users (MJ Users) perform poorly on the Iowa Gambling Task (IGT), a complex decision-making task in which monetary wins and losses guide strategy development. This functional magnetic resonance imaging (MRI) study sought to determine if the poor performance of MJ Users was related to differences in brain activity while evaluating wins and losses during the strategy development phase of the IGT. MJ Users (16) and Controls (16) performed a modified IGT in an MRI scanner. Performance was tracked and functional activity in response to early wins and losses was examined. While the MJ Users continued to perform poorly at the end of the task, there was no difference in group performance during the initial strategy development phase. During this phase, before the emergence of behavioral differences, Controls exhibited significantly greater activity in response to losses in the anterior cingulate cortex, medial frontal cortex, precuneus, superior parietal lobe, occipital lobe and cerebellum as compared to MJ Users. Furthermore, in Controls, but not MJ Users, the functional response to losses in the anterior cingulate cortex, ventral medial prefrontal cortex and rostral prefrontal cortex positively correlated with performance over time. These data suggest MJ Users are less sensitive to negative feedback during strategy development.

Alterations in ionotropic glutamate receptor subunits during binge cocaine self-administration and withdrawal in rats

Chronic cocaine use in humans and animal models is known to lead to pronounced alterations in glutamatergic function in brain regions associated with reinforcement. Previous studies have examined ionotropic glutamate receptor (iGluR) subunit protein level changes following acute and chronic experimenter‐administered cocaine or after withdrawal periods from experimenter‐administered cocaine. To evaluate whether alterations in expression of iGluRs are associated with cocaine reinforcement, protein levels were assessed after binge (8 h/day, 15 days; 24‐h access, days 16–21) cocaine self‐administration and following 2 weeks of abstinence from this binge. Western blotting was used to compare levels of iGluR protein expression (NR1–3B, GluR1–7, KA2) in the ventral tegmental area (VTA), substantia nigra (SN), nucleus accumbens (NAc), striatum and prefrontal cortex (PFC) of rats. iGluR subunits were altered in a time‐dependent manner in all brain regions studied; however, selective alterations in certain iGluR subtypes appeared to be associated with binge cocaine self‐administration and withdrawal in a region‐specific manner. In the SN and VTA, alterations in iGluR protein levels compared with controls occurred only following binge access, whereas in the striatum and PFC, iGluR alterations occurred with binge access and following withdrawal. In the NAc, GluR2/3 levels were increased following withdrawal compared with binge access, and were the only changes observed in this region. Because subunit composition determines the functional properties of iGluRs, the observed changes may indicate alterations in the excitability of dopamine transmission underlying long‐term biochemical and behavioral effects of cocaine.

Comparative Assessment of Handedness for a Coordinated Bimanual Task in Chimpanzees (Pan troglodytes), Gorillas (Gorilla gorilla), and Orangutans (Pongo pygmaeus)

Hand preferences for a coordinated bimanual task were assessed in a sample of 31 captive gorillas (Gorilla gorilla) and 19 captive orangutans (Pongo pygmaeus) and were compared with chimpanzee (Pan troglodytes) hand preferences in subjects that were matched on the basis of age, sex, and rearing history. The task required that the apes remove food from the inside edges of a symmetrical polyvinyl chloride pipe presented to them in their home cages. The results indicate significant species differences with chimpanzees showing population-level right-handedness and orangutans showing population-level left-handedness. The gorillas showed a nonsignificant trend toward right-handedness. The results are discussed in terms of possible ecological or biomechanical factors that may influence hand preferences in different ape species.

The association between frontal-striatal connectivity and sensorimotor control in cocaine users.

BACKGROUND In addition to cognitive and emotional processing dysfunction, chronic cocaine users are also impaired at simple sensorimotor tasks. Many diseases characterized by compulsive movements, repetitive actions, impaired attention and planning are associated with dysfunction in frontal-striatal circuits. The aim of this study was to determine whether cocaine users had impaired frontal-striatal connectivity during a simple movement task and whether this was associated with sensorimotor impairment. METHODS Functional MRI data were collected from 14 non-treatment seeking cocaine users and 15 healthy controls as they performed a finger-tapping task. Functional coupling was quantified by correlating the timecourses of each pair of anatomically connected regions of interest. Behavioral performance was correlated with all functional coupling coefficients. RESULTS In controls there was a significant relationship between the primary motor cortex and the supplementary motor area (SMA), as well as the SMA and the dorsal striatum during ongoing movement. Cocaine users exhibited weaker fronto-striatal coupling than controls, while the cortical-cortical coupling was intact. Coupling strength between the SMA and the caudate was negatively correlated with reaction time in the users. CONCLUSIONS The observation that cocaine users have impaired cortical-striatal connectivity during simple motor performance, suggests that these individuals may have a fundamental deficit in information processing that influences more complex cognitive processes.

Gestural communication in chimpanzees (Pan troglodytes): The influence of experimenter position on gesture type and hand preference

This study examined the influence of experimenter position on hand use in gestural communication in a sample of 127 captive chimpanzees. Hand use in gestural communication was recorded while an experimenter was positioned either left, right, or directly in front of the subject. The type of gesture was also recorded as either a food beg or whole hand point. Both hand use and gesture were consistent across experimenter positions. Overall, a significant population-level right hand bias was found, particularly for food beg gestures. These results are consistent with previous findings in chimpanzees and suggest that lateralisation in gestural communication is left hemisphere dominant.

Loss of functional specificity in the dorsal striatum of chronic cocaine users

BACKGROUND Although research into the effects of cocaine has focused on the ventral striatum, recent reports have identified a significant role for the dorsal striatum. Given the importance of the dorsal striatum in motor control, the purpose of the present study was to investigate potential sensorimotor deficits among cocaine users and the functional basis of these deficits within the striatum. METHODS Functional magnetic resonance imaging data were collected from 14 right-handed, non-treatment seeking chronic cocaine users and 14 age and gender matched controls during performance of two finger-sequencing paradigms that differentially activate the caudate (internally-guided) and the putamen (externally-guided) interleaved with blocks of rest. The total percent signal change in the dorsal striatum and the contribution of the left and right caudate and putamen were calculated and compared across groups and tasks. RESULTS Significant deficits in sensorimotor control were observed in cocaine users for both motor tasks, with the most severe impairments present during internally-guided movements. Cocaine users lacked the typical functional segregation observed in the dorsal striatum of the control subjects. The total percent signal change in the dorsal striatum was not significantly different between the groups, but cocaine users activated significantly less contralateral caudate and putamen for internally-guided versus externally-guided movements, respectively. CONCLUSION These data provide clear evidence that chronic cocaine users have significant motor performance deficits that are accompanied by disrupted processing within the dorsal striatum. These data suggest the effects of cocaine extend beyond the confines of the motivational domains of the ventral striatum.

Loss of laterality in chronic cocaine users: An fMRI investigation of sensorimotor control

Movement disturbances are often overlooked consequences of chronic cocaine abuse. The purpose of this study was to systematically investigate sensorimotor performance in chronic cocaine users and characterize changes in brain activity among movement-related regions of interest (ROIs) in these users. Functional magnetic resonance imaging data were collected from 14 chronic cocaine users and 15 age- and gender-matched controls. All participants performed a sequential finger-tapping task with their dominant, right hand interleaved with blocks of rest. For each participant, percent signal change from rest was calculated for seven movement-related ROIs in both the left and right hemisphere. Cocaine users had significantly longer reaction times and higher error rates than controls. Whereas the controls used a left-sided network of motor-related brain areas to perform the task, cocaine users activated a less lateralized pattern of brain activity. Users had significantly more activity in the ipsilateral (right) motor and premotor cortical areas, anterior cingulate cortex and the putamen than controls. These data demonstrate that, in addition to the cognitive and affective consequences of chronic cocaine abuse, there are also pronounced alterations in sensorimotor control in these individuals, which are associated with functional alterations throughout movement-related neural networks.

Choosing Money over Drugs: The Neural Underpinnings of Difficult Choice in Chronic Cocaine Users

Addiction is considered a disorder that drives individuals to choose drugs at the expense of healthier alternatives. However, chronic cocaine users (CCUs) who meet addiction criteria retain the ability to choose money in the presence of the opportunity to choose cocaine. The neural mechanisms that differentiate CCUs from non-cocaine using controls (Controls) while executing these preferred choices remain unknown. Thus, therapeutic strategies aimed at shifting preferences towards healthier alternatives remain somewhat uninformed. This study used BOLD neuroimaging to examine brain activity as fifty CCUs and Controls performed single- and cross-commodity intertemporal choice tasks for money and/or cocaine. Behavioral analyses revealed preferences for each commodity type. Imaging analyses revealed the brain activity that differentiated CCUs from Controls while choosing money over cocaine. We observed that CCUs devalued future commodities more than Controls. Choices for money as opposed to cocaine correlated with greater activity in dorsal striatum of CCUs, compared to Controls. In addition, choices for future money as opposed to immediate cocaine engaged the left dorsolateral prefrontal cortex (DLPFC) of CCUs more than Controls. These data suggest that the ability of CCUs to execute choices away from cocaine relies on activity in the dorsal striatum and left DLPFC.