Laura E. Hughes

Assisted Colonization and Rapid Climate Change

Moving species outside their historic ranges may mitigate loss of biodiversity in the face of global climate change.

Parkinson's disease and dopaminergic therapy—differential effects on movement, reward and cognition

Cognitive deficits are very common in Parkinsons disease particularly for ‘executive functions’ associated with frontal cortico-striatal networks. Previous work has identified deficits in tasks that require attentional control like task-switching, and reward-based tasks like gambling or reversal learning. However, there is a complex relationship between the specific cognitive problems faced by an individual patient, their stage of disease and dopaminergic treatment. We used a bimodality continuous performance task during fMRI to examine how patients with Parkinsons disease represent the prospect of reward and switch between competing task rules accordingly. The task-switch was not separately cued but was based on the implicit reward relevance of spatial and verbal dimensions of successive compound stimuli. Nineteen patients were studied in relative ‘on’ and ‘off’ states, induced by dopaminergic medication withdrawal (Hoehn and Yahr stages 1–4). Patients were able to successfully complete the task and establish a bias to one or other dimension in order to gain reward. However the lateral prefrontal cortex and caudate nucleus showed a non-linear U-shape relationship between motor disease severity and regional brain activation. Dopaminergic treatment led to a shift in this U-shape function, supporting the hypothesis of differential neurodegeneration in separate motor and cognitive cortico–striato–thalamo–cortical circuits. In addition, anterior cingulate activation associated with reward expectation declined with more severe disease, whereas activation following actual rewards increased with more severe disease. This may facilitate a change in goal-directed behaviours from deferred predicted rewards to immediate actual rewards, particularly when on dopaminergic treatment. We discuss the implications for investigation and optimal treatment of this common condition at different stages of disease.

Into the groove: Can rhythm influence Parkinson's disease?

Previous research has noted that music can improve gait in several pathological conditions, including Parkinsons disease, Huntingtons disease and stroke. Current research into auditory-motor interactions and the neural bases of musical rhythm perception has provided important insights for developing potential movement therapies. Specifically, neuroimaging studies show that rhythm perception activates structures within key motor networks, such as premotor and supplementary motor areas, basal ganglia and the cerebellum - many of which are compromised to varying degrees in Parkinsons disease. It thus seems likely that automatic engagement of motor areas during rhythm perception may be the connecting link between music and motor improvements in Parkinsons disease. This review seeks to describe the link, address core questions about its underlying mechanisms, and examine whether it can be utilized as a compensatory mechanism.

White matter pathology in Parkinson's disease: The effect of imaging protocol differences and relevance to executive function

Diffusion magnetic resonance imaging is increasingly used as a non-invasive method to investigate white matter structure in neurological and neuropsychiatric disease. However, many options are available for the acquisition sequence and analysis method. Here we used Parkinsons disease as a model neurodegenerative disorder to compare imaging protocols and analysis options. We investigated fractional anisotropy and mean diffusivity of white matter in patients and age-matched controls, comparing two datasets acquired with different imaging protocols. One protocol prioritised the number of b value acquisitions, whilst the other prioritised the number of gradient directions. The dataset with more gradient directions was more sensitive to reductions in fractional anisotropy in Parkinsons disease, whilst the dataset with more b values was more sensitive to increases in mean diffusivity. Moreover, the areas of reduced fractional anisotropy were highly similar to areas of increased mean diffusivity in PD patients. Next, we compared two widely used analysis methods: tract-based spatial statistics identified reduced fractional anisotropy and increased mean diffusivity in Parkinsons disease in many of the major white matter tracts in the frontal and parietal lobes. Voxel-based analyses were less sensitive, with similar patterns of white matter pathology observed only at liberal statistical thresholds. We also used tract-based spatial statistics to identify correlations between a test of executive function (phonemic fluency), fractional anisotropy and mean diffusivity in prefrontal white matter in both Parkinsons disease patients and controls. These findings suggest that in Parkinsons disease there is widespread pathology of cerebral white matter, and furthermore, pathological white matter in the frontal lobe may be associated with executive dysfunction. Diffusion imaging protocols that prioritised the number of directions versus the number of b values were differentially sensitive to alternative markers of white matter pathology, such as fractional anisotropy and mean diffusivity.

Selection and stopping in voluntary action: A meta-analysis and combined fMRI study

Voluntary action control requires selection of appropriate responses and stopping of inappropriate responses. Selection and stopping are often investigated separately, but they appear to recruit similar brain regions, including the pre-supplementary motor area (preSMA) and inferior frontal gyrus. We therefore examined the evidence for overlap of selection and stopping using two approaches: a meta-analysis of existing studies of selection and stopping, and a novel within-subject fMRI study in which action selection and a stop signal task were combined factorially. The novel fMRI study also permitted us to investigate hypotheses regarding a common mechanism for selection and stopping. The preSMA was identified by both methods as common to selection and stopping. However, stopping a selected action did not recruit preSMA more than stopping a specified action, nor did stop signal reaction times differ significantly across the two conditions. These findings suggest that the preSMA supports both action selection and stopping, but the two processes may not require access to a common inhibition mechanism. Instead, the preSMA might represent information about potential actions that is used in both action selection and stopping in order to resolve conflict between competing available responses.

Rule-Selection and Action-Selection have a Shared Neuroanatomical Basis in the Human Prefrontal and Parietal Cortex

The human capacity for voluntary action is one of the major contributors to our success as a species. In addition to choosing actions themselves, we can also voluntarily choose behavioral codes or sets of rules that can guide future responses to events. Such rules have been proposed to be superordinate to actions in a cognitive hierarchy and mediated by distinct brain regions. We used event-related functional magnetic resonance imaging to study novel tasks of rule-based and voluntary action. We show that the voluntary selection of rules to govern future responses to events is associated with activation of similar regions of prefrontal and parietal cortex as the voluntary selection of an action itself. The results are discussed in terms of hierarchical models and the adaptive coding potential of prefrontal neurons and their contribution to a global workspace for nonautomatic tasks. These tasks include the choices we make about our behavior.

Action selection: a race model for selected and non-selected actions distinguishes the contribution of premotor and prefrontal areas.

Race models have been used to explain perceptual, motor and oculomotor decisions. Here we developed a race model to explain how human subjects select actions when there are no overt rewards and no external cues to specify which action to make. Critically, we were able to estimate the cumulative activity of neuronal decision-units for selected and non-selected actions. We used functional magnetic resonance imaging (fMRI) to test for regional brain activity that correlated with the predictions of this race model. Activity in the pre-SMA, cingulate motor and premotor areas correlated with prospective selection between responses according to the race model. Activity in the lateral prefrontal cortex did not correlate with the race model, even though this area was active during action selection. This activity related to the degree to which individuals switched between alternative actions. Crucially, a follow-up experiment showed that it was not present on the first trial. Taken together, these results suggest that the lateral prefrontal cortex is not the source for the generation of action. It is more likely that it is involved in switching to alternatives or monitoring previous actions. Thus, our experiment shows the power of the race model in distinguishing the contribution of different areas in the selection of action.

Typography in Children's Reading Schemes May Be Suboptimal: Evidence from Measures of Reading Rate.

We investigated whether the layout of type in two popular children’s reading schemes was suitable for the intended reading age. 120 children read four passages of text that adopted the typography of four reading stages in each of the two schemes. The size and spacing of the texts decreased with successive stages as the intended reading age increased. The reading speed of children aged 5 to 7 years decreased as the text size decreased: in particular, these children read fastest the text designed for 5 and 6 year olds. Older children aged 8 to 11 years were neither assisted nor disadvantaged by text size. Children of all ages, particularly those susceptible to visual stress, were found to make more errors on the smaller than on the larger text. We conclude that the reading development of some children might benefit from a larger text size and spacing than is currently the norm, and that no children would be disadvantaged by such a change.

Saccadic latency in Parkinson's disease correlates with executive function and brain atrophy, but not motor severity.

Brain regions related to saccadic control are affected by Parkinsons disease (PD) pathology and a relationship between abnormal saccades and cognitive features of PD has been suggested. We measured the latency of visually-evoked saccades, and correlated best-fit parameters in a LATER neuronal decision model μ and σ (mean and SD of the distribution of reciprocal latency, i.e. speed of response), and σE (SD of the early component) with motor function, cognition and grey matter volume in 18 patients with PD and 17 controls. There was a negative correlation between verbal fluency and σ; no correlation was found between motor function and any of the latency parameters. Higher μ (shorter latency) positively correlated with grey matter volume in the prefrontal cortex, the cerebellar vermis, and the fusiform gyrus. There was a negative correlation between σ and grey matter volume in the frontal and parietal eye fields, the premotor cortex, and the lateral prefrontal cortex. σE negatively correlated with grey matter volume in the frontal eye fields and the middle frontal gyrus. Our behavioural and imaging findings point to an association between saccade latency, executive function and the structural integrity within a well-defined oculomotor network.

Selection and inhibition mechanisms for human voluntary action decisions

One can choose between action alternatives that have no apparent difference in their outcomes. Such voluntary action decisions are associated with widespread frontal–parietal activation, and a tendency to inhibit the repetition of a previous action. However, the mechanism of initiating voluntary actions and the functions of different brain regions during this process remains largely unknown. Here, we combine computational modeling and functional magnetic resonance imaging to test the selection and inhibition mechanisms that mediate trial-to-trial voluntary action decisions. We fitted an optimized accumulator model to behavioral responses in a finger-tapping task in which participants were instructed to make chosen actions or specified actions. Model parameters derived from each individual were then applied to estimate the expected accumulated metabolic activity (EAA) engaged in every single trial. The EAA was associated with blood oxygenation level-dependent responses in a decision work that was maximal in the supplementary motor area and the caudal anterior cingulate cortex, consistent with a competitive accumulation-to-threshold mechanism for action decision by these regions. Furthermore, specific inhibition of the previous actions accumulator was related to the suppression of response repetition. This action-specific inhibition correlated with the activity of the right inferior frontal gyrus, when the option to repeat existed. Our findings suggest that human voluntary action decisions are mediated by complementary processes of intentional selection and inhibition.