Saccade learning with concurrent cortical and subcortical basal ganglia loops

The Basal Ganglia is a central structure involved in multiple cortical and subcortical loops. Some of these loops are believed to be responsible for saccade target selection. We study here how the very specific structural relationships of these saccadic loops can affect the ability of learning spatial and feature-based tasks. We propose a model of saccade generation with reinforcement learning capabilities based on our previous basal ganglia and superior colliculus models. It is structured around the interactions of two parallel cortico-basal loops and one tecto-basal loop. The two cortical loops separately deal with spatial and non-spatial information to select targets in a concurrent way. The subcortical loop is used to make the final target selection leading to the production of the saccade. These different loops may work in concert or disturb each other regarding reward maximization. Interactions between these loops and their learning capabilities are tested on different saccade tasks. The results show the ability of this model to correctly learn basic target selection based on different criteria (spatial or not). Moreover the model reproduces and explains training dependent express saccades toward targets based on a spatial criterion. Finally, the model predicts that in absence of prefrontal control, the spatial loop should dominate

Saccade frequency response to visual cues during gait in Parkinson's disease: the selective role of attention

Gait impairment is a core feature of Parkinson's disease (PD) with implications for falls risk. Visual cues improve gait in PD, but the underlying mechanisms are unclear. Evidence suggests that attention and vision play an important role; however, the relative contribution from each is unclear. Measurement of visual exploration (specifically saccade frequency) during gait allows for real-time measurement of attention and vision. Understanding how visual cues influence visual exploration may allow inferences of the underlying mechanisms to response which could help to develop effective therapeutics. This study aimed to examine saccade frequency during gait in response to a visual cue in PD and older adults and investigate the roles of attention and vision in visual cue response in PD. A mobile eye-tracker measured saccade frequency during gait in 55 people with PD and 32 age-matched controls. Participants walked in a straight line with and without a visual cue (50 cm transverse lines) presented under single task and dual-task (concurrent digit span recall). Saccade frequency was reduced when walking in PD compared to controls; however, visual cues ameliorated saccadic deficit. Visual cues significantly increased saccade frequency in both PD and controls under both single task and dual-task. Attention rather than visual function was central to saccade frequency and gait response to visual cues in PD. In conclusion, this study highlights the impact of visual cues on visual exploration when walking and the important role of attention in PD. Understanding these complex features will help inform intervention development

Saccade frequency response to visual cues during gait in Parkinson's disease: the selective role of attention

Gait impairment is a core feature of Parkinson's disease (PD) with implications for falls risk. Visual cues improve gait in PD, but the underlying mechanisms are unclear. Evidence suggests that attention and vision play an important role; however, the relative contribution from each is unclear. Measurement of visual exploration (specifically saccade frequency) during gait allows for real-time measurement of attention and vision. Understanding how visual cues influence visual exploration may allow inferences of the underlying mechanisms to response which could help to develop effective therapeutics. This study aimed to examine saccade frequency during gait in response to a visual cue in PD and older adults and investigate the roles of attention and vision in visual cue response in PD. A mobile eye-tracker measured saccade frequency during gait in 55 people with PD and 32 age-matched controls. Participants walked in a straight line with and without a visual cue (50 cm transverse lines) presented under single task and dual-task (concurrent digit span recall). Saccade frequency was reduced when walking in PD compared to controls; however, visual cues ameliorated saccadic deficit. Visual cues significantly increased saccade frequency in both PD and controls under both single task and dual-task. Attention rather than visual function was central to saccade frequency and gait response to visual cues in PD. In conclusion, this study highlights the impact of visual cues on visual exploration when walking and the important role of attention in PD. Understanding these complex features will help inform intervention development

Direct and indirect effects of attention and visual function on gait impairment in Parkinson's disease: influence of task and turning

Gait impairment is a core feature of Parkinson's disease (PD) which has been linked to cognitive and visual deficits, but interactions between these features are poorly understood. Monitoring saccades allows investigation of real‐time cognitive and visual processes and their impact on gait when walking. This study explored: (i) saccade frequency when walking under different attentional manipulations of turning and dual‐task; and (ii) direct and indirect relationships between saccades, gait impairment, vision and attention. Saccade frequency (number of fast eye movements per‐second) was measured during gait in 60 PD and 40 age‐matched control participants using a mobile eye‐tracker. Saccade frequency was significantly reduced in PD compared to controls during all conditions. However, saccade frequency increased with a turn and decreased under dual‐task for both groups. Poorer attention directly related to saccade frequency, visual function and gait impairment in PD, but not controls. Saccade frequency did not directly relate to gait in PD, but did in controls. Instead, saccade frequency and visual function deficit indirectly impacted gait impairment in PD, which was underpinned by their relationship with attention. In conclusion, our results suggest a vital role for attention with direct and indirect influences on gait impairment in PD. Attention directly impacted saccade frequency, visual function and gait impairment in PD, with connotations for falls. It also underpinned indirect impact of visual and saccadic impairment on gait. Attention therefore represents a key therapeutic target that should be considered in future research

Direct and indirect effects of attention and visual function on gait impairment in Parkinson’s disease: influence of task and turning

Gait impairment is a core feature of Parkinson’s disease (PD) which has been linked to cognitive and visual deficits, but interactions between these features are poorly understood. Monitoring saccades allows investigation of real-time cognitive and visual processes and their impact on gait when walking. This study explored; 1) saccade frequency when walking under different attentional manipulations of turning and dual-task; and 2) direct and indirect relationships between saccades, gait impairment, vision and attention. Saccade frequency (number of fast eye-movements per-second) was measured during gait in 60 PD and 40 age-matched control participants using a mobile eye-tracker. Saccade frequency was significantly reduced in PD compared to controls during all conditions. However, saccade frequency increased with a turn and decreased under dual-task for both groups. Poorer attention directly related to saccade frequency, visual function and gait impairment in PD, but not controls. Saccade frequency did not directly relate to gait in PD, but did in controls. Instead, saccade frequency and visual function deficit indirectly impacted gait impairment in PD, which was underpinned by their relationship with attention. In conclusion, our results suggest a vital role for attention with direct and indirect influences on gait impairment in PD. Attention directly impacted saccade frequency, visual function and gait impairment in PD, with connotations for falls. It also underpinned indirect impact of visual and saccadic impairment on gait. Attention therefore represents a key therapeutic target that should be considered in future research

Vision and gait in Parkinson's disease: impact of cognition and response to visual cues

Ph.D. ThesisGait impairment is a core feature of Parkinson’s disease (PD) which is difficult to treat due to its multi-factorial nature. Gait dysfunction in PD has been linked to cognitive and visual deficits through separate strands of research. However cognitive and visual functions likely interact (termed visuo-cognition) and have a combined impact on gait. Attempting to further understand the roles of cognition and vision in gait in PD was the motivation behind this thesis. The primary aim was therefore to investigate visuo-cognition and its role in gait in PD. Saccade frequency during gait represents the amount of visual sampling employed when walking and is a useful online behavioural measure of visuo-cognition. However, previous investigations have been limited by lack of robust methodologies, technology and outcome measures. A key objective was therefore to establish robust saccadic measurement with mobile eye-tracking technology in PD and older adult controls. My original contributions to knowledge were that a mobile eye-tracker can measure saccadic activity during gait in PD and controls, but with variable accuracy and reliability for certain characteristics. Cognitive and visual functions were significantly related in both PD and controls, with stronger association in PD. Saccade frequency during gait was significantly reduced in people with PD compared to controls, particularly under dual task. Impaired saccade frequency can be ameliorated with a visual cue; as such intervention significantly increased saccade frequency in PD and controls which was maintained under dual task. Saccade frequency during gait was independently associated with cognitive and visual functions in PD. A structured model demonstrated that visuo-cognitive dysfunction had an indirect effect on gait in PD, with a central role for attention in all relationships involved. The major conclusion from this thesis was that gait impairment in PD is influenced by visuo-cognitive dysfunction, with implication for poor mobility and falls risk.National Institute for Health Research (NIHR) Biomedical Research Unit (BRU). Newcastle University

Dopamine and oculomotor impulsivity in health and disease.

The role of subcortical pathology in altered cognition is increasingly recognised. However, measurement and monitoring of impairments in motivation and behaviour due to subcortical disease is challenging. Basal ganglia – cortico-thalamo-cortical loops and the neurotransmitter, dopamine, are recognised to be important in modulating both reward learning and oculomotor performance. This thesis considers the use of novel and adapted oculomotor (saccadic) tasks as a means of interrogating these dynamic circuits as measures of rewarded decision-making under risk and time pressure. I first describe a novel rewarded oculomotor task, the Traffic Light Task, which provokes two distributions of saccades – one anticipatory, and one reactive. The balance of these distributions, the number of errors and the reward obtained are used to index oculomotor decision-making. Demonstrated effects of healthy aging include a significant reduction in anticipatory responding and consequent reduction in reward. I then compare behavioural oculomotor task responses in healthy controls with established “self-report” measures of impulsivity, finding significant correlations. Next, I consider a patient with focal lesions of the basal ganglia causing profound apathy. I demonstrate reduced oculomotor anticipatory responding and reward sensitivity. I then show the positive effects of dopaminergic medications (levodopa and ropinirole) upon his oculomotor decision-making in tandem with a clinical improvement in his motivational state. To further qualify this dopaminergic effect, I then assess the effects of two dopaminergic drugs (levodopa and methylphenidate) upon healthy volunteers. Finally, I use oculomotor tasks to compare patients with Parkinson’s Disease, with and without impulse control disorders, with both healthy volunteers and pathological gamblers without neurological disease. The results of these experiments raise questions regarding the development of models of basal ganglia – cortico-thalamo-cortical loops and how best to understand them