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Early Multisensory Rehabilitation of Cognitive and Perceptual Functions for Stroke Patients with Unilateral Neglect

Final Report Summary - EARLY RECOVERIES (Early Multisensory Rehabilitation of Cognitive and Perceptual Functions for Stroke Patients with Unilateral Neglect)

Stroke is one of the major causes of death worldwide, second only to coronary disease, and it is the leading cause of disability with patients needing long hospitalisation and long-term community care. Stroke patients with perceptual and cognitive impairments such as unilateral neglect (i.e. reduced awareness of visual or auditory stimuli presented to one side of space) are of particular concern as they have among the worst prognostic outcomes. Today there is a lack of consensus about optimal training strategies to alleviate neglect, thus, it remains important to attempt to develop new procedures that are effective in the long-term, that generalise outside the clinic and that are clinically applicable. It was the aim of this project to develop a novel approach to the remediation of neglect through optimising attentional enhancement procedures that have been proven to be particularly effective for normal (non-brain lesioned) individuals – namely multisensory integration.

The specific objectives of this research project were:
1. To determine the environmental parameters and the types of sensory signals that optimally enhance long-term changes in perception and attention in healthy older adults, and, through this, to establish normative data against which to compare clinical patients with brain damage.
2. To identify functions that can be improved in stroke patients with unilateral neglect, how well training effects generalize and their duration. The main objective was to establish a multisensory rehabilitation program for patients with unilateral neglect focused on early post stroke intervention, within days post stroke, targeting faster recovery.
3. To evaluate, using functional magnetic resonance imaging (fMRI), adaptive changes and plasticity in brain networks following multisensory learning in patients with stroke and in healthy adult controls, so that an understanding is gained of the neural mechanisms linked to functional recovery in neglect patients.

The first stage of this research project focused on determining the stimulus parameters that optimally enhance attention in health elderly adults, and to determine whether participants with a history of stroke can similarly gain from multisensory stimulation. Recent publications had suggested that multisensory enhancements might be a by-product of other processes such as stimulus switch costs, and may possibly be explained by race-models [e.g. Otto & Mamassian (2012) Curr. Biol. 22, 1391-96]. A series of studies were conducted using audiovisual stimuli with novel associations (e.g. red circle with a pure tone), and audiovisual stimuli with pre-established semantic or environment associations (e.g. letter-sound, picture-sound such as an image of dog and a bark, etc.). Consistent across all studies we showed that multisensory enhancements cannot be entirely accounted for by switch-costs nor race models (see Figure 1). We found multisensory enhancements to be selectively driven by the temporal coincidence of auditory and visual signals, and their relevance to the task at hand. Importantly, similar patterns of multisensory enhancements were observed in elderly participants, and a large cohort of participants with chronic stroke, including those with perceptual, cognitive and language impairments (Figure 2). In addition, we were able to demonstrate that audiovisual signals are able to improve perceptual awareness in patients with neglect.

We further investigated the effectiveness of multisensory signals and cues in complex search and working memory, which are the two most common and debilitating impairments observed in neglect. To date most multisensory studies investigated the effectiveness of multisensory signals in simple tasks, whereby the object and sound associations are relatively easy to establish. However, in complex search and working memory tasks, with simultaneous multiple object presentations, audio-visual binding is ambiguous.

We developed two original multisensory paradigms that targeted these core impairments: a perceptual search task and a spatial-memory task. Paradigms utilised sophisticated psychophysical techniques that systematically adapt in stimulus complexity (e.g. using adaptive staircases) based on participant performance (i.e. stimulus complexity increase as behavioural measures such as accuracy improve). This strategy enabled us to assess gradual changes in perceptual and learning measures over time. Another successful milestone of the program was to adapt the tasks so they can be delivered on devices that are easily portable around hospital wards (e.g. iPad) for early post stroke rehabilitation. In the future, this will facilitate the global distribution of the rehabilitation program and promote international collaboration. Work with both tasks was initially conducted with healthy adults (Figure 3), to establish the optimal stimulation parameters and strategies. These initial studies helped establish normative learning curves for healthy elderly adults, and stroke patients in general (OBJECTIVE 1). We completed data collection on all 6 preliminary studies, and we are currently working on related manuscripts to be published in peer-reviewed journals.

To ascertain whether the benefits of multisensory integration can extend to other clinical populations we further investigated the effectiveness of multisensory stimulation on two additional clinical case studies: a patient with Posterior Cortical Atrophy (PCA), a neurodegenerative disorder that profoundly affects perceptual processes, and a stoke patient with expressive aphasia and deficits in reading and number processing. Both patients show significant gain from multisensory stimulation. Our patients with expressive aphasia also showed marked improvements with multisensory training over the course of 2 weeks and 1 month post training using letters and words. These findings suggest that patients with perceptual, language and cognitive impairments, other than neglect, may benefit from multisensory training. Currently we are working on 2 additional manuscripts to further disseminate these case study findings.

The initial control studies were used to establish a randomised blind control design, comparing individuals who receive visual unisensory stimulation alone (i.e. the control intervention) and those who receive multisensory stimulation (i.e. the experimental intervention), to the effects of multisensory rehabilitation on learning, performance accuracy and speed in patients with neglect (OBJECTIVE 2). Clinical and functional MRI was used to identify brain regions that were affected by the stroke and identify brain regions that could adapt their activity and, in turn, compensate for damaged brain areas following stroke (OBJECTIVE 3). For some patients, diffusion weighted imaging (DWI) and probabilistic tractography were also recorded to identify the brain pathways by which adaptive changes are mediated. Neglect patients were recruited at 1- and 6-months post-stroke and were randomly allocated to the control or the experimental intervention. All participants were subjected to 6 sessions (each approx. 1-3 days apart across 2-3 weeks) of unisensory or multisensory rehabilitation on both the perceptual search and the spatial memory tasks. The rate of improvement across sessions was measured in order to judge the best training ‘dose’ to use in future clinical settings. To gauge recovery and its generalisation across different forms of neglect (e.g. egocentric neglect, allocentric neglect, and impaired working memory) and its long-term carry over effects, patients are followed-up using a range of clinical tests before and at 1- and 6-months post multisensory rehabilitation. Preliminary analyses suggest that training benefits may transfer and are observable at least 1-month post stroke (6-months post data is still to be collected).

In summary, this project has demonstrated that multisensory signalling may be an effective rehabilitation technique, not only for stoke patients with neglect, but also clinical populations with other perceptual, language and cognitive impairments. The benefits of multisensory processing can generalise to complex task such as search and memory. These outcomes have broad clinical and social implication. Patients with perceptual and cognitive impairments following stroke have among the worst prognostic outcomes. Better rehabilitation strategies for these patients aiming at faster recovery would not only improve prognosis, but could promote a better quality of life. Even the ageing population in general can benefit from multisensory signalling to improve functional independence and quality of life.