Advances in the Rehabilitation of Hemispatial Inattention

PURPOSE OF REVIEW: There continue to be a plethora of approaches to the rehabilitation of hemispatial inattention, from different forms of sensory stimulation (visual, auditory and somatosensory feedback), through all major modes of non-invasive brain stimulation to drug therapies. Here we summarise trials published in the years 2017-2022 and tabulate their effect sizes, with the aim of drawing on common themes that may serve to inform future rehabilitative studies. RECENT FINDINGS: Immersive virtual reality approaches to visual stimulation seem well tolerated, although they have yet to yield any clinically relevant improvements. Dynamic auditory stimulation looks very promising and has high potential for implementation. Robotic interventions are limited by their cost and are perhaps best suited to patients with a co-occurring hemiparesis. Regarding brain stimulation, rTMS continues to demonstrate moderate effects but tDCS studies have yielded disappointing results so far. Drugs, primarily aimed at the dopaminergic system, often demonstrate beneficial effects of a medium size, but as with many of the approaches, it seems difficult to predict responders and non-responders. Our main recommendation is that researchers consider incorporating single-case experimental designs into their studies as rehabilitation trials are likely to remain small in terms of patient numbers, and this is the best way to deal with all the factors that cause large between-subject heterogeneity

Functional near infrared spectroscopy as a probe of brain function in people with prolonged disorders of consciousness

Near infrared spectroscopy (NIRS) is a non-invasive technique which measures changes in brain tissue oxygenation. NIRS has been used for continuous monitoring of brain oxygenation during medical procedures carrying high risk of iatrogenic brain ischemia and also has been adopted by cognitive neuroscience for studies on executive and cognitive functions. Until now, NIRS has not been used to detect residual cognitive functions in patients with prolonged disorders of consciousness (pDOC). In this study we aimed to evaluate the brain function of patients with pDOC by using a motor imagery task while recording NIRS. We also collected data from a group of age and gender matched healthy controls while they carried out both real and imagined motor movements to command. We studied 16 pDOC patients in total, split into two groups: five had a diagnosis of Vegetative state/Unresponsive Wakefulness State, and eleven had a diagnosis of Minimally Conscious State. In the control subjects we found a greater oxy-haemoglobin (oxyHb) response during real movement compared with imagined movement. For the between group comparison, we found a main effect of hemisphere, with greater depression of oxyHb signal in the right > left hemisphere compared with rest period for all three groups. A post-hoc analysis including only the two pDOC patient groups was also significant suggesting that this effect was not just being driven by the control subjects. This study demonstrates for the first time the feasibility of using NIRS for the assessment of brain function in pDOC patients using a motor imagery task

The expression of VvMYBPA1 in tobacco remodulates the phenylpropanoid pathway and diverts the synthesis of anthocyanins into condensed tannins in flowers

Patients in Vegetative State (VS), also known as Unresponsive Wakefulness State (UWS) are deemed to be unaware of themselves or their environment. This is different from patients diagnosed with Minimally Conscious state (MCS), who can have intermittent awareness. In both states, there is a severe impairment of consciousness; these disorders are referred to as disorders of consciousness (DOC) and if the state is prolonged, pDOC. There is growing evidence that some patients who are behaviourally in VS/UWS can show neural activation to environmental stimuli and that this response can be detected using functional brain imaging (fMRI/PET) and electroencephalography (EEG). Recently, it has also been suggested that a more reliable detection of brain responsiveness and hence a more reliable differentiation between VS/UWS and MCS requires person-centred and person-specific stimuli, such as the subject's own name stimulus.In this study we obtained event related potential data (ERP) from 12 healthy subjects and 16 patients in pDOC, five of whom were in the VS/UWS and 11 in the Minimally Conscious State (MCS). We used as the ERP stimuli the subjects' own name, others' names and reversed other names. We performed a sensor level analysis using Statistical Parametric Mapping (SPM) software. Using this paradigm in 4 DOC patients (3 in MCS, and 1 in VS/UWS) we detected a statistically significant difference in EEG response to their own name versus other peoples' names with ERP latencies (~300 ms and ~700 ms post stimuli). Some of these differences were similar to those found in a control group of healthy subjects.This study shows the feasibility of using self-relevant stimuli such as a subject's own name for assessment of brain function in pDOC patients. This neurophysiological test is suitable for bed-side/hospital based assessment of pDOC patients. As it does not require sophisticated scanning equipment it can feasibly be used within a hospital or care setting to help professionals tailor medical and psycho-social management for patients

Mapping spoken language and cognitive deficits in post-stroke aphasia

Aphasia is an acquired disorder caused by damage, most commonly due to stroke, to brain regions involved in speech and language. While language impairment is the defining symptom of aphasia, the co-occurrence of non-language cognitive deficits and their importance in predicting rehabilitation and recovery outcomes is well documented. However, people with aphasia (PWA) are rarely tested on higher-order cognitive functions, making it difficult for studies to associate these functions with a consistent lesion correlate. Broca's area is a particular brain region of interest that has long been implicated in speech and language production. Contrary to classic models of speech and language, cumulative evidence shows that Broca's area and surrounding regions in the left inferior frontal cortex (LIFC) are involved in, but not specific to, speech production. In this study we aimed to explore the brain-behaviour relationships between tests of cognitive skill and language abilities in thirty-six adults with long-term speech production deficits caused by post-stroke aphasia. Our findings suggest that non-linguistic cognitive functions, namely executive functions and verbal working memory, explain more of the behavioural variance in PWA than classical language models imply. Additionally, lesions to the LIFC, including Broca's area, were associated with non-linguistic executive (dys)function, suggesting that lesions to this area are associated with non-language-specific higher-order cognitive deficits in aphasia. Whether executive (dys)function - and its neural correlate in Broca's area - contributes directly to PWA's language production deficits or simply co-occurs with it, adding to communication difficulties, remains unclear. These findings support contemporary models of speech production that place language processing within the context of domain-general perception, action and conceptual knowledge. An understanding of the covariance between language and non-language deficits and their underlying neural correlates will inform better targeted aphasia treatment and outcomes

Predicting Online Behavioural Responses to Transcranial Direct Current Stimulation in Stroke Patients with Anomia

Anomia, or difficulty naming common objects, is the most common, acquired impairment of language. Effective therapeutic interventions for anomia typically involve massed practice at high doses. This requires significant investment from patients and therapists. Aphasia researchers have increasingly looked to neurostimulation to accelerate these treatment effects, but the evidence behind this intervention is sparse and inconsistent. Here, we hypothesised that group-level neurostimulation effects might belie a more systematic structure at the individual level. We sought to test the hypothesis by attempting to predict the immediate (online), individual-level behavioural effects of anodal and sham neurostimulation in 36 chronic patients with anomia, performing naming and size judgement tasks. Using clinical, (pre-stimulation) behavioural and MRI data, as well as Partial Least Squares regression, we attempted to predict neurostimulation effects on accuracies and reaction times of both tasks. Model performance was assessed via cross-validation. Predictive performances were compared to that of a null model, which predicted the mean neurostimulation effects for all patients. Models derived from pre-stimulation data consistently outperformed the null model when predicting neurostimulation effects on both tasks’ performance. Notably, we could predict behavioural declines just as well as improvements. In conclusion, inter-patient variation in online responses to neurostimulation is, to some extent, systematic and predictable. Since declines in performance were just as predictable as improvements, the behavioural effects of neurostimulation in patients with anomia are unlikely to be driven by placebo effects. However, the online effect of the intervention appears to be as likely to interfere with task performance as to improve it

An Utterance Verification System for Word Naming Therapy in Aphasia

Anomia (word finding difficulties) is the hallmark of aphasia an acquired language disorder, most commonly caused by stroke. Assessment of speech performance using picture naming tasks is therefore a key method for identification of the disorder and monitoring patient’s response to treatment interventions. Currently, this assessment is conducted manually by speech and language therapists (SLT). Surprisingly, despite advancements in ASR and artificial intelligence with technologies like deep learning, research on developing automated systems for this task has been scarce. Here we present an utterance verification system incorporating a deep learning element that classifies ‘correct’/‘incorrect’ naming attempts from aphasic stroke patients. When tested on 8 native British-English speaking aphasics the system’s performance accuracy ranged between 83.6% to 93.6%, with a 10 fold cross validation mean of 89.5%. This performance was not only significantly better than one of the leading commercially available ASRs (Google speech-to-text service) but also comparable in some instances with two independent SLT ratings for the same dataset

Randomised, double-blind, placebo-controlled crossover study of single-dose guanfacine in unilateral neglect following stroke

OBJECTIVE: Unilateral neglect is a poststroke disorder that impacts negatively on functional outcome and lacks established, effective treatment. This multicomponent syndrome is characterised by a directional bias of attention away from contralesional space, together with impairments in several cognitive domains, including sustained attention and spatial working memory. This study aimed to test the effects of guanfacine, a noradrenergic alpha-2A agonist, on ameliorating aspects of neglect.METHODS: Thirteen right hemisphere stroke patients with leftward neglect were included in a randomised, double-blind, placebo-controlled proof-of-concept crossover study that examined the effects of a single dose of guanfacine. Patients were tested on a computerised, time-limited cancellation paradigm, as well as tasks that independently assessed sustained attention and spatial working memory.RESULTS: On guanfacine, there was a statistically significant improvement in the total number of targets found on the cancellation task when compared with placebo (mean improvement of 5, out of a possible 64). However, there was no evidence of a change in neglect patients' directional attention bias. Furthermore, Bayesian statistical analysis revealed reliable evidence against any effects of guanfacine on search organisation and performance on our sustained attention and spatial working memory tasks.CONCLUSIONS: Guanfacine improves search in neglect by boosting the number of targets found but had no effects on directional bias or search organisation, nor did it improve sustained attention or working memory on independent tasks. Further work is necessary to determine whether longer term treatment with guanfacine may be effective for some neglect patients and whether it affects functional outcome measures.TRIAL REGISTRATION NUMBER: NCT00955253.</p

The left superior temporal gyrus is a shared substrate for auditory short-term memory and speech comprehension: evidence from 210 patients with stroke

Competing theories of short-term memory function make specific predictions about the functional anatomy of auditory short-term memory and its role in language comprehension. We analysed high-resolution structural magnetic resonance images from 210 stroke patients and employed a novel voxel based analysis to test the relationship between auditory short-term memory and speech comprehension. Using digit span as an index of auditory short-term memory capacity we found that the structural integrity of a posterior region of the superior temporal gyrus and sulcus predicted auditory short-term memory capacity, even when performance on a range of other measures was factored out. We show that the integrity of this region also predicts the ability to comprehend spoken sentences. Our results therefore support cognitive models that posit a shared substrate between auditory short-term memory capacity and speech comprehension ability. The method applied here will be particularly useful for modelling structure–function relationships within other complex cognitive domains