Alex P Leff

University College London | UCL · Institute of Neurology

Background Adverse non-motor outcomes have a major impact on patients and caregivers after stroke, but knowledge of their prevalence, predictors and patterns across multiple health domains remains limited; we therefore aimed to obtain these data in a large observational prospective cohort study. Methods We included data from the Stroke Investigati...

Background Aphasia is among the most debilitating of symptoms affecting stroke survivors. Speech and language therapy (SLT) is effective, but many hours of practice are required to make clinically meaningful gains. One solution to this ‘dosage’ problem is to automate therapeutic approaches via self-supporting apps so people with aphasia (PWA) can a...

Background Adverse non-motor outcomes are common after acute stroke and likely to substantially affect quality of life, yet few studies have comprehensively assessed their prevalence, patterns, and predictors across multiple health domains. Aims We aim to identify the prevalence, patterns and the factors associated with non-motor outcomes 30 days...

Knowledge about the consequences of stroke on high-level vision comes primarily from single case studies of patients selected based on their behavioural profiles, typically patients with specific stroke syndromes like pure alexia or prosopagnosia. There are, however, no systematic, detailed, large-scale evaluations of the more typical clinical beha...

Cerebral achromatopsia is an acquired colour perception impairment caused by brain injury, and is generally considered to be rare. Both hemispheres are thought to contribute to colour perception, but most published cases have had bilateral or right hemisphere lesions. In contrast to congenital colour blindness that affects the discrimination betwee...

Background: People with language problems following stroke (aphasia) benefit from speech and language therapy. Optimising speech and language therapy for aphasia recovery is a research priority. Objectives: The objectives were to explore patterns and predictors of language and communication recovery, optimum speech and language therapy intervention...

Sleep is a physiological state necessary for memory processing, learning and brain plasticity. Patients with disorders of consciousness (DOC) show none or minimal sign of awareness of themselves or their environment but appear to have sleep-wake cycles. The aim of our study was to assess baseline circadian rhythms and sleep in patients with DOC; to...

Knowledge about the consequences of stroke on high level vision comes primarily from single case studies of patients selected based on their behavioural profiles with deficits in the recognition of a specific visual category such as faces or words. There are, however, no systematic, detailed, large-scale evaluations of the more typical clinical beh...

Background: Collation of aphasia research data across settings, countries and study designs using big data principles will support analyses across different language modalities, levels of impairment, and therapy interventions in this heterogeneous population. Big data approaches in aphasia research may support vital analyses, which are unachievable...

Background and purpose The COVID-19 pandemic and related social isolation measures are likely to have adverse consequences on community healthcare provision and outcome after acute illnesses treated in hospital, including stroke. We aimed to evaluate the impact of the COVID-19 pandemic on patient-reported health outcomes after hospital admission fo...

Hemispatial inattention (HSI), a lateralised impairment of spatial processing, is a common consequence of stroke. It is a poor prognostic indicator for functional recovery and interferes with the progress during in‐patient neurorehabilitation. Dopaminergic medication has shown promise in improving HSI in the chronic post‐stroke period but is untest...

Cerebral achromatopsia is an acquired colour perception impairment caused by brain injury. Although we lack precise knowledge about prevalence, acquired colour perception deficits are considered to be rare. While both hemispheres contribute to colour perception, most published cases have had bilateral or right hemisphere lesions. In contrast to con...

Background and Purpose Optimizing speech and language therapy (SLT) regimens for maximal aphasia recovery is a clinical research priority. We examined associations between SLT intensity (hours/week), dosage (total hours), frequency (days/week), duration (weeks), delivery (face to face, computer supported, individual tailoring, and home practice), c...

Broca’s area in the posterior half of the left inferior frontal gyrus has traditionally been considered an important node in the speech production network. Nevertheless, recovery of speech production has been reported, to different degrees, within a few months of damage to Broca’s area. Importantly, contemporary evidence suggests that, within Broca...

Stroke is a leading cause of disability, and language impairments (aphasia) after stroke are both common and particularly feared. Most stroke survivors with aphasia exhibit anomia (difficulties with naming common objects), but while many therapeutic interventions for anomia have been proposed, treatment effects are typically much larger in some pat...

Establishing whether speech and language therapy after stroke has beneficial effects on speaking ability is challenging because of the need to control for multiple non-therapy factors known to influence recovery. We investigated how speaking ability at three time points post-stroke differed in patients who received varying amounts of clinical thera...

Much of the patient literature on the visual recognition of faces, words and objects is based on single case studies of patients selected according to their symptom profile. The Back of the Brain project aims to provide novel insights into the cerebral and cortical architecture underlying visual recognition of complex stimuli by adopting a differen...

This scientific commentary refers to ‘A decision-neuroscientific intervention to improve cognitive recovery after stroke’ by Studer et al. (doi:10.1093/brain/awab128).

Background and Purpose The factors associated with recovery of language domains after stroke remain uncertain. We described recovery of overall-language-ability, auditory comprehension, naming, and functional-communication across participants’ age, sex, and aphasia chronicity in a large, multilingual, international aphasia dataset. Methods Individ...

Prior studies have reported inconsistency in the lesion sites associated with verbal short-term memory impairments. Here we asked: How many different lesion sites can account for selective impairments in verbal short-term memory that persist over time, and how consistently do these lesion sites impair verbal short-term memory? We assessed verbal sh...

Prior studies have reported inconsistency in the lesion sites associated with verbal short-term memory impairments. Here we asked: How many different lesion sites can account for selective impairments in verbal short-term memory that persist over time, and how consistently do these lesion sites impair verbal short-term memory? We assessed verbal sh...

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 a key method for both diagnosis and monitoring of responses to treatment interventions by people with aphasia (PWA). Currently, this assessment is conducted manua...

The organisational principles of the visual ventral stream are still highly debated, particularly the relative association/dissociation between word and face recognition and the degree of lateralisation of the underlying processes. Reports of dissociations between word and face recognition stem from single case-studies of category selective impairm...

BACKGROUND AND PURPOSE: Post-stroke aphasia has a major impact on peoples’ quality of life. Speech and language therapy interventions work, especially in high doses, but these doses are rarely achieved outside of research studies. Intensive Comprehensive Aphasia Programmes (ICAPs) are an option to deliver high doses of therapy to people with aphasi...

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 a key method for both diagnosis and monitoring of responses to treatment interventions by people with aphasia (PWA). Currently, this assessment is conducted manua...

BACKGROUND Stroke is a leading cause of disability, and language impairments (aphasia) after stroke are both common and particularly feared. Most stroke survivors with aphasia exhibit anomia (difficulties with naming common objects), but while many therapeutic interventions for anomia have been proposed, treatment effects are typically much larger...

The left inferior frontal cortex (LIFC) is a key region for spoken language processing, but its neurocognitive architecture remains controversial. Here we assess the domain-generality vs. domain-specificity of the LIFC from behavioural, functional neuroimaging and neuromodulation data. Using concurrent fMRI and transcranial direct current stimulati...

Broca’s area in the posterior half of the left inferior frontal gyrus has long been thought to be critical for speech production. The current view is that long-term speech production outcome in patients with Broca’s area damage is best explained by the combination of damage to Broca’s area and neighbouring regions including the underlying white mat...

We begin with the functions of the striate cortex (area V1 of the visual cortex) and end with a review of the effects of damage to striate cortex or its inputs; namely, homonymous hemifield defects. Clinical and anatomical studies accrued over the past 25 years have modified our understanding of the role of V1 in vision. We discuss the evidence tha...

While there is a long history of rehabilitation for motor deficits following cerebral lesions, less is known about our ability to improve visual deficits. Vision therapy, prisms, occluders, and filters have been advocated for patients with mild traumatic brain injury, on the premise that some of their symptoms may reflect abnormal visual or ocular...

Cognition is frequently damaged by acquired brain injury (ABI). Impaired thinking is both a symptom in its own right and also a barrier to recovery by impacting their insight and awareness and their engagement with rehabilitation. Here we consider the aims, mechanisms and contexts when the goal is to improve cognitive function in patients with ABI.

Objective The efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, ‘Listen-In’, and examined the relation between brain structure and therapy response. Methods A cross-over randomised repeated measures trial with five testing time points (12-week int...

Anomia (word finding difficulties) is the hallmark of aphasia an acquired language disorder, most commonly caused by stroke. Assessment of speech performance using pijcture 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 m...

Less is more, right? Wrong: more is more. Here we make the case that the total dose of speech and language therapy (SLT) is a key factor in improving persons with aphasia’s (PWA) outcomes. The challenge is: how can we deliver high-dose therapy when resources are stretched? We review the recent evidence for dose and timing of SLT and then describe o...

Purpose: Speech and language pathology (SLP) for aphasia is a complex intervention delivered to a heterogeneous population within diverse settings. Simplistic descriptions of participants and interventions in research hinder replication, interpretation of results, guideline and research developments through secondary data analyses. This study aimed...

Purpose: Speech and language pathology (SLP) for aphasia is a complex intervention delivered to a heterogeneous population within diverse settings. Simplistic descriptions of participants and interventions in research hinder replication, interpretation of results, guideline and research developments through secondary data analyses. This study aimed...

This chapter covers the classification of acquired aphasic syndromes. It illustrates some of the speech errors aphasic stroke patients make with videos of a patient describing a picture and attempting to repeat words. The main part of the chapter assesses the evidence base for speech and language therapy (SALT) and answers the following questions:...

We investigated the clinical effectiveness of Eye-Search, a web-based therapy app designed to improve visual search times, in a large group of patients with either hemianopia, neglect or both hemianopia and neglect. A prospective, interventional cohort design was used. For the main, impairment-based outcome measure (average visual search time), the...

Full text of this preprint here: https://psyarxiv.com/8h32m Abstract: The organisational principles of the visual ventral stream are still highly debated, specifically the relative association/dissociation between word and face recognition. Reports of dissociations between word and face recognition stem from reports of category-selective impairmen...

While the loss of mental imagery following brain lesions was first described more than a century ago, the key cerebral areas involved remain elusive. Here we report neuropsychological data from an architect (PL518) who lost his ability for visual imagery following a bilateral posterior cerebral artery (PCA) stroke. We compare his profile to three o...

Cognitive impairment is an important target for rehabilitation as it is common following stroke, is associated with reduced quality of life and interferes with motor and other types of recovery interventions. Cognitive function following stroke was identified as an important, but relatively neglected area during the first Stroke Recovery and Rehabi...

Cognitive impairment is an important target for rehabilitation as it is common following stroke, is associated with reduced quality of life and interferes with motor and other types of recovery interventions. Cognitive function following stroke was identified as an important, but relatively neglected area during the first Stroke Recovery and Rehabi...

Most neuropsychological evidence for category specific deficits in reading and face recognition comes from small-N studies of patients recruited on the basis of selective deficits. Taking a different approach, we recruited patients based on lesion location (Posterior Cerebral Artery-stroke) rather than symptomatology. 58 patients and 31 controls we...

Face and word processing have traditionally been thought to rely on highly laterlaized cognitive processes, with face processing relying more heavily on the right and and word processing more on the left hemisphere. This builds on evidence from neuropsychological case studies of patients with pure alexia and pure prosopagnosia, as well as functiona...

Background: Speech and language therapy (SLT) benefits people with aphasia following stroke. Group level summary statistics from randomised controlled trials hinder exploration of highly complex SLT interventions and a clinically relevant heterogeneous population. Creating a database of individual participant data (IPD) for people with aphasia aims...

The presence and degree of category-selective responses in the human brain remains a central research question in visual neuroscience. Evidence for category-selectivity in higher-level vision primarily stems from neuroimaging studies of healthy participants. Converging evidence also exists in patients after brain injury, however they often focus ei...

Central alexia (CA) is an acquired reading disorder co-occurring with a generalised language deficit (aphasia). The roles of perilesional and ipsilesional tissue in recovery from post-stroke aphasia are unclear. We investigated the impact of reading training (using iReadMore, a therapy app) on the connections within and between the right and left h...

Given the profound impact of language impairment after stroke (aphasia), neuroplasticity research is garnering considerable attention as means for eventually improving aphasia treatments and how they are delivered. Functional and structural neuroimaging studies indicate that aphasia treatments can recruit both residual and new neural mechanisms to...

Appendix A presents a formal derivation, from first principles, of the equation that relates: (a) the correlation between baseline scores and recovery to (b) the correlation between baseline scores and outcome scores and (c) the ratio of the standard deviations of outcomes and baselines. Appendix B presents MATLAB script to illustrate the key conse...

The proportional recovery rule asserts that most stroke survivors recover a fixed proportion of lost function. To the extent that this is true, recovery from stroke can be predicted accurately from baseline measures of acute post-stroke impairment alone. Reports that baseline scores explain more than 80%, and sometimes more than 90%, of the varianc...

Acquired language disorders after stroke are strongly associated with left hemisphere damage. When language difficulties are observed in the context of right hemisphere strokes, patients are usually considered to have atypical functional anatomy. By systematically integrating behavioural and lesion data from brain damaged patients with functional M...

Purpose of Review We now know that speech and language therapy (SALT) is effective in the rehabilitation of aphasia; however, there remains much individual variability in the response to interventions. So, what works for whom, when and how? Recent Findings This review evaluates the current evidence for the efficacy of predominantly impairment-focu...

Background: Speech and language therapy (SLT) interventions for people with aphasia are complex-for example, interventions vary by delivery model (face-to-face, tele-rehabilitation), dynamic (group, 1-to-1) and provider. Therapists tailor the functional relevance and intervention difficulty to the individual's needs. Therapy regimes are planned at...

Central alexia is an acquired reading disorder co-occurring with a generalized language deficit (aphasia). We tested the impact of a novel training app, 'iReadMore', and anodal transcranial direct current stimulation of the left inferior frontal gyrus, on word reading ability in central alexia. The trial was registered at www.clinicaltrials.gov (NC...

A recently introduced hierarchical generative model unified the inference of effective connectivity in individual subjects and the unsupervised identification of subgroups defined by connectivity patterns. This hierarchical unsupervised generative embedding (HUGE) approach combined a hierarchical formulation of dynamic causal modelling (DCM) for fM...

The development of whole-brain models that can infer effective (directed) connection strengths from fMRI data represents a central challenge for computational neuroimaging. A recently introduced generative model of fMRI data, regression dynamic causal modeling (rDCM), moves towards this goal as it scales gracefully to very large networks. However,...

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 ref...

Background The proportional recovery rule asserts that most stroke survivors recover a fixed proportion of lost function. Reports that the rule can be used to predict recovery, extraordinarily accurately, are rapidly accumulating. Here, we show that the rule may not be as powerful as it seems. Methods We provide a formal analysis of the relationsh...

Supplementary material: the omnibus analysis results in full.

This study investigated how sample size affects the reproducibility of findings from univariate voxel-based lesion-deficit analyses (e.g., voxel-based lesion-symptom mapping and voxel-based morphometry). Our effect of interest was the strength of the mapping between brain damage and speech articulation difficulties, as measured in terms of the prop...

For many years, researchers have sought to understand whether and when stroke survivors with acquired language impairment (aphasia) will recover. There is broad agreement that lesion location information should play some role in these predictions, but still no consensus on the best or right way to encode that information. Here, we address the emerg...