Marcelo L. Berthier

Aphasia therapy on a neuroscience basis

Background: Brain research has documented that the cortical mechanisms for language and action are tightly interwoven and, concurrently, new approaches to language therapy in neurological patients are being developed that implement language training in the context of relevant linguistic and non‐linguistic actions, therefore taking advantage of the mutual connections of language and action systems in the brain. A further well‐known neuroscience principle is that learning at the neuronal level is driven by correlation; consequently, new approaches to language therapy emphasise massed practice in a short time, thus maximising therapy quantity and frequency and, therefore, correlation at the behavioural and neuronal levels. Learned non‐use of unsuccessful actions plays a major role in the chronification of neurological deficits, and behavioural approaches to therapy have therefore employed shaping and other learning techniques to counteract such non‐use. We wish to thank Chris Code, Barbro Johansson, Bettina Mohr, and two anonymous referees for their comments on an earlier version of this article and for their helpful suggestions. This work was supported by the Medical Research Council (UK) and by the European Community under the “New and Emerging Science and Technologies Programme” (NESTCOM project) and by the Ministerio de Educacion y Ciencia, Spain (SEJ2007‐67793). Aims: Advances in theoretical and experimental neuroscience have important implications for clinical practice. We exemplify this in the domain of aphasia rehabilitation. Main Contribution: Whereas classical wisdom had been that aphasia cannot be significantly improved at a chronic stage, we here review evidence that one type of intensive language‐action therapy (ILAT)—constraint‐induced aphasia therapy—led to significant improvement of language performance in patients with chronic aphasia. We discuss perspectives for further improving speech‐language therapy, including drug treatment that may be particularly fruitful when applied in conjunction with behavioural treatment. In a final section we highlight intensive and rapid therapy studies in chronic aphasia as a unique tool for exploring the cortical reorganisation of language. Conclusions: We conclude that intensive language action therapy is an efficient tool for improving language functions even at chronic stages of aphasia. Therapy studies using this technique can open new perspectives for research into the plasticity of human language circuits.

Chronic effects of dopaminergic replacement on cognitive function in Parkinson's disease : A two-year follow-up study of previously untreated patients

The cognitive effects of dopaminergic treatment in Parkinsons disease (PD) are still controversial.

Memantine and constraint-induced aphasia therapy in chronic poststroke aphasia.

We conducted a randomized, double‐blind, placebo‐controlled, parallel‐group study of both memantine and constraint‐induced aphasia therapy (CIAT) on chronic poststroke aphasia followed by an open‐label extension phase.

Neuroscience insights improve neurorehabilitation of poststroke aphasia

The treatment of aphasias—acquired language disorders—caused by stroke and other neurological conditions has benefitted from insights from neuroscience and neuropsychology. Hebbian mechanisms suggest that massed practice and exploitation of residual neurological capacities can aid neurorehabilitation of patients with poststroke aphasia, and progress in basic neuroscience research indicates that the language system of the human brain is functionally interwoven with perceptual and motor systems. Intensive speech and language therapies, including constraint-induced aphasia therapy, that activate both the linguistic and concordant motor circuits utilize the knowledge gained from these advances in neuroscience research and can lead to surprisingly rapid improvements in language performance, even in patients with chronic aphasia. Drug-based therapies alone and in conjunction with behavioral language therapies also increase language performance in patients with aphasia. Furthermore, noninvasive transcranial magnetic stimulation and electrical stimulation techniques that target neuronal activity within perilesional areas might help patients with aphasia to regain lost language functions. Intensive language–action therapies that lead to rapid improvements in language skills might provide a new opportunity for investigating fast plastic neuronal changes in the areas of the brain associated with language processing. Here, we review progress in basic neuroscience research and its translational impact on the neurorehabilitation of language disorders after stroke.

Relearning and retention of verbal labels in a case of semantic dementia

Background: Previous studies looking at relearning and retention of word labels in people with semantic dementia have shown some improvement in naming immediately after the period of learning but this has not usually been maintained. Studies have also shown rigid learning of names, in the order of presentation and to the picture exemplars only, with no generalisation of learning. Aims: This study aimed to explore relearning of a small vocabulary set in a person with semantic dementia (CUB) and to examine her ability to generalise this learning. In addition, it aimed to find out how long the learning persisted after therapy was completed given that semantic dementia is a progressive disorder. Methods & Procedures: A single‐case design was used where CUB was asked to learn 28 words while a further 28 were left as controls. A “look and say” method was used daily for 1 month. As well as examining learning of the therapy and control set, CUB was asked to name 168 other exemplars of the learning set to see whether there had been any transfer of her learning from the therapy set. Outcomes & Results: CUB not only relearned a set of picture names but retained these without deliberate practice over a 6‐month period. She was also able to generalise this learning to other visually similar exemplars in testing and in daily use. The maintenance of relearning was achieved despite severe deterioration in her semantic memory. Conclusions: Possible reasons are explored as to why CUB was able to relearn and retain these words and why this may differ from all previously reported cases. Differences in amount of time spent relearning, number of items learned, therapy methods, the severity of semantic memory impairment, the degree of atrophy, and the behavioural profiles of people with semantic dementia do not provide adequate explanations for our individuals differential ability to retain her learning over 6 months. The most plausible explanation is that the person with semantic dementia generalised her learning to her everyday speech and this provided the source of maintenance for the relearned names. This work was supported by a Royal Society Travel Fellowship awarded to K. Sage. We are grateful to Dr Tomás Ojea from the Hospital Carlos Haya, Málaga for referring CUB to us, and most importantly to CUB and her family for their collaboration throughout.

Unexpected brain-language relationships in aphasia: Evidence from transcortical sensory aphasia associated with frontal lobe lesions

The syndrome of transcortical sensory aphasia (TCSA) is usually associated with extraperisylvian lesions of the left hemisphere that involve either posterior cortical regions (temporal-occipital cortex and inferior parietal cortex) or subcortical structures (thalamus). In exceptional cases, TCSA occurs in association with anterior perisylvian lesions involving the left Brocas area and its adjoining regions. This unconventional brain–language relationship is intriguing, because it contradicts the tenets of traditional aphasiology. This article reviews the extant literature of TCSA cases with frontal lesions. In the second section, the author assesses new cases of TCSA with frontal lesions in a two-part study. In Study 1 the issue of whether the language profile of TCSA with frontal lesions fits well with the diagnostic criteria of TCSA was investigated by comparing the language scores of the Western Aphasia Battery (WAB) in three groups of TCSA: Group 1: eight patients with posterior hemispheric damage; Group 2: seven patients with anterior hemispheric damage; and Group 3: four patients with anterior plus posterior hemispheric damage. Group comparisons failed to reveal statistically significant differences in demographic data and in nearly all WAB subtests. In Study 2, the pattern of language deficits was further investigated in three patients with TCSA and frontal lesions using cognitive neuropsychologycal investigations. Patients performance is discussed taking into account recent advances in the functional anatomy of language processing systems and in the interindividual differences in the organisation of language networks.

Drug therapy of post-stroke aphasia: a review of current evidence.

This review considers the role of drug therapy in the treatment of post-stroke aphasia, the evidence for efficacy of different agents, and the theory-based explanations of drug-related benefits for aphasia rehabilitation. Pharmacological interventions modulating stroke-induced disruption of diverse neurotransmitters may improve language and communication deficits in aphasic patients through facilitation of brain plasticity and long-term potentiation. However, benefits are not evident for all compounds and refinement in clinical trial designs is required. Some pharmacological trials have failed because drug treatment was not combined with speech-language therapy, while other trials combining drugs with intensive model-driven therapies also failed probably because of short-trial duration, inadequate sample selection, or lack of drug action. Preliminary data reveals that combining neuroscience-based intensive aphasia techniques (constraint-induced aphasia therapy) and drugs acting on cholinergic and glutamatergic neurotransmitter systems are associated with better outcomes than other strategies and long-term maintenance of benefits. Although further studies are needed, current state of the evidence suggests that drug therapy may play a key role in the treatment of post-stroke aphasia.

Effects of repetitive transcranial magnetic stimulation on memory subtypes: a controlled study.

Repetitive transcranial magnetic stimulation (rTMS) of human cortex may disrupt or facilitate cortical activity. The aim of the present study was to investigate the consequences of rTMS applied over different cortical areas during various memory tasks, measuring immediate, working and episodic verbal memory. The study was performed in 16 right-handed healthy men. A double-blind, cross-over, within-subject repeated measures design was used. There were five rTMS conditions: baseline without stimulation, high frequency (HF) rTMS over right and left dorsolateral prefrontal cortex (DLPFC) and over right cerebellum, and low frequency (LF) parameters over left DLPFC. Digits forwards and backwards and letter-number sequencing of the Wechsler Adults Intelligence Scale (WAIS) were used to assess immediate and working verbal memory, and logical memory of the Rivermead Behavioural Memory Test was used to assess episodic memory encoding. An analysis of variance (ANOVA) for repeated measures in the scores of each memory task according to rTMS conditions was used. Significantly lower scores in the number of memory units of the episodic memory task were observed when rTMS high frequency parameters were applied over left DLPFC (P=0.009). No significant differences were found in the other memory subtype tasks analysed during the different rTMS conditions. These findings provide evidence for the significant role of the left DLPFC in episodic verbal memory processes.

Anxiety and Depression in Caregivers are Associated with Patient and Caregiver Characteristics in Alzheimer's Disease

Objective: The aim of this study is to know the prevalence of anxiety and depression in caregivers of patients with Alzheimers disease (AD) and assess the association of caregiver burden (CB) with characteristics of both patients and caregivers. Method: Sociodemographic and clinical variables have been obtained (patients: age, gender, marital status, years of education, duration and severity of dementia, psychiatric disorders, previous history, and use of psychoactive and antidementia drugs; caregivers: age, gender, relationship with patient, and marital status). Cognition was assessed with Mini Mental State Examination (MMSE); severity of dementia was assessed with Global Deterioration Scale (GDS); caregiver burden was assessed with Hamilton Depression Rating Scale (HDRS), State-Trait Anxiety Inventory (STAI), and the number of hours of attention to the basic activities of daily-living (H-BADL). Results: More than 50% of caregivers have shown high anxiety and depression scores. Patients with longer duration of dementia, greater severity of dementia, and lower education levels significantly differ in anxiety and depression mean scores. Conclusion: The presence of CB in AD patients is strongly associated with the duration and severity of dementia and the educational level of patients. The results of this study should encourage researchers and clinicians working with elderly persons to consider these modifiable psychological states.

Arcuate fasciculus variability and repetition: The left sometimes can be right

Repetition ability is a major criterion for classifying aphasic syndromes and its status is helpful in the determination of the involved neural structures. It is widely assumed that repetition deficits correlate with injury to the left perisylvian core including the arcuate fasciculus (AF). However, descriptions of normal repetition despite damage to the AF or impaired repetition without AF involvement cast doubts on its role in repetition. To explain these paradoxes, we analyse two different aphasic syndromes - in which repetition is selectively impaired (conduction aphasia) or spared (transcortical aphasias) - in light of recent neuroimaging findings. We suggest that the AF and other white matter bundles are the anatomical signatures of language repetition and that individual variability in their anatomy and lateralisation may explain negative cases.