Are pharmacotherapeutics effective for treating aphasia?

INTRODUCTION: Aphasia is a communication disorder resulting from stroke and/or neurodegenerative conditions which involve the left cerebral hemisphere. It is a debilitating disorder affecting a person's ability to speak, understand, read, and write. Its impact on daily life necessitates therapeutic strategies to aid patients with aphasia. AREAS COVERED: In this special report, the authors speculate whether current pharmacotherapeutic strategies are effective in treating aphasia. The authors look at aphasia caused by different conditions and how this could impact therapy before providing the reader with their expert perspectives. The aim of this paper is for the reader to gain a clearer understanding of the efficacy of the current pharmacotherapeutic treatment paradigms as well as potential future developments. EXPERT OPINION: The exploration of pharmacotherapy for aphasia in vascular brain disorders and neurodegenerative diseases has received much attention in recent years with various therapeutic strategies having been put forward. In terms of whether pharmacotherapy is effective for the treatment of aphasia, there is still no clear-cut answer. Further research is needed with more studies requiring a greater emphasis on language and communication deficits. Biomarkers may also help clinicians provide their patients with a more personalized treatment plan.

Pharmacotherapy for post-stroke aphasia: what are the options?

INTRODUCTION: Aphasia is a common, long-lasting aftermath of stroke lesions. There is an increased integration of pharmacotherapy as an adjunctive strategy to speech and language therapy (SLT) for post-stroke aphasia (PSA). Nevertheless, more research in pharmacotherapy for acute and chronic PSA is necessary, including the election of drugs that target different neurotransmitter systems and deficits in specific language domains. AREAS COVERED: This article updates the role of pharmacotherapy for PSA, focusing the spotlight on some already investigated drugs and candidate agents deserving of future research. Refining the precision of drug election would require using multimodal biomarkers to develop personalized treatment approaches. There is a solid need to devise feasible randomized controlled trials adapted to the particularities of the PSA population. The emergent role of multimodal interventions combining one or two drugs with noninvasive brain stimulation to augment SLT is emphasized. EXPERT OPINION: Pharmacotherapy can improve language deficits not fully alleviated by SLT. In addition, the 'drug-only' approach can also be adopted when administering SLT is not possible. The primary goal of pharmacotherapy is reducing the overall aphasia severity, although targeting language-specific deficits (i.e. naming, spoken output) also contributes to improving functional communication. Unfortunately, there is still little information for recommending a drug for specific language deficits.

Turning the Spotlight to Cholinergic Pharmacotherapy of the Human Language System.

Even though language is essential in human communication, research on pharmacological therapies for language deficits in highly prevalent neurodegenerative and vascular brain diseases has received little attention. Emerging scientific evidence suggests that disruption of the cholinergic system may play an essential role in language deficits associated with Alzheimer's disease and vascular cognitive impairment, including post-stroke aphasia. Therefore, current models of cognitive processing are beginning to appraise the implications of the brain modulator acetylcholine in human language functions. Future work should be directed further to analyze the interplay between the cholinergic system and language, focusing on identifying brain regions receiving cholinergic innervation susceptible to modulation with pharmacotherapy to improve affected language domains. The evaluation of language deficits in pharmacological cholinergic trials for Alzheimer's disease and vascular cognitive impairment has thus far been limited to coarse-grained methods. More precise, fine-grained language testing is needed to refine patient selection for pharmacotherapy to detect subtle deficits in the initial phases of cognitive decline. Additionally, noninvasive biomarkers can help identify cholinergic depletion. However, despite the investigation of cholinergic treatment for language deficits in Alzheimer's disease and vascular cognitive impairment, data on its effectiveness are insufficient and controversial. In the case of post-stroke aphasia, cholinergic agents are showing promise, particularly when combined with speech-language therapy to promote trained-dependent neural plasticity. Future research should explore the potential benefits of cholinergic pharmacotherapy in language deficits and investigate optimal strategies for combining these agents with other therapeutic approaches.

Brain structural and functional correlates of the heterogenous progression of mixed transcortical aphasia.

Mixed transcortical aphasia (MTCA) is characterized by non-fluent speech and comprehension deficits coexisting with preserved repetition. MTCA may evolve to less severe variants of aphasias or even to full language recovery. Mechanistically, MCTA has traditionally been attributed to a disconnection between the spared left perisylvian language network (PSLN) responsible for preserved verbal repetition, and damaged left extrasylvian networks, which are responsible for language production and comprehension impairments. However, despite significant advances in in vivo neuroimaging, the structural and functional status of the PSLN network in MTCA and its evolution has not been investigated. Thus, the aim of the present study is to examine the status of the PSLN, both in terms of its functional activity and structural integrity, in four cases who developed acute post-stroke MTCA and progressed to different types of aphasia. For it, we conducted a neuroimaging-behavioral study performed in the chronic stage of four patients. The behavioral profile of MTCA persisted in one patient, whereas the other three patients progressed to less severe types of aphasias. Neuroimaging findings suggest that preserved verbal repetition in MTCA does not always depend on the optimal status of the PSLN and its dorsal connections. Instead, the right hemisphere or the left ventral pathway may also play a role in supporting verbal repetition. The variability in the clinical evolution of MTCA may be explained by the varying degree of PSLN alteration and individual premorbid neuroanatomical language substrates. This study offers a fresh perspective of MTCA through the lens of modern neuroscience and unveils novel insights into the neural underpinnings of repetition.

Dementia prevention in memory clinics: recommendations from the European task force for brain health services.

Observational population studies indicate that prevention of dementia and cognitive decline is being accomplished, possibly as an unintended result of better vascular prevention and healthier lifestyles. Population aging in the coming decades requires deliberate efforts to further decrease its prevalence and societal burden. Increasing evidence supports the efficacy of preventive interventions on persons with intact cognition and high dementia risk. We report recommendations for the deployment of second-generation memory clinics (Brain Health Services) whose mission is evidence-based and ethical dementia prevention in at-risk individuals. The cornerstone interventions consist of (i) assessment of genetic and potentially modifiable risk factors including brain pathology, and risk stratification, (ii) risk communication with ad-hoc protocols, (iii) risk reduction with multi-domain interventions, and (iv) cognitive enhancement with cognitive and physical training. A roadmap is proposed for concept validation and ensuing clinical deployment.

Donepezil alone and combined with intensive language-action therapy on depression and apathy in chronic post-stroke aphasia: A feasibility study.

This study explored the feasibility and effectiveness of a short-term (10-week) intervention trial using Donepezil administered alone and combined with intensive language action therapy (ILAT) for the treatment of apathy and depression in ten people with chronic post-stroke aphasia. Outcome measures were the Western Aphasia Battery and the Stroke Aphasia Depression Questionnaire-21. Structural magnetic resonance imaging and 18fluorodeoxyglucose positron emission tomography were acquired at baseline and after two endpoints (Donepezil alone and Donepezil-ILAT). The intervention was found to be feasible to implement. Large treatment effects were found. Donepezil alone and combined with ILAT reduced aphasia severity, while apathy and depression only improved with Donepezil-ILAT. Structural and functional neuroimaging data did not show conclusive results but provide hints for future research. Given these overall positive findings on feasibility, language and behavioral benefits, further studies in larger sample sizes and including a placebo-control group are indicated.

Spectrum of neuropsychiatric symptoms in chronic post-stroke aphasia.

BACKGROUND: Neuropsychiatric symptoms (NPS) have been insufficiently examined in persons with aphasia (PWA) because most previous studies exclude participants with language and communication disorders. AIM: To report a two-part study consisting of a literature review and an observational study on NPS in post-stroke aphasia. METHODS: Study 1 reviewed articles obtained from PubMed, PsycINFO, Google Scholar and Cochrane databases after cross-referencing key words of post-stroke aphasia to NPS and disorders. Study 2 examined language deficits and activities of daily living in 20 PWA (median age: 58, range: 28-65 years; 13 men) with the Western Aphasia Battery-Revised and the Barthel Index, respectively. Informants of these 20 PWA were proxy-evaluated with the Neuropsychiatric Inventory and domain-specific scales, including the Stroke Aphasia Depression Questionnaire-10 item version and the Starkstein Apathy Scale. In addition, an adapted version of the Hospital Anxiety and Depression Scale was directly administered to the PWA themselves. This observational study is based on the baseline assessment of an intervention clinical trial (EudraCT: 2017-002858-36; ClinicalTrials.gov identifier: NCT04134416). RESULTS: The literature review revealed a broad spectrum of NPS in PWA, including depression, anxiety, apathy, agitation/aggression, eating and sleep disorders, psychosis, and hypomania/mania. These findings alert to the need for improving assessment and treatment approaches of NPS taking into consideration their frequent occurrence in PWA. Study 2 showed that the 20 participants had mild- to-moderate aphasia severity and were functionally independent. A wide range of comorbid NPS was found in the post-stroke aphasic population (median number of NPS: 5, range: 1-8). The majority of PWA (75%) had depressive symptoms, followed by agitation/aggression (70%), irritability (70%), anxiety (65%) and appetite/eating symptoms (65%). Half of them also presented symptoms of apathy, whereas euphoria and psychotic symptoms were rare (5%). Domain-specific scales revealed that 45% of participants had apathy and 30% were diagnosed with depression and anxiety. CONCLUSION: Concurrent NPS are frequent in the chronic period of post-stroke aphasia. Therefore, further research on reliable and valid assessment tools and treatment for this aphasic population is strongly warranted.

Intensive aphasia therapy improves low mood in fluent post-stroke aphasia: Evidence from a case-controlled study.

Introduction: Depressive symptoms are a major drawback of aphasia, negatively impacting on functional outcomes. In a previous study, Intensive Language-Action Therapy (ILAT) was effective in improving depression and low mood in persons with chronic non-fluent aphasia. We present a proof-of-concept case-control study that evaluates language and mood outcomes amongst persons with fluent post-stroke aphasia.Participants: Thirteen Spanish speaking persons with fluent aphasia due to chronic stroke lesions in the left hemisphere participated in the study.Intervention: Five participants (intervention group) received ILAT for 3 h/day during two consecutive weeks, for an overall of 30 h, and 8 participants (control group) entered a waiting-list no-treatment arm.Results: The main finding was that participants receiving active treatment showed significant improvements on depression and aphasia severity scores, whereas no significant changes were found in the control group.Conclusions: The implementation of ILAT was efficient in improving clinical language deficits in people with fluent aphasia and contributes to improvement in mood after therapy.Trial registration: EUDRACT (2008-008481-12).

Protocols for cognitive enhancement. A user manual for Brain Health Services-part 5 of 6.

Cognitive complaints in the absence of objective cognitive impairment, observed in patients with subjective cognitive decline (SCD), are common in old age. The first step to postpone cognitive decline is to use techniques known to improve cognition, i.e., cognitive enhancement techniques.We aimed to provide clinical recommendations to improve cognitive performance in cognitively unimpaired individuals, by using cognitive, mental, or physical training (CMPT), non-invasive brain stimulations (NIBS), drugs, or nutrients. We made a systematic review of CMPT studies based on the GRADE method rating the strength of evidence.CMPT have clinically relevant effects on cognitive and non-cognitive outcomes. The quality of evidence supporting the improvement of outcomes following a CMPT was high for metamemory; moderate for executive functions, attention, global cognition, and generalization in daily life; and low for objective memory, subjective memory, motivation, mood, and quality of life, as well as a transfer to other cognitive functions. Regarding specific interventions, CMPT based on repeated practice (e.g., video games or mindfulness, but not physical training) improved attention and executive functions significantly, while CMPT based on strategic learning significantly improved objective memory.We found encouraging evidence supporting the potential effect of NIBS in improving memory performance, and reducing the perception of self-perceived memory decline in SCD. Yet, the high heterogeneity of stimulation protocols in the different studies prevent the issuing of clear-cut recommendations for implementation in a clinical setting. No conclusive argument was found to recommend any of the main pharmacological cognitive enhancement drugs ("smart drugs", acetylcholinesterase inhibitors, memantine, antidepressant) or herbal extracts (Panax ginseng, Gingko biloba, and Bacopa monnieri) in people without cognitive impairment.Altogether, this systematic review provides evidence for CMPT to improve cognition, encouraging results for NIBS although more studies are needed, while it does not support the use of drugs or nutrients.

Case Report: Barely Able to Speak, Can't Stop Echoing: Echolalic Dynamic Aphasia in Progressive Supranuclear Palsy.

The diagnostic criteria for progressive supranuclear palsy (PSP) incorporate two speech-language disturbances (SLDs), non-fluent/agrammatic primary progressive aphasia and progressive apraxia of speech, but overlook the inclusion of other SLDs, including dynamic aphasia (DA). Thus, there is a need to reappraise the broad spectrum of SLDs in PSP to include other presenting phenotypes. Here we report findings from the study of two elderly patients with PSP presenting with DA and irrepressible echolalia. Both patients had markedly impoverished verbal production, but their performance in other tasks (repetition and naming) and auditory comprehension were preserved or only mildly impaired. Experimental tests of DA revealed impaired word and sentence generation in response to verbal and non-verbal stimuli. Additional language and cognitive testing revealed different types of echolalia (mitigated, automatic, and echoing approval) as well as impaired inhibitory control and social cognition (mentalizing). Both patients had negative neuropsychiatric alterations (i.e., apathy, aspontaneity, and indifference/emotional flatness). Brain magnetic resonance imaging in both patients showed atrophy of the midbrain tegmentum and superior medial frontal cortex suggestive of PSP, yet further evaluation of the neural correlates using multimodal neuroimaging and neuropathological data was not performed. However, based on the already known neural basis of DA and echolalia in PSP and stroke, we suggest that, in the present cases, neurodegeneration in the midbrain tegmentum, superior medial frontal lobe, and caudate nucleus was responsible for DA and that decreased activity in these regions may play a permissive role for eliciting verbal echoing via disinhibition of the perisylvian speech-language network.

Pharmacotherapy of Traumatic Childhood Aphasia: Beneficial Effects of Donepezil Alone and Combined With Intensive Naming Therapy.

At present, language therapy is the only available treatment for childhood aphasia (CA). Studying new interventions to augment and hasten the benefits provided by language therapy in children is strongly needed. CA frequently emerges as a consequence of traumatic brain injury and, as in the case of adults, it may be associated with dysfunctional activity of neurotransmitter systems. The use of cognitive-enhancing drugs, alone or combined with aphasia therapy, promotes improvement of language deficits in aphasic adults. In this study we report the case of a 9-year-old right-handed girl, subject P, who had chronic anomic aphasia associated with traumatic lesions in the left temporal-parietal cortex. We performed a single-subject, open-label study encompassing administration of the cholinergic agent donepezil (DP) alone during 12 weeks, followed by a combination of DP and intensive naming therapy (INT) for 2 weeks and thereafter by a continued treatment of DP alone during 12 weeks, a 4-week washout period, and another 2 weeks of INT. Four comprehensive language and neuropsychological evaluations were performed at different timepoints along the study, and multiple naming evaluations were performed after each INT in order to assess performance in treated and untreated words. Structural magnetic resonance imaging (MRI) was performed at baseline. MRI revealed two focal lesions in the left hemisphere, one large involving the posterior inferior and middle temporal gyri and another comprising the angular gyrus. Overall, baseline evaluation disclosed marked impairment in naming with mild-to-moderate compromise of spontaneous speech, repetition, and auditory comprehension. Executive and attention functions were also affected, but memory, visuoconstructive, and visuoperceptive functions were preserved. Treatment with DP alone significantly improved spontaneous speech, auditory comprehension, repetition, and picture naming, in addition to processing speed, selective, and sustained attention. Combined DP-INT further improved naming. After washout of both interventions, most of these beneficial changes remained. Importantly, DP produced no side effects and subject P attained the necessary level of language competence to return to regular schooling. In conclusion, the use of DP alone and in combination with INT improved language function and related cognitive posttraumatic deficits in a child with acquired aphasia. Further studies in larger samples are warranted.

Neurocognitive signatures of phonemic sequencing in expert backward speakers.

Despite its prolific growth, neurolinguistic research on phonemic sequencing has largely neglected the study of individuals with highly developed skills in this domain. To bridge this gap, we report multidimensional signatures of two experts in backward speech, that is, the capacity to produce utterances by reversing the order of phonemes while retaining their identity. Our approach included behavioral assessments of backward and forward speech alongside neuroimaging measures of voxel-based morphometry, diffusion tensor imaging, and resting-state functional connectivity. Relative to controls, both backward speakers exhibited behavioral advantages for reversing words and sentences of varying complexity, irrespective of working memory skills. These patterns were accompanied by increased grey matter volume, higher mean diffusivity, and enhanced functional connectivity along dorsal and ventral stream regions mediating phonological and other linguistic operations, with complementary support of areas subserving associative-visual and domain-general processes. Still, the specific loci of these neural patterns differed between both subjects, suggesting individual variability in the correlates of expert backward speech. Taken together, our results offer new vistas on the domain of phonemic sequencing, while illuminating neuroplastic patterns underlying extraordinary language abilities.

Developmental Dynamic Dysphasia: Are Bilateral Brain Abnormalities a Signature of Inefficient Neural Plasticity?

The acquisition and evolution of speech production, discourse and communication can be negatively impacted by brain malformations. We describe, for the first time, a case of developmental dynamic dysphasia (DDD) in a right-handed adolescent boy (subject D) with cortical malformations involving language-eloquent regions (inferior frontal gyrus) in both the left and the right hemispheres. Language evaluation revealed a markedly reduced verbal output affecting phonemic and semantic fluency, phrase and sentence generation and verbal communication in everyday life. Auditory comprehension, repetition, naming, reading and spelling were relatively preserved, but executive function was impaired. Multimodal neuroimaging showed a malformed cerebral cortex with atypical configuration and placement of white matter tracts bilaterally and abnormal callosal fibers. Dichotic listening showed right hemisphere dominance for language, and functional magnetic resonance imaging (fMRI) additionally revealed dissociated hemispheric language representation with right frontal activation for phonology and bilateral dominance for semantic processing. Moreover, subject D also had congenital mirror movements (CMM), defined as involuntary movements of one side of the body that mirror intentional movements of the other side. Transcranial magnetic stimulation and fMRI during voluntary unimanual (left and right) hand movements showed bilateral motor cortex recruitment and tractography revealed a lack of decussation of bilateral corticospinal tracts. Genetic testing aimed to detect mutations that disrupt the development of commissural tracts correlating with CMM (e.g., Germline DCC mutations) was negative. Overall, our findings suggest that DDD in subject D resulted from the underdevelopment of the left inferior frontal gyrus with limited capacity for plastic reorganization by its homologous counterpart in the right hemisphere. Corpus callosum anomalies probably contributed to hinder interhemispheric connectivity necessary to compensate language and communication deficits after left frontal involvement.

"Need to Know" or the Strong Urge to Find Names of Unique Entities in Acquired Obsessive-Compulsive Disorder.

The two forms of obsessive-compulsive disorder (OCD), idiopathic and acquired, have been linked to abnormalities in the fronto-striato-thalamo-cortical circuitry, involving the orbitofrontal cortex, anterior cingulate cortex, thalamus, and striatum. Accumulating evidence indicates that damage to other brain regions (ie, temporal lobes) is also implicated in the pathogenesis of both types of OCD. In addition, some discrete OCD symptoms have received less attention because of their presumed low occurrence and difficultly of categorization. Among these, one intriguing and potentially severe type of obsessive thinking is the so-called "need to know" (NtK), which is a strong urge to access certain information, particularly proper names. In some patients, this monosymptomatic presentation may constitute the major feature of OCD. Here we report the cases of two patients who developed NtK obsessions with tenacious time-consuming, answer-seeking compulsions as the only or more disabling symptomatology in association with malignant tumors involving the right temporal lobe and connected fronto-subcortical circuits.

Language as a Threat: Multimodal Evaluation and Interventions for Overwhelming Linguistic Anxiety in Severe Aphasia.

Linguistic anxiety (LA) is an abnormal stress response induced by situations that require the use of verbal behavior, and it is accentuated during language testing in persons with aphasia (PWA). The presence of LA in PWA may jeopardize the interpretation of cognitive evaluations, leading to biased conclusions about the severity of the language alteration and the effectiveness of the treatments. In the present study, we report the case of a woman (Mrs. A) with severe chronic mixed transcortical aphasia due to left frontal and parietal hemorrhages that partially spared the perisylvian area. Mrs. A was treated with the dopamine agonist Rotigotine alone and combined with Intensive Language-Action Therapy (ILAT). Complementary evaluations included autonomic reactivity during the performance of different language tasks, resting state functional magnetic resonance imaging (rs-fMRI) and [18F]-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). We found that formal language testing in a clinical setting triggered a dramatic increase of automatic echolalia, perseverations and frustration, making the task completion difficult. The treatment improved aphasia, but gains were more robust when evaluation was performed by Mrs. A's husband at home than by clinicians. Autonomic evaluation under Rotigotine revealed higher reactivity during tasks tapping an impaired function in comparison with a task evaluating a preserved function (verbal repetition). Baseline 18F-FDG-PET analysis showed decreased metabolic activity in left limbic-paralimbic areas, whereas rs-fMRI revealed compensatory activity in the right hemisphere. We also analyzed the different factors (e.g., premorbid personality traits, task difficulty) that may have contributed to LA in Mrs. A during language testing. Our findings emphasize the usefulness of implicating adequately trained laypersons in the evaluation and treatment of PWA showing LA. Further studies using multidimensional evaluations are needed to disentangle the interplay between anxiety and abnormal language as well as the neural mechanisms underpinning LA in PWA.

Repetitive verbal behaviors are not always harmful signs: Compensatory plasticity within the language network in aphasia.

Repetitive verbal behaviors such as conduite d'approche (CdA) and mitigated echolalia (ME) are well-known phenomena since early descriptions of aphasia. Nevertheless, there is no substantial fresh knowledge on their clinical features, neural correlates and treatment interventions. In the present study we take advantage of three index cases of chronic fluent aphasia showing CdA, ME or both symptoms to dissect their clinical and neural signatures. Using multimodal neuroimaging (structural magnetic resonance imaging and [18]-fluorodeoxyglucose positron emission tomography during resting state), we found that despite of the heterogeneous lesions in terms of etiology (stroke, traumatic brain injury), volume and location, CdA was present when the lesion affected in greater extent the left dorsal language pathway, while ME resulted from preferential damage to the left ventral stream. The coexistence of CdA and ME was associated with involvement of areas overlapping with the structural lesions and metabolic derangements described in the subjects who showed one of these symptoms (CdA or ME). These findings suggest that CdA and ME represent the clinical expression of plastic changes that occur within the spared language network and its interconnected areas in order to compensate for the linguistic functions that previously relied on the activity of the damaged pathway. We discuss the results in the light of this idea and consider alternative undamaged neural networks that may support CdA and ME.

The Role of Verb Fluency in the Detection of Early Cognitive Impairment in Alzheimer's Disease.

BACKGROUND: Verb fluency (VF) is the less commonly used fluency test, despite several studies suggesting its potential as a neuropsychological assessment tool. OBJECTIVE: To investigate the presence of VF deficits in mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) dementia; to assess the usefulness of VF in the detection of cognitively healthy (CH) people who will convert to MCI, and from MCI to dementia; and to establish the VF cut-offs useful in the cognitive assessment of Spanish population. METHODS: 568 CH, 885 MCI, and 367 mild AD dementia individuals were administered the VF test and a complete neuropsychological battery. Longitudinal analyses were performed in 231 CH and 667 MCI subjects to search for VF predictors of diagnosis conversion. RESULTS: A worsening on VF performance from CH, MCI to AD dementia groups was found. Lower performances on VF were significantly related to conversion from CH to MCI/MCI to dementia. When the effect of time to conversion was analyzed, a significant effect of VF was found on the faster conversion from CH to MCI, but not from MCI to dementia. Moreover, VF cut-off scores and sensitivity/specificity values were calculated for 6 conditions (3 age ranges by 2 educational levels). CONCLUSION: The VF test may be a useful tool for the differential diagnosis of cognitive failure in the elderly. Since VF deficits seem to take place in early stages of the disease, it is a suitable neuropsychological tool for the detection not only of CH people who will convert to MCI, but also from MCI to dementia.

Plasticity in the Working Memory System: Life Span Changes and Response to Injury.

Working memory acts as a key bridge between perception, long-term memory, and action. The brain regions, connections, and neurotransmitters that underlie working memory undergo dramatic plastic changes during the life span, and in response to injury. Early life reliance on deep gray matter structures fades during adolescence as increasing reliance on prefrontal and parietal cortex accompanies the development of executive aspects of working memory. The rise and fall of working memory capacity and executive functions parallels the development and loss of neurotransmitter function in frontal cortical areas. Of the affected neurotransmitters, dopamine and acetylcholine modulate excitatory-inhibitory circuits that underlie working memory, are important for plasticity in the system, and are affected following preterm birth and adult brain injury. Pharmacological interventions to promote recovery of working memory abilities have had limited success, but hold promise if used in combination with behavioral training and brain stimulation. The intense study of working memory in a range of species, ages and following injuries has led to better understanding of the intrinsic plasticity mechanisms in the working memory system. The challenge now is to guide these mechanisms to better improve or restore working memory function.

Intensive Communicative Therapy Reduces Symptoms of Depression in Chronic Nonfluent Aphasia.

BACKGROUND: Patients with brain lesions and resultant chronic aphasia frequently suffer from depression. However, no effective interventions are available to target neuropsychiatric symptoms in patients with aphasia who have severe language and communication deficits. OBJECTIVE: The present study aimed to investigate the efficacy of 2 different methods of speech and language therapy in reducing symptoms of depression in aphasia on the Beck Depression Inventory (BDI) using secondary analysis (BILAT-1 trial). METHODS: In a crossover randomized controlled trial, 18 participants with chronic nonfluent aphasia following left-hemispheric brain lesions were assigned to 2 consecutive treatments: (1) intensive language-action therapy (ILAT), emphasizing communicative language use in social interaction, and (2) intensive naming therapy (INT), an utterance-centered standard method. Patients were randomly assigned to 2 groups, receiving both treatments in counterbalanced order. Both interventions were applied for 3.5 hours daily over a period of 6 consecutive working days. Outcome measures included depression scores on the BDI and a clinical language test (Aachen Aphasia Test). RESULTS: Patients showed a significant decrease in symptoms of depression after ILAT but not after INT, which paralleled changes on clinical language tests. Treatment-induced decreases in depression scores persisted when controlling for individual changes in language performance. CONCLUSIONS: Intensive training of behaviorally relevant verbal communication in social interaction might help reduce symptoms of depression in patients with chronic nonfluent aphasia.