Foreign accent syndrome: a multimodal evaluation in the search of neuroscience-driven treatments.

Foreign accent syndrome (FAS) is a rare condition which is placed in the mildest end of the spectrum of speech disorders. The impairment, not severe enough to elicit phonological errors, is associated with various alterations in the fine execution of speech sounds which cause the impression of foreignness. There is a growing interest in the study of linguistic and paralinguistic components, psychosocial aftermaths, and neural basis of FAS, but there are not yet neuroscience-driven treatments for this condition. A multimodal evaluation was conducted in a single patient with the aim of searching for clues which may assist to design neuroscience-driven therapies. The patient was a middle-aged bilingual woman who had chronic FAS. She had segmental deficits, abnormal production of linguistic and emotional prosody, impaired verbal communication, and reduced motivation and social engagement. Magnetic resonance imaging showed bilateral small lesions mainly affecting the left deep frontal operculum and dorsal anterior insula. Diffusion tensor tractography suggested disrupted left deep frontal operculum-anterior insula connectivity. Metabolic activity measured with positron emission tomography was primarily decreased in key components of networks implicated in planning and execution of speech production, cognitive control and emotional communication (Brodmann's areas 4/6/9/10/13/25/47, basal ganglia, and anterior cerebellar vermis). Compensatory increases of metabolic activity were found in cortical areas (left anterior cingulate gyrus, left superior temporal gyrus and right prefrontal cortex) associated with feedback and focal attention processes critical for monitoring and adjustment of verbal utterances. Moreover, bilateral structural and functional abnormalities probably interrupted the trajectory of the lateral and medial cholinergic pathways causing region-specific hypoactivity. The results from this study provide targets for further investigation and some clues to design therapeutic interventions.

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.

Recovery from post-stroke aphasia: lessons from brain imaging and implications for rehabilitation and biological treatments.

Aphasia, a condition defined as the partial or complete loss of language function after brain damage, is one of the most devastating cognitive deficits produced by stroke lesions. Over the past decades, there have been great advances in the diagnosis and treatment of post-stroke language and communication deficits. In particular, the advent of functional brain imaging and other brain mapping methods has advanced our understanding of how the intact and lesioned brain takes over the activity of irretrievably damaged networks in aphasic patients. This review examines the contribution of these ancillary methods to elucidate the neural changes that take place to promote improvement of language function in early, late, and very late stages of recovery. Also, functional neuroimaging is helpful to identify brain areas involved in language recovery as well as to characterize the plastic reorganization of neural networks produced by scientifically-based language therapies and biological treatments (drugs, transcranial magnetic stimulation).

Can impairment in memory, language and executive functions predict neuropsychiatric symptoms in Alzheimer's disease (AD)? Findings from a cross-sectional study.

The authors performed a cross-sectional study to examine the relationship between specific cognitive domains and behavioral and psychological symptoms in dementia (BPSD) in 125 patients with probable AD. Cognitive deficits were evaluated with the mini mental state examination (MMSE), trail-making test (TMT), Rey auditory verbal learning test (RAVLT), and semantic fluency test (SFT) and phonemic fluency test (PhFT), whereas the neuropsychiatric inventory (NPI) was used to rate BPSD. Patients' performance in cognitive tests significantly correlated with total NPI scores (p<0.0001). After controlling for demographic and clinical characteristics, cognitive impairments in memory, executive function, and language (RAVLT, TMT, PhFT, SFT) importantly estimated total NPI scores (p<0.001, multivariate regression models). These findings suggest that the evaluation of cognitive domains may have a predictive value for the occurrence of BPSD.

Atypical conduction aphasia and the right hemisphere: Cross-hemispheric plasticity of phonology in a developmentally dyslexic and dysgraphic patient with early left frontal damage.

We report the rare case of a patient, JNR, with history of mixed handedness, developmental dyslexia, dysgraphia, and attentional deficits associated with a Klippel-Trenaunay syndrome and a small subcortical frontal lesion involving the left arcuate fasciculus. In adulthood, he suffered a large right perisylvian stroke and developed atypical conduction aphasia with deficits in input and output phonological processing and poor auditory-verbal short-term memory. Lexical-semantic processing for single words was intact, but he was unable to access meaning in sentence comprehension and repetition. Reading and writing deficits worsened after the stroke and he presented a combination of developmental and acquired dysgraphia and dyslexia with mixed lexical and phonological processing deficits. This case suggest that a small lesion sustained prenatally or early in life could induce a selective rightward shift of phonology sparing the standard left hemisphere lateralisation of lexical-semantic functions.

Late-life reactivation of obsessive-compulsive disorder associated with lesions in prefrontal-subcortical circuits.

The authors describe the reactivation of obsessive-compulsive disorder (OCD) in three patients with lesions in the prefronto-subcortical circuits after decades of being asymptomatic. The patients also reported the emergence of new OCD symptoms and motor/phonic tics as well as mental rituals thematically related to the negative experience of suffering cognitive and motor deficits.

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

OBJECTIVE: 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. METHODS: Patients were randomized to memantine (20 mg/day) or placebo alone during 16 weeks, followed by combined drug treatment with CIAT (weeks 16-18), drug treatment alone (weeks 18-20), and washout (weeks 20-24), and finally, an open-label extension phase of memantine (weeks 24-48). After baseline evaluations, clinical assessments were done at two end points (weeks 16 and 18), and at weeks 20, 24, and 48. Outcome measures were changes in the Western Aphasia Battery-Aphasia Quotient and the Communicative Activity Log. RESULTS: Twenty-eight patients were included, and 27 completed both treatment phases. The memantine group showed significantly better improvement on Western Aphasia Battery-Aphasia Quotient compared with the placebo group while the drug was taken (week 16, p = 0.002; week 18, p = 0.0001; week 20, p = 0.005) and at the washout assessment (p = 0.041). A significant increase in Communicative Activity Log was found in favor of memantine-CIAT relative to placebo-CIAT (week 18, p = 0.040). CIAT treatment led to significant improvement in both groups (p = 0.001), which was even greater under additional memantine treatment (p = 0.038). Beneficial effects of memantine were maintained in the long-term follow-up evaluation, and patients who switched to memantine from placebo experienced a benefit (p = 0.02). INTERPRETATION: Both memantine and CIAT alone improved aphasia severity, but best outcomes were achieved combining memantine with CIAT. Beneficial effects of memantine and CIAT persisted on long-term follow-up.