Dementia with aphasia and mirror phenomenon: examination of the mechanism using neuroimaging and neuropsychological findings: a case report.

BACKGROUND: Aphasia often appears in persons living with dementia; however, aphasia and the mirror phenomenon are rarely present at the same time. CASE PRESENTATION: Here, we report a case of fluent conversation with a person in a mirror or a magazine, and examine the underlying mechanism using brain imaging and neuropsychological findings. We found that the appearance of the mirror phenomenon may be associated with a visuospatial dysfunction caused by a decreased function of the posterior region of the right temporal and parietal lobe. Moreover, active talking to a person in a mirror or a person in a magazine could be associated with disinhibition caused by a decline in bilateral frontal lobe function. CONCLUSIONS: This case represents a very valuable and interesting presentation because it is the first report of a long-term follow-up of the course of dementia using neurological imaging, and of the neuropsychological analysis of the mechanism of conversation with a mirror image combined with aphasia.

Correlación neurorradiológica de las afasias. Mapa cortico-subcortical del lenguaje / Neuroradiologic correlation with aphasias. Cortico-subcortical map of language

La afasia es una alteración adquirida del lenguaje debida a una lesión cerebral, que se caracteriza por errores en la producción, la denominación o la comprensión del lenguaje. Aunque la mayoría de las afasias suelen ser mixtas, desde un punto de vista práctico se clasifican en diferentes tipos según sus rasgos clínicos principales: afasia de Broca, afasia de Wernicke, afasia de conducción, afasia transcortical y alexia con o sin agrafia. Presentamos los hallazgos clínicos de los principales subtipos representándolos con casos radiológicos, y proporcionamos una revisión actualizada de la red del lenguaje con imágenes de resonancia funcional y de tractografía

Aphasia is an acquired language disorder due to a cerebral lesion; it is characterized by errors in production, denomination, or comprehension of language. Although most aphasias are mixed, from a practical point of view they are classified into different types according to their main clinical features: Broca's aphasia, Wernicke's aphasia, conduction aphasia, transcortical aphasia, and alexia with or without agraphia. We present the clinical findings for the main subtypes of aphasia, illustrating them with imaging cases, and we provide an up-to-date review of the language network with images from functional magnetic resonance imaging and tractography

Retraining speech production and fluency in non-fluent/agrammatic primary progressive aphasia.

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) presents with a gradual decline in grammar and motor speech resulting from selective degeneration of speech-language regions in the brain. There has been considerable progress in identifying treatment approaches to remediate language deficits in other primary progressive aphasia variants; however, interventions for the core deficits in nfvPPA have yet to be systematically investigated. Further, the neural mechanisms that support behavioural restitution in the context of neurodegeneration are not well understood. We examined the immediate and long-term benefits of video implemented script training for aphasia (VISTA) in 10 individuals with nfvPPA. The treatment approach involved repeated rehearsal of individualized scripts via structured treatment with a clinician as well as intensive home practice with an audiovisual model using 'speech entrainment'. We evaluated accuracy of script production as well as overall intelligibility and grammaticality for trained and untrained scripts. These measures and standardized test scores were collected at post-treatment and 3-, 6-, and 12-month follow-up visits. Treatment resulted in significant improvement in production of correct, intelligible scripted words for trained topics, a reduction in grammatical errors for trained topics, and an overall increase in intelligibility for trained as well as untrained topics at post-treatment. Follow-up testing revealed maintenance of gains for trained scripts up to 1 year post-treatment on the primary outcome measure. Performance on untrained scripts and standardized tests remained relatively stable during the follow-up period, indicating that treatment helped to stabilize speech and language despite disease progression. To identify neural predictors of responsiveness to intervention, we examined treatment effect sizes relative to grey matter volumes in regions of interest derived from a previously identified speech production network. Regions of significant atrophy within this network included bilateral inferior frontal cortices and supplementary motor area as well as left striatum. Volumes in a left middle/inferior temporal region of interest were significantly correlated with the magnitude of treatment effects. This region, which was relatively spared anatomically in nfvPPA patients, has been implicated in syntactic production as well as visuo-motor facilitation of speech. This is the first group study to document the benefits of behavioural intervention that targets both linguistic and motoric deficits in nfvPPA. Findings indicate that behavioural intervention may result in lasting and generalized improvement of communicative function in individuals with neurodegenerative disease and that the integrity of spared regions within the speech-language network may be an important predictor of treatment response.

Phonotactic processing deficit following left-hemisphere stroke.

The neural basis of speech processing is still a matter of great debate. Phonotactic knowledge-knowledge of the allowable sound combinations in a language-remains particularly understudied. The purpose of this study was to investigate the brain regions crucial to phonotactic knowledge in left-hemisphere stroke survivors. Results were compared to areas in which gray matter anatomy related to phonotactic knowledge in healthy controls. 44 patients with chronic left-hemisphere stroke, and 32 controls performed an English-likeness rating task on 60 auditory non-words of varying phonotactic regularities. They were asked to rate on a 1-5 scale, how close each non-word sounded to English. Patients' performance was compared to that of healthy controls, using mixed effects modeling. Multivariate lesion-symptom mapping and voxel-based morphometry were used to find the brain regions important for phonotactic processing in patients and controls respectively. The results showed that compared to controls, stroke survivors were less sensitive to phonotactic regularity differences. Lesion-symptom mapping demonstrated that a loss of sensitivity to phonotactic regularities was associated with lesions in left angular gyrus and posterior middle temporal gyrus. Voxel-based morphometry also revealed a positive correlation between gray matter density in left angular gyrus and sensitivity to phonotactic regularities in controls. We suggest that the angular gyrus is used to compare the incoming speech stream to internal predictions based on the frequency of sound sequences in the language derived from stored lexical representations in the posterior middle temporal gyrus.

Transcortical Sensory Aphasia after Left Frontal Lobe Infarction: Loss of Functional Connectivity.

BACKGROUND: The underlying mechanism of transcortical sensory aphasia (TSA) caused by lesions occurring in the left frontal lobe remains unclear. We attempted to investigate the mechanism with the use of functional MRI (fMRI). METHODS: We studied 2 patients with TSA after a left frontal infarction identified by diffusion-weighted MRI. As control subjects, a patient with transcortical motor aphasia and a healthy normal adult were chosen. The Korean version of Western Aphasia Battery was performed initially and at 3 months post stroke. We performed fMRI using verb generation and sentence completion tasks. Resting-state fMRI (rs-fMRI) was also obtained for network-level analysis initially and at 3 months post stroke. RESULTS: The results of diffusion- and perfusion-weighted MRI revealed no diffusion-perfusion mismatch. Initial fMRI in patients with TSA showed no reversed inter-/intrahemispheric activation patterns. rs-fMRI showed significantly decreased resting-state functional connectivity in the language network in patients with TSA compared with the control subjects. Follow-up rs-fMRI studies showed improvement in functional connectivity along with the recovery of patients' language function. CONCLUSION: Our data showed that the auditory comprehension deficits in patients with frontal lobe infarcts is attributed to difficulty accessing the posterior language area due to functional disconnection between language centers in the acute stage of stroke.

Phonological and semantic processing during comprehension in Wernicke's aphasia: An N400 and Phonological Mapping Negativity Study.

Comprehension impairments in Wernicke's aphasia are thought to result from a combination of impaired phonological and semantic processes. However, the relationship between these cognitive processes and language comprehension has only been inferred through offline neuropsychological tasks. This study used ERPs to investigate phonological and semantic processing during online single word comprehension. EEG was recorded in a group of Wernicke's aphasia n=8 and control participants n=10 while performing a word-picture verification task. The N400 and Phonological Mapping Negativity/Phonological Mismatch Negativity (PMN) event-related potential components were investigated as an index of semantic and phonological processing, respectively. Individuals with Wernicke's aphasia displayed reduced and inconsistent N400 and PMN effects in comparison to control participants. Reduced N400 effects in the WA group were simulated in the control group by artificially degrading speech perception. Correlation analyses in the Wernicke's aphasia group found that PMN but not N400 amplitude was associated with behavioural word-picture verification performance. The results confirm impairments at both phonological and semantic stages of comprehension in Wernicke's aphasia. However, reduced N400 responses in Wernicke's aphasia are at least partially attributable to earlier phonological processing impairments. The results provide further support for the traditional model of Wernicke's aphasia which claims a causative link between phonological processing and language comprehension impairments.

Auditory training changes temporal lobe connectivity in 'Wernicke's aphasia': a randomised trial.

INTRODUCTION: Aphasia is one of the most disabling sequelae after stroke, occurring in 25%-40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. TRIAL DESIGN: This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using 'Earobics' software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. METHODS: The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. RESULTS: Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. CONCLUSIONS: Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex.Clinical trial registrationThis trial was registered with EudraCT (2005-004215-30, https://eudract.ema.europa.eu/) and ISRCTN (68939136, http://www.isrctn.com/).

Degenerative jargon aphasia: unusual progression of logopenic/phonological progressive aphasia?

Primary progressive aphasia (PPA) corresponds to the gradual degeneration of language which can occur as nonfluent/agrammatic PPA, semantic variant PPA or logopenic variant PPA. We describe the clinical evolution of a patient with PPA presenting jargon aphasia as a late feature. At the onset of the disease (ten years ago) the patient showed anomia and executive deficits, followed later on by phonemic paraphasias and neologisms, deficits in verbal short-term memory, naming, verbal and semantic fluency. At recent follow-up the patient developed an unintelligible jargon with both semantic and neologistic errors, as well as with severe deficit of comprehension which precluded any further neuropsychological assessment. Compared to healthy controls, FDG-PET showed a hypometabolism in the left angular and middle temporal gyri, precuneus, caudate, posterior cingulate, middle frontal gyrus, and bilaterally in the superior temporal and inferior frontal gyri. The clinical and neuroimaging profile seems to support the hypothesis that the patient developed a late feature of logopenic variant PPA characterized by jargonaphasia and associated with superior temporal and parietal dysfunction.

[FMRI-study of speech perception impairment in post-stroke patients with sensory aphasia].

The aim of the study was to find neurophysiological correlates of the primary stage impairment of speech perception, namely phonemic discrimination, in patients with sensory aphasia after acute ischemic stroke in the left hemisphere by noninvasive method of fMRI. For this purpose we registered the fMRI-equivalent of mismatch negativity (MMN) in response to the speech phonemes--syllables "ba" and "pa" in odd-ball paradigm in 20 healthy subjects and 23 patients with post-stroke sensory aphasia. In healthy subjects active brain areas depending from the MMN contrast were observed in the superior temporal and inferior frontal gyri in the right and left hemispheres. In the group of patients there was a significant activation of the auditory cortex in the right hemisphere only, and this activation was less in a volume and intensity than in healthy subjects and correlated to the degree of preservation of speech. Thus, the method of recording fMRI equivalent of MMN is sensitive to study the speech perception impairment.

Differentiating psychosis versus fluent aphasia.

Following a stroke, a patient may present with varying degrees of neurological impairment, depending on the area of the brain which is damaged. Specifically, damage to the left cortical hemisphere may result in aphasia. The characteristic speech in a patient with an aphasia caused by a stroke can be similar to the speech in some patients with schizophrenia or other psychotic disorders. In a new patient without a reliable history who presents with suspected aphasia, it is important to include psychotic disorders as part of the differential diagnosis. Failure to differentiate psychotic disorders from aphasia could result in either a lack of treatment that would improve the patient's thought process, thought content, or language, or in a delayed treatment for a stroke, respectively. While a number of psychotic disorders exist and must be differentiated from one another in accordance with DSM-IV guidelines, speech abnormalities in patients with schizophrenia are well described in the literature. For this reason, schizophrenia is the psychotic disorder of focus in this paper. This case report illustrates a clinical situation where a patient required both a psychiatric and neurological consultation in order to determine the etiology of his language disorder. The purpose of this paper is to emphasize the need to consider both psychiatric disorders and aphasia in patients with unknown histories who present with language abnormalities, and to help the clinician critically examine the patient's speech so that, in conjunction with other clinical data, the correct diagnosis can be made and appropriate treatment initiated.

Imaging features of CNS involvement in AIDS.

Patients with acquired immunodeficiency syndrome (AIDS) are the subjects of a large part of routine neuroradiological work in the Western world currently. The World Health Organization announced that Turkish authorities had reported a cumulative total of 2544 HIV cases from 1985 to 2006, of whom 623 had developed AIDS and 140 had died. It is estimated that approximately one-third of AIDS patients develop neurological complications. The spectrum of diseases affecting the central nervous system (CNS) in AIDS patients comprises predominantly opportunistic infections and primary CNS lymphoma. Although to a lesser degree when compared with Western countries, the incidence of AIDS and related neurological diseases are on the rise also in Turkey. Therefore radiologists should recognize HIV-associated problems and their imaging features. In this review, we focus on imaging features of more common CNS diseases in HIV-seropositive patients. This essay has been prepared using radiological studies of the patients who had been managed in our hospital which is a tertiary care center with a highly motivated medical team for this peculiar disease in the years between 2002 and 2008.

Prosodic changes in aphasic speech: timing.

Controversy remains about the impairment of prosody in aphasia, particularly with regard to speech timing. This paper addresses this topic through an analysis of timing in four sets of a common morphological paradigm. The paradigm consisted of a basic form (stem) and two longer derived forms (e.g. zip, zipper, zippering). Normally, vowel durations are shorter in longer derived forms (e.g. zippering) than in the stem (e.g. zip), due to a process called 'initial shortening'. Twelve patients with aphasia (four each Broca, Wernicke, and Anomic), and 11 age-matched healthy adults were assessed. Structural (CT) and functional brain imaging (PET) were available for all patients. While all groups showed initial shortening between the stem and the derived forms, the patients with Broca's aphasia presented an inverse pattern between the two derived forms (longer initial vowel in 'zippering' than 'zipper'), and the patients with Wernicke's aphasia produced significantly longer vowel durations overall than the healthy participants. The results are related to radiological information regarding the location of structural and functional brain damage and relative preservation and loss of prosodic features in cerebral damage.

[An unusual hospitalization under constraint]. / Une mise en observation peu ordinaire.

The case report describes a 45-year old man presenting of the behavioral problems and an aphasia of Wernicke, hospitalized under constraint. The urinary screening in the search of psychotropic substances is positive for the cannabis and the amphetamines. The neurological localization is confirmed by cerebral CT-scan. The discussion relates on the differential diagnosis between a schizophasia and an aphasia of Wernicke, on the difficulty of a somatic diagnosis among patients agitated under the effect of a drug and to the tendency to hospitalize those too quickly under constraint, on the noxious effect of drugs on the brain.

Crossed Wernicke's aphasia after aneurysmal subarachnoid hemorrhage: a case report.

Crossed aphasia (CA) refers to aphasia occurring after right brain damage in right handers. In the literature, numerous CA cases following cerebral ischemia have been reported, but few met the criteria for a prompt diagnosis. The authors present the case of a 52-year-old woman with SAH caused by a right middle cerebral artery (MCA) saccular aneurysm who developed non-fluent aphasia characterized by reduced verbal output, word-finding disturbances and phonemic paraphasias in both oral and written language. 99mTc-HMPAO SPECT was also consistent with right parieto-temporal and frontoparietal ischemia with crossed cerebellar diaschisis on the right cerebellum. A diagnosis of CA was made. One year follow-up showed improvement in communication skills but persistent right fronto-temporo-parietal ischemia. Cerebral vasospasm after aneurysmal SAH symptomatology may vary from motor and sensory disturbances to cognitive disabilities. Aphasia developing after cerebral ischemia of the right hemisphere in a right-hand dominant patient following vasospasm may be a misleading symptom for the localization of the insult. Keeping a high index of suspicion may help in making the correct diagnosis. The changes in the perfusion patterns of cerebellum as assessed by SPECT study during the acute and recovery phases suggests the involvement of cerebellum in language functions.

Fluent versus nonfluent primary progressive aphasia: a comparison of clinical and functional neuroimaging features.

To better characterize fluent and nonfluent variants of primary progressive aphasia (PPA). Although investigators have recognized both fluent and nonfluent patients with PPA, the clinical and neuroimaging features of these variants have not been fully defined. We present clinical and neuropsychological data on 47 PPA patients comparing the fluent (n=21) and nonfluent (n=26) subjects. We further compared language features with PET/SPECT data available on 39 of these patients. Compared to the nonfluent PPA patients, those with fluent PPA had greater impairment of confrontational naming and loss of single word comprehension. They also exhibited semantic paraphasic errors and loss of single word comprehension. Patients with nonfluent PPA were more likely to be female, were more often dysarthric, and exhibited phonological speech errors in the absence of semantic errors. No significant differences were seen with regard to left hemisphere abnormalities, suggesting that both variants result from mechanisms that overlap frontal, temporal, and parietal regions. Of the language measures, only semantic paraphasias were strongly localized, in this case to the left temporal lobe. Fluent and nonfluent forms of PPA are clinically distinguishable by letter fluency, single word comprehension, object naming, and types of paraphasic errors. Nevertheless, there is a large amount of overlap between dysfunctional anatomic regions associated with these syndromes.

Neuroanatomical correlates of the post-stroke aphasias studied with cerebral blood flow SPECT scanning.

BACKGROUND: Researchers are not in complete agreement over the extent to which specific language functions are subserved by certain brain areas. The purpose of this article was to determine neuroanatomical correlates of aphasia following cerebrovascular accident. MATERIAL/METHODS: The participants included 50 stroke patients with a single left-hemisphere lesion and residual mild to severe aphasia. Language, assessed by the Boston Diagnostic Aphasia Examination (BDAE), was affected to various degrees by a wide range of pathologies. Single-photon emission computed tomography (SPECT) images of the brain were acquired with 740 MBq (20 mCi) of Tc-99m-labeled ECD on a triple-headed gamma camera equipped with low-energy, high-resolution collimator. Correlation between reduced cerebral perfusion and the BDAE score was analyzed. RESULTS: The most prominent perfusion abnormalities in Broca's aphasia, as determined by the laterality index, were found in the frontal lobe, and to a lesser degree, the parietal lobe and striatum, whereas the most prominent deficits in Wernicke's aphasia were found in the left temporal and parietal areas. In global aphasia, SPECT images evidenced the most extensive damage throughout the perisylvian region of the left hemisphere. CONCLUSIONS: There is need for reinterpretation of the anatomical correlation of selected aphasic syndromes, especially classic Broca's and Wernicke's aphasias. The present study highlights the integrative role of some subcortical structures in language and speech functions. The results support the usefulness of regional cerebral blood flow SPECT imaging as a diagnostic aid in the post-stroke aphasias.

Regional cerebral distribution of [Tc-99m] hexylmethylpropylene amineoxine in patients with progressive aphasia.

Progressive aphasia is a prominent clinical feature of several neurodegenerative disorders. This study used hexylmethylpropylene amineoxine (HMPAO) single photon emission computed tomography (SPECT) to estimate blood flow in areas of the brain that mediate language in patients with progressive aphasia and matched control subjects. The patient population consisted of four men and 12 women with a mean +/- SD age of 69.1 +/- 7.6. Of these, eight were classified as having a nonfluent form of aphasia, whereas the other eight had a fluent form. The patients were compared to 16 healthy volunteers who were studied with an identical protocol. The SPECT images of the brain were acquired with 740 MBq (20 mCi) of Tc-99m-labeled HMPAO on a triple-headed gamma camera equipped with fan beam collimators. The images were analyzed with a set of standardized templates. Mean counts per pixel in 33 regions of interest were compared to the mean counts in the whole supratentorial brain. A laterality index was determined for homotopic regions using the equation 100 x (R - L)/(1/2 x (R - L)). Patients with progressive aphasia had several regions of significantly decreased HMPAO uptake in the left cortex when compared to the homotopic regions on the right. The most prominent deficit in the nonfluent group, as determined by the laterality index, were found in the left dorsolateral prefrontal region (p < 0.05), whereas the most prominent deficits in the group with fluent aphasia were found in the left temporal and parietal language centers (p < 0.05). The left subcortical nuclei were differentially affected, particularly in patients with nonfluent aphasia. The HMPAO SPECT indicates that multiple regions of the left hemisphere are dysfunctional in patients with progressive aphasia. The pattern of perfusion deficits in patients with fluent aphasia appears to be distinct from the pattern in patients with nonfluent aphasia.

Atypical and typical presentations of Alzheimer's disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases.

There has been increasing awareness that some slowly progressive focal cortical syndromes can be the presenting features of Alzheimer's disease, but pathological evidence has been sparse. This clinico-pathological series presents our experience with pathologically proven atypical as well as typical Alzheimer's disease presentations. We report and compare four patterns of presentation: a typical pattern with initial amnesic syndrome (n = 4 cases), progressive visual dysfunction (n = 1), progressive biparietal syndrome (n = 2) and progressive aphasia (n = 6). The aphasic presentations include both fluent and non-fluent aphasic syndromes. The neuropsychological profiles and neuroimaging clearly reflect the presenting clinical features, and show a close relationship to the distribution of pathology in these cases. Of note was the sparing of medial temporal structures (hippocampus and/or entorhinal cortex) in several aphasic cases and the severe occipito-parietal involvement in those with prominent visuospatial disorders at presentation. Our data demonstrate the wide spectrum of Alzheimer's disease presentations. The recognition of atypical presentations of Alzheimer's disease is important when attempting to make an early accurate pre-morbid diagnosis of neurodegenerative disease.