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.     

Recurrent fluent aphasia associated with a seizure focus

The relationship between dominant hemisphere seizure activity and aphasia is unclear. Although speech arrest, expressive speech problems, and comprehension difficulties have often been associated with temporal lobe seizure activity, neologistic, paraphasic speech is rare. We report a patient with seizures following encephalitis who had recurrent episodes of fluent, severely aphasic speech with impaired comprehension which correlated with continuous, high voltage spike and slow wave activity in the left temporal region. During a several-day period of intermittent electrographic seizure activity, he had fluctuating receptive aphasia, and he developed transient paranoid psychosis following treatment. We discuss the behavioral manifestations of his left temporal seizures and correlate the changing nature of his behavior with therapeutic interventions. This case, as well as a review of others, suggests that paroxysmal fluent aphasia results from a partially treated electrographic seizure focus in the dominant temporal lobe.     

Cathodal transcranial direct current stimulation of the right Wernicke's area improves comprehension in subacute stroke patients

Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and tDCS have been found to improve naming in non-fluent post-stroke aphasic patients. Here, we investigated the effect of tDCS on the comprehension of aphasic patients with subacute stroke. We hypothesized that tDCS applied to the left superior temporal gyrus (Wernicke’s area) or the right Wernicke’s area might be associated with recovery of comprehension ability in aphasic patients with subacute stroke. Participants included right-handed subacute stroke patients with global aphasia due to ischemic infarct of the left M1 or M2 middle cerebral artery. Patients were randomly divided into three groups: patients who received anodal tDCS applied to the left superior temporal gyrus, patients who received cathodal tDCS applied to the right superior temporal gyrus, and patients who received sham tDCS. All patients received conventional speech and language therapy during each period of tDCS application. The Korean-Western Aphasia Battery (K-WAB) was used to assess all patients before and after tDCS sessions. After intervention, all patients had significant improvements in aphasia quotients, spontaneous speech, and auditory verbal comprehension. However, auditory verbal comprehension improved significantly more in patients treated with a cathode, as compared to patients in the other groups. These results are consistent with the role of Wernicke’s area in language comprehension and the therapeutic effect that cathodal tDCS has on aphasia patients with subacute stroke, suggesting that tDCS may be an adjuvant treatment approach for aphasia rehabilitation therapy in patients in an early stage of stroke.     

Theodor Meynert′s Contribution to Classical 19th Century Aphasia Studies

Carl Wernicke (1848-1905) is traditionally considered the first to have described the features of, and the brain pathology underlying, impaired auditory comprehension and related symptoms. Although Wernicke (1874) clearly and repeatedly indicates his indebtedness to Theodor von Meynert (1833-1892). this is usually understood as an acknowledgment that Meynert taught Wernicke neuroanatomy (Eggert, 1977); Wernicke′s own words in part support this interpretation. A more sophisticated historical analysis notes that, prior to Wernicke, both Johann Schmidt in 1871 and Charlton Bastian in 1869 had described the concept of receptive aphasia, but neither had supported their analyses with autopsy evidence as did Wernicke, thus not dislodging Wernicke′s claim of priority. However, a virtually unknown work by Theodor von Meynert, published in 1866, has recently been rediscovered by us ["Ein Fall von Sprachstörung, anatomisch begründet." Medizinische Jahrbücher. XII Band der Zeitschrift der K. K. Gesellleschaft der Ärzte in Wien, 22.Jahr. Pp. 152-189]. In this paper Meynert analyzes the anatomical basis for localizing the comprehension of language in the superior temporal gyros, he argues that lesions in this area should (by analogy to Broca′s earlier observations on language expression) cause impairments in language comprehension, and he presents a case of receptive aphasia with autopsy evidence of destruction of the superior temporal gyros in the left hemisphere. The patient′s aphasia was classic: impaired auditory comprehension, and fluent speech with paraphasias. It is clear that Meynert should be given historical credit for his work.     

Semantic dementia and persisting Wernicke's aphasia: linguistic and anatomical profiles

Few studies have directly compared the clinical and anatomical characteristics of patients with progressive aphasia to those of patients with aphasia caused by stroke. In the current study we examined fluent forms of aphasia in these two groups, specifically semantic dementia (SD) and persisting Wernicke’s aphasia (WA) due to stroke. We compared 10 patients with SD to 10 age- and education-matched patients with WA in three language domains: language comprehension (single words and sentences), spontaneous speech and visual semantics. Neuroanatomical involvement was analyzed using disease-specific image analysis techniques: voxel-based morphometry (VBM) for patients with SD and overlays of lesion digitized lesion reconstructions in patients with WA. Patients with SD and WA were both impaired on tasks that involved visual semantics, but patients with SD were less impaired in spontaneous speech and sentence comprehension. The anatomical findings showed that different regions were most affected in the two disorders: the left anterior temporal lobe in SD and the left posterior middle temporal gyrus in chronic WA. This study highlights that the two syndromes classically associated with language comprehension deficits in aphasia due to stroke and neurodegenerative disease are clinically distinct, most likely due to distinct distributions of damage in the temporal lobe.     

Linguistic and other psychological aspects of paroxysmal aphasia

A case of paroxysmal aphasia is reported. Aphasic spells occurred, in this patient, without modification in consciousness and without involvement of behaviors others than those related to oral and written speech and language. Longer spells successively recapitulated the clinical pictures of global, Wernicke's, conduction, and amnestic aphasia. Besides aphasiological evaluations, neurological, psychometrical, electroencephalographical, and CT-scan documents were obtained. The discussion bears on four main points: the linguistic characteristics of paroxysmal aphasia as compared to those of aphasias of other etiologies; Pierre Marie's oneness doctrine of aphasia; the mutual relationships of language and thought (in aphasia); the affective experience lived by one with severe aphasia, with special reference to the notion of anosognosia.     

Self-monitoring behavior in a case of severe auditory agnosia with aphasia

This case report describes an unusual combination of speech and language deficits secondary to bilateral infarctions in a 62-year-old woman. The patient was administered an extensive series of speech, language, and audiologic tests and was found to exhibit a fluent aphasia in which reading and writing were extremely well preserved in comparison to auditory comprehension and oral expression, and a severe auditory agnosia. In spite of her auditory processing deficits, the patient exhibited unexpected self-monitoring ability and the capacity to form acoustic images on visual tasks. The manner in which she corrected and attempted to correct her phonemic errors, while ignoring semantic errors, suggests that different mechanisms may underlie the monitoring of these errors.     

A study of language functioning in Alzheimer patients

Language functioning in Alzheimer's disease is reviewed and the performance of 25 Alzheimer patients on a standard battery is reported. All these hospitalized patients were aphasic to some degree. As a group, they differed from normals on all language variables, and from stroke patients in terms of higher fluency and lower comprehension. Spontaneous speech showed high incidence of circumlocutions and semantic jargon, but no phonemic paraphasias or target approximations. Syllabic perseverations, shouting, inappropriate laughter, and mutism were late-appearing features. Transcortical Sensory, and Wernicke's aphasias were frequent, but Broca's and Transcortical Motor aphasias notably absent. Extent of language impairment correlated with current length of hospitalization but not age. Reading, writing, and performance scores except praxis, were lower than oral language scores. Findings were discussed in relation to previous results, methodology, and language organization in the brain.     

A linguistic analysis of fluent aphasia

Fluent aphasia is a general term for those posterior aphasic syndromes which involve little or no motor difficulties and which exhibit rather normal rates of speech output. This paper is a comparative neurolinguistic study of three types of fluent aphasia. Differences as well as similarities regarding language behavior both within and across groups are analyzed. Much attention is given to anomia and to how it is confronted by each group. Various possible paraphasic processes which may be involved in the genesis of neologisms are discussed. Localization information is provided for the patients in the study, and special attention is drawn to prerequisite neuroanatomical involvement for neologistic jargon.     

The recovery processes of two English-Japanese bilingual aphasics

The recovery processes of two English-Japanese bilingual aphasics, one with Broca's aphasia and the other with Wernicke's aphasia, were investigated with special emphasis on the effect of language therapy. The degree of impairment initially manifested in English and Japanese was almost equivalent in each case, the pattern of impairment corresponding to the respective types of aphasia. In both cases, systematic, controlled language therapy was conducted. Analysis of the recovery courses revealed that language therapy was one decisive variable in the relative degree of recovery of a bilingual aphasic's two languages. The type of aphasia appeared to exert a crucial influence on the relative recovery rate of different modalities.     

Sequences of phonemic approximations in aphasia

The trends of sequences of phonemic approximations to a single target were studied in three types of aphasia (Broca's, conduction, and Wernicke's), as gathered in five tasks (spontaneous speech, repetition of meaningful words, repetition of nonsense words, reading aloud, and automatized sequences). A phonemic error ratio was defined in order to quantify the distance between each approximation of a given sequence and its target. The results of a computer analysis based on this ratio were analyzed according to three parameters. A study of three types of patients revealed that conduction aphasics exhibited the most regular trend toward the target in sequences of phonemic approximations; the analysis of the various tasks indicated that sequences produced in repetition by conduction aphasics form an exception to the regularity of this trend, and an examination of the various lengths of sequences indicated that longer sequences showed a less decisive trend toward the target than shorter sequences. The discussion bears on some theoretical aspects of the phonological production mechanism and its control: the initial strength and permanence of the internal representation of the target emerge as important factors required for the good functioning of this mechanism.     

Patterns of regional cerebral blood flow during attempted reading aloud by stutterers both on and off haloperidol medication: Evidence for inadequate left frontal activation during stuttering

Two stutterers, both recent college graduates, were subjected to regional cerebral blood flow measurements while attempting to read aloud. Each one received two measurements, one of which was under the influence of haloperidol, 3 mg daily. Both subjects showed improvement on medication, allowing a stuttering versus essentially no stuttering comparisons for each subject. Both subjects showed higher Broca's area flow in the right compared to the left hemisphere, during stuttering. Both showed higher Wernicke's area flow in the left compared to the right hemisphere, however, during stuttering. During reading aloud without stuttering, however, the Brocas's area flows were reversed, now showing a left hemisphere advantage. The results were interpreted as consistent with H. M. Sussman and P. F. MacNeilage's (1975, Neuropsychologia, 13, 19–26) proposal that stutterers exhibit conventional left cerebral dominance for speech reception, but inadequate left cerebral dominance for speech production.     

A case of thalamic aphasia with postmortem verification

This study discusses a case of aphasia after dominant thalamic lesion, a hemorrhagic infarction. Unlike other such cases, both repeated standardized assessment and postmortem verification were available. The patient was assessed at 3 weeks and again at 9 weeks postonset. The aphasia demonstrated the syndrome common to dominant thalamic hemorrhage: fluent but paraphasic output sometimes deteriorating to jargon, comprehension less impaired than this type of output usually indicates, and the least impairment in repetition. As sometimes reported in previous cases, semantic paraphasias were more common than phonemic paraphasias. The lesion was located in the dorsal aspect of the lateral nucleus, but it extended into the pulvinar, including the anterior superior lateral aspect which has been implicated in language by previous studies. Thus, data from this case are consistent with an involvement of the dominant pulvinar in language and suggest that this role involves the semantic aspects of language.     

Cortical control of conditioned and spontaneous vocal behavior in rhesus monkeys

Rhesus monkeys were trained on a discriminative conditioning of vocalizations paradigm, a task that requires volitional vocal control. The monkeys' spontaneous vocal and other social behavior was also assessed. Each monkey then underwent ablation of anterior cingulate cortex, ablation of the homologus of Broca's and Wernicke's areas, or no lesion. The anterior cingulate lesions severely disrupted both conditioned and spontaneous vocal behavior, but had no effect on nonvocal social behavior or on a discriminative conditioning task requiring a nonvocal response. The lesions of the homologs of Broca's and Wernicke's areas had no effects on the behaviors studied. These findings have implications for the comparative neurology of primate vocalization and speech.     

Support for anterior temporal involvement in semantic error production in aphasia: new evidence from VLSM

Semantic errors in aphasia (e.g., naming a horse as “dog”) frequently arise from faulty mapping of concepts onto lexical items. A recent study by our group used voxel-based lesion-symptom mapping (VLSM) methods with 64 patients with chronic aphasia to identify voxels that carry an association with semantic errors. The strongest associations were found in the left anterior temporal lobe (L-ATL), in the mid- to anterior MTG region. The absence of findings in Wernicke’s area was surprising, as were indications that ATL voxels made an essential contribution to the post-semantic stage of lexical access. In this follow-up study, we sought to validate these results by re-defining semantic errors in a manner that was less theory dependent and more consistent with prior lesion studies. As this change also increased the robustness of the dependent variable, it made it possible to perform additional statistical analyses that further refined the interpretation. The results strengthen the evidence for a causal relationship between ATL damage and lexically-based semantic errors in naming and lend confidence to the conclusion that chronic lesions in Wernicke’s area are not causally implicated in semantic error production.     

Does long term use of piracetam improve speech disturbances due to ischemic cerebrovascular diseases?

Aphasia causes significant disability and handicap among stroke survivors. Language therapy is recommended for aphasic patients, but not always available. Piracetam, an old drug with novel properties, has been shown to have mild beneficial effects on post-stroke aphasia. In the current study, we investigated the effects of 6 months treatment with piracetam on aphasia following stroke. Thirty patients with first-ever ischemic strokes and related aphasia were enrolled in the study. The scores for the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), and Gülhane Aphasia Test were recorded. The patients were scheduled randomly to receive either 4.8 g piracetam daily or placebo treatment for 6 months. At the end of 24 weeks, clinical assessments and aphasia tests were repeated. The level of improvement in the clinical parameters and aphasia scores was compared between the two groups. All patients had large lesions and severe aphasia. No significant difference was observed between the piracetam and placebo groups regarding the improvements in the NIHSS, BI and mRS scores at the end of the treatment. The improvements observed in spontaneous speech, reading fluency, auditory comprehension, reading comprehension, repetition, and naming were not significantly different in the piracetam and placebo groups, the difference reached significance only for auditory comprehension in favor of piracetam at the end of the treatment. Piracetam is well-tolerated in patients with post-stroke aphasia. Piracetam taken orally in a daily dose of 4.8 g for 6 months has no clear beneficial effect on post-stroke language disorders.     

Three variant forms of subcortical aphasia in Chinese stroke patients

Five right-handed patients with subcortical aphasia that involved the left hemisphere subcortical lesion sites were subjected to CT scans. Given their etiology, two cases were infarctions and the other three were hemorrhages. Two of the patients presented an involvement of the anterior limb of the internal capsule and of the basal ganglia and an anterior superior white-matter lesion extension. In both cases slow scanty dysarthric speech was noted; one had markedly impaired auditory comprehension, and the others were only partially impaired. The third patient presented an involvement of the posterior limb of the internal capsule and of the thalamus and a posterior paraventricular white-matter lesion extension. He had poor auditory comprehension, echolalia, and fluent speech. The last two patients presented an involvement of the internal capsule, the basal ganglia, and the thalamus and an anterior posterior paraventricular white-matter lesion extension. The latter two showed poor auditory comprehension with nonfluent and scanty spontaneous speech. The speech sounds were nonsensical monosyllabic words with a pattern similar to that of global aphasia. All patients had lasting right hemiplegia.     

Drawing: its contribution to naming in aphasia

Drawing in aphasia therapy has been used predominately as a substitution for speech or to augment communication when other modalities are non-functional. The value of drawing as a route for facilitating verbal expression has not been a focus of prior research. We compared the usefulness of drawing and writing as compensatory strategies for improving naming in individuals with aphasia. Activation patterns of writing and drawing in healthy adults were examined using fMRI. Clinical results suggest that drawing facilitated naming whereas writing diminished accurate naming responses, and that drawing quality is not relevant to this facilitatory effect. Functional MRI findings revealed strong bi-hemispheric activation of semantic and phonological networks while drawing that may support our clinical findings.     

Squaring the round: An unusual progressive graphomotor impairment with post‐mortem findings

Investigations of neurodegenerative disorders may reveal functional relationships in the cognitive system. C.S. was a 63‐year‐old right‐handed man with post‐mortem confirmed Pick's disease with a range of progressive impairments including non‐fluent aphasia, speech, limb, oculomotor, and buccofacial apraxia, but mostly intact intelligence, perception, orientation, memory, semantics, and phonology. During progression, agrammatism in writing with impairments in syntactic comprehension emerged in parallel with an unusual graphomotor deficit in drawing and writing, with an increasing deterioration of graphic short‐term memory. We investigated C.S.'s graphomotor deficit longitudinally using tests of writing and drawing on letters, words, and sentences and drawing to command and copying. We also tested C.S.'s short‐term graphemic buffer experimentally. Analysis showed deficits on selective aspects of graphomotor implementation of writing and drawing, mainly affecting the production of circles and curves, but not short straight lines in drawing and writing, and graphomotor short‐term memory, which paralleled impairments of written syntax and syntactic comprehension. We believe this to be the first detailed analysis of such an unusual progressive impairment in graphomotor production, which may be related to problems with agrammatic agraphia and impairments affecting shared components of cognition reflecting damage to shared neural networks. Alternatively, they may simply reflect the effects of coincidental damage to separate mechanisms responsible for aspects of writing, drawing, and syntactic processing. Longitudinal investigations of emerging deficits in progressive conditions like C.S.'s provides an opportunity to examine the progressive emergence of symptoms in an individual with multiple progressive impairments as they appear and examine putative relationships between them.