Reliability of motor cortex transcranial magnetic stimulation in four muscle representations.

OBJECTIVE: Motor cortex plasticity may underlie motor recovery after stroke. Numerous studies have used transcranial magnetic stimulation (TMS) to investigate motor system plasticity. However, research on the reliability of TMS measures of motor cortex organization and excitability is limited. We sought to test the reliability of these TMS measurements. METHODS: Twenty healthy volunteers were tested twice over a two-week period using TMS to determine motor threshold, map topography, and stimulus-response curves for first dorsal interosseous (FDI), abductor pollicis brevis (APB), extensor digitorum communis (EDC), and flexor carpi radialis (FCR) muscles. RESULTS: We found moderate to good test-retest reliability TMS measurements of motor threshold (ICC=0.90-0.97), map area (ICC=0.63-0.86) and location (ICC=0.69-0.86), and stimulus-response curves (ICC=0.60-0.83). CONCLUSIONS: TMS assessments of motor representation size, location, and excitability are generally reliable measures, although their reliability may vary according to the muscle under investigation. SIGNIFICANCE: These results suggest that TMS measurements of motor cortex function are reliable enough to be potentially useful in investigation of motor system plasticity.

Effects of bromocriptine in a patient with crossed nonfluent aphasia: a case report.

OBJECTIVE: Because studies have shown some positive effects of the dopaminergic agent bromocriptine for improving verbal production in patients with nonfluent aphasia, we examined its effect in a patient with an atypical form of crossed nonfluent aphasia from a right hemisphere lesion. DESIGN: Open-label single-subject experimental ABAB withdrawal design. PATIENT: A right-handed man who, after a right frontal stroke, developed nonfluent aphasia, emotional aprosodia, and limb apraxia. INTERVENTION: Escalating doses up to 20mg of bromocriptine in 2 separate phases. MAIN OUTCOME MEASURES: We measured verbal fluency (words/min in discourse, Thurstone letter fluency), expression of emotional prosody, and gesture production. RESULTS: The patient showed substantial improvement in both verbal fluency measures and no significant improvement in gesture or emotional prosody. Verbal fluency improvements continued in withdrawal phases. CONCLUSIONS: Our results are less likely caused by practice or spontaneous recovery because we observed little improvement in emotional prosody and gesture tasks. Verbal fluency improvements during treatment and withdrawal phases suggest that the effects of bromocriptine may be long-lasting in its influence on the neural networks subserving verbal initiation.

Conceptual apraxia in probable Alzheimer's disease as demonstrated by the Florida Action Recall Test.

Patients with probable Alzheimer's disease (AD) often have difficulties associated with semantic knowledge. Therefore, conceptual apraxia, a defect of action semantics and mechanical knowledge, may be an early sign of this disease. The Florida Action Recall Test (FLART), developed to assess conceptual apraxia, consists of 45 line drawings of objects or scenes. The subject must imagine the proper tool to apply to each pictured object or scene and then pantomime its use. Twelve participants with Alzheimer's disease (NINCDS-ADRDA criteria) and 21 age- and education-matched controls were tested. Nine Alzheimer's disease participants scored below a 2-standard-deviation cutoff on conceptual accuracy, and the three who scored above the cutoff were beyond a 2-standard-deviation cutoff on completion time. The FLART appears to be a sensitive measure of conceptual apraxia in the early stages of Alzheimer's disease.

Limb apraxia.

Limb apraxia is an impairment in the ability to perform skilled, purposive limb movements as the result of neurological dysfunction. In right-handed individuals, limb apraxia is associated with left hemisphere lesions. This article reviews the subtypes and neuroanatomic correlates of limb apraxia, including limb kinetic apraxia, ideomotor apraxia, ideational apraxia, and conceptual apraxia. The functional impact of limb apraxia on the individual is discussed. Strategies for the assessment and management of this disorder are reviewed.

Alterations in the functional anatomy of reading induced by rehabilitation of an alexic patient.

OBJECTIVE: The goal of the study was to measure regional cerebral blood flow (CBF) in a stroke patient with acquired phonologic alexia before and after therapy using the Auditory Discrimination in Depth (ADD) program. BACKGROUND: After rehabilitation of acquired language disorders, functional imaging can detect activity in brain structures that do not mediate language during normal conditions. However, the anatomic correlates of recovery or rehabilitation from acquired reading disorders are largely undescribed. METHODS: Cerebral SPECT scans were obtained before and after the intervention with Auditory Discrimination in Depth. The first and last activation tasks necessitated that the patient read nonwords during radionuclide uptake. Another (control) scan was acquired during performance of a nonlinguistic task shortly before the end of the ADD program. RESULTS: Before therapy, the right hemisphere was inactive during nonword reading relative to the nonlinguistic task. After treatment, nonword reading increased cerebral blood flow in the posterior right perisylvian cortices homologous to the dominant hemisphere areas engaged by reading. Brain activity also increased in Broca's area of both hemispheres. CONCLUSIONS: Dyslexia rehabilitation may facilitate right-hemisphere cortical networks in the reading process and increase engagement of phonologic articulatory motor representations in Broca's area.

Conduction aphasia and the arcuate fasciculus: A reexamination of the Wernicke-Geschwind model.

Wernicke, and later Geschwind, posited that the critical lesion in conduction aphasia is in the dominant hemisphere's arcuate fasciculus. This white matter pathway was thought to connect the anterior language production areas with the posterior language areas that contain auditory memories of words (a phonological lexicon). Alternatively, conduction aphasia might be induced by cortical dysfunction, which impairs the phonological output lexicon. We observed an epileptic patient who, during cortical stimulation of her posterior superior temporal gyrus, demonstrated frequent phonemic paraphasias, decreased repetition of words, and yet had intact semantic knowledge, a pattern consistent with conduction aphasia. These findings suggest that cortical dysfunction alone may induce conduction aphasia.

Ideomotor apraxia in Alzheimer disease and left hemisphere stroke: limb transitive and intransitive movements.

OBJECTIVE: Ideomotor apraxia was studied in patients with Alzheimer disease (AD) and unilateral left hemispheric damaged (LHD) stroke to determine whether these groups differed. BACKGROUND: Given that the neuropathology of AD is bilateral and more diffuse than the localized involvement in patients after an LHD stroke, and given that the cognitive deficits in AD are more widespread than in LHD stroke, the authors predicted that patients with these disorders would differ in response to an auditory command task administered to evaluate ideomotor apraxia, and that the two patient groups would be significantly more impaired than healthy matched control subjects. METHODS: Twenty-one persons were studied, including equal numbers of patients with AD, patients with unilateral LHD stroke, and control subjects. An auditory command test of limb apraxia was administered and videotaped to score performance and to code spatial-temporal or content errors. RESULTS: The patients with AD and LHD stroke were significantly more impaired than healthy control subjects. Whereas the patients with AD and LHD stroke were equally apraxic and did not differ in their performance of transitive limb movements, the patients with AD were significantly more impaired than the patients with stroke when performing intransitive limb movements. A positive correlation was found between severity of dementia and severity of apraxia in the patients with AD. The patients with LHD stroke were as likely to make spatial-temporal as content errors when performing intransitive limb movements, whereas the patients with AD made content errors only. Error types produced with transitive limb movements did not differ between groups; spatial-temporal errors were the most common errors made both by patients with AD and patients with LHD stroke. CONCLUSIONS: As predicted, patients with AD and with LHD stroke were impaired when producing limb movements after auditory command, and both patient groups were significantly more impaired than the healthy adults. Patients with AD were significantly more impaired than patients with stroke when performing intransitive limb movements, and error types differed by group. Patients with AD and patients with stroke were equally impaired when performing transitive movements, and error types did not differ by group. Patients with ideomotor apraxia are often degraded in their production of transitive and intransitive movements, and the observation that performance may differ depending on the type of limb movement suggests that movement representations for transitive and intransitive movements may be at least partially independent.

Apraxia differs in corticobasal degeneration and left-parietal stroke: A case study.

Corticobasal degeneration (CBD) is a progressive disorder characterized by both cortical and basal ganglia dysfunction such as asymmetrical apraxia, and akinetic rigidity, involuntary movements, and cortical sensory loss. Although apraxia is a key finding for the differential diagnosis of CBD, it has not been determined whether the features of apraxia seen in subjects with CBD are similar to those features exhibited by subjects with left-hemisphere damage from stroke. Therefore, for both clinical purposes and in order to better understand the brain mechanisms that lead to apraxia in CBD, we studied praxis in a patient with CBD and compared him to patients who are apraxic from left-parietal strokes. We used three-dimensional movement analyses to compare the features of apraxic movement. This subject with CBD was a dentist whose initial complaint had been that he "forgot" how to use his tools in the mouths of his patients. Analyses were performed on the trajectories made when using a knife to actually slice bread, and when repetitively gesturing slicing made to verbal command. Movements of the left hand, wrist, elbow, and shoulder were digitized in 3-D space. Although the CBD subject was clearly apraxic, the features of his apraxia differed markedly from those of the subjects with lesions in the left parietal lobe. For movements to command, the CBD subject showed joint coordination deficits, but his wrist trajectories were produced in the appropriate spatial plane, were correctly restricted to a single plane, and, like control subjects, were linear in path shape. However, when he was actually manipulating the tool and object, all of these aspects of his trajectories became impaired. In contrast, the deficits of the apraxic subjects with left-parietal damage were most pronounced to verbal command with their movements improving slightly although remaining impaired during actual tool and object manipulation. Unlike patients with parietal strokes, patients with CBD have degeneration in several systems and perhaps deficits in these other areas may account for the differences in praxic behavior.

Apraxia in corticobasal degeneration.

Corticobasal degeneration (CBD) is a degenerative disease that often presents with an asymmetric progressive ideomotor limb apraxia. Some apraxic subjects may fail to perform skilled purposive movements on command because they have lost the memories or representations that specify how these movements should be performed (representational deficit). In contrast, other apraxic subjects may have the movement representations but are unable to utilize the information contained in them to execute skilled purposive movements (production-execution deficit). To learn if the apraxic deficit in CBD is induced by a representational or a production-execution deficit, we tested three nondemented subjects with CBD on tasks requiring production of meaningful or meaningless gestures to command, gesture imitation, gesture discrimination, and novel gesture learning. A fourth subject with incomplete data also is presented. The results suggest that the apraxia associated with CBD is initially induced by a production-execution defect with relative sparing of the movement representations.

Crossed apraxia: implications for handedness.

Liepmann posited that right hand preference relates to left hemisphere dominance for learned skilled movements. Limb apraxia, impairment of skilled movement, typically occurs in individuals with left hemisphere (LH) lesions. The occurrence of apraxia in right-handed individuals following right-hemisphere lesions appears to refute Liepmann's hypothesis. We studied the apraxia of a right-handed man, RF, following a right frontal lesion to determine whether his apraxia paralleled the apraxia seen following LH lesions. Results of behavioral testing indicated that, like individuals with apraxia following left frontal lesions, RF was better at gesture recognition than gesture production which was significantly impaired across tasks. Kinematic motion analyses of movement linearity, planarity, and the coupling of temporospatial aspects of movements substantiated the parallel impairments in RF and patients with LH apraxia. The impairment seen in our patient with crossed apraxia provides evidence for the fractionation of systems underlying hand preference and skilled movement.

Developmental stuttering and Parkinson's disease: the effects of levodopa treatment.

The effects of dopamine on developmental stuttering was studied in a 44 year old man with developmental stuttering and Parkinson's disease during three levodopa "on" periods and three "off" periods. When compared with the "off" periods, during the "on"' periods he demonstrated an increase of speech dysfluencies. These findings lend support to the dopamine hypothesis of developmental stuttering.

Functional imaging: heterogeneity in task strategy and functional anatomy and the case for individual analysis.

To learn more about the functional anatomy of language, the authors used [99mTc]HMPAO single photon emission computed tomography (SPECT) functional imaging to study nonword rhyming, lexical-semantics and syntax. The authors did not find any task-related differences in cerebral blood flow using region-by-region analysis of variance. This led them to examine individual subject's task-related patterns of cerebral blood flow. This analysis revealed regions of interest with little or no change but also regions with changes as great as 30%. There was marked subject-to-subject variability in the pattern of blood flow, which precluded statistically significant results using analysis of variance. An alternative analytic strategy based on numbers of subjects exceeding a minimum threshold task-related change in cerebral blood flow was tested and shows promise in identifying commonalities and differences in individual task-related blood flow patterns. The authors conclude that the complex and difficult to interpret pattern of blood flow changes observed in this study reflect in considerable part the combined effects of variability in task strategy, owing in part to insufficiently constrained task performance, and variability in functional anatomy. The authors also tested the differences in results achieved with simple normalization and analysis of covariance approaches and found them to be insignificant.

Left hemispheric specialization for learned, skilled, and purposeful action.

Three-dimensional motion analyses were performed on trajectories of repetitive "slicing" gestures by 4 participants with left-hemisphere lesions and limb apraxia, 6 participants with right-hemisphere lesions, and 7 neurologically intact participants. Left hemispheric lesioned participants with apraxia, but not right hemispheric lesioned participants showed impaired coupling of spatial and temporal aspects of wrist trajectories and deficits in interjoint coordination. Both groups of brain-lesioned participants differed from control participants in the 3-D plane of the wrist motion. The deficits of some right hemispheric lesioned participants in controlling the plane of wrist motion may be a consequence of left hemispatial neglect with rightward deviations. In contrast, the deficits of apraxic participants in controlling wrist trajectories and coordinating joint motions seem to reflect a deficit in these participants for the movement plan.

Lexical access via letter naming in a profoundly alexic and anomic patient: a treatment study.

We report the results of a letter naming treatment designed to facilitate letter-by-letter reading in an aphasic patient with no reading ability. Patient M.R.'s anomia for written letters reflected two loci of impairment within visual naming: impaired letter activation from print (a deficit commonly seen in pure alexic patients who read letter by letter) and impaired access to phonology via semantics (documented in a severe multimodality anomia). Remarkably, M.R. retained an excellent ability to pronounce orally spelled words, demonstrating that abstract letter identities could be activated normally via spoken letter names, and also that lexical phonological representations were intact when accessed via spoken letter names. M.R.'s training in oral naming of written letters resulted in significant improvement in her oral naming of trained letters. Importantly, as M.R.'s letter naming improved, she became able to employ letter-by-letter reading as a compensatory strategy for oral word reading. M.R.'s success in letter naming and letter-by-letter reading suggests that other patients with a similar pattern of spared and impaired cognitive abilities may benefit from a similar treatment. Moreover, this study highlights the value of testing the pronunciation of orally spelled words in localizing the source of prelexical reading impairment and in predicting the functional outcome of treatment for impaired letter activation in reading.

Treatment of a case of phonological alexia with agraphia using the Auditory Discrimination in Depth (ADD) program.

Phonological alexia and agraphia are acquired disorders characterized by an impaired ability to convert graphemes to phonemes (alexia) or phonemes to graphemes (agraphia). These disorders result in phonological errors typified by adding, omitting, shifting, or repeating phonemes in words during reading or graphemes when spelling. In developmental dyslexia, similar phonological errors are believed to result from deficient phonological awareness, an oral language skill that manifests itself in the ability to notice, think about, or manipulate the individual sounds in words. The Auditory Discrimination in Depth (ADD) program has been reported to train phonological awareness in developmental dyslexia and dysgraphia. We used a multiple-probe design to evaluate the ADD program's effectiveness with a patient with a mild phonological alexia and mixed agraphia following a left hemisphere infarction. Large gains in phonological awareness, reading and spelling nonwords, and reading and spelling real words were demonstrated. A follow-up reassessment, 2 months posttreatment, found the patient had maintained treatment gains in phonological awareness and reading, and attained additional improvement in real word reading.

Rehabilitation of a case of pure alexia: exploiting residual abilities.

We present a case study of a 43-year-old woman with chronic and stable pure alexia. Using a multiple baseline design we report the results of two different interventions to improve reading. First, a restitutive treatment approach using an implicit semantic access strategy was attempted. This approach was designed to exploit privileged access to lexical-semantic representations and met with little success. Treatment was then switched to a substitutive treatment strategy, which involved using the patient's finger to pretend to copy the letters in words and sentences. Reading using this motor cross-cuing strategy was 100% accurate and doubled in speed after 4 weeks of intervention. We propose that this patient's inability to benefit from the implicit semantic access treatment approach may be in part related to her inability to suppress the segmental letter identification process of word recognition.

Category-specific naming deficit for medical terms after dominant thalamic/capsular hemorrhage.

Postmortem, retrograde degeneration, and electrical stimulation studies have implicated the anterior pulvinar in language processing. We examined a patient who, after a hemorrhage affecting the dominant pulvinar and internal capsule, exhibited a circumscribed anomia for medical items and conditions. No other language disturbance was noted. Five category-specific word lists, matched for word frequency, were administered in a naming-to-definition format. Results indicated that the patient exhibited a significant category-specific naming deficit for medical items and conditions compared to matched control subjects. Although medical item lists were found to differ from nonmedical item lists in imageability and abstractness, B.C.'s category-specific deficit did not seem to be caused by word frequency, concept familiarity, imageability, or abstractness. Nor could the patient's performance be explained on the basis of deficits in broader semantic classifications (i.e., animate vs inanimate or man-made vs natural). The patient was unable to retrieve medical items even when given phonemic cues for those he could not name. Findings indicate that subtotal damage in the dominant pulvinar may create category-specific deficits.

Visual-imitative dissociation apraxia.

Liepmann posited that, in right handers, the left parietal lobe contains movement formulas or representations. Therefore, performance failures may be induced by degraded representations, a failure of these representations to influence motor systems or a failure of stimuli to fully access these representations. Imitation may help the performance of subjects with degraded representations. However, patients who have impaired visual access to movement representations may perform more poorly with imitation than to verbal command. Trajectories of repetitive 'slicing' gestures made by a previously reported subject (Raymer et al.) with an infarction in the left visual association cortex (left occipital and inferior temporal lobe) that spared the parietal lobe were contrasted with those of three apraxic subjects with lesions that included the left parietal lobe and four non-brain-damaged control subjects. All subjects were asked to produce the gesture to verbal command and to imitation. Movements of the left hand, wrist, elbow and shoulder were digitized from neighboring views, reconstructed in three dimensions, and analysed graphically and numerically. The apraxic subjects with left parietal damage were unable to maintain the proper linearity and spatiotemporal attributes of their wrist motions and showed interjoint coordination deficits. Their deficits were most pronounced to verbal command, with their movements improving though remaining poorly performed when they imitated. The subject with the left occipital and inferior temporal lesion that spared parietal cortex, however, showed an opposite pattern. This subject exhibited close to normal performance when producing the movement to verbal command, but significant deficits when imitating.