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.

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.

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.

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.

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.

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.

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.

Agrammatic sentence production: the use of a temporal--spatial strategy.

We report the sentence production of a left-handed man with a right-hemisphere infarct. He demonstrated an inability to correctly map grammatical categories (subject, object) onto thematic roles (agent, patient) even for simple active sentences. The patient's performance appears to be the result of selective damage to the functional level (Garrett, 1980) of sentence production. His failure could not be accounted for by theories of agrammatism that implicate memory deficits, phonologic processing impairments, or deficits in processing complex transformations. The patient's performance revealed the consistent application of a temporal-spatial strategy in sentence production, despite adequate lexical-semantic abilities.

Asyntactic thematic role assignment: the use of a temporal-spatial strategy.

We report syntactic comprehension performance of a left-handed man with a right-hemisphere infarct. He was unable to accurately map grammatical categories (subject, object) onto thematic roles (agent, patient), despite demonstrating intact conceptual knowledge of these thematic roles. He performed poorly on both active and passive reversible sentences. His asyntactic thematic role assignment cannot be accounted for by a short-term memory impairment or any hypothesis that predicts selective vulnerability to passive sentence constructions. Rather than performing randomly, our patient used a temporal or spatial strategy in assigning thematic roles. Because he also had a production-mapping deficit and used the same temporal-spatial strategy in production tasks, we hypothesize that the mapping of thematic roles onto grammatical categories and vice versa may be a specific aspect of sentence processing that is common to sentential production and comprehension. We also raise the possibility that thematic roles have underlying spatial representations prior to being elaborated by grammar.

Joint coordination deficits in limb apraxia.

Competing models of the basis of limb apraxia were tested through analysis of joint coordination deficits in three apraxic subjects with lesions that included the left parietal lobe. Three-dimensional shoulder, elbow, wrist and hand trajectories were recorded for repetitive 'slicing' gestures made in a series of conditions in which contextual cues were introduced in a graded fashion. The apraxic subjects showed marked deficits in joint coordination across context conditions. Even when actually manipulating a tool and object, the apraxic subjects failed to show proper joint synchronization, failed to apportion their relative joint amplitudes properly, and failed to produce the correct phase relationships among pairs of arm angles. Thus, apraxic subjects not only have deficits in the spatial plan for the movement, but they also have deficits in translating those plans into the details of the angular motions at the joints, even when actually manipulating a tool and object. These data support a model of apraxia in which apraxia can result from either the destruction of visuo-kinaesthetic motor representations of learned movement, stored in posterior association cortex, or from a separation of these representations from premotor or motor areas.

Ecological implications of limb apraxia: evidence from mealtime behavior.

Humans learn skilled acts in order to effectively interact with their environment. A loss of the ability to perform skilled acts is termed apraxia. Apraxia has been thought to be of theoretical interest, but the ecological implications of apraxia are controversial and have not been fully studied. We examined ten patients with unilateral left hemisphere cerebral infarctions (eight of whom were apraxic) and compared their mealtime eating behavior to a group of neurologically normal, age-matched controls. The stroke patients were less efficient in completing the meal. They made more action errors and were less organized in the sequencing of mealtime activities. Because the patients made more errors while using tools than when performing nontool actions, their deficit could not be accounted for by an elemental motor deficit. A positive relationship was found between mealtime action errors and the severity of apraxia. These findings suggest that limb apraxia may adversely influence activities of daily living.

Selective attention and aphasia in adults: preliminary findings.

Thirteen patients with left-hemisphere stroke and history of aphasia and 13 normal controls were administered the covert orientation of visual attention task (COVAT). This task presents targets to the right or left of a central fixation point after a cue (84% of trials) or with no cue (16% of trials). Left-hemisphere damaged patients also received tests of language function at the time of the study. For targets presented 100 msec after cue onset, normal controls demonstrated equivalent responding for targets to the left and to the right of a central fixation point. Patients with left-hemisphere damage showed slower reaction times when responding to targets on the right as opposed to the left side of space when attention was first cued to the opposite side of space (invalid trials) or when attention was focused on a central fixation point (uncued trials), but they did not show slower reaction times on the right side when attention was first cued to the right (valid trials). For left-sided targets, no differences between valid, invalid, and uncued trials existed. Slower responding to right- as opposed to left-sided targets on invalid and uncued trials was correlated with impaired performance on six of seven language measures for patients with left-hemisphere damage. Implications for the relationship between language and selective attention systems in the left hemisphere are discussed.