Graphesthesia: a test of graphemic movement representations or tactile imagery?

Patients with corticobasal degeneration (CBG) often demonstrate agraphesthesia in the same hand they demonstrate apraxia. To recognize letters written in their hand subjects can develop a spatial representation and access graphemic representations. Alternatively, people can use movement working memory and match movement patterns to stored letter movement representations. To learn the method normally used without vision, normal subjects (12) had letters written on their palm either in the normal manner or in a reverse direction. If letters written on the hand are recognized by their spatial features (as when visually reading) direction should not influence letter recognition, but if letters written on the hand are recognized by movement patterns, then in the reverse condition recognition should be impaired. When letters were written normally there were no differences in error between the tactile and visual modality. When letters were written in reverse, however, normal subjects made more errors in the tactile than visual condition. Normally, people identify letters written on their hand by covertly copying (mirroring) the examiner and then access letter movement representations. This might explain why patients with CBG often have agraphesthesia associated with apraxia.

Aceruloplasminaemia with progressive atrophy without brain iron overload: treatment with oral chelation.

BACKGROUND: Hereditary aceruloplasminaemia is a disorder of iron metabolism that is characterised by iron accumulation in the brain and other visceral organs. In previously reported cases, individuals with the disorder were noted to have evidence of iron accumulation in the brain. Oral chelating agents have not been used in neurological diseases of iron metabolism. METHODS: A 54-year-old woman who presented with ataxia, lower extremity spasticity and chorea was evaluated for evidence of the source of neurological dysfunction. RESULTS: Blood studies revealed no detectable ceruloplasmin. Marked iron overload was defined by a liver biopsy, which showed a variegated pattern consistent with a primary cause of iron overload. Review of MRI scans showed progressive brain atrophy without visible iron accumulation occurring over a 5-year period. The history suggested that neurodegeneration was coincident with aggressive oral iron replacement. Oral chelation improved many symptoms. CONCLUSIONS: Our findings in this patient suggest that disorders of iron transport such as aceruloplasminaemia can be a cause of neurological symptoms such as chorea and cognitive decline, as well as progressive neurodegeneration in the absence of visible iron on MRI scans. We found that oral iron chelation was effective at improving symptoms.

Deafferentation-disconnection neglect induced by posterior cerebral artery infarction.

OBJECTIVE: To investigate patients with posterior cerebral artery (PCA) infarctions to learn whether hemispatial neglect is more frequent and severe after right than left PCA infarction; whether visual field defects (VFDs) influence the presence or severity of hemispatial neglect; and the anatomic loci of lesions that are associated with hemispatial neglect. METHODS: The authors recruited 45 patients with PCA infarction that involved only the occipital lobe or the occipital lobe plus other areas served by the PCA. All subjects received seven neglect tests within 2 months after onset. RESULTS: Overall, the frequency of hemispatial neglect was 42.2%. The frequency did not significantly differ between the right (48.0%) and left (35.0%) PCA groups, but the severity of hemispatial neglect was significantly greater in the right group. VFD alone did not influence the frequency or severity of neglect after controlling other variables. Isolated occipital lesions were rarely associated with hemispatial neglect, and it was only the occipital plus splenial lesion that significantly influenced the frequency and severity of neglect. CONCLUSIONS: This study suggests that after excluding such confounding factors as aphasia or hemiplegia, neglect frequency does not differ between the right and left posterior cerebral artery (PCA) groups, but the severity of neglect is greater after right PCA infarctions; even in the acute stage of PCA infarction; visual field defect from an isolated occipital lesion does not cause hemispatial neglect; and the injury to both the occipital lobe and the splenium of the corpus callosum is important for producing hemispatial neglect with PCA infarction.

Attentional grasp in far extrapersonal space after thalamic infarction.

Studies of animals and humans with focal brain damage suggest that attention in near and far extrapersonal space may be mediated by anatomically separate systems. Thalamic lesions have been associated with spatial neglect, but whether asymmetric attention specific to near or far space occur after thalamic damage has not been explored. It is also unclear if thalamic injury can induce contralesional defective response inhibition. We tested a woman with a left thalamic infarction who reported that, when driving, she had a tendency to veer towards people or objects on the right side of the road. Our patient and four controls performed a line bisection task with a laser pointer in near and far extrapersonal space. The experimenter marked each bisection either from the right of the presented line (right-distractor, RD) or the left (left-distractor, LD). RD and LD trials were pseudo-randomized. Our patient performed similarly to controls (mean -0.7 mm, controls -0.6 mm) on the line bisection task in near space. In far space she erred significantly rightward compared to her performance in near space (p<0.001). Controls performed similarly in near and far space. The experimenter position did not affect our patient's performance on near line bisections, nor did controls demonstrate a distractor effect for the near condition. In the far condition, however, our patient showed a significant distractor effect (LD -3.3 mm, RD 35.3 mm, p<0.001). Controls also demonstrated a distractor effect in the far condition (LD -6.4 mm, RD 0.7 mm, p<0.01), though of much smaller magnitude. Our results suggest that frontal-thalamic systems regulating visual attention may be disrupted by thalamic infarction. Such damage may produce an attentional grasp specific to far extrapersonal space.

Possible mechanisms of anosognosia: a defect in self-awareness.

Anosognosia of hemiplegia is of interest for both pragmatic and theoretical reasons. We discuss several neuropsychological theories that have been proposed to explain this deficit. Although for psychological reasons people might deny deficits, the denial hypothesis cannot account for the hemispheric asymmetries associated with this disorder and cannot explain why some patients might deny one deficit and recognize another equally disabling deficit. There is some evidence that faulty feedback from sensory deficits, spatial neglect and asomatognosia might be responsible for anosognosia in some patients. However, these feedback hypotheses cannot account for anosognosia in all patients. Although the hemispheric disconnection hypothesis is appealing, disconnection is probably only a rare cause of this disorder. The feedforward intentional theory of anosognosia suggests that the discovery of weakness is dependent on attempted action and some patients might have anosognosia because they do not attempt to move. We present evidence that supports this theory. The presence of one mechanism of anosognosia, however, does not preclude the possibility that other mechanisms might also be working to produce this disorder. Although a large population study needs to be performed, we suspect that anosognosia might be caused by several of the mechanisms that we have discussed. On the basis of the studies of impaired corporeal self-awareness that we have reviewed, we can infer that normal self-awareness is dependent on several parallel processes. One must have sensory feedback and the ability to attend to both one's body and the space where parts of the body may be positioned or acting. One must develop a representation of the body, and this representation must be continuously modified by expectations (feedforward) and knowledge of results (feedback).

Selective deficit of praxis imagery in ideomotor apraxia.

We studied imagery for learned, skilled movements (praxis imagery) in a patient with severe ideomotor apraxia and intact language abilities. This patient, who made predominantly spatial and movement errors when performing transitive movements demonstrating the use of tools (transitive gestures), was also impaired in her ability to answer imagery questions about joint movement or the spatial position of the hands during action. However, visual object imagery was spared. The finding of parallel praxis production and praxis imagery deficits in this patient suggests that the same representations used for gesture production are also activated during imagery of motor acts. Our findings also suggest that certain aspects of motor imagery may be dissociable from general object imagery.

The role of visual imagery in spelling.

Current models of spelling posit that information from the orthographic output buffer can be translated into physical letter codes for written output or into name letter codes for spoken output. It is not known, at present, whether or not visualization of these codes is necessary to spell or recognize orally spelled words. We report a 73-year-old woman who could spell words better than she could image them and who demonstrated near flawless recognition of orally spelled words. We conclude that visual imagery is not necessary to either spell or recognize orally spelled words.

Apperceptive visual agnosia: a case study.

A man with an infarction of his inferior temporal and occipital association cortex bilaterally, which spared primary visual cortex, had impaired visual recognition of objects, faces, colors, words, and gestures. Analysis of visual function indicated that the recognition failures resulted from an agnosia, rather than elemental visual impairment. Whereas his impairment of gesture recognition appeared to be related to an associative agnosia, his inability to recognize objects was related to an apperceptive agnosia. There may be four subtypes of apperceptive agnosia: one where the internal object representations or structural descriptions are impaired, another where an adequate percept cannot be derived, a third where the internal referent and percept are dissociated, and a fourth where both levels are impaired. Our patient demonstrated a failure to relate individual elements to the whole, a failure to integrate multiple elements, and a reliance on global perception. He had normal object imagery. These results suggest that, whereas internal representations were intact, he was unable to form adequate perceptual representations.

Cholinergic treatment of an amnestic man with a basal forebrain lesion: theoretical implications.

Cholinergic deficient states, such as in Alzheimer's disease, are associated with amnesia. Therapeutic trials with cholinergic augmentation in Alzheimer's disease have had only equivocal results, but mechanisms other than cholinergic deficiency may contribute to the memory deficit. Normally the diagonal band of Broca provides much of the hippocampal cholinergic input. To learn if amnesia secondary to cholinergic deficiency can be ameliorated by cholinergic augmentation, we treated an amnestic man who had a lesion located primarily in the right diagonal band of Broca with physostigmine and lecithin. During the initial best-dose-finding phase, he demonstrated an inverted U-shaped curve for immediate recall of word lists, with peak performances at 3.0 and 3.5 mg of physostigmine. Single photon emission tomography showed decreased blood flow in the medial temporal region ipsilateral to the lesion at baseline, with a reversal of the asymmetry on 3.5 mg of physostigmine. A follow-up double-blind, placebo-controlled study on 3.5 mg of physostigmine, however, failed to demonstrate that cholinergic treatment improved memory.

The contribution of an imagery code to verbal memory.

Free recall for auditorially presented spatial information was examined in a patient with a large right cerebral infarction. Despite normal verbal memory at immediate and 30-minute conditions, the patient exhibited a significant loss in verbal recall at 24 hours and a more severe deficit in the recall of the spatial components of prose passages across all delayed recall conditions. These results suggest that although the verbal code is important early in the learning process, spatial imagery exerts an increasing influence over time. Thus, reliance upon a left hemispheric mediated verbal encoding process may only allow for partial integration of linguistic and visuospatial properties.

Frontal hypermetabolism and thalamic hypometabolism in a patient with abnormal orienting and retrosplenial amnesia.

A patient with verbal amnesia and a propensity to direct his attention to the right following a retrosplenial area lesion was studied with positron emission tomography using [F-18] fluorodeoxyglucose. These studies showed that the left thalamus was hypometabolic, and the anterior 2/3 of the left hemisphere was hypermetabolic when compared with the right. There were no significant differences seen in the medial temporal lobes. Based on this study, it is posited that interruption of hippocampal input into the anterior thalamus was responsible for the amnesia, and the left frontal hyperactivity was associated with the propensity to attend contralaterally.

Hemispatial visual inattention masquerading as hemianopia.

The defect occurring when a patient fails to report a visual stimulus presented in a visual half-field may be attributed to hemianopia (deafferentation) caused by a geniculocalcarine lesion. However, failure to report a stimulus presented in a visual field may also be caused by hemispatial visual inattention. We report a patient with right thalamic and temporo-occipital lesions who had a left visual field defect when her eyes were directed either straight ahead (midsagittal plane) or toward left hemispace. However, this visual field defect abated when her eyes were directed to right hemispace, suggesting that the patient had hemispatial visual inattention rather than hemianopia.

Letter imagery deficits in a case of pure apraxic agraphia.

Pure apraxic agraphia is a condition in which motor writing is impaired but limb praxis and nonmotor writing (typing, anagram letters) are preserved. This condition is believed to result from disruption of a parietal lobe graphemic area which generates grapheme representations used to program motor-writing patterns. We report a single case of pure apraxic agraphia in which defective letter imagery was evident. Results of writing and imagery evaluations suggest that the graphemic area may be responsible for generating letter images. In this respect, clinical evaluation of letter imagery abilities in cases of apraxic agraphia may be useful in identifying subtypes of the disorder resulting in a better understanding of the neuropsychological process involved in writing.

Transcortical aphasia from ischaemic infarcts of the thalamus: a report of two cases.

Thalamic injury from various natural causes, including tumours an haemorrhage, has been reported to lead abnormalities of language. The pathophysiology of these language disorders remains controversial because the naturally occurring thalamic lesions often are associated with mass effects. Two patients are described with hypodense left thalamic lesions, shown by computed tomography, probably representing infarction. Both patients had aphasia, but neither had evidence of appreciable brain swelling or distortion, nor were cortical language areas damaged.

Thalamic neglect. Possible role of the medial thalamus and nucleus reticularis in behavior.

A patient had an ischemic infarction of the right medial thalamus, with a resultant contralateral neglect syndrome. We propose that the medial thalamic nuclei, particularly centromedian and parafascicularis (CMPF), are normally involved in the arousal-activation process by which an organism can be aroused by and respond to novel or important stimuli. Specifically, we propose that (1) the mesencephalic reticular formation subserves tonic arousal to novel or painful stimuli by inhibiting the nucleus reticularis thalami (NR) and (2) that selective attention is mediated by cortical input to NR. The CMPF is closely associated with motor systems (basal ganglia, ventrolateral nucleus of the thalamus [VL], and frontal lobes). A pathway involving CMPF, the frontal cortex, and the portion of NR associated with VL may be important in preparing the tonically aroused organism for action. Unilateral lesions of CMPF therefore induce an asymmetric hypokinesia, and bilateral lesions may induce akinetic mutism.

Thalamic neglect.

Three patients with right thalamic hemorrhage showed contralateral neglect and limb akinesia. They also had anosognosia, visuospatial disorders, and emotional flattening. In animals, neglect can be induced by lesions along a cortico-limbic-reticular loop including the intralaminar thalamic nuclei. We propose that an activation defect is responsible not only for the neglect and akinesia, but also for the visuospatial and emotional defects usually associated with right-hemisphere cortical dysfunction.