Neurobiological underpinnings of rapid white matter plasticity during intensive reading instruction.

Diffusion MRI is a powerful tool for imaging brain structure, but it is challenging to discern the biological underpinnings of plasticity inferred from these and other non-invasive MR measurements. Biophysical modeling of the diffusion signal aims to render a more biologically rich image of tissue microstructure, but the application of these models comes with important caveats. A separate approach for gaining biological specificity has been to seek converging evidence from multi-modal datasets. Here we use metrics derived from diffusion kurtosis imaging (DKI) and the white matter tract integrity (WMTI) model along with quantitative MRI measurements of T1 relaxation to characterize changes throughout the white matter during an 8-week, intensive reading intervention (160 total hours of instruction). Behavioral measures, multi-shell diffusion MRI data, and quantitative T1 data were collected at regular intervals during the intervention in a group of 33 children with reading difficulties (7-12 years old), and over the same period in an age-matched non-intervention control group. Throughout the white matter, mean 'extra-axonal' diffusivity was inversely related to intervention time. In contrast, model estimated axonal water fraction (AWF), overall diffusion kurtosis, and T1 relaxation time showed no significant change over the intervention period. Both diffusion and quantitative T1 based metrics were correlated with pre-intervention reading performance, albeit with distinct anatomical distributions. These results are consistent with the view that rapid changes in diffusion properties reflect phenomena other than widespread changes in myelin density. We discuss this result in light of recent work highlighting non-axonal factors in experience-dependent plasticity and learning.

A formal analysis of alexia in persistent aura and a comparison to acquired pure alexia.

A patient is reported with reversible pure alexia in the context of migraine with aura. Following previous, anecdotal reports, the present study is the first to formally assess word reading, writing, and other linguistic and visual processing and to compare these to a patient with stroke-related pure alexia. The reading impairment, suggestive of letter-by-letter reading, was observed across 7 days but had remitted at a 3-month follow-up. The deficit also affected recognition of letters, suggesting a functional impairment at the level of letter recognition, not just word reading. It went along with reversible abnormalities in diffusion-weighted and fluid-attenuated inversion recovery imaging in areas known to be involved in word reading.

Why are digits easier to identify than letters?

Beginning with Dejerine's report of pure alexia in 1892, numerous researchers have noted that individuals with acquired impairments of reading may show spared digit identification performance. This digit advantage has also been found in unimpaired adult readers across a number of tasks, and five main hypotheses have been proposed to explain how it arises. In this paper I consider these hypotheses in the context of recent theories of a unified alphanumeric character identification system, and evaluate them according to relevant empirical evidence. Despite some promising findings, none of the hypotheses currently provide a sufficient explanation of the digit advantage. Rather than developing new hypotheses to explain a categorical difference between digit and letter performance, I argue that future work should consider factors that affect identification performance specific to individual characters.

Radiology case of the month. Progressive slurring of speech and difficulty reading in a 62-year-old male. Final diagnosis: Metastatic small cell cancer of the prostate gland.

A 62-year-old male with controlled hypertension, coronary artery disease, and borderline diabetes presented to the emergency room after experiencing a gradual one-month progression of slurring of speech and difficulty reading. The patient maintained his vital signs throughout his ambulance ride to the hospital and was clinically stable at time of arrival to the emergency department.

Left hemiparalexia.

Three patients with left splenial lesions made paralexic errors restricted to the left end of words. Errors appeared more frequently when a correct response was highly dependent on the initial letter of the stimulus. One patient had full visual fields with hemialexia affecting the left visual field. The other two patients had complete right hemianopia. We attribute left-sided reading errors in the hemianopic patients to a retinotopically restricted disconnection pattern that selectively disrupts transfer of information originating from the peripheral left visual field. Functional resistance of the more numerous transcallosal projections representing visual field adjacent to the vertical meridian may account for such a pattern. The emergence of positional reading errors from retinotopically restricted left hemifield disconnection suggests that callosal information transfer during normal reading may primarily involve elemental sensory rather than lexical/semantic information.

Posterior cortical dementia with alexia: neurobehavioural, MRI, and PET findings.

A progressive disorder of relatively focal but asymmetric biposterior dysfunction is described in a 54 year old right handed male. Initial clinical features included letter-by-letter alexia, visual anomia, acalculia, mild agraphia, constructional apraxia, and visuospatial compromise. Serial testing demonstrated relentless deterioration with additional development of transcortical sensory aphasia, Gerstmann's tetrad, and severe visuoperceptual impairment. Amnesia was not an early clinical feature. Judgment, personality, insight, and awareness remained preserved throughout most of the clinical course. Extinction in the right visual field to bilateral stimulation was the sole neurological abnormality. Early CT was normal and late MRI showed asymmetrical bioccipitoparietal atrophy with greater involvement of the left hemisphere. Results from positron emission tomography (PET) showed bilaterally asymmetric (left greater than right) occipitotemporoparietal hypometabolism. The metabolic decrement was strikingly asymmetric with a 50% reduction in glucose consumption confined to the left occipital cortex. The picture of occipitotemporoparietal compromise verified by MRI, PET, and neurobehavioural testing would be unusual for such degenerative dementias as Alzheimer's (AD) and Pick's disease, although atypical AD with predominant occipital lobe involvement cannot be excluded. This case supports the concepts of posterior cortical dementia (PCD) as a clinically distinct entity and for the first time documents its corresponding metabolic deficit using PET.

Intermittent alexia.

A case of intermittent alexia, sometimes accompanied by severe dysgraphia and sometimes by mild dysgraphia, which had a probable migrainous origin, is described. On some occasions the patient could write to dictation, although with many errors, while unable to read words or letters. On other occasions the patient's writing to dictation was seriously disordered in terms of content and the letters were produced clumsily. Reading of numbers, colour vision and colour naming were normal although impairments on right-left orientation and visual short term memory were present and a mild finger agnosia was apparent. Blood flow scans (SPECT) taken under normal and alexic conditions support the view that the disturbance had a vascular origin.

Occipital lobe infarction and positron emission tomography.

Even though the PET study revealed a total infarct in the territory of the left PCA in our 3 cases of pure alexia, it is still obscure which part of the left occipital lobe is most closely associated with the occurrence of the pure alexia. In order to elucidate the intralobar localization of the pure alexia, it is needed to have an ideal case who shows an pure alexia due to the localized lesion within the left occipital lobe. Furthermore, high-resolution PET scanner will circumvent the problem in detecting the metabolism and blood flow in the corpus callosum which plays an important role in the pathogenesis. We have shown that the occlusion of the right PCA also produced a left unilateral agnosia which is one of the common neurological signs in the right MCA infarction. To tell whether the responsible lesion for the unilateral spatial agnosia differs between the PCA occlusion and the MCA occlusion, the correlation study should be carried out in a greater number of the subjects. Two distinctive neuropsychological manifestations, cerebral color blindness and prosopagnosia, have been considered to be produced by the bilateral occipital lesion. The PET studies disclosed reduction of blood flow and oxygen metabolism in both occipital lobes in our particular patient who exhibited cerebral color blindness and prosopagnosia.

Pure alexia in Japanese and agraphia without alexia in kanji. The ability dissociation between reading and writing in kanji vs kana.

A 60-year-old right-handed Japanese man with infarction of the left occipital lobe and inferior temporal gyrus initially showed pure alexia in kana and kanji. Later, though pure alexia in kana persisted, his kanji reading improved markedly, but with little improvement of kanji writing. We speculate that different pathways are involved in kanji reading and writing. Wernicke's area and its surrounding left middle temporal lobe might play the most important role for kanji reading when visual information is transmitted by any pathway. The pathway from Wernicke's area to the left occipital lobe via the middle and inferior temporal pathway may be indispensable for kanji writing. We postulate "agraphia without alexia in kanji" due to left inferior temporal subcortical damage.

Resolving metabolic abnormalities in a case of pure alexia.

We report resolving metabolic abnormalities corresponding to clinical improvement in a patient with pure alexia secondary to acute cerebral infarction. Local cerebral glucose metabolism (lCMRgl) was measured with positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) close to ictus and 4 1/2 months later. Serial CTs and a subsequent MRI demonstrated small, unchanging left-hemispheric lesions involving the area of the lateral geniculate body and the splenium of the corpus callosum. PET demonstrated the evolution of the metabolic abnormality resulting from intrahemispheric (lateral geniculate) and interhemispheric (splenium) disconnection in the absence of occipital lobe infarction. This case illustrates that cerebral disconnection can result in the syndrome of pure alexia. The factors accounting for focal hypometabolism in the absence of cerebral infarction are discussed.

Alexia with agraphia due to the left posterior inferior temporal lobe lesion--neuropsychological analysis and its pathogenetic mechanisms.

We report three cases of alexia with agraphia due to the left posterior inferior temporal lesions. In Case 1, the reading disability was more prominent in the use of Kana than in the use of Kanji, which is similar to previously reported cases of alexia with agraphia due to angular gyrus lesion. In Cases 2 and 3, by contrast, the reading disability was more prominent in the use of Kanji than in the use of Kana. In spontaneous writing and dictation, the disability was more pronounced in the use of Kanji compared with the use of Kana. In each of the three cases, the CT scan and positron emission tomography showed a localized lesion in the lower part of the left posterior temporal lobe. A typical form of an alexia with agraphia could be caused not only by the left angular lesion but also by the left posterior inferior temporal lesion. We discuss the neuropsychological analysis and pathogenetic mechanisms of alexia with agraphia due to the left posterior inferior temporal lesion in the comparison of alexia with agraphia caused by the left angular lesion.

Alexia without agraphia: clinical-computed tomographic correlations.

Four patients with alexia without agraphia had CT lesions which correlated with the clinical findings. All lesions were vascular; two were spontaneous intracerebral hematomas and two were ischemic infarctions in the posterior cerebral artery distribution. The lesions were located in the posterior portion of the dominant hemisphere. The location of the lesion correlated with the presence or absence of visual field abnormalities.

The anatomic basis of pure alexia.

The behavioral and anatomic correlates of pure alexia were analyzed in 16 patients. Right homonymous hemianopia failed to appear in three patients, who had right achromatopsia instead. Color anomia and unilateral optic ataxia were seen in six patients. Memory defects were found in two patients. Visual agnosia was noted in two. No patient had visual disorientation. The crucial anatomic correlate of alexia was a lesion of the paraventricular white matter of the left occipital lobe, capable of compromising both interhemispheric and intrahemispheric visual pathways. The lesion associated with color anomia was in the mesial occipitotemporal junction of the left hemisphere.

Semantic paralexia: a release of right hemispheric function from left hemispheric control.

In an unselected group of aphasics those patients who produced semantic paralexias had significantly larger lesions than those without semantic paralexias. The possible mechanisms of the release of "alternative" right hemisphere reading from left hemisphere control are discussed.

CT scan studies of aphasia.

CT scan studies of lesion localization in aphasic patients have in general confirmed the traditional locus of damage within the left hemisphere for the major syndromes. Some interesting exceptions have come to light, such as the possible occurrence of global aphasia with a partial lesion (anterior or posterior) of the language zone. The study of correlations in vivo has underlined the importance of considering time since onset in the evaluation of the clinical picture. Description of atypical aphasias associated with subcortical lesions and correlation of lesion site with specific, partial aspects of linguistic impairment are two areas where CT scan studies are increasing our understanding of the language machinery in the brain.

Conduction aphasia, syntactic alexia, and the anatomy of syntactic comprehension.

Syntactic alexia is the inability to comprehend graphically presented sentences when the meaning depends on syntax. Although previously described in association with Broca's aphasia and attributed solely to the frontal lobe portion of the lesions, syntactic alexia has not been reported to accompany conduction aphasia. We studied three patients who had conduction aphasia from temporoparietal lesions and syntactic alexia. None of them had lesions in Broca's area. Broca's aphasics and our patients with conduction aphasia have a syntactic comprehension disturbance. Since Broca's aphasics and our patients have lesions that may extend into the supramarginal gyrus, we postulate that this area may be critical for comprehending syntax.