White matter disconnectivity fingerprints causally linked to dissociated forms of alexia.

For over 150 years, the study of patients with acquired alexia has fueled research aimed at disentangling the neural system critical for reading. An unreached goal, however, relates to the determination of the fiber pathways that root the different visual and linguistic processes needed for accurate word reading. In a unique series of neurosurgical patients with a tumor close to the visual word form area, we combine direct electrostimulation and population-based streamline tractography to map the disconnectivity fingerprints characterizing dissociated forms of alexia. Comprehensive analyses of disconnectivity matrices establish similarities and dissimilarities in the disconnection patterns associated with pure, phonological and lexical-semantic alexia. While disconnections of the inferior longitudinal and posterior arcuate fasciculi are common to all alexia subtypes, disconnections of the long arcuate and vertical occipital fasciculi are specific to phonological and pure alexia, respectively. These findings provide a strong anatomical background for cognitive and neurocomputational models of reading.

Can the right hemisphere read? A behavioral and disconnectome study on implicit reading in a patient with pure alexia.

Patients with pure alexia have major difficulties in reading aloud. However, they often perform above chance level in reading tasks that do not require overt articulation of the target word - like lexical decision or semantic judgment - a phenomenon usually known as "implicit reading." There is no agreement in the literature on whether implicit reading should be attributed to relative sparing of some left hemisphere (LH) reading centers or rather to signs of compensatory endeavors by the right hemisphere (RH). We report the case of an 81-year-old patient (AA) with pure alexia due to a lesion involving the left occipital lobe and the temporal infero-mesial areas, as well as the posterior callosal pathways. Although AA's reading was severely impaired and proceeded letter by letter, she showed an above-chance-level performance for frequent concrete words in a tachistoscopic lexical decision task. A structural disconnectome analysis revealed that AA's lesion not only affected the left occipital cortex and the splenium: it also disconnected white-matter tracts meant to connect the visual word-form system to decision-related frontal areas within the LH. We suggest that the RH, rather than the LH, may be responsible for patient AA's implicit reading.

When mild pure alexia may not be reducible to hemianopic alexia.

Individuals with pure alexia often have visual field defects such as right homonymous hemianopia. Relatively few attempts have been made to develop criteria to differentiate pure alexia from hemianopic alexia. In this Commentary we provide concrete suggestions to distinguish the two disorders. We also report on additional assessments with two previously reported cases for whom the diagnosis of pure alexia was called into question and an alternative proposal was offered that the reading deficits were instead due to hemianopia. We show that the results of clinical and neuropsychological tests do not support the account that the reading impairment was caused by the visual field defect. In particular, for both cases, the right homonymous hemianopia was not complete, and a split-field reading task demonstrated an inability also to read words presented in the intact left visual field. In conclusion, pure alexics may indeed show fairly modest word-length effects; however, the presence of right homonymous hemianopia and a non-extreme gradient of reading speed alone are not sufficient grounds to put in doubt the diagnosis. We propose that a fuller clinical and neuropsychological examination taking into account the possible confounding effects of the visual field defects will help to distinguish pure alexia from hemianopic alexia.

Reading on the right when there's nothing left? Probabilistic tractography reveals hemispheric asymmetry in pure alexia.

We present a patient with reading inexpertise and right hemianopia following left posterior cerebral artery (PCA) stroke. We examine the extent of disruption to reading performance and the extent of white matter tract damage relative to a patient with more limited PCA infarction and isolated right hemianopia. We show white matter disconnection of the temporal occipital fusiform cortex in our pure alexia patient. Connectivity-based laterality indices revealed right hemisphere laterality in the alexia patient; this was not associated with improved reading function. We speculate that the degree of premorbid laterality may be a critical factor affecting the extent of reading dysfunction in alexia.

Alexia Without Agraphia in a Right-Handed Individual Following Right Occipital Stroke.

Alexia without agraphia is a disconnection syndrome that typically involves damage to the occipital lobe, with splenium involvement, in the dominant left hemisphere. We describe an exceptionally rare case of a right-handed individual displaying this deficit following a right-sided occipital stroke. A report of a single case of a 65-year-old man is presented with data from appointments with the neurology and neuropsychology departments that occurred approximately 10 and 12 months following the patient's stroke. During the evaluation, he exhibited a marked deficit in his ability to read, with vision grossly intact. His ability to write single words and short phrases from dictation was intact, but he was later unable to read them. This case demonstrates the complexity of the organization of language in the human brain. Although a large majority of individuals exhibit language dominance in their left hemispheres, it remains possible that some right-handed individuals may show atypical organization of language. This highlights the need for clinicians to consider atypical cortical organization when observed deficits may not necessarily match expected lesions within the cortex.

To read or not to read: a neurophysiological study.

Pure alexia (PA) has been associated with visual deficits or a failure to activate the visual word form area (VWFA). We report a patient with pure alexia due to posterior cortical atrophy, in whom event-related potentials revealed a delay in the P100 component and an absent N170 compared with controls. Furthermore, there was a tendency for a larger delay in P100 latencies associated with incorrectly read words. This suggests that some cases of PA might result from deficits in visual perception, signaled by the P100 early potential which could lead to an inability to consistently activate the VWFA, marked by the absent N170.

Fast word reading in pure alexia: "fast, yet serial".

Pure alexia is a severe impairment of word reading in which individuals process letters serially with a pronounced length effect. Yet, there is considerable variation in the performance of alexic readers with generally very slow, but also occasionally fast responses, an observation addressed rarely in previous reports. It has been suggested that "fast" responses in pure alexia reflect residual parallel letter processing or that they may even be subserved by an independent reading system. Four experiments assessed fast and slow reading in a participant (DN) with pure alexia. Two behavioral experiments investigated frequency, neighborhood, and length effects in forced fast reading. Two further experiments measured eye movements when DN was forced to read quickly, or could respond faster because words were easier to process. Taken together, there was little support for the proposal that "qualitatively different" mechanisms or reading strategies underlie both types of responses in DN. Instead, fast responses are argued to be generated by the same serial-reading strategy.

Progressive Wallerian Degeneration of the Corpus Callosal Splenium in a Patient with Alexia Without Agraphia: Advanced MR Findings.

The corpus callosal splenium is an uncommon location for Wallerian degeneration (WD), which may be mistaken for new pathology on magnetic resonance imaging (MRI). We describe the case of a 69-year-old woman with a left posterior cerebral artery infarct in whom progressive WD of the splenium of the corpus callosum seen on MRI was misinterpreted as new infarction or neoplasm. We address how magnetic resonance spectroscopy, perfusion MRI, diffusion tensor MRI, and serial imaging were utilized in establishing the correct diagnosis. Interestingly, the patient also presented with alexia without agraphia, which has never been reported in association with splenial WD. It is conceivable that WD affected critical splenial association fibers resulting in this uncommon dissociation syndrome.

Do patients with pure alexia suffer from a specific word form processing deficit? Evidence from 'wrods with trasnpsoed letetrs'.

It is widely accepted that letter-by-letter reading and a pronounced increase in reading time as a function of word length are the hallmark features of pure alexia. Why patients show these two phenomena with respect to underlying cognitive mechanisms is, however, much less clear. Two main hypotheses have been proposed, i.e. impaired discrimination of letters and deficient processing of word forms. While the former deficit can easily be investigated in isolation, previous findings favouring the latter seem confounded. Applying a word reading paradigm with systematically manipulated letter orders in two patients with pure alexia, we demonstrate a word form processing deficit that is not attributable to sublexical letter discrimination difficulties. Moreover, pure alexia-like fixation patterns could be induced in healthy adults by having them read sentences including words with transposed letters, so-called 'jumbled words'. This further corroborates a key role of deficient word form processing in pure alexia. With regard to basic reading research, the present study extends recent evidence for relative, rather than precise, encoding of letter position in the brain.

Pure alexia caused by separate lesions of the splenium and optic radiation.

Pure alexia is severe difficulty in reading and understanding written language but with normal oral language and writing abilities. We report a patient with pure alexia caused by two different infarct lesions in the left lateral thalamus and the left splenium of the corpus callosum. A 56-year-old right-handed man was admitted to hospital with right homonymous hemianopia associated with pure alexia. He could write kana characters but not kanji. His cranial magnetic resonance imaging revealed two different infarct lesions in the left optic radiation and the left splenium of the corpus callosum. Magnetic resonance angiography showed mild stenosis at the origin of the right vertebral artery and stenosis of the left distal posterior cerebral artery. The mechanism of developing pure alexia can be simply explained by disconnection. We assumed that agraphia of kanji was caused by the effect of ischemia and edema following transient obstruction in branches from the distal posterior cerebral artery.

Implicit reading in Chinese pure alexia.

A number of recent studies have shown that some patients with pure alexia display evidence of implicit access to lexical and semantic information about words that they cannot read explicitly. This phenomenon has not been investigated systematically in Chinese patients. We report here a case study of a Chinese patient who met the criteria for pure alexia and had lesions in the left occipitotemporal region and the splenium of the corpus callosum. His explicit and implicit reading was evaluated with various stimuli in a number of tasks. We found that despite his severe impairment in overt reading and the definition of any characters, his performance was well above chance in various implicit tasks. His accuracy with respect to lexical decisions was so high that his performance was almost normal. These findings provide unequivocal evidence for the existence of implicit reading in Chinese patients with pure alexia and further support the involvement of the right hemisphere.

About the role of visual field defects in pure alexia.

Pure alexia is an acquired reading disorder characterized by a disproportionate prolongation of reading time as a function of word length. Although the vast majority of cases reported in the literature show a right-sided visual defect, little is known about the contribution of this low-level visual impairment to their reading difficulties. The present study was aimed at investigating this issue by comparing eye movement patterns during text reading in six patients with pure alexia with those of six patients with hemianopic dyslexia showing similar right-sided visual field defects. We found that the role of the field defect in the reading difficulties of pure alexics was highly deficit-specific. While the amplitude of rightward saccades during text reading seems largely determined by the restricted visual field, other visuo-motor impairments-particularly the pronounced increases in fixation frequency and viewing time as a function of word length-may have little to do with their visual field defect. In addition, subtracting the lesions of the hemianopic dyslexics from those found in pure alexics revealed the largest group differences in posterior parts of the left fusiform gyrus, occipito-temporal sulcus and inferior temporal gyrus. These regions included the coordinate assigned to the centre of the visual word form area in healthy adults, which provides further evidence for a relation between pure alexia and a damaged visual word form area. Finally, we propose a list of three criteria that may improve the differential diagnosis of pure alexia and allow appropriate therapy recommendations.

Agraphia for kanji resulting from a left posterior middle temporal gyrus lesion.

OBJECTIVE: To clarify whether agraphia or alexia occurs in lesions of the left posterior middle temporal gyrus. METHODS: We assessed the reading and writing abilities of two patients with this lesion using kanji (Japanese morphograms) and kana (Japanese syllabograms). RESULTS: Patient 1 first presented with pure alexia more impaired for kana after an infarction in the left middle and inferior occipital gyri and right basal occipital cortex, and after a second infarction in the left posterior middle temporal gyrus adjoining the first lesion he showed alexia with agraphia for kanji and worsened alexia for kana; kanji alexia recovered over the following six to 10 months. Patient 2 presented with alexia with agraphia for kanji following a hemorrhage in the left posterior middle and inferior temporal gyri, which resolved to agraphia for kanji at two months after onset. Kana nonword reading was also slightly impaired, but became normal by six months post-onset. In both patients, kanji agraphia was mostly due to impaired character recall. CONCLUSION: The present patients demonstrate that damage to the left posterior middle temporal gyrus alone can cause agraphia for kanji. If the adjacent mid fusiform/inferior temporal gyri (Area 37) are spared, the kanji alexia is transient.

Alexia with and without agraphia: an assessment of two classical syndromes.

BACKGROUND: Current cognitive models propose that multiple processes are involved in reading and writing. OBJECTIVE: Our goal was to use linguistic analyses to clarify the cognitive dysfunction behind two classic alexic syndromes. METHODS: We report four experiments on two patients, one with alexia without agraphia following occipitotemporal lesions, and one with alexia with agraphia from a left angular gyral lesion. RESULTS: The patient with occipital lesions had trouble discriminating real letters from foils and his reading varied with word-length but not with linguistic variables such as part of speech, word frequency or imageability. He read pseudo-words and words with regular spelling better, indicating preserved use of grapheme-to-phoneme pronunciation rules. His writing showed errors that reflected reliance on 'phoneme-to-grapheme' spelling rules. In contrast, the patient with a left angular gyral lesion showed better recognition of letters, words and their meanings. His reading was better for words with high imageability but displayed semantic errors and an inability to use 'grapheme-to-phoneme' rules, features consistent with deep dyslexia. His agraphia showed impaired access to both an internal lexicon and 'phoneme-to-grapheme' rules. CONCLUSION: Some cases of pure alexia may be a perceptual word-form agnosia, with loss of internal representations of letters and words, while the angular gyral syndrome of alexia with agraphia is a linguistic deep dyslexia. The presence or absence of agraphia does not always distinguish between the two; rather, writing can mirror the reading deficits, being more obvious and profound in the case of an angular gyral syndrome.

Alexia without agraphia in Creutzfeldt-Jakob disease.

Progressive dementia uncommonly presents with focal deficits referable to posterior cortical dysfunction. We describe a 62 year-old man who presented with progressive visual disturbance in whom detailed cognitive testing documented alexia without agraphia. The only finding from diagnostic investigations was hypoperfusion of the posterior left temporoparietal region on brain SPECT scan. He rapidly progressed and Creutzfeldt-Jakob disease (CJD) was confirmed at autopsy. Although reading disorders may develop in association with posterior cortical atrophy due to CJD, this is the first reported autopsy-confirmed case presenting as alexia without agraphia.

Differential reorganization of fusiform gyrus in two types of alexia after stroke.

Lesions affecting the left fusiform gyrus (FG) commonly result in dyslexia and recovery largely depends on efficient reorganization of the reading network. We performed a follow-up fMRI study to elucidate the reorganization patterns of the FG according to the recovery of reading ability in two patients (MH with pure alexia and KM with alexia with agraphia) after stroke involving the left FG. Initially, MH was an effortful letter-by-letter (LBL) reader, and she improved to become a proficient LBL reader. The initial fMRI results showed scattered activation on occipital and ventral temporal cortex during reading, which was localized to right FG in the follow-up study. KM's severe alexia with agraphia did not improve, even after 6 months had passed since the onset of the alexia. The initial and follow-up fMRI results showed no significant activation in the bilateral FG or central higher language areas during word reading. Our results suggest that the reorganization of the FG is different according to the type of alexia and the amount of clinical recovery in each patient. Also, the successful reorganization of the visual component of reading in the right FG is responsible for the recovery of LBL reading in pure alexia.

The rises and falls of disconnection syndromes.

In a brain composed of localized but connected specialized areas, disconnection leads to dysfunction. This simple formulation underlay a range of 19th century neurological disorders, referred to collectively as disconnection syndromes. Although disconnectionism fell out of favour with the move against localized brain theories in the early 20th century, in 1965, an American neurologist brought disconnection to the fore once more in a paper entitled, 'Disconnexion syndromes in animals and man'. In what was to become the manifesto of behavioural neurology, Norman Geschwind outlined a pure disconnectionist framework which revolutionized both clinical neurology and the neurosciences in general. For him, disconnection syndromes were higher function deficits that resulted from white matter lesions or lesions of the association cortices, the latter acting as relay stations between primary motor, sensory and limbic areas. From a clinical perspective, the work reawakened interest in single case studies by providing a useful framework for correlating lesion locations with clinical deficits. In the neurosciences, it helped develop contemporary distributed network and connectionist theories of brain function. Geschwind's general disconnectionist paradigm ruled clinical neurology for 20 years but in the late 1980s, with the re-emergence of specialized functional roles for association cortex, the orbit of its remit began to diminish and it became incorporated into more general models of higher dysfunction. By the 1990s, textbooks of neurology were devoting only a few pages to classical disconnection theory. Today, new techniques to study connections in the living human brain allow us, for the first time, to test the classical formulation directly and broaden it beyond disconnections to include disorders of hyperconnectivity. In this review, on the 40th anniversary of Geschwind's publication, we describe the changing fortunes of disconnection theory and adapt the general framework that evolved from it to encompass the entire spectrum of higher function disorders in neurology and psychiatry.