Selected references 

Seghier, M. L., Neufeld, N. H., Zeidman, P., Leff, A. P., Mechelli, A., Nagendran, A. et al. (2012). Reading without the left ventral occipito-temporal cortex. Neuropsychologia, 50, 3621-3635.
Notes: The left ventral occipito-temporal cortex (LvOT) is thought to be essential for the rapid parallel letter processing that is required for skilled reading. Here we investigate whether rapid written word identification in skilled readers can be supported by neural pathways that do not involve LvOT. Hypotheses were derived from a stroke patient who acquired dyslexia following extensive LvOT damage. The patient followed a reading trajectory typical of that associated with pure alexia, re-gaining the ability to read aloud many words with declining performance as the length of words increased. Using functional MRI and dynamic causal modelling (DCM), we found that, when short (three to five letter) familiar words were read successfully, visual inputs to the patient's occipital cortex were connected to left motor and premotor regions via activity in a central part of the left superior temporal sulcus (STS). The patient analysis therefore implied a left hemisphere "reading-without-LvOT" pathway that involved STS. We then investigated whether the same reading-without-LvOT pathway could be identified in 29 skilled readers and whether there was inter-subject variability in the degree to which skilled reading engaged LvOT. We found that functional connectivity in the reading-without-LvOT pathway was strongest in individuals who had the weakest functional connectivity in the LvOT pathway. This observation validates the findings of our patient's case study. Our findings highlight the contribution of a left hemisphere reading pathway that is activated during the rapid identification of short familiar written words, particularly when LvOT is not involved. Preservation and use of this pathway may explain how patients are still able to read short words accurately when LvOT has been damaged
Wellcome Trust Centre for Neuroimaging, Institute of Neurology, UCL, London WC1N 3BG, UK. Electronic address: m.seghier@fil.ion.ucl.ac.uk

Starrfelt, R., Habekost, T., & Leff, A. P. (2009). Too little, too late: reduced visual span and speed characterize pure alexia. Cerebral Cortex, 19, 2880-2890.
Notes: Whether normal word reading includes a stage of visual processing selectively dedicated to word or letter recognition is highly debated. Characterizing pure alexia, a seemingly selective disorder of reading, has been central to this debate. Two main theories claim either that 1) Pure alexia is caused by damage to a reading specific brain region in the left fusiform gyrus or 2) Pure alexia results from a general visual impairment that may particularly affect simultaneous processing of multiple items. We tested these competing theories in 4 patients with pure alexia using sensitive psychophysical measures and mathematical modeling. Recognition of single letters and digits in the central visual field was impaired in all patients. Visual apprehension span was also reduced for both letters and digits in all patients. The only cortical region lesioned across all 4 patients was the left fusiform gyrus, indicating that this region subserves a function broader than letter or word identification. We suggest that a seemingly pure disorder of reading can arise due to a general reduction of visual speed and span, and explain why this has a disproportionate impact on word reading while recognition of other visual stimuli are less obviously affected
Department of Psychology, Center for Visual Cognition, Copenhagen University, DK-1361 Copenhagen, Denmark. randi.starrfelt@psy.ku.dk

Leff, A. P. & Behrmann, M. (2008). Treatment of reading impairment after stroke. Current Opinion in Neurology, 21, 644-648.
Notes: PURPOSE OF REVIEW: Reading impairments after left or right hemisphere stroke are common yet receive little attention from clinicians and therapists. In this review, we focus on the classification of acquired alexia and the current theory and practice underlying the rehabilitation of this diverse set of disorders. RECENT FINDINGS: The underlying behavioural impairments that dictate reading ability in the acquired alexias are becoming better understood; this, in turn, has led to targeted therapies being undertaken, mainly on a single subject basis. In hemianopic alexia, the most 'peripheral' of the acquired alexias, where text reading speed is determined largely by damage to the visual field, therapies have been directed at improving reading eye movements. In 'pure' alexia, techniques are usually aimed at improving whole-word recognition. In central alexic syndromes, where other language functions are also involved, the emphasis has been on strengthening connections between lexical and semantic representations, strengthening phonological representations, or both, and their association with lexical/semantic knowledge. SUMMARY: Despite targeted approaches to the rehabilitation of patients with alexia caused by stroke, there is still a preponderance of largely descriptive, single-case studies in the literature. In some syndromes, small trials have been attempted and the hope is that, in the future, more systematic investigations will be carried out so rehabilitation efforts can be built on a strong theoretical and empirical foundation. Well designed, single-case studies continue to play an important role in informing therapy, as these disorders are, by nature, heterogeneous
Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, UK. a.leff@fil.ion.ucl.ac.uk

Leff, A. P., Spitsyna, G., Plant, G. T., & Wise, R. J. (2006). Structural anatomy of pure and hemianopic alexia. Journal of Neurology, Neurosurgery and Psychiatry, 77, 1004-1007.
Notes: BACKGROUND: The two most common types of acquired reading disorder resulting from damage to the territory of the dominant posterior cerebral artery are hemianopic and pure alexia. Patients with pronounced hemianopic alexia have a right homonymous hemianopia that encroaches into central or parafoveal vision; they read individual words well, but generate inefficient reading saccades when reading along a line of text. Patients with pure alexia also often have a hemianopia but are more disabled, making frequent errors on individual words; they have sustained damage to a brain region that supports efficient word identification. OBJECTIVE: To investigate the differences in lesion site between hemianopic alexia and pure alexia groups, as rehabilitative techniques differ between the two conditions. METHODS: High-resolution magnetic resonance images were obtained from seven patients with hemianopic alexia and from six patients with pure alexia caused by a left occipital stroke. The boundary of each lesion was defined and lesion volumes were then transformed into a standard stereotactic space so that regional comparisons could be made. RESULTS: The two patient groups did not differ in terms of damage to the medial left occipital lobe, but those with pure alexia had additional lateral damage to the posterior fusiform gyrus and adjacent tissue. CONCLUSIONS: Clinicians will be able to predict the type of reading disorder patients with left occipital lesions have from simple tests of reading speed and the distribution of damage to the left occipital lobe on brain imaging. This information will aid management decisions, including recommendations for reading rehabilitation.

Leff, A. P., Crewes, H., Plant, G. T., Scott, S. K., Kennard, C., & Wise, R. J. (2001). The functional anatomy of single-word reading in patients with hemianopic and pure alexia. Brain, 124, 510-521.
Notes: MRC Clinical Sciences Centre, Cyclotron Unit, Hammersmith Hospital, London W12 0NN, UK. alexander.leff@ic.ac.uk
We investigated single-word reading in normal subjects and patients with alexia following a left occipital infarct, using PET. The most posterior brain region to show a lateralized response was at the left occipitotemporal junction, in the inferior temporal gyrus. This region was activated when normal subjects, patients with hemianopic alexia and patients with an incomplete right homonymous hemianopia, but no reading deficit, viewed single words presented at increasing rates. This same area was damaged in a patient with pure alexia ("alexia without agraphia") and no hemianopia, who read words slowly using a letter-by-letter strategy. Although the exact level of the functional deficit is controversial, pure alexia is the result of an inability to map a percept of all the letters in a familiar letter string on to the mental representation of the whole word form. However, the commonest deficit associated with "pure" alexia is a right homonymous field defect; an impairment that may, by itself, interfere with single-word reading because of inability to see the letters towards the end of a word. The relative contributions of pure and hemianopic alexia in individual patients needs to be assessed, as the latter has been shown to respond well to specific rehabilitation programmes