Argye Hillis

Department of Neurology, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD







Selected references on reading and alexia


Cloutman, L. L., Newhart, M., Davis, C. L., Heidler-Gary, J., & Hillis, A. E. (2011). Neuroanatomical correlates of oral reading in acute left hemispheric stroke. Brain and Language, 116, 14-21.
Notes: Oral reading is a complex skill involving the interaction of orthographic, phonological, and semantic processes. Functional imaging studies with nonimpaired adult readers have identified a widely distributed network of frontal, inferior parietal, posterior temporal, and occipital brain regions involved in the task. However, while functional imaging can identify cortical regions engaged in the process under examination, it cannot identify those brain regions essential for the task. The current study aimed to identify those neuroanatomical regions critical for successful oral reading by examining the relationship between word and nonword oral reading deficits and areas of tissue dysfunction in acute stroke. We evaluated 91 patients with left hemisphere ischemic stroke with a test of oral word and nonword reading, and magnetic resonance diffusion-weighted and perfusion-weighted imaging, within 24-48h of stroke onset. A voxel-wise statistical map showed that impairments in word and nonword reading were associated with a distributed network of brain regions, including the inferior and middle frontal gyri, the middle temporal gyrus, the supramarginal and angular gyri, and the middle occipital gyrus. In addition, lesions associated with word deficits were found to be distributed more frontally, while nonword deficits were associated with lesions distributed more posteriorly
Department of Neurology, Johns Hopkins University School of Medicine, USA.

Hillis, A. E. (2008). Chapter 15 Cognitive processes underlying reading and writing and their neural substrates. Handbook of Clinical Neurology, volume 88. P.J.Vinken & G.W.Bruyn.Amsterdam:Elsevier, , 311-322.
Notes: Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA

Hillis, A. E. (2007). Alexia and agraphia in acute and chronic stroke. In O.Godefroy & J. Bogousslavsky (Eds.), The behavioral and cognitive neurology of stroke (pp. 102-125). Cambridge: Cambridge University Press.

Philipose, L. E., Gottesman, R. F., Newhart, M., Kleinman, J. T., Herskovits, E. H., Pawlak, M. A. et al. (2007). Neural regions essential for reading and spelling of words and pseudowords. Annals of Neurology, 62, 481-492.
Notes: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
OBJECTIVE: To identify dysfunctional brain regions critical for impaired reading/spelling of words/pseudowords by evaluating acute stroke patients on lexical tests and magnetic resonance imaging, before recovery or reorganization of structure-function relationships. METHODS: A series of 106 consenting patients were administered oral reading and spelling tests within 24 hours of left supratentorial stroke onset. Patients underwent diffusion- and perfusion-weighted magnetic resonance examination the same day to identify regions of hypoperfusion/infarct of 16 Brodmann areas. RESULTS: Simultaneous logistic regression analysis demonstrated that dysfunction of left Brodmann areas 40 (supramarginal gyrus) and 37 (posterior-inferior temporal/fusiform gyrus) best predicted impairment in reading words (odds ratio [OR], 6.20 [95% confidence interval (CI), 1.54-24.96] and 2.71 [95% CI, 0.87-8.45], respectively), reading pseudowords (OR, 39.65 [95% CI 3.9-400.78] and 4.41 [95% CI, 1.1-17.51], respectively), spelling words (OR, 14.11 [95% CI 1.37-144.93] and 7.41 [95% CI, 1.48-37.24], respectively), and spelling pseudowords (OR, 4.84 [95% CI, 0.73-32.13] and 7.74 [95% CI, 1.56-38.51], respectively). Whole-brain voxel-wise analyses demonstrated voxel clusters within these regions that were most strongly associated with task deficits. INTERPRETATION: Results indicate that a shared network of regions including parts of left Brodmann areas 37 and 40 is necessary for reading and spelling of words and pseudowords. Further studies may define the precise roles of these brain regions in language. Identification of any neural regions specific to one of these tasks or one type of stimuli will require study of more patients with selective deficits

Hillis, A. E., Newhart, M., Heidler, J., Marsh, E. B., Barker, P., & Degaonkar, M. (2005). The neglected role of the right hemisphere in spatial representation of words for reading. Aphasiology, 19, 225-238.
Notes:  Dr. A.E. Hillis, Department of Neurology, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD 21287
Background: Previous studies have indicated that focal brain damage can result in different types of "neglect dyslexia" (reading errors specific to the side of printed material contralateral to the side of brain damage). Aims: To identify the sites of lesions (or dysfunctional brain tissue) responsible for distinct types of neglect dyslexia, to inform a functional neuroanatomical model of brain regions involved in early stages of reading. Methods & procedures: A battery of tests of hemispatial neglect and reading designed to distinguish neglect dyslexia in different reference frames (viewer-centred, stimulus-centred, and object-centred) was administered to 95 patients within 48 hours of onset of nondominant hemisphere stroke. Magnetic resonance diffusion and perfusion imaging was obtained on the same day as testing. Associations between each type of neglect dyslexia and areas of hypoperfusion and/or infarct were evaluated using chi-squared tests. Outcomes & results: Viewer-centred neglect dyslexia was associated with hypoperfusion and/or infarct in right angular and supramarginal gyri and visual association cortex ("dorsal stream"). Stimulus-centred neglect dyslexia was associated with hypoperfusion and/or infarct of right superior temporal cortex ("ventral stream"). Object-centred neglect dyslexia was observed only with hypoperfusion and/or infarct of non-dominant superior temporal cortex in left-handed individuals. Conclusions: The identified associations provide evidence that different regions of cortex are critical for spatial attention to, or processing of, representations of words with distinct coordinate frames in the reading task.

Hillis, A. E. & Heidler, J. (2005). Contributions and limitations of the cognitive neuropsychological approach to treatment: Illustrations from studies of reading and spelling therapy. Aphasiology, 19, 985-993.
Notes: Dr. A.E. Hillis, Department of Neurology, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287
Background: Cognitive neuropsychological research is focused on improving the understanding of cognitive processes and representations underlying normal tasks such as reading and spelling, on the basis of impaired performance of these tasks after brain damage. Functional architectures of cognitive tasks developed through this approach have often assisted speech-language pathologists and other therapists in understanding the task to be treated, and in identifying the impaired and spared components of the task to be treated in each individual with brain damage. Aims: To review the benefits and limitations of this approach, focusing on illustrations from treatment of reading and spelling, and to provide ideas about how the limitations might be addressed. Contributions: We provide examples that demonstrate how disruption of particular cognitive functions in the process of reading or spelling might be identified and rationally treated. Additionally, we provide some illustrations of how limitations of this approach might be addressed by considering evidence from cognitive neuroscience regarding neural mechanisms of recovery and learning. Conclusions: Insights from cognitive neuropsychology should be integrated with insights from neuroscience in developing rehabilitation strategies.

Hillis, A. E., Newhart, M., Heidler, J., Barker, P., Herskovits, E., & Degaonkar, M. (2005). The roles of the "visual word form area" in reading. NeuroImage, 24, 548-559.
Notes: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. argye@JHMI@edu
Activation of the left midfusiform gyrus in response to reading words and pseudowords is such a reliable finding in functional imaging that this region has been called "the visual word form area" (VWFA). However, this label has recently been challenged, because activation in VWFA is also observed in other lexical tasks. We evaluated whether VWFA is necessary, sufficient, or specialized for reading by examining how frequently acute lesions in VWFA disrupt tasks that require access to written word forms versus other lexical tasks. We administered lexical tasks with spoken and written input and output, and identified damage or dysfunction of VWFA and other regions of interest (ROI) on diffusion- and perfusion-weighted imaging (DWI and PWI) in 80 patients within 24 h of onset of acute left ischemic stroke. Associations between abnormalities in each region of interest and impairment on lexical tasks were evaluated with chi-squared tests. Damage or dysfunction of VWFA was not significantly associated with impairment of written word comprehension or lexical decision, but was significantly associated with impairment on all tasks requiring lexical output: oral reading and oral naming (visual or tactile input), and written naming. We account for these results and results from functional imaging by proposing that the left midfusiform gyrus normally has two roles in reading: (1) computation of location- and modality-independent grapheme sequences from written word stimuli, and (2) a modality-independent stage of lexical processing that links modality-specific input and output representations. VWFA is not necessary for the former because the right homologue of VWFA can immediately assume this role

Marsh, E. B. & Hillis, A. E. (2005). Cognitive and neural mechanisms underlying reading and naming: evidence from letter-by-letter reading and optic aphasia. Neurocase, 11, 325-337.
Notes: The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
We report detailed analysis of language performance in a patient, RMI, a 55-year-old man who presented with a homonymous hemianopsia, optic aphasia, and alexia without agraphia (with letter-by-letter reading) acutely after stroke. MRI showed infarct in the left occipital and medial temporal lobe and hypoperfusion of the entire posterior cerebral artery territory, including the splenium. Extensive language testing revealed severely impaired picture naming and oral reading, with relatively spared tactile naming and recognition of orally spelled words, consistent with impaired access to lexical and semantic representations from vision. In addition, he had a milder deficit in accessing lexical representations for output from all input modalities. RMI's execution of various language tasks provided considerable insight into the mechanisms that underlie oral reading. His performance indicated that both semantic access and orthographic to phonologic conversion mechanisms were partially intact. When information from these two impoverished systems was coupled (the picture of an object presented with its written name), his ability to read/name improved significantly, consistent with the hypothesis that partially accessed semantic information from vision can combine with partially accessed sublexical orthographic to phonologic conversion mechanisms to access phonological representations for output. Furthermore, his written word and picture recognition improved to normal at a time when magnetic resonance perfusion imaging demonstrated reperfusion of the splenium. We interpret these results, as well as results from previous studies in the literature, within a model of the neural regions critical for various cognitive processes underlying reading

Hillis, A. E. & Tuffiash, E. (2002). Neuroanatomical aspects of reading. In A.E.Hillis (Ed.), The handbook of adult language disorders: Integrating cognitive neuropsychology, neurology, and rehabilitation  (pp. 15-25). New York: Psychology Press.

Hillis, A. E. (2002). Models of the reading process. In A.E.Hillis (Ed.), The handbook of adult language disorders: Integrating cognitive neuropsychology, neurology, and rehabilitation (pp. 3-14). New York: Psychology Press.

Beeson, P. M. & Hillis, A. E. (2001). Comprehension and production of written words. In R.Chapey (Ed.), Language intervention strategies in aphasia and related neurogenic communication disorders (4 ed., pp. 572-604). Baltimore,MD: Lippincott Williams & Wilkins.

Hillis, A. E., Kane, A., Barker, P., Beauchamp, N., Gordon, B., & Wityk, R. (2001). Neural substrates of the cognitive processes underlying reading: Evidence from magnetic resonance perfusion imaging in hyperacute stroke. Aphasiology, 15, 919-931.
Notes: Dr. A.E. Hillis, Department of Neurology, Johns Hopkins Hospital, Meyer 5-185, 600 N. Wolfe Street, Baltimore, MD 21287, United States
Although it is widely agreed that reading aloud entails multiple cognitive processes, there is little evidence for localisation of these processes. We investigated regions of brain dysfunction associated with impairment of each process. Forty patients were studied within 24 hours of onset of dominant hemisphere stroke, using: (1) a battery of tasks to identify impaired processes underlying reading, and (2) magnetic resonance perfusion imaging (MRPI) and diffusion-weighted imaging (DWI). Impairment of each component of reading, except motor speech, was highly correlated with one or more regions of hypoperfusion identified by MRPI, but not with areas of infarct on DWI

Hillis, A. E. & Caramazza, A. (1995). Spatially specific deficits in processing graphemic representations in reading and writing. Brain and Language, 48, 263-308.
Notes: Department of Cognitive Science, Johns Hopkins University, USA We report the performance of two brain-damaged subjects, HB and ML, whose spelling performance is characterized by selective impairment in processing the side of words contralateral to their brain damage. A striking feature of these patients' performance was the fact that their spelling errors in all tasks--written naming, written and oral spelling, and delayed copy transcription- -almost exclusively concerned the right half of words (in the case of HB) or the left half of words (in the case of ML), regardless of length of the target response. These patterns of performance are interpreted as indicating damage at the level of the grapheme description computed in all spelling tasks. We also discuss the additional observations that HB tended to complete words with nonrandom letter sequences in misspelling the final half of the word and that ML tended to preserve the initial letter of the word (in forward but not backward spelling) even when she made errors on other letters in the initial half of the word. Finally, the relationship between these spatially specific impairments of reading and writing and their relationship to spatially specific deficits in non-lexical tasks is reviewed


Anders Gade