Search PubMed⌕ Search

Biomedical subjects

A E Hillis

Publications and source records attributed to A E Hillis.

At least 19 recordsLinked to original sources

Subcortical aphasia and neglect in acute stroke: the role of cortical hypoperfusion.

We have hypothesized that most cases of aphasia or hemispatial neglect due to acute, subcortical infarct can be accounted for by concurrent cortical hypoperfusion. To test this hypothesis, we demonstrate: (i) that pure subcortical infarctions are associated with cortical hypoperfusion in subjects with aphasia/neglect; (ii) that reversal of cortical hypoperfusion is associated with resolution of the aphasia; and (iii) that aphasia/neglect strongly predicts cortical ischaemia and/or hypoperfusion. We prospectively evaluated a consecutive series of 115 patients who presented within 24 h of onset or progression of stroke symptoms, with MRI sequences including diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI), and detailed testing for aphasia or hemispatial neglect. The association between aphasia or neglect and cortical infarct (or dense ischaemia) on DWI and cortical hypoperfusion indicated by PWI, was evaluated with chi-squared analyses. Fisher exact tests were used for analyses with small samples. Cases of DWI lesion restricted to subcortical white matter and/or grey matter structures (n = 44) were examined for the presence of aphasia or neglect, and for the presence of cortical hypoperfusion. In addition, subjects who received intervention to restore perfusion were evaluated with DWI, PWI, and cognitive tests before and after intervention. Finally, the positive predictive value of the cognitive deficits for identifying cortical abnormalities on DWI and PWI were calculated from all patients. Of the subjects with only subcortical lesions on DWI in this study (n = 44), all those who had aphasia or neglect showed concurrent cortical hypoperfusion. Among the patients who received intervention that successfully restored cortical perfusion, 100% (six out of six) showed immediate resolution of aphasia. In the 115 patients, aphasia and neglect were much more strongly associated with cortical hypoperfusion (chi(2) = 57.3 for aphasia; chi(2) = 28.7 for neglect; d.f. = 1; P < 0.000001 for each), than with cortical infarct/ischaemia on DWI (chi(2) = 8.5 for aphasia; chi(2) = 9.7 for neglect; d.f. = 1; P < 0.005 for each). Aphasia showed a much higher positive predictive value for cortical abnormality on PWI (95%) than on DWI (62%), as did neglect (100% positive predictive value for PWI versus 74% for DWI). From these data we conclude that aphasia and neglect due to acute subcortical stroke can be largely explained by cortical hypoperfusion.

Adult↗

Restoring blood pressure reperfused Wernicke's area and improved language.

Longitudinal clinical and imaging data from a patient who sustained a left frontal-temporal stroke with hypoperfusion of the adjacent Wernicke's area are reported. His language deficits were partially ameliorated by pharmacologically increasing his blood pressure, and were exacerbated when blood pressure dropped. There was a striking temporal and statistical correlation between mean arterial pressure and language accuracy. MR perfusion imaging showed that language gains were accompanied by improved perfusion of Wernicke's area when mean arterial pressure was increased.

Blood Pressure↗

Hypoperfusion of Wernicke's area predicts severity of semantic deficit in acute stroke.

Based on earlier findings that the presence of word comprehension impairment (a deficit in the meaning of words, or lexical semantics) in acute stroke was strongly associated with the presence of hypoperfusion or infarct in Wernicke's area, we tested the hypothesis that the severity of word comprehension impairment was correlated with the magnitude of delay in perfusion of Wernicke's area on magnetic resonance perfusion-weighted imaging. Eighty patients were prospectively studied within 24 hours of onset or progression of acute left hemisphere stroke symptoms, with diffusion-weighted imaging, perfusion-weighted imaging, and detailed language tests. For 50 patients without infarct in Wernicke's area, we found a strong Pearson correlation between the rate of errors on a word comprehension test and the mean number of seconds of delay in time-to-peak concentration of contrast in Wernicke's area, relative to the homologous region on the right. These results add further evidence for the crucial role of Wernicke's area (Brodmann's area 22) in word comprehension and indicate that the magnitude of delay on PWI may be a gross indicator of tissue dysfunction.

Adult↗

Reperfusion of specific brain regions by raising blood pressure restores selective language functions in subacute stroke.

We report a series of six single subject studies examining the effects of pharmacological blood pressure elevation on regional brain perfusion and language function. Previous reports indicate that hypoperfusion of specific brain regions, as delineated by magnetic resonance perfusion weighted imaging (PWI), is associated with disruption of selective lexical functions. On this basis, we hypothesized that reperfusion of the same regions, in the absence of infarct in that region, would restore the associated lexical function. We present five patients with impaired lexical-semantics associated with poor perfusion, but not infarction, of Brodmann's area 22 (BA 22), and one patient with impaired lexical-semantics and a superimposed deficit in retrieving the phonological representations of words, associated with poor perfusion Brodmann's area 37 (BA 37) as well as BA 22. Each patient was treated with induced blood pressure elevation to increase perfusion of the ischemic and dysfunctional tissue. Daily testing of naming and comprehension, with stimulus sets matched for frequency, familiarity, and length, showed improved lexical-semantics in the patients who showed reperfusion of BA 22 and improved oral naming (but not lexical-semantics) in the patient who showed reperfusion of BA 37. These cases illustrate that loss of function with hypoperfusion of a circumscribed area of the brain, and recovery of the same function with improved perfusion of that brain region, can reveal brain/language relationships prior to reorganization after brain injury.

Acute Disease↗

Correlation of aphasia and/or neglect with cortical infarction in a subpopulation of RANTTAS.

Classically in neurology, aphasia and neglect were accepted as reliable markers of cortical lesions. The actual prognostic values of aphasia and neglect have yet to be formally tested. This analysis sought to determine the predictive accuracy of aphasia and/or neglect in acute stroke for cortical infarction. Data from the RANTTAS investigation of tirilazad mesylate in stroke patients were reanalyzed, comparing acute National Institutes of Health Stroke Scale (NIHSS) measures of aphasia and neglect to lesion location on day 7-10 CT scans. Correlations between the presence of aphasia and/or neglect and the presence of a cortical lesion were only in the moderate range, and positive predictive values were far from perfect, as would be expected. 'Subcortical' aphasia or neglect was more likely in large, subcortical lesions. Aphasia and neglect, as determined in the acute setting by the NIHSS, are only moderately associated with cortical infarct identified on follow-up CT scans. If selective neuroprotection is envisioned for acute stroke patients, more accurate markers of cortical infarction may be needed.

Aphasia↗

MR perfusion imaging reveals regions of hypoperfusion associated with aphasia and neglect.

OBJECTIVE: To evaluate diffusion-weighted imaging (DWI) and MR perfusion imaging (MRPI) as tools for identifying regions of infarct and hypoperfusion associated with aphasia and neglect in hyperacute stroke. Secondary goal: to establish a functional correlate of a radiologically defined "ischemic penumbra." METHODS: Forty subjects underwent DWI, MRPI, and standardized tests for lexical deficits or hemispatial neglect within 24 hours of stroke onset or progression. Ten patients had repeat DWI, MRPI, and cognitive testing after 3 days (in some cases after reperfusion therapy). Pearson correlations between error rate on cognitive testing and volume of abnormality on DWI versus MRPI were determined at each time period, and regions of hypoperfusion corresponding to specific cognitive deficits were identified. RESULTS: Error rate was more strongly correlated with volume of hypoperfused tissue on MRPI (r = 0.65 to 0.93; p < 0.01 to p < 0.0003) than with volume of lesion on DWI (r = 0.54 to 0.75; p = 0.14 to p < 0.01) for dominant and nondominant hemisphere stroke, at each time point. Forty-eight percent of aphasic patients and 67% of those with hemispatial neglect had either no infarct or only small subcortical infarct on DWI, but had focal cortical hypoperfusion. Patients who had successful reperfusion therapy showed resolution of the hypoperfused territory beyond the infarction on repeat MRPI and showed resolution of corresponding deficits. CONCLUSIONS: MRPI shows regions of hypoperfused cortex associated with lexical deficits or hemispatial neglect, even when DWI shows no infarct or only small subcortical infarct. MRPI-DWI mismatch indicates regions of functionally salvageable tissue.

Aphasia↗

Cognitive impairments after surgical repair of ruptured and unruptured aneurysms.

OBJECTIVES: To determine the frequency and severity of neuropsychological impairments associated with aneurysmal subarachnoid haemorrhage, and associated with repair of intracerebral aneurysms. METHODS: Two groups of patients who underwent repair of intracerebral aneurysms were studied: patients with unruptured aneurysms (n=20) and patients with ruptured aneurysms (n=27). All patients were administered a battery of standardised neuropsychological tests about 3 months after surgery. A subset of 12 patients with unruptured aneurysms were administered the battery both before and after elective repair of the aneurysm(s). A subset of six patients with ruptured aneurysms were given the test at both 3 months and 1 year after surgery. RESULTS: As previously reported for patients with ruptured aneurysms, patients with both ruptured and unruptured aneurysms performed, as a group, significantly below published norms on many of the neuropsychological tests after surgery. However, there were significant differences between preoperative and postoperative performance in the unruptured aneurysm group only on a few tests: measures of word fluency, verbal recall, and frontal lobe function. Performance of patients with ruptured aneurysms was significantly below that of patients with unruptured aneurysms only on a few tests of verbal and visual memory. In addition, group differences compared with published norms reflected severely impaired performance by a minority of patients, rather than moderately impaired performance in a majority of patients. CONCLUSIONS: Although patients who undergo repair of ruptured aneurysms perform, as a group, below published norms on many neuropsychological tests, significant impairments are seen in a minority of patients. Some of the impairments are associated with subarachnoid haemorrhage, whereas others (found in patients who underwent repair of unruptured aneurysms) are due to general effects of neurosurgery and perioperative management. Finally, some of the postoperative deficits are merely a reflection of premorbid weaknesses.

Adult↗

Making sense out of jargon: a neurolinguistic and computational account of jargon aphasia.

OBJECTIVE: To identify the cognitive and neuroanatomic bases of neologistic jargon aphasia with spared comprehension and production of written words. METHODS: Detailed analysis of performance across experiments of naming, reading, writing, repetition, and word/picture matching by a 68-year-old woman (J.B.N.) served to identify which cognitive mechanisms underlying naming and word comprehension were impaired. J.B.N.'s impairments were then simulated by selectively "lesioning" a computer model of word production that has semantic, word form, and subword phonologic levels of representation (described by Dell in 1986). RESULTS: In comprehension experiments, J.B.N. made far more errors with spoken word input than with written word or picture input (chi-square = 40-59; df = 1; p < 0.0001) despite intact auditory discrimination. In naming experiments (with picture, definition, or tactile input), J.B.N. made far more errors in spoken output relative to written output (chi-square = 14-56; df = 1; p < 0.0001). These selective impairments of spoken word processing were simulated by reducing connection strength between word-level and subword-level phonologic units but maintaining full connection strength between word-level and semantic units in Dell's model. The simulation yielded a distribution of error types that was nearly identical to that of J.B.N., and her CT and MRI scans showed a small subarachnoid hemorrhage in the left sylvian fissure without infarct. Cerebral angiogram showed focal vasospasm in sylvian branches of the left middle cerebral artery. CONCLUSION: Focal left perisylvian dysfunction can result in a highly selective "disconnection" between word-level and subword-level phonologic representations manifest as neologistic jargon aphasia with intact understanding and production of written words.

Aged↗

When a rose is a rose in speech but a tulip in writing.

We report the pattern of performance on language tasks by a neurologically impaired patient, RCM, who makes semantic errors in writing to dictation and in written naming, but makes very few errors at all (and no semantic errors) in spoken naming, oral reading, or spontaneous speech. RCM also shows a significant effect of concreteness on spelling accuracy and other features of so-called "deep dysgraphia." However, it is shown that, unlike previously reported patients described as deep dysgraphic, RCM has intact semantic processing but impairment in accessing lexical-orthographic representations, at least for the items tested. These results demonstrate that the collection of features labelled as "deep dysgraphia" can arise from damage to different cognitive processes. Detailed analyses of RCM's performance across lexical tasks, at two different time periods of recovery, provide evidence that lexical orthographic representations can be either directly activated by lexical semantic representations, or activated by the interaction of lexical semantic and sublexical information from phonology-to-orthography conversion mechanisms.

Aged↗

Mechanisms of spatial attention revealed by hemispatial neglect.

We report performance by a patient, NG, with hemispatial neglect after nondominant stroke, in detecting briefly (200 msec) presented visual targets. NG's detection of targets (gaps in circles) was determined by the location of the target in the space in which stimuli appeared. Gaps on the neglected side of a circle at fixation were rarely detected when circles of uniform size were always presented at fixation. The same targets in the same location were detected far more often in blocks that also included targets presented on each side of the central circle, or in blocks that included larger target stimuli. In these blocks, the window of space in which stimuli appeared was larger, such that the target fell closer to the center of this "window". These results indicate that the spatial extent of attention, and of hemispatial neglect, can be modified on the the basis of expectations and task requirements.

Aged↗

Dissociable coordinate frames of unilateral spatial neglect: "viewer-centered" neglect.

Detailed analyses of reading and nonlexical tasks by three patients with unilateral spatial neglect (USN) secondary to stroke indicate that the USN in each of these patients affects the left side (contralateral to brain damage) of the viewer, with respect to the viewer's head, mid-sagittal plane of the body, or line of sight. In one case, the neglect was further specified as concerning the left side of the viewer's line of sight (the left half of her residual visual field). Thus, the frame of reference of USN in these three cases appears to have viewer-centered (in at least one case, specifically retinotopic) coordinates. The performance of these patients is contrasted to that of other patients in the literature whose USN appears to have a frame of reference with stimulus-centered or object-centered coordinates. These results are interpreted within a model of visual processing (adapted from Marr, 1980 and others) with at least three coordinate frames. It is argued that USN can affect one or more of these coordinate frames independently.

Aged↗

Unilateral spatial neglect in dissociable frames of reference: a comment on Farah, Brunn, Wong, Wallace, and Carpenter (1990)

We comment on a paper by Farah et al. in which it is claimed that averaged performance on a letter naming task by a group of patients with left unilateral spatial neglect (USN) provides evidence that spatial allocation of attention is defined by environment-centered and viewer-centred coordinates, but not by object-centred coordinates. We re-analyze the raw data from that paper, and present statistical analyses of the data from individual subjects which show dissociations in the coordinate frames used by the individual subjects with USN. The data from individual cases demonstrate that object-centered USN occurs alone (without evidence of USN in other reference frames) in some cases, and in association with USN in other reference frames other cases. In contrast to the conclusions drawn from the group performance, results from individual subjects provide evidence for the role of dissociable frames of reference, including an object-centred coordinate frame, in the spatial allocation of attention.

Attention↗

Treatment of naming disorders: new issues regarding old therapies.

I report a series of single case studies involving an aphasic patient, H.G., which illustrates both the usefulness and the limitations of cognitive neuropsychological models and methods in aphasia rehabilitation. The first set of experiments analyze H.G.'s pattern of performance across lexical tasks in order to identify the loci of her damage to the cognitive mechanisms underlying the tasks of naming, comprehension, repetition, reading, and spelling. The second set of studies evaluates her response to two different types of treatment and identifies a few of the variables that influence the effectiveness of treatment.

Adult↗

Lexical organization of nouns and verbs in the brain.

The analysis of neuropsychological disorders of lexical processing has provided important clues about the general organization of the lexical system and the internal structure of the processing components. Reports of patients with selective dysfunction of specific semantic categories such as abstract versus concrete words, living things versus inanimate objects, animals, fruits and vegetables, proper names and so forth, support the hypothesis that the neural organization of the semantic processing component is organized in these categories. There are reports of selective dysfunction of the grammatical categories noun and verb, suggesting that a dimension of lexical organization is the grammatical class of words. But the results reported in these studies have not provided unambiguous evidence concerning two fundamental questions about the nature and the locus of this organization within the lexical system. Is the noun-verb distinction represented in the semantic or in the phonological and orthographic lexicons? Is grammatical-class knowledge represented independently of lexical forms or is it represented separately and redundantly within each modality-specific lexicon? Here we report the performance of two brain-damaged subjects with modality-specific deficits restricted principally (H.W.) or virtually only (S.J.D) to verbs in oral and written production, respectively. The contrasting performance suggests that grammatical-class distinctions are redundantly represented in the phonological and orthographic output lexical components.

Aphasia↗

Deficit to stimulus-centered, letter shape representations in a case of "unilateral neglect".

A brain-damaged subject is described whose pattern of performance in various reading tasks can be explained by proposing damage at a level of the word recognition process in which a representation with stimulus-centered, rather than retinal- or word-centered, coordinates is processed. Analysis of her reading performance as a function of topographical arrangement of letters, position of errors in the letter string, and the effects of letter spacing and of adding a prefix or suffix provide evidence not only for the existence of this level of representation (the letter-shape map in a model proposed by Caramazza and Hillis [3]), but also for specific assumptions about its functioning and structure.

Attention↗

Mechanisms for accessing lexical representations for output: evidence from a category-specific semantic deficit.

We report the performance of a neurologically impaired patient, JJ, whose oral reading of words exceeded his naming and comprehension performance for the same words--a pattern of performance that has been previously presented as evidence for "direct, nonsemantic, lexical" routes to output in reading. However, detailed analyses of JJ's reading and comprehension revealed two results that do not follow directly from the "direct route" hypothesis: (1) He accurately read aloud all orthophonologically regular words and just those irregular words for which he demonstrated some comprehension (as indicated by correct responses or within-category semantic errors in naming and comprehension tasks); and (2) his reading errors on words that were not comprehended at all (but were recognized as words) were phonologically plausible (e.g., soot read as "suit"). We account for these results by proposing that preserved sublexical mechanisms for converting print to sound, together with partially preserved semantic information, serve to mediate the activation of representations in the phonological output lexicon in the task of reading aloud. We present similar arguments for postulating an interaction between sublexical mechanisms and lexical output components of the spelling process.

Aged↗