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1996
Maldjian, J, Atlas S, Howard RS, Greenstein E, Alsop D, Detre JA, Listerud J, D’Esposito, Flamm ES.  1996.  Functional magnetic resonance imaging of regional brain activity in patients with intracerebral arteriovenous malformations before surgical or endovascular therapy., 1996 Mar. Journal of neurosurgery. 84:477-83. Abstract1996maldjian.pdf

Functional magnetic resonance (MR) imaging was performed in six patients harboring proven intracerebral arteriovenous malformations (AVMs) using a noninvasive blood oxygen level-dependent technique based on the documented discrepancy between regional increases in blood flow and oxygen utilization in response to regional brain activation. Statistical functional MR maps were generated and overlaid directly onto conventional MR images obtained at the same session. In the six patients studied, a total of 23 separate functional MR imaging activation studies were performed. Of these, two runs were discarded because of motion artifacts. All of the remaining 21 studies demonstrated activation in or near expected regions for the paradigm employed. Qualitatively reproducible regional localizations of functional activity in unexpected sites were also seen. The authors’ findings indicating aberrant mapping of cortical function may be explained on the basis of the plasticity of brain function, in that the developing brain can take over function that would normally have been performed by regions of brain encompassed by the lesion. Preliminary results in this study’s small number of cases also indicate that activity demonstrated within the confines of the apparent AVM nidus may help predict the development of a posttherapy deficit. The authors demonstrate that functional MR imaging can be successfully and reproducibly performed in patients with intracerebral AVMs. Notwithstanding the paucity of normative data using functional MR imaging, the author’ findings support cortical reorganization associated with these congenital lesions. Blood oxygen level-dependent MR imaging is a noninvasive method used to localize areas of eloquent cortex in patients harboring AVMs; it may prove to be of value in treatment planning.

Robinson, KM, Grossman M, White-Devine T, D’Esposito.  1996.  Category-specific difficulty naming with verbs in Alzheimer’s disease., 1996 Jul. Neurology. 47:178-82. Abstract1996robinson.pdf

We studied 20 patients with Alzheimer’s disease (AD) on a picture-naming task consisting of frequency-matched pairs of nouns and verbs that were homophonic and homographic (e.g., paint). Intragroup comparisons revealed that verb naming is significantly more difficult for patients with AD than noun naming. An error analysis demonstrated that patients with AD produce significantly more semantic and descriptive errors for verbs than nouns. We correlated verb naming and noun naming with measures of grammatical comprehension, lexical retrieval, and visuoperceptual processing, but there were no selective effects for verbs compared with nouns. Differences in the mental representation of concepts underlying verbs and nouns may account, in part, for the relative difficulty naming with verbs in AD.

Grossman, M, D’Esposito, Hughes E, Onishi K, Biassou N, White-Devine T, Robinson KM.  1996.  Language comprehension profiles in Alzheimer’s disease, multi-infarct dementia, and frontotemporal degeneration., 1996 Jul. Neurology. 47:183-9. Abstract1996grossman4.pdf

We assessed language functioning in 116 age-, education-, and severity-matched patients with the clinical diagnosis of Alzheimer’s disease (AD), multi-infarct dementia (MID) due to small-vessel ischemic disease, or a frontotemporal form of degeneration (FD). Assessments of comprehension revealed that patients with AD are significantly impaired in their judgments of single word and picture meaning, whereas patients with FD had sentence comprehension difficulty due to impaired processing of grammatical phrase structure. Patients with MID did not differ from control subjects in their comprehension performance. Traditional aphasiologic measures did not distinguish between AD, MID, and FD. Selective patterns of comprehension difficulty in patients with different forms of dementia emphasize that language deficits cannot be explained entirely by the compromised memory associated with a progressive neurodegenerative illness.

Grossman, M, Mickanin J, Robinson KM, D’Esposito.  1996.  Anomaly judgments of subject-predicate relations in Alzheimer’s disease., 1996 Aug. Brain and language. 54:216-32. Abstract1996grossman.pdf

Claims that patients with probable Alzheimer’s disease (AD) have semantic memory difficulty have received equivocal support. A common assumption has been that defining or core information determines the truth value of word meaning on measures requiring semantic memory such as category membership judgments or confrontation naming, but this assumption may not be valid. In the present study, we assessed the comprehension of subject-predicate sentences independent of their truth value by asking AD patients to judge the coherence of statements such as "The tulip is tall" or "*The tulip is jealous." We found that AD patients are significantly more impaired than controls at judging the coherence of these simple subject-predicate sentences. Moreover, AD patients were more successful at judging the coherence of statements that contain attributes with a narrow scope of reference compared to attributes with a broad scope of reference. These findings support the hypothesis that AD patients have a semantic memory impairment and suggest a specific deficit processing the network of semantic relations underlying word meaning in semantic memory.

Ween, JE, Alexander M, D’Esposito, Roberts M.  1996.  Factors predictive of stroke outcome in a rehabilitation setting., 1996 Aug. Neurology. 47:388-92. Abstract1996ween.pdf

Accurate outcome prediction following stroke is important for proper delivery of poststroke care. It has been difficult to determine specific factors that provide reliable and accurate predictions of outcome, particularly for patients with intermediate deficit severities. Age and severity of deficit have repeatedly been found to be most reliable, but only as rough estimates and for patients at either extreme of the disability spectrum. This paper reports a prospective study of consecutive rehabilitation admissions (N = 536) to determine the influence of preselected factors. Outcome was analyzed in terms of functional improvement and disposition. Patients younger than 55 years or with an admission Functional Independence Measure (FIM) greater than 80 almost universally went home. Admission FIMs less than 40 were associated with nearly certain nursing home discharge. The comprehensive FIM score was a stronger predictor of outcome than motor impairment in isolation. An admission FIM of 60 or greater was associated with a higher probability of functional improvement during rehabilitation. Small-vessel strokes had the best outcome. Intracerebral hemorrhages improved more than ischemic strokes but more slowly. Right hemisphere lesions did worse than left. Comorbidities influenced outcome only when several conditions accumulated. The absence of a committed caregiver at home increased the risk of nursing home discharge. Suggestions for rehabilitation triage are given.

Alsop, D, Detre JA, D’Esposito, Howard RS, Maldjian JA, Grossman M, Listerud J, Flamm ES, Judy KD, Atlas S.  1996.  Functional activation during an auditory comprehension task in patients with temporal lobe lesions., 1996 Aug. NeuroImage. 4:55-9. Abstract1996alsop.pdf

Functional magnetic resonance imaging (fMRI) was used to map regional brain activation during an auditory comprehension task in two normal controls and two patients with left temporal lobe lesions. Activity in the superior temporal and angular gyrus regions was detected in all normal subjects. In the patients, the spatial distribution of activation ipsilateral to the lesions differed from the pattern observed in contralateral cortex or in control subjects. These studies highlight the potential of fMRI for mapping abnormal functional anatomy in the human brain.

Kroll, NEA, Knight RT, Metcalfed E, Wolfe ES, Tulving E.  1996.  Cohesion failure as a source of memory illusions. Journal of Memory and Language. Abstract1996kroll.pdf

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McGlinchey-Berroth, R, Milberg W, Verfaellie M, Grande L, D’Esposito, Alexander M.  1996.  Semantic processing and orthographic specificity in hemispatial neglect. Abstract1996mcglincheyberroth.pdf

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White-Devine, T, Grossman M, Robinson K, Onishi K, Biassou N.  1996.  Verb confrontation naming and word-picture matching in Alzheimer’s disease. Neuropsychology. Abstract1996whitedevine.pdfWebsite

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Grossman, M, Galetta S, Ding X-S, Morrison D, D’Esposito, Robinson K, Jaggi J, Alavi A, Reivich M.  1996.  Clinical and positron emission tomography studies of visual apperceptive agnosia. Neuropsychiatry, Neuropsychology & Behavioral Neurology. AbstractWebsite

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1995
Grossman, M, Robinson KM, Onishi K, Thompson H, Cohen J, D’Esposito.  1995.  Sentence comprehension in multiple sclerosis., 1995 Oct. Acta neurologica Scandinavica. 92:324-31. Abstract

INTRODUCTION: Explanations of sentence processing difficulty in aphasia have implicated slowed information processing speed. We tested this hypothesis by evaluating sentence comprehension in multiple sclerosis (MS), and relating comprehension performance to measures of information processing speed. MATERIAL & METHODS: Twenty right-handed, high school-educated, non-demented, native English speakers with clinically definite MS and 16 age- and education-matched control subjects were examined on 3 different sentence comprehension measures that stress grammatical appreciation. Performance was related to quantitative assessments of mental information processing speed. RESULTS: Group-wide analyses demonstrated a trend toward sentence comprehension difficulty in MS. Analyses of individual patient profiles identified a subgroup of MS patients who were consistently impaired to a significant extent across all sentence comprehension tasks. Their sentence comprehension difficulty was associated with selectively compromised mental information processing speed. CONCLUSION: Sentence comprehension difficulty in MS is associated with slowed information processing speed. This finding supports the claim that information processing speed contributes to sentence processing.

D’Esposito, Detre JA, Alsop D, Shin RK, Atlas S, Grossman M.  1995.  The neural basis of the central executive system of working memory., 1995 Nov 16. Nature. 378:279-81. Abstractdesposito1995_the_neural_basis_of_the_central_executive_system_of_working_memory_nature.pdf

Working memory refers to a system for temporary storage and manipulation of information in the brain, a function critical for a wide range of cognitive operations. It has been proposed that working memory includes a central executive system (CES) to control attention and information flow to and from verbal and spatial short-term memory buffers. Although the prefrontal cortex is activated during both verbal and spatial passive working memory tasks, the brain regions involved in the CES component of working memory have not been identified. We have used functional magnetic resonance imaging (fMRI) to examine brain activation during the concurrent performance of two tasks, which is expected to engage the CES. Activation of the prefrontal cortex was observed when both tasks are performed together, but not when they are performed separately. These results support the view that the prefrontal cortex is involved in human working memory.

D’Esposito.  1995.  Profile of a neurology residency., 1995 Nov. Archives of neurology. 52:1123-6. Abstract1995despoarchneurol.pdf

The pattern and frequency of patient encounters during the Boston (Mass) University adult neurology residency program (1988 to 1991) for one resident was compared with that in general neurology practice as well as with the frequency of neurologic disorders in the US population. A total of 1332 new patients (85% adult, 15% pediatric) were seen during a 3-year period. This total represented 970 inpatients (73% of all patients) and 362 outpatients (27%). The resident encountered more patients in the hospital (7.5 admissions or 13 consultations per week) and fewer patients in the clinic (2.5 new outpatients per week) than does the average community neurologist (two admissions, 8.7 consultations, and 13.2 new outpatients). The most common diagnosis for an admission encounter was acute ischemic infarct; for a consultation, metabolic encephalopathy; and for an outpatient encounter, radiculopathy. Less prevalent neurologic disorders in the United States (eg, cognitive, demyelinating, movement, and neoplastic disorders) were encountered more frequently in residency than were very prevalent neurologic disorders (eg, headache and trauma). This is the first reported summary of all patients one resident actually encountered during neurology training. The patient encounter profile suggests that this residency training overemphasized acute inpatient care of less prevalent neurologic disorders compared with outpatient care of more prevalent disorders commonly seen in a neurology practice. Accumulation of similar data from other residencies and practicing neurologists can help residency directors assess the changing needs of residents in training and guide curriculum in response to changes in practice patterns.

D’Esposito, Alexander M.  1995.  Subcortical aphasia: distinct profiles following left putaminal hemorrhage., 1995 Jan. Neurology. 45:38-41. Abstract1995desposito2.pdf

Numerous reports of aphasia after subcortical lesions have produced incomplete agreement about basic clinico-anatomic correlations. Some disagreement has arisen from methodologic differences. To control for some of the common differences, we analyzed 13 patients with left putaminal hemorrhage controlled for location–subcortical but not thalamic, and for time postonset–studied in both acute and postacute epochs. There was no apparent correlation between lesion site and acute language profiles. During the postacute epoch, there were several distinct correlations between lesion site (postacute decreased CT density) and specific aphasia dimensions–nonfluency, impaired comprehension, and perhaps impaired repetition. Our correlations were compatible with comparably controlled cases in the literature. A corollary result of this study is that patients fluent during the early epoch are likely to have a better outcome, and those initially nonfluent have a poor prognosis for language recovery.

Fischer, R, Alexander M, D’Esposito, Otto R.  1995.  Neuropsychological and neuroanatomical correlates of confabulation., 1995 Feb. Journal of clinical and experimental neuropsychology. 17:20-8. Abstract

In the present exploratory investigation we report nine confabulatory patients of comparable age, education, and general level of intelligence in the acute epoch of recovery after rupture and clipping of ACoA aneurysms. Five of the nine cases had "spontaneous" confabulation, severe anterograde amnesia, markedly poor attentional and executive functions, and denial of illness. These patients all had multiple lesions that involved basal forebrain, ventral frontal lobe, and striatum. The other four patients manifested only "momentary" or "provoked" confabulations. These patients also had severe anterograde amnesia but showed relatively mild deficits in executive functions. These patients had lesions restricted to the basal forebrain except for one who had additional orbital frontal damage. Analysis of these two groups of confabulatory patients suggests that there is a common profile of deficits and anatomic foundation associated with confabulation; "spontaneous" confabulation appears to require extensive, simultaneous disruption of medial basal forebrain and frontal cognitive systems resulting in profound executive and memory deficits, whereas more limited lesions to the basal forebrain or orbital frontal cortex will result in "transient" or "provoked" confabulatory responses and a more restricted profile of cognitive deficits.

Biassou, N, Grossman M, Onishi K, Mickanin J, Hughes E, Robinson KM, D’Esposito.  1995.  Phonologic processing deficits in Alzheimer’s disease., 1995 Dec. Neurology. 45:2165-9. Abstract1995biassou.pdf

We investigated phonologic production in patients with mild to moderate Alzheimer’s disease (AD) on a repetition task. AD patients produced significantly more speech errors than age-matched controls. AD patients’ errors, unlike those of controls, resulted in the transformation of real words into pseudowords, occurred disproportionately in word-initial positions, and were not influenced by the phonologic environment. This pattern of errors suggests a lexical phonologic retrieval deficit in AD.

D’Esposito, Verfaellie M, Alexander M, Katz DI.  1995.  Amnesia following traumatic bilateral fornix transection., 1995 Aug. Neurology. 45:1546-50. Abstract1995desposito.pdf

There is controversy regarding the effect of isolated fornix damage on human memory. We report a patient who suffered a traumatic penetrating head injury that resulted in a significant and persistent anterograde amnesia. CT revealed a lesion that involved the region of the proximal, posterior portion of both fornices without evidence of damage to other hippocampal pathways or to other structures known to be critical for memory, such as the hippocampus, thalamus, or basal forebrain. The unique location of the lesion in this patient provides evidence supporting the role of isolated fornix lesions in amnesia.

Grossman, M, Peltzer L, D'Esposito M, Alavi A, Reivich M.  1995.  Recovery of function after focal cerebral insult: a PET activation study. Neuropsychological Explorations of Memory and Cognition: Essays in Honor of Nelson Butters. , New York: Plenum Press Abstract

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D’Esposito, Alexander M.  1995.  The clinical profiles, recovery and rehabilitation of memory disorders. Neurorehabilitation. Abstract

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1994
Wolfe, N, Babikian VL, Linn RT, Knoefel JE, D’Esposito, Albert ML.  1994.  Are multiple cerebral infarcts synergistic?, 1994 Feb Archives of neurology. 51:211-5. Abstract

OBJECTIVE: The goal of this study was to characterize the cumulative effects of multiple strokes on cognition. DESIGN: We conducted a prospective, longitudinal case study with neuropsychological, neurological, and radiological evaluations. SETTING: Research was conducted at the Boston (Mass) Veterans Administration Medical Center, Neurology Service, on successive inpatient hospital admissions. PATIENT: We followed up a 66-year-old right-handed man with multiple subcortical lacunae during a 3.5-year period during which he suffered two additional cortical infarctions. MAIN OUTCOME MEASURES: Each evaluation included approximately 3 hours of neuropsychological testing spanning a range of cognitive domains (attention, language, memory, visuospatial functions, response inhibition, and mental flexibility), full neurological examination, and computed tomographic scan. RESULTS: The patient’s stepwise cognitive decline was characterized by unexpected exacerbation of "frontal" neurobehavioral features following the occurrence of two posterior cortical lesions. At initial evaluation, the computed tomographic scan showed bilateral subcortical lacunae in basal ganglia and periventricular white matter, and symptoms included dysarthria and perseveration. The second evaluation, following a left posterior parietal lesion, revealed a range of new frontal features, including impulsivity, pull-to-stimulus, and difficulty shifting set. Following a subsequent right occipital infarct, further frontal lobe impairments emerged: forced grasp reflex and incontinence. CONCLUSIONS: We hypothesize that the cumulative effects of infarcts were synergistic. That is, the posterior cortical infarcts elicited frontal features that would not be expected from a simple sum of these lesions’ effects.

Grossman, M.  1994.  Patterns of cognitive impairment in relapsing-remitting and chronic-progressive multiple sclerosis. Neuropsychiatry, Neuropsychology & Behavioral Neurology. AbstractWebsite

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1993
D’Esposito, McGlinchey-Berroth R, Alexander M, Verfaellie M, Milberg WP.  1993.  Dissociable cognitive and neural mechanisms of unilateral visual neglect., 1993 Dec. Neurology. 43:2638-44. Abstract

We administered two experimental tasks to 16 patients with neglect following unilateral right hemisphere strokes, designed to probe processing of information in the neglected left visual field. A semantic priming/lexical decision task examined implicit processing of stimuli presented to the neglected field, and a discrimination task required explicit recognition of the same stimuli. We grouped patients according to three patterns of performance: (1) poor discrimination in the left visual field but intact priming, (2) normal priming and discrimination in both fields, and (3) normal priming but poor discrimination in both fields. Although patients in group 1 had posterior lesions, patients in groups 2 and 3 had extensive deep anterior lesions. These results suggest that the clinical phenomenon of unilateral visual neglect can be the surface manifestation of deficits in two different and interacting processes–attentional processes (group 1) and intentional processes (group 2)–or it may be a global attentional disturbance superimposed on these deficits (group 3).

1991
D’Esposito.  1991.  The Pharmacology of Memory. Abstract

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