Biomedical subjects
Publications and source records attributed to D Tranel.
The primate brain appears to store knowledge in widely distributed neural systems. Recent evidence suggests that these systems are specialized with respect to their capacity for supporting acquisition and retrieval of different domains and levels of knowledge.
A host of recent investigations and new theoretical models have advanced our understanding of the neural underpinnings of speech and language in humans. The application of positron emission tomography (PET) techniques to the investigation of language has provided corroborating evidence regarding the role of left hemisphere structures previously associated with language, together with some intriguing new findings. Innovative ideas regarding the ontogeny of language have come from studies of deaf infants who appear to babble with signs in much the same way that hearing infants babble vocally. A number of investigators have focused on the controversial syndrome known as progressive aphasia, and new evidence has supported the importance of this syndrome from both diagnostic (e.g. providing clues regarding neuropathology) and scientific (e.g. yielding information about the organization of lexical access structures in left temporal lobe) perspectives.
The aging population of the United States and many other countries guarantees that disorders common in elderly persons will continue to become more prevalent. In the past decade or so, we already have witnessed the beginning of this trend, with the rapid rise in the number of patients with degenerative dementia, especially Alzheimer's disease. On another track, sophisticated and timely medical and surgical interventions have produced a growing number of patients who survive serious head injury. These patients are typically young, and may live for many decades after their brain injury. In both examples, a core feature of the condition is impaired cognition and behavior; that is, defects in higher-level capacities such as memory, intellectual function, language, and decision-making. Neuropsychological assessment cannot be viewed as a luxury in cases such as these but rather, as a vital component of the neurodiagnostic evaluation. The neuropsychologist uses a set of standardized instruments to measure cognition and behavior in a comprehensive and precise manner, yielding rich information that may assist in accurate diagnosis, prudent management, and optimal rehabilitation. The neuropsychological examination may provide the only means with which to detect alterations in brain function, as in cases of mild head injury or low-level toxic exposure, which may not be revealed through other procedures. Finally, neuropsychological assessment will continue to play a key role in the scientific programs that are dedicated to advancing our understanding of the neural substrates of complex behavior.
A subject with circumscribed damage to mesial and nonmesial risk anterior temporal structures (which included the left entorhinal cortex and hippocampus and the left anterolateral association cortices) maintains accurate nonverbal records of past experiences, and acquires accurate new nonverbal records. However, he has a severe defect in the retrieval and acquisition of specific verbal tags denoting those records. This dissociation is revealed by standard neuropsychological tasks, and by experimental probes focused on (1) retrieval of previously learned verbal and nonverbal entities; and (2) acquisition of new visuoverbal relationships. The results extend our current understanding of the manner in which mesial and nonmesial structures in the anterior temporal lobe contribute to the formation and storage of verbal and nonverbal records.
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We examined the sensitivity and specificity of the Wisconsin Card Sorting Test (WCST) as a measure of frontal lobe damage in 91 subjects with stable focal brain lesions. Anatomical information about the location and extent of brain damage was obtained from MR and CT transparencies. No significant differences in WCST performance were found between subjects with frontal vs. nonfrontal damage. Some subjects with extensive frontal lobe damage performed well on the WCST, and some subjects with damage outside of the frontal lobes failed. The optimal cutoff scores for discriminating frontal from nonfrontal subjects correctly classified only 62% of the subjects. Further analysis of WCST performances associated with damage to various subregions of the frontal lobes also failed to reveal any reliable relationships. These findings indicate that performance on the WCST cannot be interpreted in isolation as an index of frontal lobe damage.
Following damage to ventromedial frontal cortices, adults with previously normal personalities develop defects in decision-making and planning that are especially revealed in an abnormal social conduct. The defect repeatedly leads to negative personal consequences. The physiopathology of this disorder is an enigma. We propose that the defect is due to an inability to activate somatic states linked to punishment and reward, that were previously experienced in association with specific social situations, and that must be reactivated in connection with anticipated outcomes of response options. During the processing that follows the perception of a social event, the experience of certain anticipated outcomes of response options would be marked by the reactivation of an appropriate somatic state. Failure to reactivate pertinent somatic markers would deprive the individual of an automatic device to signal ultimately deleterious consequences relative to responses that might nevertheless bring immediate reward (or, alternatively, signal ultimately advantageous outcomes relative to responses that might bring immediate pain). As an example, activation of somatic markers would (1) force attention to future negative consequences, permitting conscious suppression of the responses leading to them and deliberate selection of biologically advantageous responses, and (2) trigger non-conscious inhibition of response states by engagement of subcortical neurotransmitter systems linked to appetitive behaviors. An investigation of this theory in patients with frontal damage reveals that their autonomic responses to socially meaningful stimuli are indeed abnormal, suggesting that such stimuli fail to activate somatic states at the most basic level. On the contrary, elementary unconditioned stimuli (e.g. a loud noise) produce normal autonomic responses.
Patient Boswell, who is severely amnesic for both retrograde and anterograde material, can provide the correct state name for a particular city, given the name of the city, e.g. given 'Denver' he will respond 'Denver ... Colorado', an ability that, by itself, would suggest that he knows about each item in the set and about their connection. However, he cannot name cities in a state, and he is unable to provide even superficial information about the unique characteristics of most cities and states. We investigated this phenomenon with several experiments. In the first (State Completion), Boswell was given names of cities in the U.S.A., and asked to provide the associated state name; in the second (City Generation) we asked him to provide names of cities located in particular states. For State Completion, Boswell correctly supplied state names for 53% of the items, and he improved to 94% correct in a forced choice paradigm. For City Generation, his performance was markedly inferior to that of controls; in fact, he produced only 4 city names for a total of 27 different states. In another experiment, in which Boswell was asked to give specific characteristics of cities and states, he was also severely defective. The dissociations suggest that the ability to complete a well-learned verbal set (e.g. Denver-Colorado), given its first component, implies nothing about (1) the underlying verbal or non-verbal knowledge associated with either item in the set, or (2) their relationship to one another. The maintenance of this ability depends on a circumscribed cortical region of the dominant hemisphere, which includes Brodmann's field 22 and part of fields 21 and 37.
We conducted an extensive neuropsychological investigation in a patient with bilateral amygdala damage due to Urbach-Wiethe disease. The patient had significant defects in nonverbal visual memory, in social behavior, and in "executive control" functions, findings consistent with the proposal, based on experimental animal work, that the amygdala plays important roles in memory and in the modulation of social and emotional behavior. General intellect and language were normal. A psychophysiological study showed that she had normal electrodermal activity (skin conductance responses), an important finding in view of the role that has been attributed to the amygdala in the central control of autonomic responses.
Populations of patients with strokes or tumors constitute the most frequently used subjects in neuropsychological research, and these populations are often combined when the investigation aims at establishing brain-behavior relationships. We compared these two populations with respect to their neuropsychological profiles. Seventeen subjects with tumors were individually matched to subjects with unilateral strokes on the basis of lesion location. Despite close matching of lesions, there were major differences in the neuropsychological impairments of the two groups, eg, all subjects with stroke in the left hemisphere had more severe language defects than did their counterparts with tumors, and some tumor subjects performed normally on all neuropsychological tests. These findings demonstrate that the cognitive and/or behavioral consequences of tumors or strokes in similar locations can be radically different. The two patient types should be treated separately for the purpose of neuropsychological research.
Magnetic resonance (MR) imaging is a sensitive means of detecting haemorrhagic and nonhaemorrhagic forms of brain injury. This study correlates the neurobehavioural (NB) deficits in 49 adult patients with lesions detected by MR imaging. MR imaging was performed 2-19 days following trauma, analyzed for the injury type and graded for severity. A battery of NB tests was performed prior to hospital discharge or at the time of initial follow-up visit (31 patients). 15 patients were so severely impaired that testing could not be done and 3 died prior to discharge. The NB test scores were grouped into 3 levels of impairment. The overall NB scores were compared with MR lesion severity ratings and a positive correlation found (r = 0.47). In addition, lesion severity, type and location resulted in specific NB deficits. We conclude that the lesion location and severity can be accurately identified by acute phase MR are associated with specific types of neurobehavioural deficits in a high percentage of testable patients.
The auditory perception of temporal and spectral information was studied in subjects with lesions in the temporoparietal region of the left (LH group), or right (RH group) hemisphere (n = 5 in each group) and in five normal controls. The temporal tasks included gap detection and two complex pattern perception tasks in which subjects had to identify the placement of the two closest tones (separated by the shortest interval) within a sequence of six tones. The spectral tasks involved pitch matching and frequency discrimination. The results showed a "double dissociation": (1) the LH group was impaired in their ability to perceive temporal information, but the perception of spectral information was normal, and (2) the RH group was impaired in their ability to perceive spectral information, but the perception of temporal information was normal. The findings are consistent with the notion that temporal processing is a function of left-hemisphere structures and that spectral processing is a function of right-hemisphere structures.
The anatomical basis and cognitive profile of diencephalic amnesia remain unclear. We report a two-part study. First, we studied 4 patients with bilateral medial thalamic infarctions using magnetic resonance imaging and comprehensive neuropsychological testing. All patients were followed for more than 1 year. Using a stereotactic method, we plotted the lesions in an atlas delineating the probable structure involved. Secondly, in 2 monkeys, using autoradiography, we traced the pathway from the amygdala to the dorsomedial nucleus, paying particular attention to the intrathalamic course of the amygdalothalamic projections. Our findings were (1) patients develop amnesia when infarctions are located anteriorly; (2) in patients with amnesia, the lesions can be small and strategically located, probably interfering with both hippocampal-related neural structures such as the mamillothalamic tract, and amygdala-related neural structures such as the ventroamygdalofugal pathway; and (3) a specific component of the latter is situated lateral but immediately adjacent to the mamillothalamic tract in the monkey, enabling both structures to be damaged bilaterally by small mirror image lesions. The amnesia is characterized by deficits in anterograde verbal and visual learning and in retrograde amnesia, but motor learning is preserved. We raise the possibility that bilateral diencephalic lesions may interfere particularly with temporal aspects of memory.
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Although Pick's disease is generally considered as a dementia characterized by signs of frontal lobe dysfunction, it can present with selective language defects rather than with cognitive decline. In this study, we report prospective and serial clinical, neuropsychological, and neuroradiologic observations in a 59-year-old man whose prominent disturbance was in the retrieval and learning of names denoting concrete entities and actions. Postmortem study confirmed the diagnosis of Pick's disease and revealed that neuronal loss and gliosis were most prominent in left anterior temporal cortices. The findings are in keeping with evidence that the left anterior temporal cortices and interconnected hippocampal system are critically involved in the learning and retrieval of verbal lexical items. The evidence from this patient, along with similar evidence from the literature we reviewed, suggests that when patients present with a progressive aphasia characterized by anomia, Pick's disease should be considered as the probable diagnosis.
We report four cases of biopsy proved cerebral amyloid angiopathy demonstrated by MR imaging. White matter signal hyperintensities on T2-weighted spin-echo pulse sequences were present in three patients. We believe the white matter lesions associated with cerebral amyloid angiopathy are not specific to this disorder but rather reflect hypoperfusion of distal white matter resulting from vascular disease.
We reviewed 49 patients with Wernicke's aphasia resulting from a stroke. Their aphasia was classified on the basis of comprehensive neuropsychological testing. Wernicke's aphasia was more common in older patients and in men. Cerebral infarction occurred in 38 patients (78%) and intracerebral hemorrhage in seven (14%); the remaining four patients (8%) developed aphasia after surgery for aneurysmal subarachnoid hemorrhage. Embolic events were the most common etiology of Wernicke's aphasia in the 38 patients with cerebral infarction, with cardiac emboli in 40% and large-vessel atheroemboli from a carotid source in 16%. In patients with Wernicke's aphasia secondary to infarction, an embolic source should be sought. Patients with Wernicke's aphasia should have computed tomography to exclude intracerebral hemorrhage before institution of anticoagulant therapy.