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Biomedical subjects

J Grafman

Publications and source records attributed to J Grafman.

At least 73 records · Page 4Linked to original sources

Losing their configural mind. Amnesic patients fail on transverse patterning.

A configural theory of human amnesia is proposed. The theory predicts that amnesic patients will exhibit selective deficits on tasks that normal subjects perform by learning new configurations of stimulus elements. This prediction is supported by results for four amnesic patients who learned a nonconfigural control task but failed to learn the configural transverse patterning task even after extensive practice. Matched normal subjects easily learned both tasks. The theory provides unique and viable accounts of the central results in the human amnesia literature. Relations between the configural approach and other theories are discussed.

Adult↗

Linguistic processing during repetitive transcranial magnetic stimulation.

To determine if linguistic processing could be selectively disrupted with repetitive transcranial magnetic stimulation (rTMS), rTMS was performed during a picture-word verification task. Seven right-handed subjects were trained in two conditions: picture-word verification, which required the subject to verify whether the picture of an object matched the subtitle name on the same page, and frame verification, which required subjects to verify whether there was a rectangular frame around the combined object picture and subtitle. Half of the trials were performed during rTMS. The effects of rTMS on performance were evaluated at the following four scalp positions: left anterior (the area where rTMS produced speech arrest), a mirror site on the right, and two positions in the left and right parietal region. Stimulation over the left deltoid muscle served as a control. Subjects had less difficulty in making picture-word matching decisions during unstimulated compared with stimulated trials at the left anterior and posterior positions. No significant difference in accuracy was detected in the frame verification condition, but response times in the frame verification condition were longer with stimulation at the left anterior position. Because rTMS of the dominant hemisphere affected linguistic processing independent of speech motor output, we confirm that rTMS may be used to investigate language and other cognitive functions.

Adult↗

Progressive supranuclear palsy: a survey of the disease course.

BACKGROUND: The most accurate knowledge about progressive supranuclear palsy (PSP) comes from small sample studies that preclude precise estimation of the proportion of PSP patients affected with various symptoms and the examination of factors predicting survival time. OBJECTIVE: To describe the course of PSP in a large clinically diagnosed sample of PSP patients and to identify factors predicting survival time. METHODS: We surveyed the caregivers of 318 living and 119 deceased patients with progressive supranuclear palsy. The main outcome measures were a principal symptom severity questionnaire and a signs and symptoms questionnaire. RESULTS: The estimated age of PSP symptom onset depends critically on how symptom onset is defined, with estimates differing by as much as 1.5 years. Men and women were represented equally (51.6% versus 48.4%) in the living sample, but men formed 61.8% of the deceased sample. Men were diagnosed later than women following symptom onset (33.4 versus 24.1 months) and died earlier following the diagnosis (37.0 versus 47.6 months). Motor and visual symptoms appeared first, followed by emotional and personality problems, cognitive impairment, and sleep changes. Whereas motor symptoms eventually affected almost every patient, emotional/personality and cognitive symptoms did not. The early onset, presence of falls, slowness, and inability to move eyes downward early in the development of the disease predicted survival time. CONCLUSION: PSP is a rapidly progressive disease dominated by motor symptoms, and it affects men more frequently than women.

Affective Symptoms↗

Caregiving in progressive supranuclear palsy.

BACKGROUND: Basic issues regarding factors influencing progressive supranuclear palsy (PSP) patient caregiver burden remain unresolved, including whether and how disease severity and duration influence caregiver burden. OBJECTIVE: To examine the relation between PSP patient caregiver burden and disease severity, describe the time course of caregiver burden in relation to disease progression, and identify the contribution of other factors (e.g., patient memory and behavioral problems, caregiver gender) to caregiver burden. METHODS: Mail survey of 180 caregivers of PSP patients (living at home and cared for by nonprofessionals) who were members of the Society for Progressive Supranuclear Palsy. The survey included the Burden Interview, an instrument measuring caregiver burden by inquiring how they feel about different aspects and demands of caregiving. RESULTS: Caregiver burden was related to both PSP disease severity (r = 0.40) and disability/need for assistance (r = 0.43). The relation between burden and disease duration was nonlinear, following the same time course as disease severity; the burden increased during the first 18 months postdiagnosis and leveled off thereafter. Women reported more burden than men (caregiver sex delta r2 = 0.05), even after controlling for disease severity and duration (delta r2 = 0.22) and patient gender (delta r2 < 0.01; NS), patient depression (delta r2 = 0.09), and aggressiveness (delta r2 = 0.02). CONCLUSION: Burden in PSP is related to disease severity, disease duration, and caregiver gender (even after controlling for patient's memory, patient depression, and aggression).

Aged↗

Patients with chronic fatigue syndrome and accurate feeling-of-knowing judgments.

Many Chronic Fatigue Syndrome (CFS) patients complain of memory impairments which have been difficult to document empirically. Subjective complaints of memory impairment may be due to a deficit in metamemory judgment. CFS patients and matched controls were tested with a computerized Trivia Information Quiz that required them to rate their confidence about correctly recognizing an answer in a multiple choice format that they had been unable to remember in a fact-recall format. Even though CFS patients reported significantly greater amounts of fatigue, cognitive, and physical symptoms, the accuracy of their confidence levels and recognition responses were similar to controls. This finding suggests that a metamemory deficit is not the cause of the memory problems reported by CFS patients.

Adult↗

Event-related desynchronization (ERD) in the alpha frequency during development of implicit and explicit learning.

To understand the role of the motor cortex in implicit and explicit learning, we studied alpha event-related desynchronization (ERD) while 13 right-handed individuals performed a variation of the serial reaction time task (SRTT). EEG signals were recorded simultaneously from 29 scalp locations and the ERD was computed. During data collection, all subjects developed implicit knowledge, demonstrated by shortening of the response time, and explicit knowledge of the test sequence. The average ERD maps of all 13 subjects demonstrated that during the initial learning, there was a decline in alpha band power that was maximal over the contralateral central region. The ERD reached a transient peak amplitude at a point when the subjects attained full explicit knowledge, and diminished subsequently. The transient peak in ERD was highly significant at C3. These electrophysiologic findings support previous studies which have demonstrated that motor activity changes as behavior changes over the course of learning.

Adult↗

Multiple visuospatial working memory buffers: evidence from spatiotemporal patterns of brain activity.

Numerous studies have shown that the visual system involves different cortical pathways in the perception of object (ventral visual pathway) and spatial (dorsal visual pathway) information. The present study was concerned with whether human visuospatial working memory divides along similar lines. We used event-related brain potentials (ERPs) recorded from scalp of normal humans to show the existence of different buffering systems for the retention of object and spatial visual information. Subjects were presented with object or spatial stimuli to be retained for a 3.6-sec interval. The ERPs isolated brain activity associated with retention from earlier storage and later retrieval processes. The ERP scalp topographies indicated that the underlying patterns of brain activation were different during retention of object and spatial information.

Adult↗

PET imaging of maze processing.

Covered maze traversal models nonverbal planning, involving sequential execution of moves using learned spatial maps. To determine the neural substrate involved in maze processing, eleven adults underwent [H(2)15O]-PET while performing motor control, following the computer; visual control, choosing the wall with more dead-ends; uncovered maze, traversing fully visible mazes; covered maze, traversing mazes only locally visible. Maze processing lateralizes to the right hemisphere: uncovered maze versus controls revealed area 23 and 29 activation; covered maze versus controls activated areas 8, 10 and 19. The extrastriate region may store path information, evoked by prefrontal areas for spatial planning and navigation.

Adolescent↗

A restricted 'spotlight' of attention in visual object recognition.

We describe a patient (NJ), with a progressive visual disturbance, who showed an impairment in identifying larger visually-presented objects relative to their smaller counterparts. NJ showed this size effect for line drawings of objects, words and single letters. When presented with large letters comprised of smaller letters and asked to give speeded identification responses to either the large or small letters, NJ was grossly impaired at identifying the large letter. Additionally, when presented with a context meant to bias responding to either the large or small letter, NJ showed faster and more accurate responding in the small direction, but not in the large direction. We interpret these results as indicative of an impaired 'spotlight' of attention, which is deployed across the visual array, and is necessary for providing the selective visual attention responsible for the integration of visual features.

Aged↗

Modality-specific processing streams in verbal working memory: evidence from spatio-temporal patterns of brain activity.

The present study was concerned with whether there are separate, modality-specific processing "streams" in verbal working memory for information that is heard or read. We used event-related brain potentials (ERPs) recorded from scalp of normal humans to show between-modality differences in spatio-temporal patterns of brain activity during retention in working memory of aurally or visually presented verbal information. The ERP patterns suggested that a sustained, automatically maintained auditory store was activated by auditory presentation and a transient, visual-verbal store was activated by visual presentation. In addition to these modality-specific differences, the ERPs indicated that the phonological loop was activated in both modalities and further suggested that the onset of phonological loop activation was earlier for auditory presentation.

Acoustic Stimulation↗

Executive functions in multiple sclerosis: an analysis of temporal ordering, semantic encoding, and planning abilities.

Previous studies have consistently demonstrated impairments in conceptual reasoning and set-shifting abilities in patients with multiple sclerosis (MS). Other executive functions have been less frequently examined. We compared 44 MS patients and 48 demographically matched controls on a temporal-ordering and semantic-encoding task and on a test of planning (Tower of Hanoi). Compared with controls, MS patients experienced deficient semantic encoding and planning but unimpaired temporal-order memory. For both tasks, post hoc analyses indicated that chronic-progressive MS patients contributed most to the group differences. A combination of poor planning and slowed information-processing speed was hypothesized to have contributed to MS patients' impaired Tower of Hanoi performance. Further research is needed to explore the possible relationship between semantic-encoding and planning deficits in MS and social and occupational disabilities.

Cues↗

A study of the performance of patients with frontal lobe lesions in a financial planning task.

It has long been argued that patients with lesions in the prefrontal cortex have difficulties in decision making and problem solving in real-world, ill-structured situations, particularly problem types involving planning and look-ahead components. Recently, several researchers have questioned our ability to capture and characterize these deficits adequately using just the standard neuropsychological test batteries, and have called for tests that reflect real-world task requirements more accurately. We present data from 10 patients with focal lesions to the prefrontal cortex and 10 normal control subjects engaged in a real-world financial planning task. We also introduce a theoretical framework and methodology developed in the cognitive science literature for quantifying and analysing the complex data generated by problem-solving tasks. Our findings indicate that patient performance is impoverished at a global level but not at the local level. Patients have difficulty in organizing and structuring their problem space. Once they begin problem solving, they have difficulty in allocating adequate effort to each problem-solving phase. Patients also have difficulty dealing with the fact that there are no right or wrong answers nor official termination points in real-world planning problems. They also find it problematic to generate their own feedback. They invariably terminate the session before the details are fleshed out and all the goals satisfied. Finally, patients do not take full advantage of the fact that constraints on real-world problems are negotiable. However, it is not necessary to postulate a 'planning' deficit. It is possible to understand the patients' difficulties in real world planning tasks in terms of the following four accepted deficits: inadequate access to 'structured event complexes', difficulty in generalizing from particulars, failure to shift between 'mental sets', and poor judgment regarding adequacy and completeness of a plan.

Brain Diseases↗

Frontal and parietal networks for conditional motor learning: a positron emission tomography study.

Studies on nonhuman primates show that the premotor (PM) and prefrontal (PF) areas are necessary for the arbitrary mapping of a set of stimuli onto a set of responses. However, positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) in human subjects have failed to reveal the predicted rCBF changes during such behavior. We therefore studied rCBF while subjects learned two arbitrary mapping tasks. In the conditional motor task, visual stimuli instructed which of four directions to move a joystick (with the right, dominant hand). In the evaluation task, subjects moved the joystick in a predetermined direction to report whether an arrow pointed in the direction associated with a given stimulus. For both tasks there were three rules: for the nonspatial rule, the pattern within each stimulus determined the correct direction; for the spatial rule, the location of the stimulus did so; and for the fixed-response rule, movement direction was constant regardless of the pattern or its location. For the nonspatial rule, performance of the evaluation task led to a learning-related increase in rCBF in a caudal and ventral part of the premotor cortex (PMvc, area 6), bilaterally, as well as in the putamen and a cingulate motor area (CM, area 24) of the left hemisphere. Decreases in rCBF were observed in several areas: the left ventro-orbital prefrontal cortex (PFv, area 47/12), the left lateral cerebellar hemisphere, and, in the right hemisphere, a dorsal and rostral aspect of PM (PMdr, area 6), dorsal PF (PFd, area 9), and the posterior parietal cortex (area 39/40). During performance of the conditional motor task, there was only a decrease in the parietal area. For the spatial rule, no rCBF change reached significance for the evaluation task, but in the conditional motor task, a ventral and rostral premotor region (PMvr, area 6), the dorsolateral prefrontal cortex (PFdl, area 46), and the posterior parietal cortex (area 39/40) showed decreasing rCBF during learning, all in the right hemisphere. These data confirm the predicted rCBF changes in premotor and prefrontal areas during arbitrary mapping tasks and suggest that a broad frontoparietal network may show decreased synaptic activity as arbitrary rules become more familiar.

Adult↗

Activation of the primary visual cortex by Braille reading in blind subjects.

Primary visual cortex receives visual input from the eyes through the lateral geniculate nuclei, but is not known to receive input from other sensory modalities. Its level of activity, both at rest and during auditory or tactile tasks, is higher in blind subjects than in normal controls, suggesting that it can subserve nonvisual functions; however, a direct effect of non-visual tasks on activation has not been demonstrated. To determine whether the visual cortex receives input from the somatosensory system we used positron emission tomography (PET) to measure activation during tactile discrimination tasks in normal subjects and in Braille readers blinded in early life. Blind subjects showed activation of primary and secondary visual cortical areas during tactile tasks, whereas normal controls showed deactivation. A simple tactile stimulus that did not require discrimination produced no activation of visual areas in either group. Thus in blind subjects, cortical areas normally reserved for vision may be activated by other sensory modalities.

Blindness↗

Brain activation during script event processing.

Regional cerebral blood flow was measured with positron emission tomography in seven normal volunteers while they performed various script event verification tasks. The left frontal lobe, left anterior cingulate and the anterior part of the left superior temporal gyrus were more activated in the script event membership and action categorization conditions, whereas the right frontal lobe, left superior temporal gyrus and the middle temporal gyrus bilaterally were more activated in the script event temporal order verification condition. These results indicate that the temporal ordering of script events and determining whether an event belongs to a particular script or action category are processed by distinctive distributed neuronal networks.

Adult↗

Dyscalculia and dyslexia after right hemisphere injury in infancy.

OBJECTIVE: To use the findings from neuropsychological evaluation and functional magnetic resonance imaging (fMRI) to assess interhemispheric reorganization of function after early unilateral brain injury. DESIGN AND METHODS: The study focused on one case of early brain injury that resulted in both dyscalculia and dyslexia. Brain injury was studied using both structural and fMRI. Intellectual function was evaluated using the Wechsler Intelligence Scale for Children, Third Edition, while visuospatial skills were assessed using the Block Design subtest of the Wechsler Intelligence Scale for Children, Third Edition, and Judgment of Line Orientation subtest. The Selective Reminding Test and the Recurring Figures Test were used to evaluate memory and orientation; language and speech skills were evaluated using the Boston Naming Test, Controlled Oral Word Association, Gates-MacGinitie Reading Test, and color naming. Various methods were used to study arithmetic skills, including the Wide Range Achievement Test-Revised and the Peabody Individual Achievement Test. The control group for fMRI consisted of nine normal subjects. SETTING: Neuropsychological laboratory in primary care hospital. PATIENT: A 17-year-old boy who had sustained a closed head injury associated with a partially depressed, right parietal skull fracture, and right temporal hemorrhage in a motor vehicle crash at age 7 months (November 9, 1977). Subsequent social behavior was normal, but the patient had difficulty throughout school in mathematics and spelling and was characterized as having a "short attention span." INTERVENTION: None. MAIN OUTCOME MEASURES: Standardized tests of arithmetic and reading supplemented by an assessment of calculation and quantitative skills. While performing calculations, fMRI disclosed predominantly left hemisphere activation involving the frontal and posterior parietal regions, whereas this task produced bilateral activation of the supramarginal gyrus in seven of nine normal subjects. RESULTS: Neuropsychological findings confirmed the presence of dyscalculia and dyslexia despite normal intellectual functioning. Visuospatial skills ranged from the low normal to average level. The fMRI findings were consistent with early interhemispheric transfer of visuospatial skills normally committed to the right parietal area to the left parietal region. The patient's dyscalculia and reading ability raise a question of acquired left parietal dysfunction as a consequence of the competition between verbal and visuospatial functions for left hemisphere representation. CONCLUSION: Interhemispheric reorganization of function may be bidirectional rather than a feature unique to the left hemisphere substrate for language.

Adolescent↗

Visualizing cortical activation during mental calculation with functional MRI.

Cortical activation during arithmetic calculation (silent subtraction by sevens) was compared to that observed during a control condition for which subjects were required to count forward by ones. Nine normal subjects underwent 1.5-T functional magnetic resonance imaging while performing these tasks. All subjects showed bilateral premotor, posterior parietal, and prefrontal cortex activation during serial calculation. There was a large degree of individual variation in activation outside of these areas. These results confirm the role of posterior parietal cortex in arithmetic calculation and implicate other regions, including prefrontal cortex.

Adult↗