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Biomedical subjects

J Grafman

Publications and source records attributed to J Grafman.

At least 55 records · Page 3Linked to original sources
PubMed2000

Frontotemporal dementia with novel tau pathology and a Glu342Val tau mutation.

It is unclear how tau gene mutations cause frontotemporal dementia (FTD) with parkinsonism linked to chromosome 17 (FTDP-17), but those in exon 10 (E10) or the following intron may be pathogenic by altering E10 splicing, perturbing the normal 1:1 ratio of four versus three microtubule-binding repeat tau (4R:3R tau ratio) and forming tau inclusions. We report on a 55-year old woman with frontotemporal dementia and a family history of FTDP-17 in whom we found a novel E12 (Glu342Val) tau gene mutation, prominent frontotemporal neuron loss, intracytoplasmic tau aggregates, paired helical tau filaments, increased 4R tau messenger RNA, increased 4R tau without E2 or E3 inserts, decreased 4R tau with these inserts, and a 4R:3R tau ratio greater than 1 in gray and white matter. Thus, this novel Glu342Val mutation may cause FTDP-17 by unprecedented mechanisms that alter splicing of E2, E3, and E10 to preferentially increase 4R tau without amino terminal inserts and promote aggregation of tau filaments into cytopathic inclusions.

Brain↗
PubMed1999

Metabolic abnormalities detected by 1H-MRS in dyscalculia and dysgraphia.

Proton MRS was performed in a patient with developmental acalculia. The results indicated a focal, wedge-shaped defect in the left temporoparietal brain region near the angular gyrus, with differential decreases in N-acetyl-aspartate, creatine, and choline. These results support the hypothesis that developmental acalculia, like acquired acalculia, is associated with left posterior hemisphere lesions.

Adolescent↗
PubMed1999

Procedural learning is impaired in patients with prefrontal lesions.

OBJECTIVES: To 1) determine the effect of prefrontal cortex lesions on procedural learning (PL), measured by a serial reaction-time task (SRTT); 2) confirm whether visuomotor PL is lateralized to one hemisphere; and 3) clarify the relation between visuomotor sequence learning and verbal sequence learning, working memory, and executive functions. BACKGROUND: Previous cognitive neuroscience research has implicated the prefrontal cortex in visuomotor PL but there is a lack of studies examining patients with prefrontal cortex lesions. METHODS: We studied 22 patients with strictly unilateral prefrontal cortex lesions (traumatic, ischemic, hemorrhagic, or tumors) and 52 cognitively intact controls matched for age, sex, and educational level. We administered to subjects long (10-item sequence) and short (4-item sequence) versions of the SRTT. With the long version, each hand was evaluated separately. Learning was indicated by the shortening of response times (RT) and decrease in errors across the sequential blocks and, most importantly, the rebound increase in RTs and errors when comparing the last sequence block with the next random block. Frontal lobe functions and verbal sequence learning were also assessed. RESULTS: Patients with unilateral prefrontal cortex lesions show PL impairment that involves both hands, although more errors were observed when the hand contralateral to the lesion was performing. Only those patients whose lesions were >2 cm in diameter were impaired. Neuropsychologic evaluation indicated impaired verbal sequence learning and executive function deficits. Patients with poorer working memory and verbal sequence learning were also more impaired in visuomotor sequence learning. CONCLUSIONS: The prefrontal cortex has a role in PL and is part of the neural circuit that mediates this type of learning.

Adult↗
PubMed1999

The role of the anterior prefrontal cortex in human cognition.

Complex problem-solving and planning involve the most anterior part of the frontal lobes including the fronto-polar prefrontal cortex (FPPC), which is especially well developed in humans compared with other primates. The specific role of this region in human cognition, however, is poorly understood. Here we show, using functional magnetic resonance imaging, that bilateral regions in the FPPC alone are selectively activated when subjects have to keep in mind a main goal while performing concurrent (sub)goals. Neither keeping in mind a goal over time (working memory) nor successively allocating attentional resources between alternative goals (dual-task performance) could by themselves activate these regions. Our results indicate that the FPPC selectively mediates the human ability to hold in mind goals while exploring and processing secondary goals, a process generally required in planning and reasoning.

Brain Mapping↗
PubMed1999

Associative learning impairments in patients with frontal lobe damage.

The performance of 18 frontal lobe lesion (FL) and 10 frontal lobe dementia (FLD) patients on an associative memory test was compared with the performance of their matched normal controls. The FL group was severely impaired on cued and free recall and was moderately impaired on a recognition condition. Left FL patients performed the poorest on the cued and free recall conditions. The FLD patients were moderately impaired on the free recall condition only but there was a subgroup of FLD patients with additional left temporal atrophy who appeared severely impaired on both cued and free recall. These findings indicate that both left frontal and temporal lobe damage can impair associative learning and that this impairment is more strikingly seen with free rather than cued recall.

Adult↗
PubMed1999

Selective visual attention in patients with frontal lobe lesions or Parkinson's disease.

Visual selective attention and response competition were tested in patients with frontal lobe lesions or with Parkinson's disease, and matched normal controls. The target stimuli were presented with flanking distractors that were either compatible, incompatible, or neutral to the target stimulus. The distance between the target and distractors was systematically varied. A control condition without distractors was also included. Subjects' response times to target stimuli and accuracy were measured. Both patient groups responded significantly slower and less accurately than their respective matched normal controls across all interference conditions and spatial distances. However, they did not show significantly greater interference or facilitation effects. Thus, the data suggest that the cognitive processes underlying selective attention are, in general, spared in patients with frontal lobe lesions or basal ganglia dysfunction.

Adult↗
PubMed1999

Transcranial magnetic stimulation can measure and modulate learning and memory.

The potential uses for Transcranial Magnetic Stimulation (TMS) in the study of learning and memory range from a method to map the topography and intensity of motor output maps during visuomotor learning to inducing reversible lesions that allow for the precise temporal and spatial dissection of the brain processes underlying learning and remembering. Single-pulse TMS appears to be adequate to examine motor output maps but repetitive TMS (rTMS) appears necessary to affect most cognitive processes in measurable ways. The results we have reviewed in this article indicate that rTMS may have a potential clinical application in patients with epilepsy in whom it is important to identify the lateralization of verbal memory. Single-pulse TMS can help identify changes in motor output maps during training, that may indicate improved or diminished learning and memory processes following a stroke or other neurological insult. Other evidence indicates that rTMS may even have the capability of facilitating various aspects of memory performance. From a research perspective. rTMS has demonstrated site- and time-specific effects primarily in interfering with explicit retrieval of episodic information from long-term memory. rTMS may also be able to modulate retrieval from semantic memory as evidenced by response-time and accuracy changes after rTMS. All these findings suggest that the use of transcranial magnetic stimulation in the study of learning and memory will increase in the future and that it is already a valuable tool in the cognitive neuroscientists' belt.

Blinking↗
PubMed1999

Frontal lobe lesions and electrodermal activity: effects of significance.

Several studies have shown that cortical damage, especially to the right hemisphere and to frontal lobes, may attenuate skin conductance responses selectively to psychologically significant stimuli. We tested this hypothesis in 32 patients with frontal lesions, verified by computer assisted tomography and magnetic resonance imaging, and 45 healthy controls. Patients and controls were given a protocol which included a rest period, a series of innocuous tones, and a reaction time task. Patients were given a second protocol in which they viewed slides with positive and negative emotional content and neutral slides. Results showed attenuated electrodermal activity (EDA) during task instructions and smaller skin conductance responses to reaction-time stimuli in patients compared to controls but few differences under passive conditions or in orienting responses to simple tones. Patients with lateral prefrontal and paraventricular lesions were especially low in EDA in the reaction time task, and those with right and bilateral lesions in the cingulate gyrus and/or frontal operculum had attenuated EDA in both protocols. We conclude that the effects of certain frontal lesions are on the psychological response to significance which is indexed by EDA rather than directly on EDA per se.

Adult↗
PubMed1999

Distinct prefrontal activations in processing sequence at the sentence and script level: an fMRI study.

Neuropsychological studies have shown that the prefrontal cortex is important in planning and monitoring everyday behaviour. In this study, using functional magnetic resonance imaging (fMRI), we investigated whether specific prefrontal regions are involved in processing a sequence of actions. Subjects were required to perform two different tasks: Script-event order and Sentence-word order. Script sequence and word sequence processing were found to activate partially overlapping areas which are known to be implicated in language processing. In addition, the Script-task activated a large area in the dorsolateral prefrontal cortex (Brodmann area 6 and 8, BA 6 and 8), in both the left and right hemispheres, as well as the left supplementary motor area and left angular gyrus (BA 39). Our results suggest that these prefrontal areas may be more specifically involved in the process of analysing sequential links in the action domain.

Adult↗
PubMed1999

Concept formation and concept shifting in frontal lesion and Parkinson's disease patients assessed with the California Card Sorting Test.

Concept formation and shifting abilities of 17 frontal lesion (FL) and 8 Parkinson's disease (PD) patients were assessed with the California Card Sorting Test. FL patients demonstrated a significantly greater number of perseverative responses and deficits in strategy planning, strategy initiation, and concept formation and did not benefit from abstract cues in comparison with their matched normal control (NC) participants. PD patients also demonstrated an increased number of perseverative responses under selected conditions in comparison with their matched NCs, but their ability to explain their sorts, to extract and express the sorting principles, and to sort with the help of abstract and concrete cues depended on their general cognitive status.

Aged↗
PubMed1999

Learning in Parkinson's disease: eyeblink conditioning, declarative learning, and procedural learning.

OBJECTIVE: To assess the degree of learning ability in Parkinson's disease. METHODS: Three different learning tasks: eyeblink classical conditioning with delay and trace paradigms, the California verbal learning test (CVLT), and a serial reaction time task (SRTT) were studied in patients with Parkinson's disease and normal (control) subjects. RESULTS: In the eyeblink conditioning tasks, both patients and normal subjects showed significant learning effects without between group differences. In the CVLT, patients remembered significantly fewer words than normal subjects in both short term and long term cued recall tasks. In the SRTT, normal subjects had significantly reduced response time and error rates across blocks of repeated sequence trials, whereas patients had significantly reduced error, but not response time rates. CONCLUSION: Impairment of nigrostriatal pathways selectively affects performance in complex learning tasks that are competitive and require alertness such as the SRTT, but not in simple learning procedures such as eyeblink conditioning.

Adult↗
PubMed1998

Normal postexercise facilitation and depression of motor evoked potentials in postpolio patients.

We studied the effects of exercise on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation in healthy subjects and postpolio patients. Subjects performed repeated sets of isometric exercise until the muscle fatigued. In both groups, the mean MEP amplitude immediately after each exercise set was approximately twice that of the baseline amplitude, indicating similar postexercise facilitation, and after fatigue was approximately half that of the baseline amplitude, indicating similar postexercise depression. We conclude that the intracortical component of central fatigue is normal in postpolio patients.

Adult↗
PubMed1998

Deficit in evaluating pre-determined sequences of script events in patients with Parkinson's disease.

The purpose of the present study was to assess how the striato-frontal system contributes to the manipulation of goal-directed actions. We studied a group of ten patients with Parkinson's disease (PD) in order to investigate which aspects of action knowledge processing are impaired and to define the conditions under which the deficits may occur. PD patients committed errors of sequence and inserted distractors in tasks that required them to order pre-determined events belonging to a given script in a typical sequence. Rather than attributing errors of event sequencing to a deficit of script "syntax" knowledge, we suggest that the difficulties manifested by PD patients were due to an impairment of a switching mechanism that is necessary for processing information in parallel.

Adult↗
PubMed1998

Distinct frontal regions for processing sentence syntax and story grammar.

Time is a fundamental dimension of cognition. It is expressed in the sequential ordering of individual elements in a wide variety of activities such as language, motor control or in the broader domain of long range goal-directed actions. Several studies have shown the importance of the frontal lobes in sequencing information. The question addressed in this study is whether this brain region hosts a single supramodal sequence processor, or whether separate mechanisms are required for different kinds of temporally organised knowledge structures such as syntax and action knowledge. Here we show that so-called agrammatic patients, with lesions in Broca's area, ordered word groups correctly to form a logical sequence of actions but they were severely impaired when similar word groups had to be ordered as a syntactically well-formed sentence. The opposite performance was observed in patients with dorsolateral prefrontal lesions, that is, while their syntactic processing was intact at the sentence level, they demonstrated a pronounced deficit in producing temporally coherent sequences of actions. Anatomical reconstruction of lesions from brain scans revealed that the sentence and action grammar deficits involved distinct, non-overlapping sites within the frontal lobes. Finally, in a third group of patients whose lesions encompassed both Broca's area and the prefrontal cortex, the two types of deficits were found. We conclude that sequence processing is specific to knowledge domains and involves different networks within the frontal lobes.

Analysis of Variance↗
PubMed1998

Sustained attention deficits in patients with lesions of posterior cortex.

Patients with lesions to posterior cortex were compared to controls, matched for age and education, on tests on sustained attention. One test was a simple reaction time task requiring subjects to respond whenever they saw an 'X'. The other was a Continuous Performance Test that required subjects to respond to an 'X' but refrain from responding to other letters. The patients missed more targets than control subjects on both tests. On the Continuous Performance Test the difference between patients and controls increased with time on task, suggesting a sustained attention deficit similar to that previously observed in patients with right frontal lesions. However, whereas frontal patients showed a tendency toward greater impairment when the rate of stimulus presentation was relatively slow, the posterior patients performed significantly worse when the stimuli were presented at a faster rate.

Analysis of Variance↗
PubMed1998

Overestimation and unreliability in "feeling-of-doing" judgements about temporal ordering performance: impaired self-awareness following frontal lobe damage.

"Feeling-of-doing" accuracy in a temporal ordering task in 33 patients with frontal lobe lesions and a matched control group was investigated. The temporal ordering task used word lists that had high, medium, or no semantic interrelatedness. Patients with frontal lobe lesions showed an impairment in temporal ordering across all three word lists. Both groups performed better on the lists with higher semantic interrelatedness. Patients with frontal lobe lesions overestimated their ability to order words accurately. On the less semantically interrelated lists, metamemory judgment in patients with frontal lesions did not correlate with their performance. These results indicate that both temporal order judgment and metacognitive decisions about temporal order judgment are subserved by the prefrontal cortex and further clarifies the role of the frontal lobes in behavioral monitoring.

Adult↗
PubMed1998

Neural networks for Braille reading by the blind.

To explore the neural networks used for Braille reading, we measured regional cerebral blood flow with PET during tactile tasks performed both by Braille readers blinded early in life and by sighted subjects. Eight proficient Braille readers were studied during Braille reading with both right and left index fingers. Eight-character, non-contracted Braille-letter strings were used, and subjects were asked to discriminate between words and non-words. To compare the behaviour of the brain of the blind and the sighted directly, non-Braille tactile tasks were performed by six different blind subjects and 10 sighted control subjects using the right index finger. The tasks included a non-discrimination task and three discrimination tasks (angle, width and character). Irrespective of reading finger (right or left), Braille reading by the blind activated the inferior parietal lobule, primary visual cortex, superior occipital gyri, fusiform gyri, ventral premotor area, superior parietal lobule, cerebellum and primary sensorimotor area bilaterally, also the right dorsal premotor cortex, right middle occipital gyrus and right prefrontal area. During non-Braille discrimination tasks, in blind subjects, the ventral occipital regions, including the primary visual cortex and fusiform gyri bilaterally were activated while the secondary somatosensory area was deactivated. The reverse pattern was found in sighted subjects where the secondary somatosensory area was activated while the ventral occipital regions were suppressed. These findings suggest that the tactile processing pathways usually linked in the secondary somatosensory area are rerouted in blind subjects to the ventral occipital cortical regions originally reserved for visual shape discrimination.

Adult↗