Biomedical subjects

S Corkin

Publications and source records attributed to S Corkin.

At least 19 recordsLinked to original sources

PubMed2006

Neuroimaging H.M.: a 10-year follow-up examination.

In 1997, Corkin et al. described the anatomical boundaries of the amnesic patient H.M.'s surgical resection, based on a comprehensive analysis of magnetic resonance imaging (MRI) scans collected in 1992 and 1993 (Corkin et al. (1997) J Neurosci 17:3964-3979). We subsequently scanned H.M. on several occasions, employing more advanced data acquisition and analysis methods, and now describe additional details about his brain anatomy and pathology. This account combines results from high-resolution T1-weighted scans, which provide measures of cortical and subcortical morphometry, diffusion tensor images, which provide quantitative information about white matter microstructure and the anatomy of major fasciculi, and T2-weighted images, which highlight damage to deep white matter. We applied new MRI analysis techniques to these scans to assess the integrity of areas throughout H.M.'s brain. We documented a number of new changes, including cortical thinning, atrophy of deep gray matter structures, and a large volume of abnormal white matter and deep gray matter signal. Most of these alterations were not apparent in his prior scans, suggesting that they are of recent origin. Advanced age and hypertension likely contributed to these new findings.

Aged↗

PubMed2005

Age-related changes in prefrontal white matter measured by diffusion tensor imaging.

Age-related degeneration of brain white matter (WM) has received a great deal of attention, with recent studies demonstrating that such changes are correlated with cognitive decline and increased risk for the development of age-related neurodegenerative disease. Past studies have used magnetic resonance imaging (MRI) to measure the volume of normal and abnormal tissue signal as an index of tissue pathology. More recently, diffusion tensor MRI (DTI) has been employed to obtain regional measures of tissue microstructure, such as fractional anisotropy (FA), providing better spatial resolution and potentially more sensitive metrics of tissue damage than traditional volumetric measures. We used DTI to examine the regional basis of age-related alterations in prefrontal WM. As expected from prior volumetric and DTI studies, prefrontal FA was reduced in older adults (OA) compared to young adults (YA). Although WM volume has been reported to be relatively preserved until late aging, FA was significantly reduced by middle age. Much of prefrontal WM showed reduced FA with increasing age. Ventromedial and deep prefrontal regions showed a somewhat greater reduction compared to other prefrontal areas. Prefrontal WM anisotropy correlated with prefrontal WM volume, but the correlation was significant only when the analysis was limited to participants over age 40. This evidence of widespread and regionally accelerated alterations in prefrontal WM with aging illustrates FA's potential as a microstructural index of volumetric measures.

Adult↗

PubMed2004

Age-related alterations in white matter microstructure measured by diffusion tensor imaging.

Cerebral white matter (WM) undergoes various degenerative changes with normal aging, including decreases in myelin density and alterations in myelin structure. We acquired whole-head, high-resolution diffusion tensor images (DTI) in 38 participants across the adult age span. Maps of fractional anisotropy (FA), a measure of WM microstructure, were calculated for each participant to determine whether particular fiber systems of the brain are preferentially vulnerable to WM degeneration. Regional FA measures were estimated from nine regions of interest in each hemisphere and from the genu and splenium of the corpus callosum (CC). The results showed significant age-related decline in FA in frontal WM, the posterior limb of the internal capsule (PLIC), and the genu of the CC. In contrast, temporal and posterior WM was relatively preserved. These findings suggest that WM alterations are variable throughout the brain and that particular fiber populations within prefrontal region and PLIC are most vulnerable to age-related degeneration.

Adult↗

PubMed2001

Beware of frontal lobe deficits in hippocampal clothing.

The Wisconsin card-sorting test (WCST) is a commonly used clinical tool for the detection of frontal lobe dysfunction, specifically executive dysfunction. Patients with lesions outside the frontal lobes sometimes show deficits on the WCST, however, and some researchers have implicated hippocampal dysfunction as the cause of the deficit. But a critical role for the hippocampus seems to be untenable because amnesic patients with bilateral medial temporal lobe (MTL) lesions perform the WCST normally. In the case of epileptic patients, an alternative explanation of the card-sorting impairment is the propagation of abnormal discharges from MTL to frontal lobe structures, causing remote interference with executive circuits.

Journal Article↗

PubMed2001

Bilateral medial temporal lobe damage does not affect lexical or grammatical processing: evidence from amnesic patient H.M.

In the most extensive investigation to date of language in global amnesia, we acquired data from experimental measures and examined longitudinal data from standardized tests, to determine whether language function was preserved in the amnesic patient H.M. The experimental measures indicated that H.M. performed normally on tests of lexical memory and grammatical function, relative to age- and education-matched control participants. Longitudinal data from four Wechsler subtests (Information, Comprehension, Similarities, and Vocabulary), that H.M. had taken 20 times between 1953 (preoperatively) and 2000, indicated consistent performance across time, and provided no evidence of a lexical memory decrement. We conclude that medial temporal lobe structures are not critical for retention and use of already acquired lexical information or for grammatical processing. They are, however, required for acquisition of lexical information, as evidenced in previous studies revealing H.M.'s profound impairment at learning new words.

Adult↗

PubMed2001

H.M. revisits the Tower of Hanoi Puzzle.

To address the controversy of whether an intact procedural memory system alone can support the learning of the recursive strategy for solving the Tower of Hanoi Puzzle, the authors tested 2 amnesic patients, H.M. and P.N. Contrary to the report of N. J. Cohen, H. Eichenbaum, B. S. Deacedo, and S. Corkin (1985), both patients failed to master the recursive strategy under the active-interaction condition. In contrast, normal control participants were able to master the strategy under identical testing conditions. The failure of H.M. and P.N. could not be attributed to the differences between the original and current testing conditions. In addition, neither patient showed frontal lobe dysfunction or impairment in procedural memory. Together with evidence provided by theoretical analyses of this puzzle as well as studies on normal participants, the authors conclude that declarative memory plays a vital role in the acquisition of the recursive strategy for solving the Tower of Hanoi Puzzle.

Aged↗

PubMed2000

Referred phantom sensations and cortical reorganization after spinal cord injury in humans.

To test the hypothesis that cortical remapping supports phantom sensations, we examined referred phantom sensations and cortical activation in humans after spinal-cord injury (SCI) at the thoracic level (T3-T12). Of 12 SCI subjects, 9 reported phantom sensations, and 2 reported referred phantom sensations. In both of these subjects, referred phantom sensations were evoked by contact in reference zones (RZ) that were not adjacent in the periphery and were not predicted to be adjacent in the postcentral gyrus (PoCG), suggesting that representations separated by centimeters of cortical space were simultaneously engaged. This finding was supported by functional MRI (fMRI). In a subject with a T6-level complete SCI, contact in RZ on the left or right forearm projected referred phantom sensations to the ipsilateral chest. During fMRI, contact in either forearm RZ evoked activity in the central PoCG (the position of the forearm representation) and the medial PoCG (the position of the chest representation) with >/=1.6 cm of nonresponsive cortex intervening. In contrast, stimulation in non-RZ forearm and palm regions in this subject and in lesion-matched SCI subjects evoked central but not medial PoCG activation. Our findings support a relation between PoCG activation and the percept of referred phantom sensations. These results, however, present an alternative to somatotopic cortical reorganization, namely, cortical plasticity expressed in coactivation of nonadjacent representations. The observed pattern suggests that somatotopic subcortical remapping, projected to the cortex, can support perceptual and cortical reorganization after deafferentation in humans.

Adult↗

PubMed2000

Differences between Pick disease and Alzheimer disease in clinical appearance and rate of cognitive decline.

OBJECTIVES: To define the cognitive characteristics of Pick disease (PcD), and to determine which features distinguish PcD from Alzheimer disease (AD), in a cross-sectional and longitudinal study. METHODS: The participants were 44 patients with PcD (10 pathologically verified), 121 patients with AD (14 pathologically verified), and 60 normal control subjects. We obtained information regarding the initial symptom of dementia from each patient's caregiver, estimated global dementia severity by the Blessed Dementia Scale and the Activities of Daily Living Scale, and assessed specific cognitive domains by administering 10 tests of memory, language, visuospatial, and reasoning abilities and selective attention. RESULTS: Among initial symptoms reported by caregivers, personality change and language impairment were significantly more common in PcD than AD; deficits in memory were common in both groups but more prevalent in AD (P<.001). At initial cognitive testing, the scores of patients with PcD were inferior to those of normal controls on all tests, except on a measure of visuospatial function; the scores of patients with AD were inferior to those of controls on all tests. Patients with PcD were superior to patients with AD on measures of explicit memory (P<.001) and visuospatial function (P = .001) but had greater impairments on the Activities of Daily Living Scale (P<.05). During the course of illness, patients with PcD declined significantly faster than those with AD on language tests and on global measures of dementia severity (P<.05), whereas measures of explicit memory and visuospatial and reasoning abilities worsened equally in both patient groups. CONCLUSIONS: There is a characteristic cognitive profile and course of dementia in PcD. Nonetheless, cognitive test performance does not clearly distinguish PcD from AD.

Activities of Daily Living↗

PubMed2000

An fMRI investigation of cortical contributions to spatial and nonspatial visual working memory.

The experiments presented in this report were designed to test the hypothesis that visual working memory for spatial stimuli and for object stimuli recruits separate neuronal networks in prefrontal cortex. We acquired BOLD fMRI data from subjects while they compared each serially presented stimulus to the one that had appeared two or three stimuli previously. Three experiments failed to reject the null hypothesis that prefrontal cortical activity associated with spatial working memory performance cannot be dissociated from prefrontal cortical activity associated with nonspatial working memory performance. Polymodal regions of parietal cortex (inferior and superior parietal lobules), as well as cortex surrounding the superior frontal sulcus (and encompassing the frontal eye fields), also demonstrated equivalent levels of activation in the spatial and object conditions. Posterior cortical regions associated with the ventral visual processing stream (portions of lingual, fusiform, and inferior temporal gyri), however, demonstrated greater object than spatial working memory-related activity, particularly when stimuli varied only along spatial or featural dimensions. These experiments, representing fMRI studies of spatial and object working memory in which the testing procedure and the stimuli were identical in the two conditions, suggest that domain-specific visual working memory processing may be mediated by posterior regions associated with domain-specific sensory processing.

Adolescent↗

PubMed2000

Segregation of somatosensory activation in the human rolandic cortex using fMRI.

The segregation of sensory information into distinct cortical areas is an important organizational feature of mammalian sensory systems. Here, we provide functional magnetic resonance imaging (fMRI) evidence for the functional delineation of somatosensory representations in the human central sulcus region. Data were collected with a 3-Tesla scanner during two stimulation protocols, a punctate tactile condition without a kinesthetic/motor component, and a kinesthetic/motor condition without a punctate tactile component. With three-dimensional (3-D) anatomical reconstruction techniques, we analyzed data in individual subjects, using the pattern of activation and the anatomical position of specific cortical areas to guide the analysis. As a complimentary analysis, we used a brain averaging technique that emphasized the similarity of cortical features in the morphing of individual subjects and thereby minimized the distortion of the location of cortical activation sites across individuals. A primary finding of this study was differential activation of the cortex on the fundus of the central sulcus, the position of area 3a, during the two tasks. Punctate tactile stimulation of the palm, administered at 3 Hz with a 5.88(log10.mg) von Frey filament, activated discrete regions within the precentral (PreCG) and postcentral (PoCG) gyri, corresponding to areas 6, 3b, 1, and 2, but did not activate area 3a. Conversely, kinesthetic/motor stimulation, 3-Hz flexion and extension of the digits, activated area 3a, the PreCG (areas 6 and 4), and the PoCG (areas 3b, 1, and 2). These activation patterns were observed in individual subjects and in the averaged data, providing strong evidence for the existence of a distinct representation within area 3a in humans. The percentage signal changes in the PreCG and PoCG regions activated by tactile stimulation, and in the intervening gap region, support this functional dissociation. In addition to this distinction within the fundus of the central sulcus, the combination of high-resolution imaging and 3-D analysis techniques permitted localization of activation within areas 6, 4, 3a, 3b, 1, and 2 in the human. With the exception of area 4, which showed inconsistent activation during punctate tactile stimulation, activation in these areas in the human consistently paralleled the pattern of activity observed in previous studies of monkey cortex.

Adult↗

PubMed1999

Visual discrimination after anterior temporal lobectomy in humans.

OBJECTIVE: To determine whether right anterior temporal lobectomy (RTL) results in perceptual deficits, and whether the perception of particular stimulus features (i.e., shape, motion, color) is affected differentially. BACKGROUND: RTL results in abnormal visual discrimination, recognition, and recall of pictorial material that cannot be easily specified verbally, such as designs and faces. It is unclear whether stimuli must be conceptually meaningful to elicit perceptual deficits. METHODS: Tests were constructed to assess a wide spectrum of basic visual discrimination abilities with simple, meaningless stimuli. The performance of nine patients who underwent left temporal lobectomy (LTL) and nine patients who underwent RTL were compared with that of normal control individuals. The mean excision size along lateral cortex was 3.7 cm for the LTL group and 5.6 cm for the RTL group; mean mesial excision size was 5.2 cm for LTL and 4.6 cm for RTL. RESULTS: Basic visual discrimination capacities were demonstrated to be essentially intact after LTL and RTL, except for a mild loss of blue color discrimination after RTL. CONCLUSIONS: There is little evidence that RTL produces perceptual impairments limited to the domain of pattern perception, or generalizable to nonmeaningful stimuli. The perceptual loss after RTL may be largely restricted to extraction of meaning, and related to the disruption of the circuits that connect the outcome of visual analysis to previously stored semantic information.

Adult↗

PubMed1999

Visual discrimination and attention after bilateral temporal-lobe lesions: a case study.

We studied a woman (Case 1) who acquired achromatopsia, prosopagnosia, and memory loss after sustaining bilateral temporal-lobe lesions. Given her symptoms and locus of lesion, the affected area may be related to the monkey visual area IT. In order to examine her deficits, we assessed her basic discrimination capacities in several domains. She performed normally when stimuli differed in contrast, size, or motion. her performance was abnormal for patterned targets, and was markedly impaired when the patterned targets were less prominent than distractors. This impairment decreased with practice. These symptoms partially resemble the deficits that have been found in monkeys with lesions in visual cortical area V4.

Adult↗

PubMed1999

An evaluation of the concurrent discrimination task as a measure of habit learning: performance of amnesic subjects.

Habit learning has been defined as an association between a stimulus and a response that develops slowly and automatically through repeated reinforcement. Concurrent discrimination (CD) learning, in which subjects learn to choose the rewarded objects in a series of pairs, is believed to be an example of habit learning in monkeys. Studies of human amnesic subjects, however, have produced equivocal results, revealing impaired or absent learning on the same CD tasks that monkeys with medial temporal-lobe (MTL) lesions learn normally. One possible explanation for impaired performance in human amnesic subjects is that, unlike monkeys, human subjects use explicit memory to solve CD problems. To test this hypothesis, we administered a 10-object pair CD learning task to two amnesic subjects, HM and PN, and normal control subjects (NCS). Both amnesic subjects have severe anterograde amnesia with little ability to form explicit memories. On the CD task, they demonstrated little or no learning and acquired no explicit knowledge of the task procedures or reward contingencies. In contrast, NCS learned the task quickly and easily using explicit memory strategies. These results suggest that CD tasks cannot be learned by habit in human subjects, and emphasize the discrepancies between the human and monkey literature on habit learning.

Aged↗

PubMed1999

Manipulation of familiarity reveals a necessary lexical component of the word-stem completion priming effect.

These experiments were motivated by the idea that many types of nondeclarative memory are by-products arising from the plasticity that is inherent in much of the nervous system. We hypothesized that two types of repetition priming, word-stem completion (WSC) priming and perceptual identification (PI) priming, rely on different mechanisms because the WSC task and the PI task engage different cognitive and brain processes. We tested this hypothesis by manipulating word familiarity. The results, impaired WSC priming but intact PI priming with unfamiliar words, indicate that WSC priming relies primarily on a modification mechanism, whereas PI priming relies primarily on an acquisition mechanism. Our conclusions are consistent with component processes theories of nondeclarative memory.

Adolescent↗

PubMed1998

Impaired word-stem completion priming but intact perceptual identification priming with novel words: evidence from the amnesic patient H.M.

We hypothesized that word-stem completion (WSC) priming and perceptual identification (PI) priming, two types of repetition priming, rely on different cognitive and neural mechanisms: WSC priming on a modification mechanism that influences lexical retrieval, and PI priming on plasticity in pre-lexical perceptual systems. We compared the priming performance of the amnesic patient H.M. with words that came into common usage after the onset of his amnesia, and thus were novel to him (post-1965 words), and with familiar (pre-1953) words. We also tested age- and education-matched normal control subjects (NCS) and a patient with anterograde amnesia of recent onset (P.N.). The modification hypothesis predicted that H.M. would fail to show WSC priming with post-1965 words because pre-existing lexical representations of the test stimuli would be necessary for priming to occur. H.M.'s WSC priming score in the post-1965 condition did not differ from 0, and was inferior to the performance of NCS and of P.N. In contrast, H.M. displayed normal WSC priming in the pre-1953 condition. H.M. also showed robust and equivalent levels of PI priming in both conditions. A final experiment demonstrated preserved post-1965 word PI priming in H.M. when his baseline performance was matched with his post-1965 WSC priming baseline score. Our results challenge models that assume that most kinds of verbal repetition priming rely on the same or similar perceptual mechanisms.

Adult↗

PubMed1998

Time-dependent motor memory processes in amnesic subjects.

Functional properties of motor memory change with the passage of time. The time-dependent nature of memories in humans has also been demonstrated for certain "declarative" memories. When the declarative memory system is damaged, are the time-dependent properties associated with motor memories intact? To approach this question, we examined five subjects with global amnesia (AMN), including subject H.M., and a group of age-matched control subjects. The task was to make reaching movements to visually presented targets. We found that H.M. (but not the other subjects) was significantly impaired in the ability to perform the visuomotor kinematic transformations required in this task, to accurately move the hand in the direction specified by a target. With extensive practice, H.M.'s performance improved significantly. At this point, a force field was imposed on the hand. With practice in field A, H.M. and other AMN subjects developed aftereffects and maintained these aftereffects for 24 h. To quantify postpractice properties associated with motor memories, subjects learned field B on day 2 and at 5 min were retested in field A. In both subject groups, performance in field A was significantly worse than their own naive performance a day earlier. The aftereffects indicated persistence of the just-learned but now inappropriate motor memory. After 4 h of rest, subjects were retested in B. Performance was now at naive levels. The aftereffects at 4 h indicated a reduced influence of the memory of field A. The time-dependent patterns of motor memory perseveration, as measured at 5 min and 4 h, were not different in the AMN and normal control groups.

Aged↗

PubMed1998

Functional MRI for studying episodic memory in aging and Alzheimer's disease.

Anatomic and functional neuroimaging have a potential for clarifying the differential diagnosis of dementia and for evaluating new treatments for memory impairment. Our neuroimaging research examines the neural abnormalities underlying memory impairment in aging and Alzheimer's disease. We use data from high-resolution magnetic resonance imaging (MRI) to measure hippocampal volumes, and data from high-speed echo-planar imaging to evaluate cortical physiology. The results obtained with neuroimaging techniques are then related to the subject's performance on memory tasks (encoding and retrieval) performed inside the scanner during functional MRI.

Aging↗

PubMed1997

H. M.'s medial temporal lobe lesion: findings from magnetic resonance imaging.

Although neuropsychological studies of the amnesic patient H. M. provide compelling evidence that normal memory function depends on the medial temporal lobe, the full extent of his surgical resection has not been elucidated. We conducted magnetic resonance imaging studies to specify precisely the extent of his bilateral resection and to document any other brain abnormalities. The MRI studies indicated that the lesion was bilaterally symmetrical and included the medial temporal polar cortex, most of the amygdaloid complex, most or all of the entorhinal cortex, and approximately half of the rostrocaudal extent of the intraventricular portion of the hippocampal formation (dentate gyrus, hippocampus, and subicular complex). The collateral sulcus was visible throughout much of the temporal lobe, indicating that portions of the ventral perirhinal cortex, located on the banks of the sulcus, were spared; the parahippocampal cortex (areas TF and TH) was largely intact. The rostrocaudal extent of the ablation was approximately 5.4 cm (left) and 5.1 cm (right). The caudal 2 cm, approximately, of the hippocampus body (normal length, approximately 4 cm) was intact, although atrophic. The temporal stem was intact. Outside the temporal lobes, the cerebellum demonstrated marked atrophy, and the mammillary nuclei were shrunken. The lateral temporal, frontal, parietal, and occipital lobe cortices appeared normal for age 66 years. The mediodorsal thalamic nuclei showed no obvious radiological changes. These findings reinforce the view that lesions of the hippocampal formation and adjacent cortical structures can produce global and enduring amnesia and can exacerbate amnesia beyond that seen after more selective hippocampal lesions.

Aged↗