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Biomedical subjects

M Seidenberg

Publications and source records attributed to M Seidenberg.

At least 19 recordsLinked to original sources
PubMed2005

Modulation of the semantic system by word imageability.

A prevailing neurobiological theory of semantic memory proposes that part of our knowledge about concrete, highly imageable concepts is stored in the form of sensory-motor representations. While this theory predicts differential activation of the semantic system by concrete and abstract words, previous functional imaging studies employing this contrast have provided relatively little supporting evidence. We acquired event-related functional magnetic resonance imaging (fMRI) data while participants performed a semantic similarity judgment task on a large number of concrete and abstract noun triads. Task difficulty was manipulated by varying the degree to which the words in the triad were similar in meaning. Concrete nouns, relative to abstract nouns, produced greater activation in a bilateral network of multimodal and heteromodal association areas, including ventral and medial temporal, posterior-inferior parietal, dorsal prefrontal, and posterior cingulate cortex. In contrast, abstract nouns produced greater activation almost exclusively in the left hemisphere in superior temporal and inferior frontal cortex. Increasing task difficulty modulated activation mainly in attention, working memory, and response monitoring systems, with almost no effect on areas that were modulated by imageability. These data provide critical support for the hypothesis that concrete, imageable concepts activate perceptually based representations not available to abstract concepts. In contrast, processing abstract concepts makes greater demands on left perisylvian phonological and lexical retrieval systems. The findings are compatible with dual coding theory and less consistent with single-code models of conceptual representation. The lack of overlap between imageability and task difficulty effects suggests that once the neural representation of a concept is activated, further maintenance and manipulation of that information in working memory does not further increase neural activation in the conceptual store.

Adolescent↗
PubMed2004

Cerebellar atrophy in temporal lobe epilepsy affects procedural memory.

The authors examined a cognitive function mediated by the cerebellum, classical eyeblink conditioning, and its relationship to cerebellar volume in healthy controls (n = 59) and temporal lobe epilepsy subjects (n = 77). Controls demonstrated better conditioning, larger cerebellar volumes, and an association between conditioning and cerebellar volume that was not observed in epilepsy patients. These findings provide support for the hypothesis that cerebellar atrophy in epilepsy affects procedural memory.

Acoustic Stimulation↗
PubMed2004

The nature and course of neuropsychological morbidity in chronic temporal lobe epilepsy.

OBJECTIVE: To characterize the nature and degree of cognitive morbidity in patients with chronic temporal lobe epilepsy compared with healthy control subjects, determine the association between the duration of epilepsy and cognitive morbidity, and ascertain whether there are factors that moderate the association between duration of disorder and cognitive impairment. METHODS: Temporal lobe epilepsy (n = 96) and healthy control (n = 82) subjects were assessed with a comprehensive neuropsychological battery. Test performances were adjusted for age, gender, and education and transformed to a common metric (z scores). Analyses included group comparisons and correlations of duration of epilepsy with cognitive morbidity. RESULTS: Patients with temporal lobe epilepsy exhibited not only worse memory function (p < 0.05) but worse performance across measures of intelligence, language, executive function, and motor speed (p < 0.05). Chronicity of epilepsy was related to worsening mental status (r = 0.42, p < 0.001). This relationship was particularly evident among those individuals with less (r = 0.58, p < 0.001) compared with more (r = 0.25, NS) cerebral reserve, operationally defined by years of formal education. CONCLUSIONS: Neuropsychological morbidity in chronic temporal lobe epilepsy is widespread in nature despite a focal epileptic process. Cross-sectional analyses demonstrate that increasing duration of epilepsy is associated with worsening mental status. Individuals with less educational attainment (low cerebral reserve) exhibit especially poor cognitive function in association with chronicity of epilepsy.

Adolescent↗
PubMed2001

Object naming and semantic knowledge in temporal lobe epilepsy.

Object-naming impairment is common among temporal lobe epilepsy (TLE) patients, but other aspects of semantic memory have received limited attention in this population. This study examined object-naming ability and depth of semantic knowledge in healthy controls (n = 29) and patients with early onset TLE (n = 21). After administration of the Boston Naming Test (BNT), the authors asked participants to provide detailed definitions of 6 BNT objects. The TLE group demonstrated a significant deficit relative to controls in both object-naming ability and semantic knowledge for the target objects, even after controlling for IQ. In a multiple regression analysis that included other neuropsychological test scores as independent variables, the semantic knowledge score was the only significant predictor of patients' object-naming performance. Thus, at the group level, early onset TLE patients have a semantic knowledge deficit that contributes to dysnomia.

Adolescent↗
PubMed2001

Memory outcome after left anterior temporal lobectomy in patients with expected and reversed Wada memory asymmetry scores.

PURPOSE: The ideal candidate for anterior temporal lobectomy surgery shows a Wada memory asymmetry (WMA) score characterized by better memory performance in the hemisphere contralateral to the seizure focus relative to the ipsilateral (surgical) hemisphere. However, some surgical candidates show a reversed WMA or better Wada memory performance in the hemisphere of surgical interest relative to the hemisphere contralateral to the seizure focus. To date, no data are available contrasting memory and seizure outcome for these two Wada groups. The present study compared memory and seizure outcome after left anterior temporal lobectomy (L-ATL) in patients showing expected and reversed WMA scores, and also examined the relationship of the individual hemisphere Wada memory scores for predicting verbal memory outcome after L-ATL. METHODS: We compared 6-month postoperative verbal memory change scores and seizure outcome in L-ATL patients with either an expected (n=12) or reversed WMA (n=9) pattern on Wada memory testing. RESULTS: L-ATL patients showing a reversed WMA score had a poorer verbal memory outcome and poorer seizure control after surgery compared with patients showing a WMA score in the expected direction. CONCLUSIONS: L-ATL patients with a reversed WMA score have a greater risk for memory morbidity and poorer seizure outcome than do patients with a WMA score in the expected direction. The WMA score was the best predictor of memory outcome after L-ATL. When the WMA score is not considered, both individual Wada hemisphere scores (contralateral and ipsilateral) provided significant and independent contribution to predicting postoperative verbal memory functioning. These findings are discussed in the context of the functional reserve and hippocampal adequacy models of memory change after temporal lobectomy.

Adult↗
PubMed2000

Preoperative FDG-PET temporal lobe hypometabolism and verbal memory after temporal lobectomy.

OBJECTIVE: To examine the relationship of preoperative fluorodeoxyglucose (FDG)-PET asymmetry in temporal lobe metabolism and memory outcome after anterior temporal lobectomy (ATL). METHODS: In a university-based epilepsy surgery center, 60 ATL patients (27 left, 33 right) were divided into two groups: no/mild (n = 21) or moderate/ severe (n = 39) asymmetry in temporal lobe hypometabolism as determined by FDG-PET. All patients were nonretarded, at least 18 years of age, left-hemisphere speech dominant, without MRI abnormalities other than hippocampal atrophy, and with unilateral temporal lobe origin of intractable complex partial seizures. Neuropsychological measures of intelligence and verbal and visual memory function were assessed preoperatively and 6 months postoperatively. RESULTS: Left ATL patients with no/mild asymmetry in FDG-PET temporal lobe metabolism exhibited significantly greater verbal memory decline compared with left ATL patients with moderate/severe hypometabolism. There was no significant relationship between PET asymmetry and pre- to postsurgical IQ change. No significant relationship was observed between extent of PET hypometabolism and memory outcome for right ATL patients. CONCLUSIONS: FDG-PET asymmetry can be added to the preoperative clinical markers that appear useful in predicting verbal memory decline after left ATL.

Adult↗
PubMed2000

Neural systems underlying the recognition of familiar and newly learned faces.

Memory for famous faces can be used to examine the neural systems underlying retrieval from long-term memory. To date, there have been a limited number of functional neuroimaging investigations examining famous face recognition. In this study, we compared recognition of famous faces to recognition of newly learned faces. Whole-brain, event-related functional magnetic resonance imaging was used to image regional changes in neural activity in 11 subjects during the encoding of unfamiliar faces and during familiarity judgments for: (1) newly learned faces, (2) unfamiliar face distractors, and (3) famous faces. Image analyses were restricted to correct recognition trials. Recognition accuracy and response time to famous and recently learned faces were equivalent. Recognition of famous faces was associated with a widespread network of bilateral brain activations involving the prefrontal, lateral temporal, and mesial temporal (hippocampal and parahippocampal regions) regions compared to recognition of recently encoded faces or unfamiliar faces seen for the first time. Findings are discussed in relation to current proposals concerning the neural regions thought to participate in long-term memory retrieval and, more specifically, in relation to retrieval of information from the person identity semantic system.

Adult↗
PubMed2000

Comorbid psychiatric symptoms in temporal lobe epilepsy: association with chronicity of epilepsy and impact on quality of life.

Purpose. The goals of this work were to determine: (1) the nature and extent of differences in self-reported psychiatric symptoms between patients with temporal lobe epilepsy and matched healthy controls, (2) the relationship between chronicity (duration) of temporal lobe epilepsy and comorbid interictal psychiatric symptoms, and (3) the impact of comorbid psychiatric symptoms on self-reported health-related quality of life. Methods. Patients with temporal lobe epilepsy (n = 54) and healthy controls (n = 38) were administered the Symptom Checklist-90-Revised (SCL-90-R) to assess the nature and severity of psychiatric symptomatology and epilepsy patients completed the Quality of Life in Epilepsy-89 (QOLIE-89) to define health-related quality of life. Among epilepsy patients the SCL-90-R scales were examined in relation to chronicity of temporal lobe epilepsy as well as the impact of comorbid emotional-behavioral distress on health-related quality of life. Results. Compared with healthy controls, patients with epilepsy exhibited significantly higher (worse) scores across all but one of the 12 SCL-90-R scales. Among patients with epilepsy, increasing chronicity was associated with significantly higher (worse) scores across all SCL-90-R scales and increased emotional-behavioral distress was associated with lower (worse) scores across all 17 QOLIE-89 scales. Conclusion. Comorbid interictal psychiatric symptoms are elevated among patients with temporal lobe epilepsy compared with healthy controls and appear to be modestly associated with increasing chronicity (duration) of epilepsy. This comorbid emotional-behavioral distress is specifically associated with a significantly poorer health-related quality of life, and suggests that quality-of-life research should devote greater attention to the potential impact of comorbid psychiatric distress.

Journal Article↗
PubMed2000

Verbal working memory in HIV-seropositive drug users.

Recent evidence suggests that HIV-seropositive drug users are impaired on tasks of visuospatial working memory compared with drug users seronegative for HIV. In the current study we evaluated the performance of 30 HIV-seropositive male drug users and 30 risk-matched seronegative controls on two measures of verbal working memory, the Listening Span and the verbal Self Ordered Pointing Task. Impaired working memory performance was significantly more common among HIV-seropositive persons compared to controls, with the highest incidence of deficit among symptomatic participants. These findings indicate that working memory deficits in persons with HIV are not domain-specific and can be demonstrated reliably in drug users.

Adult↗
PubMed2000

Psychiatric comorbidity in chronic epilepsy: identification, consequences, and treatment of major depression.

The purpose of this article is to review the topic of interictal psychiatric comorbidity among adult patients with chronic epilepsy, focusing specifically on those studies that have used contemporary psychiatric nosology. Five specific issues are addressed: (a) the risk and predominant type(s) of psychiatric comorbidity in chronic epilepsy, (b) adequacy of recognition and treatment of psychiatric comorbidity, (c) the additional burdens that comorbid psychiatric disorders impose upon patients with chronic epilepsy, (d) the etiology of these disorders, and (e) strategies for treatment. Current appreciation for these issues in epilepsy is contrasted to related fields (e.g., primary care, psychiatry, and epidemiology), where considerable attention has been devoted to the identification, consequences, and treatment of psychiatric comorbidity. The issue of psychiatric comorbidity in epilepsy is reviewed with the aim of identifying a clinical and research agenda that will advance understanding of at least one important psychiatric condition associated with epilepsy-namely, major depression.

Absenteeism↗
PubMed2000

Interactions of alcuronium, TMB-8, and other allosteric ligands with muscarinic acetylcholine receptors: studies with chimeric receptors.

A series of ligands that allosterically modulate the binding of classical ligands to muscarinic receptors was evaluated at wild-type and chimeric receptors. All of the ligands studied had highest affinity toward the M(2) subtype and lowest affinity toward the M(5) subtype. The chimeric receptors were mostly M(5) sequence; the amount of M(2) sequence ranged from about 6 to just under 30%. Alcuronium and TMB-8 had much higher affinity for the chimeric receptor that included the M(2) second outer loop of the receptor plus flanking regions of TM4 and TM5 than for any of the other chimeric receptors (the affinities of which remained similar to that of the M(5) subtype). However, this chimera retained the negative cooperativity between alcuronium and the classical antagonist N-methylscopolamine that is characteristic of M(5) (these ligands are positively cooperative at M(2)). Verapamil, tetrahydroaminoacridine, and d-tubocurarine were also sensitive to that chimeric substitution, although verapamil and tetrahydroaminoacridine had even higher affinity for a chimera with M(2) sequence in TM7. None of these ligands shared gallamine's sensitivity to a region of the third outer loop, but studies in which obidoxime reversed the allosteric effects of gallamine and other ligands suggested that they nevertheless compete for a common site. In summary, although the present data are consistent with previous studies that have suggested that allosteric ligands bind to the outermost regions of muscarinic receptors, it appears that different allosteric ligands may derive subtype selectivity from different regions of the receptor.

Acetylcholine↗
PubMed2000

Site-directed mutagenesis implicates a threonine residue in TM6 in the subtype selectivities of UH-AH 37 and pirenzepine at muscarinic receptors.

The structural basis for the selectivity of the antagonist UH-AH 37 at human muscarinic acetylcholine receptors was investigated by expressing mutant receptors in COS-7 cells. Previous studies have demonstrated that the interaction between UH-AH 37 and [(3)H]N-methylscopolamine in equilibrium assays is competitive and that the high affinity of UH-AH 37 for the M(5) subtype, compared to M(2), is due to an epitope in the sixth transmembrane domain (TM6) or the third outer loop of the receptor. By mutating each nonconserved residue in this region of M(2) and M(5) to its counterpart in the other receptor, we identified a threonine residue in the middle of TM6 uniquely responsible for the higher affinity of the M(5) receptor (M(1), M(3), and M(4) receptors also carry a threonine at that location and also have high affinity for UH-AH 37). The mutant receptor in which the corresponding alanine of the M(2) receptor was replaced by threonine, M(2)(401)ala --> thr, expressed enhanced affinity for pirenzepine as well as for UH-AH 37. The chick M(2) receptor, which expresses anomalously high affinity for pirenzepine, differs from its mammalian counterparts by the presence of a threonine at this position. Affinities of AF-DX 116 and 4-DAMP, as well as the allosteric potency of UH-AH 37, were not sensitive to the M(2)(401) ala --> thr mutation.

Amino Acid Sequence↗
PubMed1999

Competitive and allosteric interactions of 6-chloro-5,10-dihydro-5-[(1-methyl-4-piperidinyl)acetyl]-11H-di benzo[b,e][1, 4]diazepine-11-one hydrochloride (UH-AH 37) at muscarinic receptors, via distinct epitopes.

6-Chloro-5,10-dihydro-5-[( 1-methyl-4-piperidinyl)acetyl]-11H-dibenzo[b,e][1,4]diazepine-11one++ + hydrochloride (UH-AH 37) is an analog of pirenzepine that has previously been reported to interact with classical muscarinic antagonists in a competitive manner, yet its binding has also been found to be sensitive to the same epitope as is that of the allosteric ligand gallamine. The present study was carried out with wild-type and chimeric muscarinic receptors to determine whether UH-AH 37 might also have an allosteric mode of action. In assays that detect only allosteric interactions, UH-AH 37 slowed the rate of dissociation of [3H]N-methylscopolamine (NMS) from all five muscarinic receptor subtypes, with the highest apparent affinity at m2. By contrast, studies carried out under equilibrium conditions have found UH-AH 37 to have the lowest affinity for the m2 subtype. Studies with m2/m5 chimeric receptors found the allosteric potency of UH-AH 37 to be sensitive to an epitope in the seventh transmembrane domain (TM). Again, this contrasts with equilibrium studies, wherein an epitope in the sixth TM has been implicated. Simultaneous analysis of the interactions between UH-AH 37 and [3H]NMS at the m2 receptor under equilibrium and non-equilibrium conditions found that a simple allosteric model could not accommodate both sets of data. On the other hand, the model did accommodate such data for gallamine; gallamine also displays concordance in order-of-potency and epitope sensitivity between equilibrium and non-equilibrium assays. Based on these results, we conclude that UH-AH 37 interacts at the classical muscarinic binding site with high affinity and at a second (allosteric) site with lower affinity.

Allosteric Regulation↗
PubMed1999

Synaptophysin immunoreactivity in temporal lobe epilepsy-associated hippocampal sclerosis.

We have previously devised a semiquantitative grading system for hippocampal sclerosis (HS) in specimens resected for intractable temporal lobe epilepsy. The grades range from zero to four based on the amount and distribution of neuronal loss and gliosis. In the present study hippocampal sections from 25 patients who had temporal lobe epilepsy and had previously been assigned a grade were examined with synaptophysin immunohistochemistry, and the synaptic content in specific hippocampal fields was correlated with the results of the HS grading system. There was evidence of both significant synaptic loss and increased synaptic density in different fields of the hippocampus with increasing HS. A marked decrement of synaptic inmmunostaining was present in fields CA1 and CA4 that were highly correlated with HS grade. Sector CA4 seemed to respond in a more graded or continuous way to the pathological insults occurring in temporal lobe epilepsy than did CA1, which appeared to exhibit an all or nothing response. Also, while the width of the outer part of the molecular layer of the dentate (mid) gyrus decreased with increasing HS grade, the inner part of the mid became wider and showed an increased synaptic density so that the overall width of the mid was increased in the high-grade group. We conclude that quantitative measurement of synaptic loss in CAI and CA4 using synaptophysin immunohistochemistry is a sensitive method for detecting HS and correlates well with the empirically derived HS grading scale, with CA4 exhibiting a more graded response than CA1. In addition, a plasticity response in the inner part of the mld in patients with high-grade HS has been confirmed and quantitated.

Adult↗
PubMed1999

Neuropsychological and behavioral status of children with complex partial seizures.

Neuropsychological and behavioral status were examined in 57 children aged 7 to 16 years with complex partial seizures (CPS) and compared with 27 sibling control children of the same age. Epilepsy had a significant effect on both cognitive and behavioral adjustment measures. Children with CPS had significant impairment across all seven cognitive domains assessed, reflective of a profile of relatively diffuse and generalized cognitive dysfunction. Age at onset of recurrent seizures was the strongest and most consistent predictor of adequacy of cognitive functioning; earlier age at onset was associated with poorer cognitive status. Children with CPS also had more problems compared with sibling control children on measures of social and school competence and internalizing behavior problems, but not externalizing behaviors. Further, frequency of seizure activity in the past year, rather than age at seizure onset, emerged as the strongest predictor of these behavioral difficulties. These findings are discussed in the context of understanding the impact of CPS on cognition and behavioral adjustment, and identifying the contribution of various aspects of the neurodevelopmental course of CPS to these issues.

Achievement↗
PubMed1999

Site-directed mutagenesis reveals two epitopes involved in the subtype selectivity of the allosteric interactions of gallamine at muscarinic acetylcholine receptors.

Gallamine allosterically modulates the binding of classical muscarinic ligands with a potency order of M(2) > M(1),M(4) > M(3), M(5). We have suggested previously that the M(2)/M(5) and M(2)/M(3) selectivities are attributable to an epitope in the sixth transmembrane region or third outer loop (o3) region of the receptor. In this study, analysis of numerous point mutations in this region of the M(5) receptor found that a mutation of V --> N resulted in an increased affinity toward gallamine, suggesting that the asparagine residue at M(2)(419) is responsible for gallamine's M(2)/M(5) selectivity. Mutations in the other subtypes indicated that the acidic residues found at this position in M(1) and M(4) are associated with slightly higher affinity toward gallamine, whereas the valine and lysine residues of M(5) and M(3), respectively, are associated with significantly lower affinity. In the o2 region, replacement of an acidic sequence of M(2) (EDGE) by the corresponding neutral sequence of M(1) (LAGQ) reduced the affinity toward gallamine, as reported previously by others; the converse substitution of the acidic sequence into M(1) significantly increased affinity for gallamine. Substitution of the M(1) sequence into this region of M(5) markedly reduced affinity toward gallamine, whereas substitution into M(4) had no effect. All of the above mutations are consistent with gallamine binding with a similar orientation at each subtype, such that it interacts with acidic residues in the o2 region of M(3) and M(5) and with acidic residues in the o3 region of M(1) and M(4); gallamine appears to interact with both regions of the M(2) subtype.

Allosteric Regulation↗
PubMed1999

Co-morbid psychiatric disorder in chronic epilepsy: recognition and etiology of depression.

This article briefly presents one approach to conceptualizing known and suspected risk factors for co-morbid psychiatric disorder in epilepsy. The utility of this model is then reviewed by examining selected neurobiologic, psychosocial, and iatrogenic risk factors for a common co-morbid psychiatric disorder, interictal depression. Finally, data are presented concerning the rates of current and lifetime mood disorders among a sample of 76 patients with chronic complex partial seizures, the degree to which co-morbid depression has been recognized and treated in chronic epilepsy, and the health-related quality of life status associated with current and past mood disorders. Finally, these findings are related to the larger literature concerned with the recognition and treatment of depression.

Adult↗