Semantic memory activation in amnestic mild cognitive impairment.

Cognitively intact older individuals at risk for developing Alzheimer's disease frequently show increased functional magnetic resonance imaging (fMRI) brain activation presumably associated with compensatory recruitment, whereas mild cognitive impairment (MCI) patients tend not to show increased activation presumably due to reduced neural reserve. Previous studies, however, have typically used episodic memory activation tasks, placing MCI participants at a performance disadvantage relative to healthy elders. In this event-related fMRI study, we employed a low effort, high accuracy semantic memory task to determine if increased activation of memory circuits is preserved in amnestic MCI when task performance is controlled. Fifty-seven participants, aged 65-85 years, comprised three groups (n = 19 each): amnestic MCI patients; cognitively intact older participants at risk for developing Alzheimer's disease based on having at least one ApoE epsilon4 allele and a positive family history of Alzheimer's disease (At Risk); and cognitively intact participants without Alzheimer's disease risk factors (Control). fMRI was conducted on a 3T MR scanner while participants performed a famous name discrimination task. Participants also underwent neuropsychological testing outside the scanner; whole brain and hippocampal atrophy were assessed from anatomical MRI scans. The three groups did not differ on demographic variables or on fame discrimination performance (>87% correct for all groups). As expected, the amnestic MCI participants demonstrated reduced episodic memory performance. Spatial extent of activation (Fame--Unfamiliar subtraction) differentiated the three groups (Control = 0 ml, At Risk = 9.7 ml, MCI = 34.7 ml). The MCI and At Risk groups showed significantly greater per cent signal change than Control participants in 8 of 14 functionally defined regions, including the medial temporal lobe, temporoparietal junction, and posterior cingulate/precuneus. MCI participants also showed greater activation than Controls in two frontal regions. At Risk, but not MCI, participants showed increased activity in the left hippocampal complex; MCI participants, however, evidenced increased activity in this region when hippocampal atrophy was controlled. When performance is equated, MCI patients demonstrate functional compensation in brain regions subserving semantic memory systems that generally equals or exceeds that observed in cognitively intact individuals at risk for Alzheimer's disease. This hyperactivation profile in MCI is even observed in the left hippocampal complex, but only when the extent of hippocampal atrophy is taken into consideration.

Language acquisition and use: learning and applying probabilistic constraints.

What kinds of knowledge underlie the use of language and how is this knowledge acquired? Linguists equate knowing a language with knowing a grammar. Classic "poverty of the stimulus" arguments suggest that grammar identification is an intractable inductive problem and that acquisition is possible only because children possess innate knowledge of grammatical structure. An alternative view is emerging from studies of statistical and probabilistic aspects of language, connectionist models, and the learning capacities of infants. This approach emphasizes continuity between how language is acquired and how it is used. It retains the idea that innate capacities constrain language learning, but calls into question whether they include knowledge of grammatical structure.

Language function in childhood idiopathic epilepsy syndromes.

PURPOSE: To examine the impact of diverse syndromes of focal and generalized epilepsy on language function in children with new and recent onset epilepsy. Of special interest was the degree of shared language abnormality across epilepsy syndromes and the unique effects associated with specific epilepsy syndromes. METHODS: Participants were 136 youth with new or recent-onset (diagnosis within past 12 months) epilepsy and 107 healthy first-degree cousin controls. The participants with epilepsy included 20 with Temporal Lobe Epilepsy (TLE; M age = 12.99  years, SD = 3.11), 41 with Benign Epilepsy with Centrotemporal Spikes (BECTS; M age = 10.32, SD = 1.67), 42 with Juvenile Myoclonic Epilepsy (JME; M age = 14.85, SD = 2.75) and 33 with absence epilepsy (M age = 10.55, SD = 2.76). All children were administered a comprehensive test battery which included multiple measures of language and language-dependent abilities (i.e., verbal intelligence, vocabulary, verbal reasoning, object naming, reception word recognition, word reading, spelling, lexical and semantic fluency, verbal list learning and delayed verbal memory). Test scores were adjusted for age and gender and analyzed via MANCOVA. RESULTS: Language abnormalities were found in all epilepsy patient groups. The most broadly affected children were those with TLE and absence epilepsy, whose performance differed significantly from controls on 8 of 11 and 9 of 11 tests respectively. Although children with JME and BECTS were less affected, significant differences from controls were found on 4 of 11 tests each. While each group had a unique profile of language deficits, commonalities were apparent across both idiopathic generalized and localization-related diagnostic categories. DISCUSSION: The localization related and generalized idiopathic childhood epilepsies examined here were associated with impact on diverse language abilities early in the course of the disorder.

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.

Specific language impairment: a deficit in grammar or processing?

Specific Language Impairment (SLI) is observed in children who fail to acquire age-appropriate language skills but otherwise appear to be developing normally. There are two main hypotheses about the nature of these impairments. One assumes that they reflect impairments in the child's innate knowledge of grammar. The other is that they derive from information-processing deficits that interfere with several aspects of language learning. There is considerable evidence that SLI is associated with impaired speech processing; however, the link between this deficit and the kinds of grammatical impairments observed in these children has been unclear. We suggest that the link is provided by phonology, a speech-based code that plays important roles in learning linguistic generalizations and in working memory.

Mood state in unilateral temporal lobe epilepsy.

The purpose of this investigation was to reexamine the relationship between self-reported depression and laterality of temporal lobe epilepsy and to determine the contribution of associated frontal lobe dysfunction in predisposing patients to depression. Sixty-four patients with complex partial seizures of left (n = 26) or right (n = 38) temporal lobe origin were administered several self-report measures of mood state (Beck Depression Inventory, Center for Epidemiological Studies-Depression scale, Beck Anxiety Inventory), and a test of frontal lobe function [Wisconsin Card Sorting Test (WCST)]. There were no overall differences between the left and right temporal lobe groups on the measures of depression and anxiety. However, the left temporal lobe group exhibited a significant relationship between the degree of associated frontal lobe dysfunction (as indicated by increased perseverative responding on the WCST) and dysphoric mood state. For the right temporal lobe group there was a nonsignificant inverse relationship between mood state and indices of frontal lobe dysfunction. These results (1) are consistent with the broader psychiatric literature, which has implicated a relationship between depression and left frontal lobe dysfunction, (2) suggest that previous conflicting reports of depression/left temporal lobe epilepsy relationships are due in part to variations in the intactness of frontal lobe function, and (3) suggest that the presence of associated frontal lobe dysfunction may be a consideration in understanding interictal psychopathology in epilepsy.

Neuropsychological characteristics of the syndrome of mesial temporal lobe epilepsy.

OBJECTIVE: To identify the neuropsychological features of the syndrome of mesial temporal lobe epilepsy (MTLE), a surgically remediable epileptic syndrome defined by the presence of hippocampal sclerosis, using a broad and comprehensive neuropsychological test battery. SETTING: Epilepsy surgery center. PATIENTS: After scalp adn invasive electroencephalographic monitoring, a consecutive series of 107 adults were found to have intractable complex partial seizures of unilateral left (n = 62) or right (n = 45) temporal lobe origin. Patients were included if they were not retarded and had left hemisphere dominance for speech but no magnetic resonance imaging abnormalities other than hipocampal sclerosis. Histopathological analyses of resected hippocamppi showed that 66 patients had hippocampal sclerosis (MTLE+), and 41 did not have evidence of significant hippocampal sclerosis (MTLE-). INTERVENTIONS: None. MAIN DEPENDENT MEASURES: A comprehensive battery of neuropsychological tests that included measures of intelligence, academic achievement, language, visuoperceptual or visuospatial function, memory and learning, attention, and problem-solving abilities. RESULTS: The syndrome of MTLE was associated with considerable generalized cognitive impairment (in intelligence, academic achievement, language, and visuospatial functions), but not related to adequacy of performances in other selected cognitive domains (attention or concentration, executive functions). Material-specific memory effects were obtained-primarily for verbal memory in association with left-sided MTLE. CONCLUSIONS: Distinct neuropsychological features of spared, compromised, and laterality-specific cognitive impairments characterize the syndrome of MTLE. This information needs to be incorporated into formal syndrome criteria.

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.

Improvement in neuropsychological performance in patients with refractory seizures after intensive diagnostic and therapeutic intervention.

Tests of cognitive, perceptual, motor, and memory function were administered to patients with refractory seizures before and after intensive treatment on a specialized epilepsy unit. Improved test performance related to withdrawal of barbiturates and an overall reduction in the number of antiepileptic drugs but not with reduction of seizure frequency.

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.

Patients with pseudoseizures: intellectual and cognitive performance.

We compared cognitive and intellectual performance of patients with pseudoseizures (pseudoseizure-only group), pseudoseizures and epilepsy (mixed seizure group), and generalized epileptic seizures (generalized seizure group). The pseudoseizure-only group performed significantly better on all measures except those of simple motor function. There were no significant differences between those with mixed and generalized seizures. Therefore, cognitive and intellectual performances of patients with pseudoseizures are influenced by the presence or absence of concomitant epilepsy, and suggest that it is necessary to distinguish patients with and without epilepsy in studies of pseudoseizures.

Hippocampal sclerosis and verbal encoding ability following anterior temporal lobectomy.

Previous research has shown that the degree of verbal memory decline following left anterior temporal lobectomy (ATL) is inversely related to the extent of neuronal dropout in resected left hippocampus. The goal of this investigation was to clarify further the nature of the free recall impairment and to determine the relative contribution of verbal retrieval and encoding processes. Seventy-six patients who underwent left (n = 46) or right (n = 30) ATL were classified according to the presence or absence of hippocampal sclerosis and pre- to postoperative changes in free recall, cued recall and recognition memory for verbal material were examined. Surgically induced free recall impairments were selectively associated with resection of nonsclerotic left hippocampus and represented a 29-35% decline in verbal learning ability. These free recall deficits were due to postoperative impairment in verbal encoding efficiency, not retrieval difficulties. Assessment of false positive recognition errors indicated that resection of nonsclerotic left hippocampus selectively impaired the ability to encode stimulus uniqueness within correct semantic fields. The clinical and theoretical significance of these results are discussed.

Phonology, reading acquisition, and dyslexia: insights from connectionist models.

The development of reading skill and bases of developmental dyslexia were explored using connectionist models. Four issues were examined: the acquisition of phonological knowledge prior to reading, how this knowledge facilitates learning to read, phonological and nonphonological bases of dyslexia, and effects of literacy on phonological representation. Compared with simple feedforward networks, representing phonological knowledge in an attractor network yielded improved learning and generalization. Phonological and surface forms of developmental dyslexia, which are usually attributed to impairments in distinct lexical and nonlexical processing "routes," were derived from different types of damage to the network. The results provide a computationally explicit account of many aspects of reading acquisition using connectionist principles.

A distributed, developmental model of word recognition and naming.

A parallel distributed processing model of visual word recognition and pronunciation is described. The model consists of sets of orthographic and phonological units and an interlevel of hidden units. Weights on connections between units were modified during a training phase using the back-propagation learning algorithm. The model simulates many aspects of human performance, including (a) differences between words in terms of processing difficulty, (b) pronunciation of novel items, (c) differences between readers in terms of word recognition skill, (d) transitions from beginning to skilled reading, and (e) differences in performance on lexical decision and naming tasks. The model's behavior early in the learning phase corresponds to that of children acquiring word recognition skills. Training with a smaller number of hidden units produces output characteristic of many dyslexic readers. Naming is simulated without pronunciation rules, and lexical decisions are simulated without accessing word-level representations. The performance of the model is largely determined by three factors: the nature of the input, a significant fragment of written English; the learning rule, which encodes the implicit structure of the orthography in the weights on connections; and the architecture of the system, which influences the scope of what can be learned.

The lexical nature of syntactic ambiguity resolution [corrected].

Ambiguity resolution is a central problem in language comprehension. Lexical and syntactic ambiguities are standardly assumed to involve different types of knowledge representations and be resolved by different mechanisms. An alternative account is provided in which both types of ambiguity derive from aspects of lexical representation and are resolved by the same processing mechanisms. Reinterpreting syntactic ambiguity resolution as a form of lexical ambiguity resolution obviates the need for special parsing principles to account for syntactic interpretation preferences, reconciles a number of apparently conflicting results concerning the roles of lexical and contextual information in sentence processing, explains differences among ambiguities in terms of ease of resolution, and provides a more unified account of language comprehension than was previously available.

Understanding normal and impaired word reading: computational principles in quasi-regular domains.

A connectionist approach to processing in quasi-regular domains, as exemplified by English word reading, is developed. Networks using appropriately structured orthographic and phonological representations were trained to read both regular and exception words, and yet were also able to read pronounceable nonwords as well as skilled readers. A mathematical analysis of a simplified system clarifies the close relationship of word frequency and spelling-sound consistency in influencing naming latencies. These insights were verified in subsequent simulations, including an attractor network that accounted for latency data directly in its time to settle on a response. Further analyses of the ability of networks to reproduce data on acquired surface dyslexia support a view of the reading system that incorporates a graded division of labor between semantic and phonological processes, and contrasts in important ways with the standard dual-route account.

Teenagers' preferences regarding the presence of family members, peers, and chaperones during examination of genitalia.

During physical examination that include the genitalia, teenagers are typically separated from their parents and females are provided with a chaperone. To assess teenagers' attitudes regarding this practice, 140 females and 60 males awaiting treatment in a general adolescent clinic were asked their opinion about a physical examination that include the genitalia. Teenagers indicated whether they would want to be accompanied during the examination, and by whom, as a function of the hypothetical clinical situation that varied the sex and familiarity of the physician. Choices reflected teenagers' age and sex, rather than physician characteristics. Young males and females strongly preferred to be accompanied, generally by a family member. With increasing age, males preferred to be alone with the physician whereas females preferred to be accompanied. Regardless of sex and age, virtually none chose the company of peers. Despite strong development differences, however, there also were pronounced individual differences among teenagers of the same age. Our results suggest that service delivery be adapted to the particular preference expressed by individual teenagers. Needs assessment for adolescent programs may best be achieved by conducting similar surveys in local clinical settings.

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.

Language and connectionism: the developing interface.

After a difficult initial period in which connectionism was perceived as either irrelevant or antithetical to linguistic theory, connectionist concepts are now beginning to be brought to bear on basic issues concerning the structure, acquisition, and processing of language, both normal and disordered. This article describes some potential points of further contact between connectionism and linguistic theory. I consider how connectionist concepts may be relevant to issues concerning the representation of linguistic knowledge; the role of a priori constraints on acquisition; and the poverty of the stimulus argument. I then discuss whether these models contribute to the development of explanatory theories of language.

On the bases of two subtypes of developmental [corrected] dyslexia.

This study examined whether there are different subtypes of developmental dyslexia. The subjects were 51 dyslexic children (reading below the 30th percentile in isolated word recognition), 51 age-matched normal readers, and 27 younger normal readers who scored in the same range as the dyslexics on word recognition. Using methods developed by Castles and Coltheart (1993), we identified two subgroups who fit the profiles commonly termed "surface" and "phonological" dyslexia. Surface subjects were relatively poorer in reading exception words compared to nonwords; phonological dyslexics showed the opposite pattern. However, most dyslexics were impaired on reading both exception words and nonwords compared to same-aged normal readers. Whereas the surface dyslexics' performance was very similar to that of younger normal readers, the phonological dyslexics' was not. The two dyslexic groups also exhibited a double dissociation on two validation tasks: surface subjects were impaired on a task involving orthographic knowledge but not one involving phonology; phonological dyslexics showed the opposite pattern. The data support the conclusion that there are at least two subtypes of developmental dyslexia. Although these patterns have been taken as evidence for the dual-route model, we provide an alternative account of them within the Seidenberg and McClelland (1989) connectionist model. The connectionist model accounts for why dyslexics tend to be impaired on both exception words and nonwords; it also suggests that the subtypes may arise from multiple underlying deficits. We conclude that performance on exception words and nonwords is not sufficient to identify the basis of dyslexic behavior; rather, information about children's performance on other tasks, their remediation experiences, and the computational mechanisms that give rise to impairments must be taken into account as well.