Acute effects of ketamine on memory systems and psychotic symptoms in healthy volunteers.
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N-methyl-D-aspartate (NMDA) receptor antagonists have been demonstrated to induce schizophrenia-like symptoms and cognitive impairment in humans. The NMDA receptor has been strongly implicated in memory, but research to date on the effects of NMDA antagonists has examined only some aspects of human memory functions. This study used a double-blind, placebo-controlled, independent groups design with 54 healthy volunteers to examine the effects of infusions of two doses (0.4, 0.8 mg/kg) of the NMDA antagonist ketamine upon the five human memory systems, aspects of executive functioning and schizophrenia-like and dissociative symptoms. Ketamine produced a dose-dependent impairment to episodic and working memory and a slowing of semantic processing. Ketamine also impaired recognition memory and procedural learning. Attention, perceptual priming and executive functioning were not affected following the drug. In addition, ketamine induced schizophrenia-like and dissociative symptoms, which were not correlated with the cognitive measures. These data suggest that, in humans, ketamine produces a selective pattern of impairments to working, episodic, and procedural memory but not to perceptual priming, attention or aspects of executive functioning. (+info)
Behavioral and neurofunctional changes over time in healthy and aphasic subjects: a PET Language Activation Study.
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BACKGROUND AND PURPOSE: Follow-up neuroimaging studies of aphasia never addressed a comparison between aphasic and healthy subjects. Investigation of changes over time in healthy subjects during language tasks seems a prerequisite before interpretation of longitudinal changes in aphasic patients. METHODS: Six healthy subjects and 8 aphasic patients were PET scanned twice (PET1 and PET2) at a 1-year interval during a word generation task. Using SPM99, language-rest main effect was compared at PET1 and PET2 in each group, whereas group effect was assessed at each session. Correlations were analyzed in each group between performance indexes and changes in regional cerebral flood flow (rCBF) between the 2 sessions. RESULTS: Language performances were improved in both groups. rCBF decreased from PET1 to PET2 in the healthy group and increased in the aphasic group in perisylvian regions bilaterally. Correlations between performance and rCBF changes across sessions were similar in the 2 groups; positive correlations involved superior temporal cortexes bilaterally, and negative correlations concerned superior frontal and medial temporal regions. CONCLUSIONS: Increased perisylvian activation over time probably reflects improved performance at the expenses of cognitive effort in aphasic patients. Decreased activation in different neural systems suggests a familiarization effect with reduced emotional load. (+info)
The role of syntactic complexity in treatment of sentence deficits in agrammatic aphasia: the complexity account of treatment efficacy (CATE).
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This experiment examined the hypothesis that training production of syntactically complex sentences results in generalization to less complex sentences that have processes in common with treated structures. Using a single subject experimental design, 4 individuals with agrammatic aphasia were trained to comprehend and produce filler-gap sentences with wh-movement, including, from least to most complex, object-extracted who-questions, object clefts, and sentences with object-relative clausal embedding. Two participants received treatment first on the least complex structure (who-questions), and 2 received treatment first on the most complex form (object-relative constructions), while untrained sentences and narrative language samples were tested for generalization. When generalization did not occur across structures, each was successively entered into treatment. Results showed no generalization across sentence types when who-questions were trained; however, as predicted, object-relative training resulted in robust generalization to both object clefts and who-questions. These findings support those derived from previous work, indicating not only that generalization occurs across structures that are linguistically related, but also that generalization is enhanced when the direction of treatment is from more complex to less complex constructions. This latter finding supports the authors' newly coined "complexity account of treatment efficacy" (CATE). (+info)
A family aggregation study: the influence of family history and other risk factors on language development.
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Substantial evidence continues to accrue for familial transmission of specific language impairment (SLI). The incidence in families with a history of SLI is estimated at approximately 20%-40%, whereas in the general population the estimated incidence is about 4%. Typical aggregation studies compare data on the speech and language status of parents and siblings of individuals with SLI (the probands) to similar data from family members of control individuals with no speech or language disorder history. In the present study, family aggregation of SLI was examined for a unique sample of children who were ascertained before 6 months of age and thus did not have SLI, but were born into a family with a positive history of SLI (FH+). No study to date has examined the pattern of affectance in families of children ascertained at such a young age. In addition, the ratio of boys to girls born into such families was investigated, as previous studies have suggested alterations in the expected gender ratios. Consistent with prior research, SLI was found to aggregate in families; the average affectance rate in FH+ families was 32%, with significantly more boys (41%) reported as having SLI than girls (16%). A comparison of FH+ and control families (FH-) on sociodemographic factors and medical history revealed differences in the overall rate of autoimmune diseases; FH+ families reported a significantly higher incidence (35%) compared to FH- families (9%). Finally, the 3-year language abilities of a subset of 32 children from FH+ families were compared with those of 60 children from FH- families. Children from FH+ families scored significantly lower on standardized measures of language and were more likely to fall below the 16th percentile (28%) than children from FH- families (7%). These results provide converging evidence that children from FH+ families are indeed at greater risk of developing language delay compared to children from control families. (+info)
Difference of signal change by a language task on autistic patients using functional MRI.
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OBJECTIVE: Cerebral function with a language task was evaluated by functional magnetic resonance imaging (MRI), and the differences of activated pattern and signal changes were compared between autistic patients and normal controls. METHODS: Ten autistic and ten normal subjects were tested by fMRI with a language task requiring the attribution of complex mental states. Activation maps analyzed between two groups were generated and the asymmetry indexes calculated by the quotient of activated pixels of the right frontal lobe divided by those of the left frontal lobe were statistically compared by unpaired t-test. RESULTS: Both the autistic and the normal subjects showed activation at the bilateral prefrontal cortical areas and the ventral occipito-temporal regions. However, the autistic patients demonstrated more activation at the right frontal lobe than the normal controls. Thus it was considered that in the autistic patients the right-hemisphere was more dominant for the language task than that of the normal controls. The result is consist to the theory that autism is related to early left-hemisphere dysfunction. CONCLUSIONS: We considered that fMRI may be a useful non-invasive method to evaluate the cerebral functional abnormality in autistic patients. (+info)
Separable effects of semantic priming and imageability on word processing in human cortex.
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Understanding the neural representation of semantic concepts is at the core of understanding human knowledge and experience. Competing cognitive theories suggest that these neural representations are based on either a unitary semantic code or on multiple semantic codes. We contrasted these theories using event-related fMRI in a semantic priming study. Pairs of words were presented that were either semantically related or unrelated and were either high or low imageable. The unitary view predicts that there should be little or no difference between neural activity evoked by high and low imageable words when presented in a related context, but large differences in neural activity when there is an unrelated context. In contrast to this view, we provide evidence for functionally and anatomically separable effects of context and imageability in human cortex, suggesting that semantic knowledge consists of multiple representational codes. (+info)
A new interference score for the Stroop test.
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A New interference calculation method for the Stroop test was developed based upon a neuropsychological model of the suppression of word reading in favor of color naming. Polynomial regression equations show a significant relationship between word reading and the New interference score that closely fits the underlying prediction of the New model, while the Golden [Stroop Color and Word Test, Stoelting Co., IL, Wood Dale, 1978] model (Old) produces only a random relationship. Constructs of developmental maturation and lateralized brain damage are supported by the New but not the Old method. The New compared to the Old method also gives a significant reduction in scores in a small sample of demented patients. It would be advisable to use this New model in both cognitive and neuropsychological comparisons of different lesions or different stimulus and response demands. The New model will also help promote finer clinical inferences when an understanding relative to the patient's own baselines is necessary. (+info)
Semantic memory and verbal working memory correlates of N400 to subordinate homographs.
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N400 is an event-related brain potential that indexes operations in semantic memory conceptual space, whether elicited by language or some other representation (e.g., drawings). Language models typically propose three stages: lexical access or orthographic- and phonological-level analysis; lexical selection or word-level meaning and associate activation; and lexical integration, sentence- and discourse-level operations. The exact stage that N400 reflects is unknown, although opinion favors lexical integration over lexical selection. Surprisingly, little research has assessed relationships between neuropsychological measures of semantic memory fund of information or verbal working memory capacity and N400. Subjects performed a homograph disambiguation comprehension task with minimal working memory load. Short sentences read: The noun was adjective/verb. The nouns were either homographs or unambiguous. The adjective/verb was disambiguating for the homograph, and congruent or incongruent for the unambiguous noun. The primary noun of interest was the subordinate homograph. Comprehension of the subordinate meaning should correlate with semantic memory stores, reflecting greater knowledge. If N400 primarily reflects lexical access operations, it should also correlate with measures of semantic knowledge. If N400 reflects lexical integration, it should correlate with measures of working memory capacity. Comprehension errors were associated with semantic memory stores, but not working memory capacity. N400 was related to working memory capacity, but not semantic knowledge, suggesting that N400 primarily reflects late-stage working memory operations. N400 to subordinate disambiguating words was larger with greater working memory capacity, and thus may index the absolute capacity of working memory rather than difficulty in contextual integration. (+info)