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Computational principles of working memory in sentence comprehension.

Understanding a sentence requires a working memory of the partial products of comprehension, so that linguistic relations between temporally distal parts of the sentence can be rapidly computed. We describe an emerging theoretical framework for this working memory system that incorporates several independently motivated principles of memory: a sharply limited attentional focus, rapid retrieval of item (but not order) information subject to interference from similar items, and activation decay (forgetting over time). A computational model embodying these principles provides an explanation of the functional capacities and severe limitations of human processing, as well as accounts of reading times. The broad implication is that the detailed nature of cross-linguistic sentence processing emerges from the interaction of general principles of human memory with the specialized task of language comprehension.

Attention↗

Effect of vagus nerve stimulation on creativity and cognitive flexibility.

OBJECTIVE: The purpose of this study was to determine whether vagus nerve stimulation influences cognitive flexibility and creativity. METHODS: Ten subjects, in whom vagus nerve stimulators had been implanted for the treatment of intractable seizures, performed tasks that assessed cognitive flexibility (solving anagrams), creativity (Torrance Test), and memory (Hopkins Verbal Learning Test) during actual and sham vagus nerve stimulation. RESULTS: Vagus nerve stimulation impaired cognitive flexibility and creativity, but these results could not be explained by the induction of a general encephalopathy because VNS did not impair learning and improved retention. CONCLUSIONS: The means by which vagus nerve stimulation impairs cognitive flexibility and creative thinking is probably related to increased activity of the locus coeruleus-central adrenergic system that increases the signal-to-noise ratio and improves the brain's ability to attend to sensory input, but decreases its ability to recruit large-scale networks.

Adult↗

The effects of propranolol on cognitive function and quality of life: a randomized trial among patients with diastolic hypertension.

PURPOSE: We sought to determine whether propranolol has adverse effects on cognitive function, depressive symptoms, and sexual function in patients treated for diastolic hypertension. SUBJECTS AND METHODS: We performed a placebo-controlled trial among 312 men and women, 22 to 59 years of age, who had untreated diastolic hypertension (90 to 104 mm Hg). Patients were randomly assigned to treatment with propranolol (80 to 400 mg/day) or matching placebo tablets. Thirteen tests of cognitive function were assessed at baseline, 3 months, and 12 months. Five tests measured reaction time to, or accuracy in, interpreting visual stimuli; one test measured the ability to acquire, reproduce, and change a set of arbitrary stimulus-response sets; and seven tests measured memory or learning verbal information. Depressive symptoms and sexual function were assessed by questionnaires at baseline and 12 months. RESULTS: There were no significant differences by treatment assignment for 11 of the 13 tests of cognitive function at either 3 or 12 months of follow-up. Compared with placebo, participants treated with propranolol had slightly fewer correct responses at 3 months (33 +/- 3 [mean +/- SD] versus 34 +/- 2, P = 0.02) and slightly more errors of commission at 3 months (4 +/-5 versus 3 +/- 3, P = 0.04) and at 12 months (4 +/- 4 versus 3 +/- 3, P = 0.05). At 12 months, depressive symptoms and sexual function and desire did not differ by treatment assignment. CONCLUSIONS: Treatment of hypertension with propranolol had limited adverse effects on tests of cognitive function that were of questionable clinical relevance, and there were no documented adverse effects on depressive symptoms or sexual function. Selection of beta-blockers for treatment of hypertension should be based on other factors.

Adrenergic beta-Antagonists↗

Benefits of off-pump bypass on neurologic and clinical morbidity: a prospective randomized trial.

BACKGROUND: Neurologic and clinical morbidity after coronary artery bypass grafting (CABG) can be significant. By avoiding cardiopulmonary bypass, off-pump CABG (OPCAB) may reduce morbidity. METHODS: Sixty patients (30 CABG and 30 OPCAB) were prospectively randomized. Neurocognitive testing was performed before the operation and 2 weeks and 1 year after the operation. Neurologic testing to detect stroke and (99m)Tc-HMPAO whole-brain single photon emission computed tomography scanning to assess cerebral perfusion were performed before the operation and 3 days afterward. Bilateral middle cerebral artery transcranial Doppler scanning was performed intraoperatively to detect cerebral microemboli. All examiners were blinded to treatment group. Clinical morbidity and costs were compared. RESULTS: Coronary artery bypass grafting was associated with more cerebral microemboli (575 +/- 278.5 CABG versus 16.0 +/- 19.5 OPCAB (median +/- semiinterquartile range) and significantly reduced cerebral perfusion after the operation to the bilateral occipital, cerebellar, precunei, thalami, and left temporal lobes (p < or = 0.01). Cerebral perfusion with OPCAB was unchanged. Compared with base line, OPCAB patients performed better on the Rey Auditory Verbal Learning Test (total and recognition scores) at both 2 weeks and at 1 year (p < or = 0.05), whereas CABG performance was statistically unchanged for all cognitive measures. Patients who underwent CABG had more chest tube drainage (1389 +/- 1256 mL CABG versus 789 +/- 586 mL OPCAB, p = 0.02) and required more blood (3.9 +/- 5.8 U CABG versus 1.2 +/- 2.2 U OPCAB, p = 0.02), fresh frozen plasma (3.0 +/- 6.0 U CABG versus 0.5 +/- 2.2 U OPCAB, p = 0.03), and hours of postoperative use of dopamine (16.3 +/- 21.2 hours CABG versus 7.3 +/- 9.7 hours OPCAB, p = 0.04). These differences culminated in higher costs for CABG ($23,053 +/- $5,320 CABG versus $17,780 +/- $4,390 OPCAB, p < 0.0001). One stroke occurred with CABG, compared with none with OPCAB (p = NS). One OPCAB patient died because of a pulmonary embolus (p = NS). CONCLUSIONS: Compared with CABG, OPCAB may reduce neurologic and clinical morbidity as well as cost.

Aged↗

Outcome 3 to 5 years after moderate to severe traumatic brain injury.

OBJECTIVE: To investigate neuropsychologic, emotional, and functional status and quality of life (QOL) 3 to 5 years after moderate to severe traumatic brain injury (TBI). DESIGN: Observational cohort. SETTING: Level I trauma center. PARTICIPANTS: Consecutive adult admissions with TBI involving intracranial abnormalities, prospectively followed up for 3 to 5 years, with 80% follow-up. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Neuropsychologic functioning (Paced Auditory Serial Addition Test, California Verbal Learning Test), emotional status (Center for Epidemiologic Studies Depression Scale, Brief Symptom Inventory), functional status (Functional Status Examination, Glasgow Outcome Scale, Medical Outcomes Study 36-Item Short-Form Health Survey, employment), and perceived QOL. RESULTS: Significant functional limitations were observed in all areas. Recovery to preinjury levels ranged from 65% of cases in personal care to approximately 40% in cognitive competency, major activity, and leisure and recreation. Brain injury severity, measured by the modified Abbreviated Injury Scale, related to functional status and neuropsychologic functioning, but not to emotional or QOL measures. Length of impaired consciousness appeared to contribute to outcome more than did anatomic lesions. CONCLUSIONS: The results provide representative estimates of long-term morbidity in patients with TBI involving intracranial lesions. The magnitude of morbidity was high. Although direct costs of TBI have received the most attention, the long-term consequences and their cost implications are much larger, unfold over time, and are borne by the survivors, their families, and the public subsidy system.

Activities of Daily Living↗

Is postural control associated with mental functioning in the persistent postconcussion syndrome?

OBJECTIVE: To investigate whether balance is associated with mental functioning after mild traumatic brain injury (MTBI). DESIGN: Experimental two-group design. SETTING: Outpatient rehabilitation department. PATIENTS AND OTHER PARTICIPANTS: From a consecutive sample of referred MTBI patients, 15 subjects who complained of imbalance were included (8 men and 7 women, age 35.9+/-8.6yrs). Subjects with detectable neurologic impairments were excluded. Twenty healthy control subjects of the same age group also were tested. MAIN OUTCOME MEASURES: In both groups, a force platform recorded center-of-pressure (CP) fluctuations during standing and weight shifting in different conditions. For the patients, attention and mental speed were assessed with the Symbol-Digit Substitution Test of the Wechsler Adult Intelligence Scale (Dutch version), verbal learning and memory were assessed with the 15-Words Test, and emotional distress was assessed with the Symptom Checklist-90. RESULTS: Compared with controls, patients showed an overall increase of 60% in CP velocity and an overall weight-shifting speed 25% slower (p < .005), indicating static and dynamic postural instability. Only performance on the Symbol-Digit Substitution Test was associated with both static and dynamic balance (p < .02), giving an explained variance of over 40%. CONCLUSION: The results indicate a possible association of balance with cognitive performance but not with emotional well-being after MTBI, suggesting an organic rather than a functional cause of postural instability. Further research is needed to assess the possible clinical implications.

Adult↗

Further exploration memory bias in compulsive washers.

The aim of the present study was to replicate Radomsky and Rachman's findings on memory bias in obsessive-compulsive disorder (OCD), using the same procedure but an increased sample size, more specific control groups, and a full analysis of contamination attribution data. Sixteen OCD-washers, 16 OCD-checkers, 16 social phobic patients and 16 non-anxious controls were presented with 50 'clean' or 'dirty' objects. After this incidental encoding phase, participants were asked to freely recall the objects, to rate their anxiety when almost touching each object, and, finally, to attribute each object to one of the two contamination conditions ('clean' or 'dirty'). Verbal episodic memory was also assessed with the California Verbal Learning Test. The results indicate that, contrary to Radomsky and Rachman's findings, OCD-washers did not differ from the other participants in their memory for 'clean' and 'dirty' objects. However, the OCD-washers recalled more accurately the 'dirty' source of contamination than the 'clean' source. This result was specific to the OCD-washers, and suggests a memory bias for contextually threatening information. The differences between our findings and those published by Radomsky and Rachman's are discussed.

Adult↗

Patterns of cortical activity and memory performance in Alzheimer's disease.

BACKGROUND: Declarative memory changes are the hallmark of Alzheimer's disease, although their functional neuroanatomy is not restricted to a single structure. Factor analysis provides statistical methods for evaluating patterns of cerebral changes in regional glucose uptake. METHODS: Thirty-three Alzheimer's patients and 33 age- and gender-matched control subjects were studied with magnetic resonance imaging and positron emission tomography with [(18)F] deoxyglucose. During the tracer-uptake period, subjects performed a serial verbal learning task. Cortical activity was measured in 32 regions of interest, four in each lobe on both hemispheres. RESULTS: Factor analysis with varimax rotation identified seven factors explaining 80% of the variance ("parietal cortex," "occipital cortex," "right temporo-prefrontal areas," "frontal cortex," "motor strip," "left temporal cortex," and "posterior temporal cortex"). Relative to control subjects, Alzheimer's patients showed significantly reduced values on the factors occipital cortex, right temporo-prefrontal areas, frontal cortex, and left temporal cortex. The factor temporo-prefrontal areas showed large differences between patients with good and poor performance, but little difference when control subjects were similarly divided. CONCLUSIONS: Findings suggest that Alzheimer's disease is characterized by altered patterns of cortical activity, rather than deficits in a single location, and emphasize the importance of right temporo-prefrontal circuitry for understanding memory deficits.

Aged↗

Neurocognitive correlates of the COMT Val(158)Met polymorphism in chronic schizophrenia.

BACKGROUND: Neurocognitive deficits are recognized as a cardinal feature of schizophrenia, but the determinants of these deficits remain unknown. Recent reports have suggested that a functional polymorphism, Val(158)Met in exon III of the catechol-O-methyltransferase gene, shares approximately 4% variance with performance on the Wisconsin Card Sorting Test. These findings led to suggestions that the catechol-O-methyltransferase polymorphism may exert its effects by modulating prefrontal dopamine function, but few other neurocognitive measures have been examined, leaving open questions about phenotypic specificity. METHODS: We examined the effects of the catechol-O-methyltransferase Val(158)Met polymorphism in 58 individuals with chronic schizophrenia who completed a battery of 15 neurocognitive tests, which were reduced to four reliable neurocognitive domain scores. We examined the effects of genotype on these four domains and on global neurocognitive ability. RESULTS: The Met allele was associated with better performance in the Processing Speed and Attention domain, but not with other domain scores measuring executive and visuoperceptual functions, declarative verbal learning and memory, simple motor ability, or global neurocognitive function. Genotype shared approximately 11% of variance with Processing Speed and Attention scores, and approximately 2% of variance with Wisconsin Card Sorting Test scores. CONCLUSIONS: The findings provide independent support for the hypothesis that the catechol-O-methyltransferase Val(158)Met polymorphism influences neurocognitive function in schizophrenia, and suggest that the functional effects may be expressed on measures of Processing Speed and Attention. This information may prompt reconsideration of the "prefrontal dopamine" hypothesis and invites examination of a broader range of effects in efforts to refine the neurocognitive phenotype that is most relevant to variation in catechol-O-methyltransferase expression.

Adult↗

Neuropsychological performance in schizotypal personality disorder: evidence regarding diagnostic specificity.

BACKGROUND: Individuals with schizotypal personality disorder (SPD) share cognitive deficits with schizophrenic patients, suggesting that these deficits represent a core feature of the schizophrenia spectrum. We investigated the neuropsychological profile in SPD patients compared with two comparison groups: healthy volunteers (HV) and patients who met criteria for another non-schizophrenia spectrum personality disorder (NSS). METHODS: We tested 48 DSM-III-R SPD patients, 22 NSS and 32 HV on a neuropsychologic battery that included the California Verbal Learning Test (CVLT), Trail Making A and B, the DOT test of working memory, the Stroop Color-Word Interference, the Paced Auditory Serial Addition Test (PASAT), the Wechsler Memory Scale Visual Reproduction Test (WMSV-R), and the Wechsler Adult Intelligence Scale vocabulary and block design. RESULTS: Normative standards for performance were created using the HV group. SPD patients performed significantly worse compared with HVs; specifically, SPD patients demonstrated impaired performance on the PASAT and the WMSV-R immediate and delayed recall compared to HV. Moreover, SPD patients were impaired in the PASAT and the WMSV-R immediate condition compared with the NSS group. The NSS patients did not differ from HV on any of the cognitive tasks. The interpersonal factor of the schizotypal symptoms inversely correlated with the PASAT score (r = -.32, p <.006). CONCLUSIONS: Compared with HVs, SPD patients demonstrate modest cognitive impairment. These differences reached statistical significance for the PASAT (an auditory working memory task), and the WMSV-R immediate and delayed recall (a learning-recall test). In contrast, performance of NSS patients did not differ from that of HVs. The types of deficits observed in SPD patients are qualitatively similar to but milder than those seen in patients with schizophrenia.

Adult↗

Relationships between neuropsychological and oculomotor measures in schizophrenia patients and normal controls.

Establishing the relationship between oculomotor and neuropsychological impairments might facilitate a more coherent description of schizophrenia-associated neurocognitive deficits. Therefore, we assessed several aspects of neuropsychological and oculomotor function in 25 medicated schizophrenia patients and 24 age-matched controls. Neuropsychological tasks included the Wisconsin Cart Sort Test (WCST), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test, and finger tapping speed. Oculomotor functions assessed included smooth pursuit, initiation of smooth pursuit, predictive pursuit, fixation, visually guided saccades, remembered saccades, and antisaccades. Among the schizophrenia patients, predictive pursuit performance correlated significantly with finger tapping (dominant hand), TMT (both parts), and one WCST measure (categories completed). The only other significant correlation among the schizophrenia patients was between antisaccade performance and part A of the TMT. Perseverative errors during the WCST and antisaccade performance were the only measures significantly correlated among the normals. Closely related neurocognitive deficits may be responsible for impairments in TMT, WCST, predictive pursuit, and antisaccade performance in schizophrenia.

Adult↗

Different components in word-list forgetting of pure amnesics, degenerative demented and healthy subjects.

This study investigated the contribution of different components of the serial position curve to the accelerated forgetting rate displayed by amnesic and degenerative demented patients in word-list recall. For this purpose, we analyzed immediate and 15 min delayed recall performances on Rey's 15-word learning task of 16 pure amnesic, 15 Alzheimer's demented and 81 healthy subjects. Results documented that in all groups most forgetting occurred at the expense of terminal items of the word list. Nevertheless, both amnesic and demented patients showed a disproportionately larger memory loss on the recent part of the serial position curve than healthy subjects. Finally, amnesics (but not AD patients) suffered from a significantly larger forgetting rate for primacy items than normal controls. These data demonstrate that a critical deficit in memory disordered patients is represented by a failure in transferring information from a transitory memory status to a more durable storing condition. At least in amnesic patients, our results also suggest "true" long-term forgetting, presumably due to decay or to the intervening inaccessibility of previously stored memory representations.

Adult↗

Memory for what it is and memory for what it means: a single case of Korsakoff's amnesia.

A single case of Korsakoff's syndrome, showing classic circumscribed amnesia on traditional neuropsychological tests, performed a number of learning tasks previously used in primates to demonstrate the different anatomical basis of memory systems used to learn about the properties of objects or to learn about rules of responding. The patient (CJ) performed in a manner very similar to lesioned monkeys in that he could learn evaluative tasks (e.g. a red object is nice), but not rule based tasks (e.g. a red object means go left). In consequence CJ learned an object discrimination task in a manner qualitatively different from a group of non-amnesic controls. Although he could not learn rule based tasks, CJ could perform them once he had been given the rule. Detailed analysis of learning showed that CJ could choose the object he had chosen previously, but could not say where it had been or whether he had been rewarded. Furthermore he could recognise a word as familiar, while not remembering its source. We propose that he has a specific impairment in a memory system concerned with the representation of the signification of objects in particular contexts, while representation of the properties of objects remains intact.

Alcohol Amnestic Disorder↗

Recall and recognition memory in Parkinson's disease.

This study is concerned with recall and recognition memory in patients with Parkinson's disease. The results show that the Parkinson group was significantly impaired on tests of free recall compared to a group of age matched controls. By contrast, when given tests of recognition memory for the same items their performance was practically identical. In recall, significant main effects are reported for serial position and list presentation but no qualitative differences were observed between the two groups on these measures, both of which showed a primacy and recency effect. However, the control subjects recalled significantly more words in their original order of presentation than the patient group, a difference which appears to have occurred at the level of input. It was concluded that although the patient group was able to adopt and use similar strategies to the control subjects, they were less efficient in using these, a difficulty which was attributed to limited capacity due to mental slowness.

Aged↗

Spontaneous recovery of impaired memory span: does comprehension recover?

We have previously described a patient, T.B., who had a memory span of two digits and a sentence span of three words. He showed no evidence of effects of either phonological similarity or word length on span and his deficit was interpreted as reflecting the impaired functioning of the phonological loop component of working memory. Analysis of his language comprehension indicated normal processing of short sentences, together with a marked deficit in understanding long sentences, whether these were presented visually or auditorily (Baddeley and Wilson, 1988). When re-tested after several years, T.B.'s memory span had increased to nine digits, and showed clear effects of phonological similarity and word length. His performance on a series of language comprehension tests indicated a complete recovery, although he continued to show impairment on two tests of phonological awareness. These results are consistent with the proposed link between phonological working memory and language comprehension. In addition, they indicate a dissociation between short-term phonological memory and phonological awareness.

Awareness↗

Memory disorders in Alzheimer's disease and the organization of human memory.

The Squire and Zola-Morgan parallel organization model of the memory and the Tulving hierarchical model were developed mainly through the study of amnesic patients. The predictions of these two models are different, the first being more open to double dissociations and less restrictive than the second. Alzheimer's Disease is characterized by a differential impairment of the memory systems and by an interindividual variability which may take the form of dissociations between preserved and disturbed abilities in some patients. The objective of this study was to use the memory dysfunctions of patients with AD to test the validity of the two models. Analysis of the group data provided an average profile of memory disturbance consistent both with much of the data given in AD literature and with the two models. Using a multiple single-case strategy, we demonstrated several simple dissociations which are for the greater part compatible with the two models. Two of the dissociations underline the limits of the Tulving model, which otherwise accounts for a lot of results. The study supports the relevance of AD for the understanding of the cognitive architecture of the human memory.

Aged↗

Hormone replacement therapy in postmenopausal women with Alzheimer's disease: a randomized, prospective study.

OBJECTIVE: To compare the therapeutic efficacy of hormone replacement therapy (HRT) and tacrine in Alzheimer's disease. DESIGN: Six-month, randomized, open-label study. SETTING: University hospital. PATIENT(S): Fifty-five women with mild to moderate Alzheimer's disease were randomly assigned to tacrine (n = 26) or HRT (n = 29). INTERVENTION(S): In the tacrine group, an initial dose of 40 mg/day was increased up to 160 mg/day. In the HRT group, conjugated equine estrogen was given to patients without uteri (n = 3) or together with micronized progesterone to patients with uteri (n = 26). MAIN OUTCOME MEASURE(S): Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test, Boston Naming Test, Controlled Oral Word Association Test, Geriatric Depression Scale, Hamilton Depression Scale (HDS), and Instrumental Activities of Daily Living (IADL). RESULT(S): Thirty-three patients who completed the outcome measures (tacrine, 17; HRT, 16) were included in an intent-to-treat analysis. The results did not differ between groups except for IADL, which rated more highly after HRT. Apolipoprotein E genotype effects were assessed. MMSE and HDS scores were improved after tacrine treatment in epsilon 4-negative patients. CONCLUSION(S): Overall efficacy of estrogen plus progesterone combination was similar to tacrine for cognition and mood, but greater for ADL. In epsilon 4-negative patients, tacrine is preferable for cognition and mood.

Alzheimer Disease↗