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Functionally activated brain imaging (O-15 PET and fMRI) in the study of learning and memory after traumatic brain injury.

Advances in functional imaging technology and cognitive neuropsychology have resulted in paradigms in which participants can perform cognitive tasks during functional image acquisition. We will discuss the application of two approaches (oxygen-15 positron emission tomography and functional magnetic resonance imaging) that have recently been used to examine components of learning and memory following traumatic brain injury (TBI). Activated functional brain imaging findings that we will discuss may suggest possible functional reallocation and reorganization of brain substrates involved in verbal learning and memory following brain injury. The findings also are clearly in line with other research that indicates a prominent role for the frontal lobes in learning and memory functioning, and support the concept of distributed neural networks for memory-related functions, cognitive load, and the potential for examining brain re-organization after injury.

Brain Injuries↗

Electrical brain activity and response to olanzapine in schizophrenia: a study with LORETA images of P300.

The aim of this study was to evaluate the change in the distribution for the P300 generator, as demonstrated by Low Resolution Electromagnetic Tomography (LORETA) images, in patients with schizophrenia during treatment with olanzapine. Data were obtained from five right-handed patients treated with olanzapine for 6 months. Five right-handed normal volunteers also participated in the study. LORETA images of P300 in response to the odd-ball auditory discrimination task revealed a left dominant lateralized high current source density in the temporal lobes in all control subjects. Although this pattern of brain activation was not evident in patients at baseline, 6-month treatment with olanzapine recovered the left dominant pattern of the electrical density in the temporal regions, such as the Heschl gyrus, and improved performance on a test of verbal learning and memory. Scores of the Brief Psychiatric Rating Scale and the Global Assessment of Functioning Scale also improved during treatment. These results provide the first suggestion that enhancement of verbal memory and the functional status by treatment with some antipsychotic drugs may be associated with modulations of the anatomical configuration of electrical brain activity in patients with schizophrenia.

Adult↗

Frontal fluency and memory functioning among multiple sclerosis patients in Hong Kong.

THE PRIMARY OBJECTIVE: The frontal fluency and memory functioning among Chinese patients with multiple sclerosis (MS) were investigated in order to identify cross-cultural differences in the impact of MS on cognitive functions. RESEARCH DESIGN, METHODS AND PROCEDURES: Cognitive profiles of 11 Chinese patients with MS were compared to that of their corresponding matched healthy volunteers. Since MS is of low prevalence in Hong Kong, the present sample is considered representative of patients with MS in the Hong Kong Island district. Frontal fluency and memory measures, namely Chinese Rey Auditory Verbal Learning Test, Aggie Figure Learning Test, Word Fluency Test (fruit/vegetable and animal categories), and Design Fluency Test were administered one-on-one to the participants to evaluate their cognitive functions along the verbal-non-verbal axis. MAIN OUTCOMES AND RESULTS: Results indicated that patients with MS performed poorer on non-verbal, but not verbal measures in this study relative to their healthy counterparts. These deficits cannot be explained by clinical or demographic variables. CONCLUSIONS: These findings further support the speculation of a verbal-non-verbal distinction for cognitive deficits in patients with MS in Hong Kong.

Adult↗

Methamphetamine dependence is associated with neurocognitive impairment in the initial phases of abstinence.

This study documented the association between neurocognitive impairment and methamphetamine dependence in a sample of 27 methamphetamine-dependent individuals who achieved 5 to 14 days of continuously monitored abstinence and in 18 control subjects. Methamphetamine-dependent individuals performed significantly worse than control subjects on neurocognitive measures sensitive to attention/psychomotor speed, on measures of verbal learning and memory, and on executive systems measures sensitive to fluency. These findings are the first to demonstrate that methamphetamine dependence is associated with impairments across a range of neurocognitive domains in a sample of users whose abstinence was continuously monitored with the use of urine screening.

Adult↗

Attention and memory functioning among pediatric patients with medulloblastoma.

OBJECTIVE: To test the hypotheses that memory and attention deficits are prevalent in survivors of childhood medulloblastoma (MB) and that these deficits are associated with problems with academic achievement. METHODS: The medical charts of 38 child survivors of MB, who were administered the California Verbal Learning Test, Child Version (CVLT-C), Conners' Continuous Performance Test (CPT), and the Wechsler Individual Achievement Test (WIAT) as part of a comprehensive neurocognitive test battery, were retrospectively reviewed. RESULTS: Although no significant verbal memory deficits were found, 8 of 11 CPT variables were significantly below the standardization mean (p < or = .01). Additionally, stepwise regression analyses found that increased omission errors were significantly associated with lower reading and math performance (p < or = .01). CONCLUSIONS: These findings confirm previous reports of attention deficits among survivors of MB and provide a better understanding of how the dysfunction of particular attentional substrates (e.g., perceptual sensitivity, response bias) may result in learning problems in this population.

Adolescent↗

Piracetam as an aid to learning in dyslexia. Preliminary report.

Sixteen male dyslexic children were seen again when adults and matched with 14 student volunteers for a 21-day trial of piracetam. It was found, using a double-blind cross-over technique, that dyslexics significantly increased their verbal learning by 15.0% and students by 8.6% (over and above their placebo increase).

Child↗

Memory and learning in pediatric bipolar disorder.

OBJECTIVE: To test the hypothesis that patients with pediatric bipolar disorder (PBPD) would demonstrate impairment relative to diagnosis-free controls of comparable age, gender, and IQ on measures of memory functioning. METHOD: The authors administered a battery of verbal and visuospatial memory tests to 35 outpatients with PBPD and 20 healthy controls who participated as volunteers in this study. Groups did not differ on age, gender, or IQ. RESULTS: Consistent with findings in adults with BPD, patients with PBPD performed more poorly than controls on measures of verbal learning/memory and delayed facial recognition memory. Impaired memory was particularly evident in patients with comorbid PBPD/attention-deficit/hyperactivity disorder or acute mood symptoms. CONCLUSIONS: These findings suggest that deficits in verbal learning and memory, as well as some aspects of visuospatial memory, characterize patients with narrow phenotype PBPD. Further research is needed, however, to clarify the roles of comorbid attention-deficit/hyperactivity disorder and acute mood state in the emergence of these deficits. Given the apparent continuity in memory dysfunction between adult BPD and narrow phenotype PBPD, research aimed at elucidating underlying neural mechanisms for this set of deficits is warranted.

Bipolar Disorder↗

Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial.

CONTEXT: Postmenopausal estrogen therapy has been posited to have some beneficial effects on aging processes, but its use has risks. Isoflavones, estrogenlike compounds naturally occurring in plant foods, might confer positive effects with fewer adverse effects. OBJECTIVE: To investigate whether soy protein with isoflavones improves cognitive function, bone mineral density, and plasma lipids in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial of 202 healthy postmenopausal women aged 60 to 75 years, recruited from a population-based sample in the Netherlands, conducted between April 2000 and September 2001. INTERVENTION: Participants were randomly assigned to receive 25.6 g of soy protein containing 99 mg of isoflavones (52 mg genistein, 41 mg daidzein, and 6 mg glycetein or total milk protein as a powder on a daily basis for 12 months. MAIN OUTCOME MEASURES: Cognitive function was assessed using the following instruments: dementia, Mini-Mental State Examination; memory, Rey Auditory Verbal Learning Test, immediate recall, delayed recall, and recognition, the Digit Span forward and reversed, and the Doors test; complex attention tasks, Digit Symbol Substitution and Trailmaking, A1, A2, and B; and verbal skills, Verbal Fluency A and N, animals and occupations, and the Boston Naming Task. Bone mineral density of the hip and lumbar spine was assessed using dual-energy x-ray absorptiometry scanning. Lipid assessment included lipoprotein(a), total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides. RESULTS: A total of 175 women completed the baseline and at least 1 postintervention analysis and were included in the modified intent-to-treat analysis. Adherence was good (median plasma genistein levels, 17.2 and 615.1 nmol/L for placebo and soy group, respectively). Cognitive function, bone mineral density, or plasma lipids did not differ significantly between the groups after a year. CONCLUSION: This double-blind randomized trial does not support the hypothesis that the use of soy protein supplement containing isoflavones improves cognitive function, bone mineral density, or plasma lipids in healthy postmenopausal women when started at the age of 60 years or later.

Bone Density↗

The modified Location Learning Test: norms for the assessment of spatial memory function in neuropsychological patients.

This study examines the applicability of the modified Location Learning Test (mLLT) as a test of spatial memory in neuropsychological patients. Three groups of participants were examined: stroke patients, patients with diabetes mellitus and healthy participants (N=411). Three error measures were computed, the Total Score (index of overall performance), the Learning Index (the learning curve over subsequent trials) and the Delayed Recall Score, measuring decay over time. The Learning Index was the most sensitive measure, showing differences between the three groups as well as lateralization effects within the stroke group. Also, the mLLT correlated significantly with the Rey Auditory Verbal Learning Test, as well as with age and education level. Regression-based normative data were computed based on the healthy participants. In all, the mLLT appears to be a sensitive and valid test for the detection of object-location memory impairments in clinical groups.

Adolescent↗

Amnesic and anxiolytic effects of intravenous diazepam in dental anxiety.

The effects of intravenous administration of diazepam (average 20 mg) on learning, performance and mood were assessed in dental patients. These patients required sedation due to excessive anxiety in a dental situation, or because they were to undergo stressful surgery. On a verbal learning task, subjects recalled and recognized significantly fewer words from a list presented after drug administration than from a list presented prior to drug administration, when tested at the end of the treatment period. When tested after treatment, subjects recognised few of a series of picture postcards that had been presented to them during the course of treatment. Subjects showed no significant impairments after diazepam treatment on digit-symbol substitution, symbol copying or number cancellation tasks compared to pre-treatment scores; however, there was a small but significant reduction in the number of finger-taps made. Mood-rating scales showed significant increases in sedation and well-being after diazepam treatment compared to pre-treatment scores, and also a significant reduction in anxiety levels. This study shows that the amnesic effects of diazepam are present in a "real-life" stress situation.

Anti-Anxiety Agents↗

Neurocognitive and functional assessment of patients with brain metastases: a pilot study.

The outcome of patients with brain metastases is generally poor. Survival alone is not necessarily a good measure of clinical outcome. Measures of neurocognitive function and the impact of the disease and treatments on functional status also need to be considered. Although these parameters have been measured in patients with primary brain tumors, they have not been as thoroughly evaluated in patients with brain metastases. The Mini-Mental State Examination provides limited assessment of neurocognitive domains impaired in brain tumor patients. It is less sensitive to mild impairment, does not avoid memorized learning from repeat administration, and does not have validated alternative forms necessary for non-English speaking patients. To determine the feasibility of using a more comprehensive neurocognitive test battery, motor, verbal, executive, and daily functions were assessed in 30 patients with brain metastases. The test battery included the Hopkins Verbal Learning Tests, Controlled Oral Word Association Test, Grooved Pegboard Test, Trailmaking Tests A and B, and the Barthel Index. In this study, there was complete patient compliance, with average test completion time of 23 +/- 6 minutes. Despite high functional status, most patients demonstrated impairment in memory and fine motor domains. Neurocognitive test batteries can and should be used in patients with brain metastases enrolled in clinical trials.

Activities of Daily Living↗

[Memory complaints and memory deficits in healthy and depressed elderly individuals].

The objective of this study is: a) to determine if there is a relationship between memory complaints and depression and b) to compare actual verbal memory and memory complaints in depressed elderly patients and normal elderly individuals. The California Verbal Learning test (CVLT) was applied to measure memory performance. A questionnaire was used to evaluate complaints about memory. Depression was measured by the Beck Depression Inventory (BDI). The results show that depressive patients do not have deficits in verbal memory compared with normal aging individuals. There is an association between memory complaints and depressive symptoms. The depressive patients are significantly superior to the normal persons in memory complaints and depressive symptoms. The two groups are not different in objective measures of memory and learning tasks.

Aged↗

Improving recreational, residential, and vocational outcomes for patients with schizophrenia.

As Roder and colleagues propose, we have seen three eras in the development and refinement of social skills training for individuals with schizophrenia. In the 1960s, skills training relied on the use of operant conditioning, as exemplified by the token economy. Reinforcement contingencies succeeded in activating patients with negative symptoms and in improving their social behavior. Contemporary psychiatric rehabilitation can profit from the identification and use of reinforcers to motivate anergic individuals who lack insight to participate actively in community-based programs. During the second era, in the 1970s, social learning through modeling, coaching, role playing, and behavioral assignments was introduced into skills training. These techniques were used to improve nonverbal skills, such as eye contact, fluency of speech, gestures, and facial expression, as well as conversational skills, assertiveness, and emotional expressiveness. Intervention programs of the third and current era are incorporating cognitive methods into the skills training enterprise. For example, in the modules for training social and independent living skills developed and validated by Liberman and his colleagues at the University of California at Los Angeles (1), the deficits in attention, memory, and verbal learning often experienced by persons with schizophrenia are overcome by repetition, shaping of incremental behavioral improvements, video modeling, and feedback for galvanizing attention. Procedural learning techniques that do not rely on the brain capacities that mediate verbal awareness and insight are also used. In this month's Rehab Rounds column, Roder and his colleagues present another example of a skills training approach of the third era that includes elements of cognitive remediation. As autonomous offsprings of integrated psychological therapy (IPT), which was originally developed by Hans Brenner and Volker Roder and their colleagues at the University of Bern in Switzerland (2), the new programs address deficits in the residential, vocational, and recreational domains of community functioning. Overall, social skills training has been shown to be effective in the acquisition and maintenance of skills and their transfer to community life. Moreover, evidence is accumulating that structured and systematic skills training is more effective than other psychosocial treatments with which it has been compared, such as supportive group therapy and expressive modes of occupational therapy.

Activities of Daily Living↗

Performance of children with ADHD on tests sensitive to frontal lobe dysfunction.

The performances of 20 children with attention deficit hyperactivity disorder (ADHD) were compared with those of 20 matched normal controls on a battery of neuropsychological tests. The ADHD children exhibited impaired function in reading comprehension, verbal learning and memory, and on the Information, Arithmetic, Digit Span, Block Design, and Coding subtests of the Wechsler Intelligence Scale for Children-Revised, but they performed nearly normally on measures of verbal and design fluency and on the Wisconsin Card Sorting Test. The hypothesis that disturbances in frontal lobe function related to impulse control may be responsible for the cognitive impairments observed in ADHD was not supported. Inability to control and direct attention appears to be more central to the pathophysiology of this disorder.

Attention↗

Effects of haloperidol on recall and information processing in verbal and spatial learning.

1. Normal male subjects were tested with either a multi-trial word list learning test or a spatial analogue prior to administration of either 4 mg. or 10 mg. of oral haloperidol. Six hours after drug administration subjects who had previously received the verbal test were administered the spatial test, and vice versa, so for each test there was a no-drug control group, a group tested after receiving 4 mg. of haloperidol, and a group tested after a 10 mg. dose. 2. Both the verbal and spatial learning tests yield multidimensional measures of components of memory and learning, including measures sensitive to effort-demanding and more automatic information processing operations. 3. Results showed no differences for either test among the pre-drug control group and the 4 mg. and 10 mg. groups, with only one minor exception. 4. The lack of significant results cannot be attributed to insensitivity of the test instruments used, since previous studies have documented sensitivity to a number of clinical conditions and to aging. 5. Results have implications regarding clinical effects of haloperidol. A theory that links dopaminergic functioning with effortful information processing underlying memory and learning was not supported.

Adult↗

Correlations between verbal memory performance and electrocorticographically determined suppression of electrical brain activity in intracarotid amobarbital tests.

As a part of presurgical evaluation, bilateral intracarotid amobarbital procedures (IAPs) were performed in 42 patients (84 tests) with long-standing, medically intractable complex-partial seizures. During the IAPs, electrocorticographic (ECoG) recording was carried out via bilaterally implanted subdural electrodes. Five distinct patterns of suppression of electrical brain activity were observed: (1) an isoelectric line; (2) a burst-suppression pattern; (3) polyphasic waves; (4) high-voltage beta; and (5) low-voltage beta activity. Further, two types of specific reactions of the epileptic focus were detectable: (1) spike-burst-suppression patterns (SBS; 11 left; 7 right; 6 in both IAPs) and amobarbital-induced spikes (7 left; 4 right). ECoG suppression patterns as well as SBS and spike induction showed great variability in duration and overall occurrence. To determine the influence of these amobarbital-induced ECoG changes on results of IAP memory testing, performance in a verbal learning task was analyzed according to the ECoG patterns predominant during encoding. In left IAPs, it was found that SBS at the beginning of or during encoding had a significant negative effect on verbal memory. In right IAPs, verbal memory performance improved significantly with the decline of ECoG suppression. Hence, verbal memory performance in IAPs is significantly affected by specific ECoG suppression patterns and activation of the epileptic focus.

Adolescent↗

Impaired higher order implicit sequence learning on the verbal version of the serial reaction time task in patients with Parkinson's disease.

Although neuroimaging studies have strongly implicated basal ganglia involvement in implicit sequence learning, serial reaction time (SRT) studies with Parkinson's disease (PD) patients have yielded mixed results. The present research sought to examine the ability of people with PD to implicitly learn sequences with different sequential structures and to objectively assess explicit knowledge. A version of the SRT task that reduces motor demands was used to compare 19 patients with PD but not dementia and 37 matched controls. PD patients showed less implicit sequence-specific learning for both sequences and reduced response time improvement over sequential trials for the more complex sequence. A closer examination revealed that the deficit involved higher order sequential associations as well as the learning of pairwise information.

Aged↗