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The role of frontal and parietal cortex in cognitive processing: tests of spatial and sequence functions.

Normal monkeys and monkeys with resection of anterior frontal or posterior parietal cortex were trained to press a panel next to a green panel as a test of extrapersonal spatial orientation and to press a panel next to their own prior press as a test of personal spatial orientation. All monkeys also learned two sets of sequence problems in which the solutions were made independent of spatial location by randomly shifting the locations of the stimuli after each response within a trial. The Parietal Group was significantly impaired on the extrapersonal 'next-to' task but not the more difficult personal 'next-to' task. The Frontal Group was impaired on both the personal and the extrapersonal 'next-to' tasks but only when the relevant cues shifted spatial locations from trial to trial. The performance of the Parietal Group completely overlapped that of the Normal Group on the sequence problems regardless of the level of testing sophistication the monkeys had attained. In contrast, the Frontal Group demonstrated a significant impairment in learning sequences but only when the monkeys were naive. Once they became sophisticated they learned each sequence at a normal rate. Their poor performance was attributed to the lack of stability in the spatial location of the stimuli. The data support the view that a distinction between personal and extrapersonal spatial orientation is relevant to posterior parietal function but indicate that neither sequencing per se nor personal spatial orientation or spatial memory per se is dependent on intact frontal functioning. Rather, the frontal cortex is involved with a higher-order control essential to allow the monkey to perceive the reliable aspects of stimuli contained in a stimulus context full of unreliable noise and to further allow for flexible response pattern appropriate to the demands of a variable context.

Animals↗

Timeout as a reinforcer for errors in a serial position task.

After learning to press keys in a predetermined serial position sequence, with timeouts scheduled as a consequence of errors, monkeys developed stereotyped errors. As soon as a new trial started, the animals would make an error. On trial after trial, they pressed the same incorrect key at the first member of the sequence, even though they had previously learned the sequence. First-member errors occurred even when sequences of fully bright keys marking correct choices were presented. When timeout was eliminated as a consequence of one first-member error, subjects switched to an error that did produce the timeout. When all first-member errors failed to produce timeout the monkeys ceased responding. Both prefeeding and reduction in reinforcement density resulted in stereotyped errors occurring earlier in the session.

Journal Article↗

Implicit and explicit knowledge decay at different rates: a dissociation between priming and recognition in artificial grammar learning.

An experiment tested the common assumption that implicit and explicit knowledge are forgotten at different rates. In a training phase participants responded to sequences of letters generated by a finite-state grammar by pressing corresponding letters on a keyboard. A control group responded to randomized sequences. Participants were tested immediately following training and after intervals of seven and fourteen days. During each test participants responded to the letters of old and new sequences, and performed a concurrent recognition test. Priming was indexed by the time taken to respond to the sequences. In the immediate test both priming and recognition were substantially greater than the control group. In the delayed tests the level of priming remained unchanged but recognition had declined. The data indicate that priming and recognition decay at different rates, and are discussed with reference to both single and dual process models of memory.

Adult↗

The dual-task SRT procedure: fine-tuning the timing.

In the standard sequential reaction time study, subjects are presented with a repeating sequence of targets to which they must respond as rapidly as possible. With practice reaction times decrease, suggesting a learned ability to exploit the repeating patterns in the display. In a common variation, a second task is interposed, typically a tone-counting task in which subjects must keep track of the frequency with which particular tones occur. In the canonical experiment, these tones appear at varying times in the interval between the subjects' response to a target and the next target. Data are presented that show that this latter variable (the RSOA, response-secondary stimulus onset asynchrony) actually plays an important but previously hidden role in these experiments. A model based on an extension of the notion of the psychological refractory period is introduced to explain these findings.

Adult↗

Rate variables and automatized naming in developmental dyslexia.

The rate variable in rapid automatized naming (RAN) was investigated in 50 adolescent and 40 adult students with developmental dyslexia, in matched normal controls, and in learning-disabled students without reading difficulties. Visual stimuli depicting familiar colors and common objects were presented in isolation at three film speeds and three exposure times. Film speed and exposure time contributed as independent variables to error rate; and dyslexic subjects of both age groups made significantly more naming errors than controls. Dyslexic subjects also responded with longer naming latencies than controls when the same RAN stimuli were presented in a continuous sequential mode as a matrix of rows and columns. Naming latencies in the sequential presentation were highly correlated with naming errors in the film version. The implications of reduced naming rates for nongraphological stimuli in developmental dyslexia are discussed.

Adolescent↗

Development of a computer-based battery designed to screen adults for neuropsychological impairment.

The initial step in the development of a new computer-based neuropsychological testing system is described. A new hardware-software system and a screening battery consisting of an orientation task and five cognitive tests has been implemented. This novel screening battery is designed for use in identifying individuals among exposed groups who may require more extensive follow-up neuropsychological evaluation. Sophisticated, but currently available, and relatively inexpensive hardware and software technology are employed, introducing an improvement over existing computer-based batteries. Use of a digitized speech production device for producing instructions facilitates testing of illiterate subjects, use of auditory stimulus materials, and relatively easy translation of the testing instructions to other languages. Use of a pen-based notebook computer enables responding by the subject in a manner that is both natural and analogous to that used in existing paper-and-pencil testing instruments. Five neuropsychological tests were developed to cover a range of cognitive domains: 1) verbal list learning and recognition memory, 2) visual memory span, 3) conceptual and motor tracking, 4) psychomotor speed and accuracy, and 5) delayed verbal recognition. The screening instrument has been pilot-tested for feasibility of use among outpatients at an occupational medicine clinic and among community-dwelling older adults. This instrument is intended to provide a standardized efficient, cost-effective method for widespread use in occupational medicine and public health to detect and track subclinical neurotoxic effects and to prevent additional harmful exposure. Additional aspects of development of the computer-based testing system are discussed.

Adult↗

Verbal memory in schizophrenia: sex differences over repeated assessments.

There is conflicting evidence regarding the presence and direction of gender differences in verbal memory capacity in schizophrenia. We examined gender differences in verbal memory performance in schizophrenia and their interactions with repeated assessments and psychiatric symptoms. California Verbal Learning Test (CVLT) data were collected from 28 outpatients diagnosed with schizophrenia. The CVLT was administered on five occasions, 3 months apart. CVLT data were examined using repeated measures analyses, using maximum likelihood estimates, with Brief Psychiatric Rating Scale (BPRS) scores at assessments 1-5 as a time-varying covariate. There were significant main effects of time and gender, with scores improving over time, and women performing better than men. There was also a significant time by gender interaction. The BPRS covariate effect was not significant. Results are discussed in terms of implications for gender-informed approaches to rehabilitation treatments.

Adolescent↗

Cortico-striatal contributions to category learning: dissociating the verbal and implicit systems.

To better characterize the neuropsychological mechanisms of implicit and verbalizable category learning, the author studied weather prediction task (WPT) and information integration task (IIT) performance in patients with Parkinson's disease (PD) and healthy older and younger adults. Both older adults and patients with PD were impaired on the WPT, but only patients were impaired on the IIT, suggesting the 2 tasks rely on dissociable systems. Whereas the IIT appeared to rely on implicit processes, results suggest WPT classification depends on explicit processes. Awareness of underlying structure, hypothesis testing ability, and working memory capacity were all related to accuracy on the WPT but not the IIT. The variability commonly noted in WPT performance may reflect individual differences in hypothesis testing ability.

Adolescent↗

Mild memory impairment in healthy older adults is distinct from normal aging.

Mild memory impairment was detected in 28% of a sample of healthy community-dwelling older adults using the delayed recall trial of a word list learning task. Statistical analysis revealed that individuals with memory impairment also demonstrated relative deficits on other measures of memory, and tests of executive function, processing speed and global cognition, as measured by the CERAD and CogState batteries and CANTAB paired associate learning task. These relative deficits cannot be explained by age-related changes, education, intelligence, mood, health-related factors, or the individuals' ApoEepsilon4 status. Memory-impaired individuals (n = 30) did not recognize the extent of their memory and cognitive difficulties beyond the general complaints expressed by normal elderly (n = 77) within the study and their apparent difficulties did not appear to impact on their participation in life activities. These findings suggest it is unlikely that the memory and cognitive difficulties demonstrated by individuals with mild memory impairment reflect normal aging. Rather it is possible that such impairment may signal early neurodegenerative processes worthy of further investigation.

Aged↗

Prose memory deficits associated with schizophrenia.

Memory of contextual information is essential to one's quality of living. This study investigated if the different components of prose memory, across three recall conditions: first learning trial immediate recall, fifth learning trial immediate recall, and 30-min delayed recall, are differentially impaired in people with schizophrenia, relative to healthy controls. A total of 39 patients with schizophrenia and 39 matched healthy controls were recruited. Their prose memory, in terms of recall accuracy, temporal sequence, recognition accuracy and false positives, commission of distortions, and rates of learning, forgetting, and retention were tested and compared. After controlling for the level of intelligence and depression, the patients with schizophrenia were found to commit more distortions. Furthermore, they performed poorer on recall accuracy and temporal sequence accuracy only during the first initial immediate recall. On the other hand, the rates of forgetting/retention and recognition accuracy were comparable between the two groups. These findings suggest that people with schizophrenia could be benefited by repeated exposure to the materials to be remembered. These results may have important implications for rehabilitation of verbal declarative memory deficits in schizophrenia.

Adult↗

Hippocampal contribution to verbal recent memory following dominant-hemisphere temporal lobectomy.

The effects of hippocampal encroachment in the language dominant-hemisphere were studied in 41 patients who underwent previous temporal lobectomy (TL). Patients undergoing dominant-hemisphere TL including anterior hippocampus (n = 13) performed significantly worse than nondominant TL patients (n = 16) on a verbal learning test (Selective Reminding; p less than or equal to .00001), thereby confirming the sensitivity of this procedure to lateralized temporal-lobe dysfunction. However, no significant difference was present on this or other primary measures of material-specific memory when contrasting dominant TL patients in whom the anterior hippocampus was spared (n = 12) to those in whom anterior hippocampus was resected. These data suggest that more extensive and posterior mesial temporal-lobe resection is not necessarily associated with a greater verbal material-specific memory deficit following dominant-hemisphere temporal lobectomy.

Adult↗

Word list learning and prediction of recall after frontal lobe lesions.

The effect of frontal lobe lesions on the accuracy of prediction of recall in a word list learning task was studied. Fifty-nine patients with a focal brain lesion and 21 non-brain-damaged control patients memorized a word list by selective reminding and predicted before each recall trial the number of words they would be able to recall. The patients with left frontal lesions, who were inferior to the patients with right frontal lesions and the control patients in word list recall, overpredicted their recall more than the other brain-damaged patients or the control patients, especially on the 1st trial. The patients with right frontal lesions were less accurate in the prediction of recall than the patients with right posterior lesions or the control patients.

Adult↗

An assessment of verbal recall, recognition and fluency abilities in patients with Huntington's disease.

Two investigations concerned with the memory deficits of patients with Huntington's Disease (HD) were performed. In the first experiment, early and advanced HD patients showed superior recognition memory than did alcoholic Korsakoff patients on modified recall and recognition forms of the Rey Auditory Verbal Learning Test. In contrast, on a letter fluency test (FAS) requiring the patients to search their semantic memories, both HD groups produced fewer correct words and perseveration errors than did the alcoholic Korsakoff group. In the second experiment, HD patients and Korsakoff patients were compared in their and recognition of short passages. While the HD and Korsakoff patients were equally impaired on recall tests, the HD patients evidenced significantly better recognition memory than did the amnesic group. As on the fluency test, the prose of the Korsakoff patients was characterized by intrusion (i.e., perseverative) errors. The results of the two experiments indicate that HD and Korsakoff patients' memory deficits are related to deficiencies in retrieval and an increased sensitivity to proactive interference, respectively.

Alcohol Amnestic Disorder↗

Effects of (+)-HA-966, CGS-19755, phencyclidine, and dizocilpine on repeated acquisition of response chains in pigeons: systemic manipulation of central glycine sites.

The effects of i.m. injections of (+)-HA-966, a glycine-site antagonist at the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, its enantiomer (-)-HA-966, the competitive glutamate antagonist CGS-19755, the uncompetitive glutamate antagonists phencyclidine and dizocilpine, and the micro opioid agonist morphine were evaluated in a repeated acquisition task in pigeons. All of the drugs produced dose-dependent decreases in rates of responding. The NMDA receptor and channel blockers and (+)-HA-966 appeared to have a greater effect on acquisition than did morphine at doses that did not fully suppress responding. The rate suppression and learning impairment produced by a large dose of (+)-HA-966 (100 mg/kg) were completely prevented by coadministration of the glycine-site agonist D-serine (560 mg/kg) but not by its enantiomer, L-serine (1000 mg/kg). D-Serine, however, produced incomplete antagonism of the effects of dizocilpine and phencyclidine and failed to alter those of CGS-19755. These findings provide evidence that reducing the activity of the NMDA subtype of the glutamate receptor through pharmacological action at any of three sites produces similar decrements in acquisition, and those produced through antagonism of the glycine site are differentially sensitive to the glycine-site agonist D-serine.

Animals↗

Effects of caffeine on mood and memory.

The effects of caffeine on mood and memory tasks were investigated in a double-blind study of 95 healthy young adults who were randomly assigned to three doses: 0, 200, and 400 mg of oral administration of caffeine. Subjects completed a battery of tasks once predrug and several times postdrug. Caffeine, in general, showed nonsignificant effects on cognitive, learning, and memory performance. The exception is that 200 mg caffeine facilitated performance on the relatively more difficult cancellation (addition and multiplication) tasks than the digit cancellation task. In addition caffeine decreased boredom and relaxation, and increased other ratings of subjective moods--anxiousness, tenseness, and nervousness. The reduction in boredom or fatigue is associated with the repetitive nature of the task and the period of time during which the tasks were repeated. In general, high-to-moderate users of caffeine recalled more words than low users, particularly at the beginning of the lists. Results are discussed in terms of the effects of caffeine on task difficulty and sensitivity and the relative potency of caffeine doses on behavior. User effect is suggested as an important consideration of memory assessment.

Adult↗

Effects of opioids and phencyclidine in combination with naltrexone on the acquisition and performance of response sequences in monkeys.

In each of three components of a multiple schedule, monkeys were required to emit a different sequence of four responses in a predetermined order on four levers. Sequence completions produced food under a fixed-ratio schedule. Errors produced a brief timeout. One component of the multiple schedule was a repeated-acquisition task where the four-response sequence changed each session (learning). The second component of the multiple schedule was also a repeated-acquisition task, but acquisition was supported through the use of a stimulus fading procedure (faded learning). In a third component of the multiple schedule, the sequence of responses remained the same from session to session (performance). Heroin, methadone, cyclazocine and phencyclidine each produced dose-related decreases in overall response rate. At high doses which produced equivalent rate-decreasing effects, cyclazocine and phencyclidine generally produced greater disruption of accuracy in the learning component than did heroin or methadone. Naltrexone 5.6 microgram/kg shifted to the right by approximately 1/2-log unit the heroin and methadone dose-effect curves, but produced little or no change in the cyclazocine dose-effect curves. At 56 micrograms/kg naltrexone completely antagonized both the rate-decreasing and error-increasing effects of heroin and methadone. The same dose of naltrexone tended to produce greater antagonism of the effects of cyclazocine on accuracy than on rate, which was shifted by only 1/4-log unit. In contrast, naltrexone failed to antagonize the effects of phencyclidine on either rate or accuracy. Thus it would appear that while cyclazocine and phencyclidine produce similar disruptions in the accuracy of a discrimination, the effects of each are differentially sensitive to antagonism by naltrexone.

Animals↗

Behavioral effects of cocaine alone and in combination with ethanol or marijuana in humans.

Intranasal cocaine (COC) and oral ethanol (ETOH) were administered to one group of seven research volunteers during daily experimental sessions. Following the determination of baseline subjective and performance measures, an ETOH cocktail (0, 19.4, 38.7 or 58.1 g of ETOH in lemonade) was consumed over a 10-min period. COC hydrochloride (4, 48, 96 mg) was inhaled 35-min after the start of ETOH drinking. In a separate experiment, seven research volunteers received intravenous cocaine and smoked marijuana (MJ), alone and in combination during daily experimental sessions. Following the determination of baseline measures, a 1-g MJ cigarette (0-2.7% delta 9-THC, w/w) was smoked and 13 min after the start of MJ smoking COC hydrochloride (0, 16, 32 mg) was given intravenously. ETOH increased simple-reaction time and decreased DSST trials. COC decreased DSST trials, increased incorrect responses on a list-learning task and attenuated the effect of ETOH on DSST performance. Only combinations of the high COC dose and the high MJ dose increased errors on a repeated acquisition task. Intranasal COC increased ratings of 'Stimulated,' and 'High' and LSD scores on the ARCI which were unaffected by ETOH. Increased ratings of 'Sedated' following ETOH alone were attenuated by intranasal (i.n.) COC. Intravenous COC and smoked MJ alone both increased ratings of 'Stimulated' and 'High.' There was a trend for combinations of i.v. COC and MJ to prolong these elevations. The results suggest that the interactive effects of COC in combination with ETOH or MJ, after acute administration, are subtle and in need of further analyses to better understand polydrug abuse.

Administration, Intranasal↗

Suppressing versus releasing a habit: frequency-dependent effects of prefrontal transcranial magnetic stimulation.

When subjects are required to generate a random sequence of numbers they typically produce too many forward and backward 'counts' (e.g. 5-6, 4-3). This counting bias is interpreted as the consequence of an interference by overlearned tendencies to arrange numbers according to their natural order. Inhibition of such well-learned routines is known to rely on frontal lobe functioning. We examined differential effects of slow (1 Hz) and fast (10 Hz) repetitive transcranial magnetic stimulation (rTMS) over the left or right dorsolateral prefrontal cortex (DLPFC) on random number generation (RNG) performance. Eighteen healthy men performed an RNG task. Those subjects stimulated over the left DLPFC showed a frequency-dependent rTMS effect: counting bias was significantly reduced after the 1 Hz stimulation compared with baseline, but significantly exaggerated after the 10 Hz stimulation compared with 1 Hz stimulation. In contrast, the sequences of the subjects stimulated over the right DLPFC showed the well-known excess of counting in all conditions (i.e. baseline, 1 Hz and 10 Hz). These findings confirm the functional importance of specifically the left DLPFC in sequential response production and show, for the first time, that rTMS affects cognitive processing in a frequency-dependent manner.

Adult↗