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Biomedical subjects

D S Woodruff-Pak

Publications and source records attributed to D S Woodruff-Pak.

At least 37 records · Page 2Linked to original sources
PubMed1995

Larger nondeclarative than declarative deficits in learning and memory in human aging.

This study used classical conditioning as a measure of nondeclarative learning and compared it with verbal learning as a declarative measure. Eighty participants were tested using 1 of 2 paradigms (400-ms and 750-ms delay) for eyeblink classical conditioning (EBCC) and the California Verbal Learning Test (CVLT). Large age differences were observed in the nondeclarative EBCC task, even in the 750-ms paradigm, which is more optimal for older adults. Age differences in the nondeclarative EBCC task were larger in the 400-ms paradigm and equal in the 750-ms paradigm to the magnitude of age differences in the declarative CVLT task. Partial correlations (removing the variance that was due to age) showed no relation between performance on the nondeclarative and declarative tasks. The results contradict the common assumption that, in the same participants, nondeclarative learning and memory are more resistant to the effects of aging than are declarative learning and memory and suggest that nondeclarative learning and memory are not unitary.

Adolescent↗
PubMed1995

Longitudinal investigation of eyeblink classical conditioning in elderly human subjects.

Eyeblink classical conditioning (EBCC) is an important tool in the study of learning, memory, and aging, but few longitudinal data have been collected on EBCC in humans of any age. Our aim was to determine if EBCC would remain stable across time. Fifteen subjects with an initial mean age of 83.2 years ("old-old") were tested three times in just over 2 years, and a subset of 8 of these subjects were tested a fourth time after the third year. Fifteen additional subjects with a mean age of 69.1 years ("young-old") were tested two times in just over one year. Subjects were tested with identical procedures in the 400 msec delay EBCC paradigm. Cognitively normal young-old and old-old adults showed stability in EBCC. In the old-old group, poor EBCC (< 25% conditioned responses; CRs) predicted significantly poorer Blessed Information Memory Concentration scores. Old-old subjects with poor initial EBCC were more likely to become demented or die than were old-old subjects producing over 25% CRs.

Aged↗
PubMed1995

Fragile-X and Down's syndrome: are there syndrome-specific cognitive profiles at low IQ levels?

Individuals with either fragile-X syndrome or Down's syndrome with IQ scores less than 40 were assessed on the Down Syndrome Mental Status Exam. The results of the testing were examined for syndrome-specific cognitive profiles. No evidence for syndrome-specific cognitive profiles were found. These same individuals were then classified as high or low IQ, and each group was examined for IQ-level-specific profiles. Unique IQ level cognitive profiles were found. Classifying the individuals with regard to aetiology obscured IQ-level-specific strengths and weaknesses. Researchers and developers of curricula are cautioned against generalizing cognitive profiles to all IQ levels of a specific genetic syndrome.

Activities of Daily Living↗
PubMed1994

A nicotinic agonist (GTS-21), eyeblink classical conditioning, and nicotinic receptor binding in rabbit brain.

The septo-hippocampal cholinergic system is of demonstrated involvement in eyeblink classical conditioning (EBCC). To determine if a nicotinic cholinergic agonist, GTS-21, would facilitate acquisition of EBCC in older rabbits, three doses (0.1, 0.5, 1.0 mg/kg) in sterile saline vehicle and vehicle alone were administered to older rabbits (n = 48; mean age = 29.8 months). A control group of vehicle-treated young rabbits (n = 12; mean age = 3.5 months) was included. Rabbits were conditioned for fifteen 90-trial sessions in the 750 ms delay paradigm with a tone conditioned stimulus and corneal airpuff unconditioned stimulus. Dependent measures of trials to learning criterion, percentage of conditioned responses (CRs) and CR amplitude consistently showed significant improvement in older rabbits treated with 0.5 and 1.0 mg/kg of GTS-21. Acquisition was similar in vehicle-treated young and GTS-treated older rabbits. Vehicle-treated older rabbits conditioned more poorly than vehicle-treated young rabbits. No non-associative learning effects were observed in GTS-21 treated animals. Nicotinic receptor binding was similar in all groups of older rabbits, indicating that GTS-21 administration over a 15-day period did not affect nicotinic receptors. Alzheimer's disease (AD) has been associated with significant loss of nicotinic cholinergic receptors, and patients diagnosed with probable AD are seriously impaired on EBCC. These results demonstrating that the nicotinic agonist, GTS-21, facilitated EBCC in older rabbits suggest that the compound should receive additional investigation for its potential to affect cognition in AD.

Aging↗
PubMed1994

Nefiracetam (DM-9384): effect on eyeblink classical conditioning in older rabbits.

The nootropic compound nefiracetam was evaluated in 88 older rabbits in a 750-ms delay paradigm of eyeblink classical conditioning (EBCC). Rabbits (mean age = 28.7 months) were assigned in groups of eight to one of six conditions in experiment 1: paired tone conditioned stimulus (CS)-corneal airpuff unconditioned stimulus (US) presentations and 1, 3, or 10 mg nefiracetam/kg or sterile saline vehicle; explicitly unpaired CS and US presentations and 3 mg nefiracetam/kg or sterile saline vehicle. Animals in the paired conditions received 10 daily sessions of 90 paired trials and animals in the unpaired conditions received 10 daily sessions of 180 unpaired CS and US presentations. The six conditions in experiment 2 were 5, 10, and 15 mg nefiracetam/kg and vehicle in 15 sessions of paired presentations; 10 mg nefiracetam/kg and vehicle in 15 sessions of unpaired conditioning. In both experiments 1 and 2, acquisition measured by trials to learning criterion was significantly faster at the 10 mg/kg dose of nefiracetam. In the repeated measures analyses comparing six doses in the paired conditions, all dependent measures [percentage conditioned responses (CRs), CR amplitude, and response latency] indicated significantly better conditioning in rabbits treated with 10 mg nefiracetam/kg, but this dose did not increase motor responding or responding in the unpaired condition. Nefiracetam facilitated acquisition of EBCC in older rabbits. EBCC is performed poorly by older humans and is seriously impaired in Alzheimer's disease. These preclinical data in an animal model with clear parallels in humans suggest that nefiracetam may prove effective as a cognition enhancer in clinical trials.

Acoustic Stimulation↗
PubMed1994

Nicotinic cholinergic system involvement in eyeblink classical conditioning in rabbits.

A nicotinic cholinergic antagonist, mecamylamine (MEC), was administered to rabbits tested on eyeblink classical conditioning (EBCC) in the 750-ms delay paradigm for 10 90-trial sessions. Nicotinic receptors were measured in 3 brain regions in 5 treatment groups: paired conditioned stimulus-unconditioned stimulus (CS-US) presentations with (a) vehicle, young; (b) vehicle, older; (c) 0.5 mg/kg MEC, young; unpaired CS-US with (d) 0.5 mg/kg MEC, young; and (e) vehicle, young. Daily MEC injections disrupted acquisition in young rabbits (769 trials to learning criterion vs. 323 trials for vehicle-treated young rabbits). MEC-treated young rabbits learned similarly to older rabbits. Brain nicotinic receptors were not affected by 10 daily MEC injections. To our knowledge, this experimental protocol, using a low MEC dose to selectively inhibit nicotinic cholinergic receptors, is the first to demonstrate a role for nicotinic cholinergic receptors in EBCC.

Animals↗
PubMed1993

Cerebellar cortical lesions and reacquisition in classical conditioning of the nictitating membrane response in rabbits.

Portions of cerebellar cortex, particularly Larsell's hemisphere VI, have been identified as involved but not essential for the acquisition and retention of classical conditioning of the nictitating membrane (NM) response in rabbit. The present experiment was undertaken to examine the effect of lesions of cerebellar cortical regions projecting to anterior dorsolateral interpositus nucleus. Lesions of relatively equal size, including hemisphere VI and additionally more medial, anterior, or lateral cerebellar cortex were made after rabbits were classically conditioned. The effect of these cerebellar cortical lesions on retention to tone versus light conditioned stimulus (CS) and the timing of the conditioned response was evaluated. In spite of relatively large cerebellar cortical lesions, reacquisition of the conditioned NM response occurred quite rapidly. Whether the lesion was more medial and anterior or more lateral did not affect retention. Retention was significantly poorer with light CS than with tone CS. Timing of CRs was not affected by these lesions of cerebellar cortex, but the lesions spared most of the anterior lobe. The parasagittal zone C3 covering the longitudinal band of tissue from anterior lobe to the paramedian lobule and projecting to dorsolateral anterior interpositus requires additional exploration for its role in classical NM conditioning.

Animals↗
PubMed1993

Delay classical conditioning in young and older rabbits: initial acquisition and retention at 12 and 18 months.

Classical conditioning of the nictitating membrane-eyeblink response in young (7 months old) and older (36 months old) New Zealand white rabbits in a delay paradigm with a 400-ms conditioned stimulus-unconditioned stimulus interval was examined for initial acquisition and retention. Older animals required significantly more acquisition trials to reach learning criterion. Age differences in acquisition were temporary. Older rabbits responded at a level comparable to that of young rabbits such that total performance over the 630 trials of acquisition was not different. Rabbits in the explicitly unpaired control groups exhibited no age differences in unconditioned response amplitude or latency measures. Twelve- and 18-month retests demonstrated no significant age effects on retention. Patterns of retention differed between the age groups. Older rabbits required fewer trials to obtain the learning criterion at each phase of testing. Younger rabbits maintained a stable performance throughout training.

Aging↗
PubMed1993

Eyeblink classical conditioning in H.M.: delay and trace paradigms.

H.M., a well-known subject with bilateral removal of medial-temporal-lobe structures and profound amnesia, performed eyeblink classical conditioning (EBCC) for 21 90-trial sessions in the 400-ms delay and 900-ms trace paradigms. A 2nd amnesic subject with temporal lobe lesions and 2 normal control subjects (NCSs) were also conditioned. Acquisition occurred in both paradigms for all subjects. Acquisition in the delay paradigm was prolonged in H.M. (perhaps because of his cerebellar degeneration in the vermis and hemispheres), but not in the 2nd amnesic subject. Amnesic subjects and NCSs showed more rapid acquisition in the trace than in the delay paradigm. Two years after initial EBCC, H.M. attained learning criterion in the trace paradigm in 1/10th as many trials. No recollection of the experimenters, apparatus, instructions, or procedure was manifested by H.M. Results suggest that humans can condition in the 400-ms delay and 900-ms trace EBCC paradigms with the hippocampus radically excised.

Aged↗
PubMed1991

Classical eyeblink conditioning in adulthood: effects of age and interstimulus interval on acquisition in the trace paradigm.

Effects of age and interstimulus interval (ISI) were examined in eyeblink classical conditioning with a trace paradigm. Sixty young adults were trained in Experiment 1 with 6 interstimulus intervals (ISIs): 400, 900, 1,200, 1,500, 1,800, and 2,100 ms. The purpose was to find an ISI value for humans that would result in nonoptimal acquisition. ISIs of 1,200 ms and longer were nonoptimal. Adults aged 17-81 years were trained in Experiment 2 with a nonoptimal 1,800-ms ISI in the trace paradigm. Young and middle-aged subjects demonstrated equivalent levels of acquisition, and only older subjects conditioned more poorly. Aging appears to affect conditioning in the long-ISI trace paradigm as well as in the short-ISI delay paradigm.

Adolescent↗
PubMed1991

Effect of BMY 21502 on classical conditioning of the eyeblink response in young and older rabbits.

BMY 21502, a substituted pyrrolidionone, has been found to enhance a simple form of learning in older rabbits. In humans, this simple type of learning, classical conditioning of the eyeblink response, declines in normal aging and is seriously impaired in Alzheimer's disease (AD). We have demonstrated that eyeblink classical conditioning reliably discriminates patients diagnosed with probable AD from non-demented, age-matched elderly subjects. Older organisms can be classically conditioned, but they condition at a much slower rate than younger organisms. Our preliminary analyses indicate age differences in distribution of protein kinase C in the hippocampus. Here we also report that older rabbits that are administered two different doses of BMY 21502 classically condition at a rate approximating that of young rabbits.

Aging↗
PubMed1990

Eyeblink conditioning discriminates Alzheimer's patients from non-demented aged.

Classical conditioning of the eyeblink response in rabbits is a model system useful in research on the neurobiology of learning, memory and aging, and it has implications for Alzheimer's disease (AD). The hippocampus and cerebellum are brain structures of demonstrated involvement in eyeblink conditioning. AD profoundly impairs the septo-hippocampal cholinergic system; thus, AD patients should show greater impairment of eyeblink conditioning than non-demented, age-matched subjects. Twenty probable AD patients and 20 non-demented age-matched subjects were classically conditioned in the delay paradigm. While control subjects showed clear evidence of acquisition (31.54% conditioned responses [CRs]), probable AD patients showed significant impairment (10.77% CRs). Eyeblink classical conditioning may be useful for AD research and assessment.

Aged↗
PubMed1990

Purkinje cell number related to rate of classical conditioning.

The cerebellar cortex is normally involved (but not essential) in acquisition of the classically conditioned nictitating membrane response. Cerebellar Purkinje cells probably play a role in acquisition, but these cells are vulnerable to hypoxia, ischemia, and aging. Since large age differences exist in rate of conditioning, we suspected that the number of Purkinje cells in individual rabbits would correlate with learning rate. Purkinje cell counts were undertaken in 12 rabbits aged 3-50 months. The correlation between trials to learning criterion and Purkinje cells was -0.79. A second study used 18 3-month-old rabbits. Even with age held constant, the correlation was -0.60. Individual variation in Purkinje cell number accounts for significant variability in learning rate.

Aging↗
PubMed1988

Classical conditioning of the eyeblink response in the delay paradigm in adults aged 18-83 years.

To determine if age differences in classical conditioning of the eyelid response begin to appear in middle age in humans as they do in animals, adult subjects aged 18-83 years were trained in the delay conditioning paradigm. Large age effects occurred. Statistically significant differences first appeared in the decade of the 40s. Within-age-group variability was large. To reduce variability, subjects were classified by the magnitude of their unconditioned response (UR). Regardless of age, subjects with low amplitude URs conditioned poorly. In the normal UR amplitude group, the correlation between age and total percentage conditioned responses (CRs) was -.58. Eyeblink rate and voluntary responding did not account for age differences in conditioning, and it was unlikely that hearing acuity or corneal sensitivity caused the differences. Parallels between human and animal eyelid conditioning are considered, and it is suggested that age changes in the cerebellum may affect conditioning in aging mammals, including humans.

Adolescent↗
PubMed1988

No apparent age differences in hippocampal theta frequency in rabbits aged 3-50 months.

Evidence has accumulated to suggest that the hippocampus is impaired by aging processes. Hippocampal EEG was examined in 3- to 50-month-old rabbits before they were classically conditioned in the trace paradigm. Hippocampal EEG was recorded from electrodes implanted proximal to the pyramidal layer of CA1. There were no age differences in hippocampal EEG frequency over the age range of 3-50 months. Animals were subsequently trained in a trace classical conditioning paradigm, and there were large age differences in acquisition and retention. Results suggest that rabbits as young as 2.5 years old show behavioral deficits in conditioning, but hippocampal EEG frequency was not correlated with the age differences in behavior.

Aging↗
PubMed1986

Rapid transfer of training occurs when direct mossy fiber stimulation is used as a conditioned stimulus for classical eyelid conditioning.

Fifteen rabbits were classically conditioned using stimulation of the right pontine nuclei as a conditioned stimulus and a corneal airpuff as an unconditioned stimulus. After conditioning criterion was reached, the stimulation conditioned stimulus was transferred to the left pontine nuclei and the rate of conditioned response acquisition observed. Our results indicate that when electrodes were placed symmetrically in the right and left pontine nuclei, extremely rapid transfer of training occurred. Together with previous data, the present data supply further indirect evidence that the site of neural plasticity which underlies acquisition and retention of classically conditioned skeletal muscle responses is located efferent to the pontine nuclei, namely in the cerebellum.

Animals↗
PubMed1985

Trace conditioning: abolished by cerebellar nuclear lesions but not lateral cerebellar cortex aspirations.

The trace conditioning paradigm in which the conditioned stimulus-unconditioned stimulus (CS-US) interval is longer and the US and CS do not overlap requires retention of a 'trace' of the CS to associate it with the US. This task is difficult, requiring for learning about 5 times the number of trials to criterion as the standard delay task. The present study was undertaken to determine if: the cerebellar interpositus nucleus is essential in trace as well as in delay conditioning; and the lateral cerebellar cortex is involved when CS-US association over longer time intervals is required. Sixteen adult male New Zealand white rabbits had recording and in some cases lesion electrodes surgically implanted before training. They were trained daily with 126 paired trials of tone CS and airpuff US. The trace period between CS offset and US onset was 500 ms. Mean number of trials to criterion of 8/9 CRs was 466.9 trials. After a day of overtraining the animals had one of 3 surgeries: electrolytic lesion of the left cerebellar interpositus nucleus (n = 3); aspiration of the left lateral cerebellar cortex (HVI and HVIIA) and underlying cerebellar nuclei (n = 4); or aspiration of HVI and HVIIA only (n = 9). Rabbits with only HVI and HVIIA removed exhibited a transient decrease in CRs but relearned with significant savings. The amplitude, area and latency of pre- and postlesion conditioned responses (CRs) was similar. When the interpositus nucleus was damaged, the animals' capacity for CRs on the side ipsilateral to the lesion was permanently abolished. It is concluded that the cerebellar interpositus nucleus but not the overlying lateral cerebellar cortex is essential for retention of trace classical conditioning. Nevertheless, the temporary abolition of CRs by removal of lateral cerebellar cortex suggests that the cerebellar cortex does play an important role in learning and retention of the trace conditioned response.

Animals↗