Biomedical subjects

Edward J Golob

Publications and source records attributed to Edward J Golob.

11 recordsLinked to original sources

PubMed2006

Vascular volume and blood-brain barrier permeability measured by dynamic contrast enhanced MRI in hippocampus and cerebellum of patients with MCI and normal controls.

PURPOSE: To measure the cerebrovascular volume and blood-brain barrier (BBB) permeability indices in hippocampus and cerebellum of patients with mild cognitive impairment (MCI) using dynamic contrast-enhanced MRI (DCE-MRI), and compare to that of normal controls. MATERIALS AND METHODS: A total of 11 MCI subjects and 11 healthy elderly controls participated in this prospective study. DCE-MRI was performed to measure the contrast enhancement kinetics. The early enhancement percentage (at 50 seconds after injection) was defined as the vascular volume index, and the ratio between the four to five-minute enhancement relative to the 50-second enhancement was defined as the BBB permeability index. RESULTS: The enhancement kinetics measured from hippocampus of MCI individuals demonstrated a lower magnitude and slower decay than healthy controls, suggesting that they had a smaller vascular volume (significant in the right side; P <0.001) and a higher BBB permeability (not reaching significance level). The vascular volume index was significantly correlated with naming ability (P 0.05). CONCLUSION: These results suggest that changes in cerebrovasculature may occur in hippocampus of MCI. DCE-MRI may provide a noninvasive means to measure the subtle BBB leakage associated with the cerebrovascular pathology commonly found in Alzheimer's disease.

Aged↗

PubMed2006

Memory evaluation in mild cognitive impairment using recall and recognition tests.

Amnestic mild cognitive impairment (MCI) is a selective episodic memory deficit that often indicates early Alzheimer's disease. Episodic memory function in MCI is typically defined by deficits in free recall, but can also be tested using recognition procedures. To assess both recall and recognition in MCI, MCI (n = 21) and older comparison (n = 30) groups completed the USC-Repeatable Episodic Memory Test. Subjects memorized two verbally presented 15-item lists. One list was used for three free recall trials, immediately followed by yes/no recognition. The second list was used for three-alternative forced-choice recognition. Relative to the comparison group, MCI had significantly fewer hits and more false alarms in yes/no recognition, and were less accurate in forced-choice recognition. Signal detection analysis showed that group differences were not due to response bias. Discriminant function analysis showed that yes/no recognition was a better predictor of group membership than free recall or forced-choice measures. MCI subjects recalled fewer items than comparison subjects, with no group differences in repetitions, intrusions, serial position effects, or measures of recall strategy (subjective organization, recall consistency). Performance deficits on free recall and recognition in MCI suggest a combination of both tests may be useful for defining episodic memory impairment associated with MCI and early Alzheimer's disease.

Aged↗

PubMed2006

Absence of postexercise and delayed facilitation of motor cortex excitability in restless legs syndrome: evidence of altered cortical plasticity?

STUDY OBJECTIVE: Restless legs syndrome (RLS) is a neurologic disorder with well-defined clinical and diagnostic criteria but the pathophysiology of which is unclear. Previous studies have suggested alterations in motor cortex function in RLS. We aimed to compare motor cortex plasticity in subjects with RLS versus healthy controls. DESIGN: Biphasic single-pulse transcranial magnetic stimulation (TMS) of the nondominant hemisphere was used to define motor evoked potential (MEP) amplitude, motor threshold, and silent period. Subjects also performed 3 blocks (30-s, 60-s, and 90-s duration) of a bimanual motor task (exercise condition). Amplitude of MEPs elicited immediately after each block, and then after a 15-minute rest period were compared with baseline. The time course of intracortical inhibition was also tested using paired-pulse TMS at 1- to 6-millisecond interstimulus intervals. SETTING: Clinical neurophysiology laboratory in a General Hospital. STUDY PARTICIPANTS: For the single-pulse TMS procedures, the RLS group included 11 patients affected by primary RLS and the control group included 11 age- and sex-matched normal subjects. For the paired-pulse TMS procedures, there were 9 patients and 6 controls. INTERVENTIONS: None. RESULTS: There were no group differences in motor threshold and MEP amplitudes, but the silent period was significantly shorter in subjects with RLS. Compared with baseline, control subjects had larger MEP amplitudes after 30 and 60 seconds of exercise and also after the rest period. In contrast, MEP amplitudes in patients with RLS were not significantly different from baseline after any of the exercise conditions or following the rest period. Patients with RLS also had decreased short-latency paired-pulse inhibition. CONCLUSIONS: Findings show abnormal motor cortex inhibition and cortical excitability differences in RLS. We suggest the possibility of alterations in movement-related cortical plasticity in RLS.

Arousal↗

PubMed2005

Event-related potentials accompanying motor preparation and stimulus expectancy in the young, young-old and oldest-old.

Although aging is accompanied by neurobiological changes and increased susceptibility to many neurological disorders, little is known about neurophysiological changes that start in old age. Here, neurophysiological changes during old age were assessed by recording brain potentials associated with motor preparation and stimulus expectancy (contingent negative variation, CNV) in young-old (60-69), oldest-old (85-98), and young (17-23) subjects. Individual trials began by a button press, followed 2.5 s later by either a low or high pitch tone. In the "motor" condition subjects responded following high pitch tones (P=0.20); in the "non-motor" condition subjects did not respond. Motor condition CNV amplitudes in the oldest old were more positive than the young and young-old groups, which were similar. In the non-motor condition, the young-old and oldest-old had similar CNV amplitudes that were positive in polarity, and were significantly different from young subjects. Motor potentials before button presses that started the trials were comparable among groups. Results show that neural activity associated with motor preparation and stimulus expectancy changes during advanced age, and that group differences can be modulated by task requirements.

Acoustic Stimulation↗

PubMed2004

Passive movements of the head do not abolish anticipatory firing properties of head direction cells.

Neurons in the anterior dorsal thalamic nucleus (ADN) of the rat selectively discharge in relation to the animal's head direction (HD) in the horizontal plane. Temporal analyses of cell firing properties reveal that their discharge is optimally correlated with the animal's future directional heading by approximately 24 ms. Among the hypotheses proposed to explain this property is that ADN HD cells are informed of future head movement via motor efference copy signals. One prediction of this hypothesis is that when the rat's head is moved passively, the anticipatory time interval (ATI) will be attenuated because the motor efference signal reflects only the active contribution to the movement. The present study tested this hypothesis by loosely restraining the animal and passively rotating it through the cell's preferred direction. Contrary to our prediction, we found that ATI values did not decrease during passive movement but in fact increased significantly. HD cells in the postsubiculum did not show the same effect, suggesting independence between the two sites with respect to anticipatory firing. We conclude that it is unlikely that a motor efference copy signal alone is responsible for generating anticipatory firing in ADN HD cells.

Action Potentials↗

PubMed2004

Age-related differences in auditory event-related potentials during a cued attention task.

OBJECTIVE: To determine if aging is associated with differences in attentional regulation using behavioral and event-related potential (ERP) measures. METHODS: Younger (n=13;M=20 years) and older (n=12;M=76 years) subjects performed an auditory cued attention task. Verbal cues correctly (valid) or incorrectly (invalid) predicted the ear receiving a target tone 1.5 s later, or were uninformative (neutral). Targets were either 'high' (2000 Hz) or 'low' (1000 Hz) pitch monaural tones. Subjects pressed one of 4 buttons to indicate target ear and pitch. ERPs following cues and targets (P50, N100, P200, slow waves), and negative slow potentials (CNV) between cues and targets were assessed. RESULTS: Cue information had significant effects on reaction time for both groups (valid valid) but not older subjects. Target slow waves were also affected by cue information (invalid>valid), and the difference was larger and lasted longer in older subjects. Slow waves following cues were significantly larger in older subjects, but the subsequent CNV amplitudes were comparable among groups. CONCLUSIONS: When performing a cued attention task, age differences are present in transient ERPs following cues and targets. SIGNIFICANCE: Age differences in ERPs associated with attentional regulation support the hypothesis that attentional changes contribute to cognitive aging.

Acoustic Stimulation↗

PubMed2004

Visual encoding differentially affects auditory event-related potentials during working memory retrieval.

Previous working memory studies using auditory stimuli at both encoding and retrieval show amplitude decreases in event-related potentials (N100 and late positive wave, LPW) at retrieval as a function of memory load. This study tested if these effects are associated with phonological or semantic coding by presenting visual stimuli at encoding and auditory stimuli at retrieval. We hypothesized that event-related potentials associated with phonological but not semantic coding would be affected by modality differences at encoding and retrieval. Memory sets having one, three, or five visual digits were followed by auditory probes that subjects classified as present or absent from the set. Reaction time increased and LPW amplitudes decreased with increases in memory load, but there were no significant effects of memory load on N100 amplitude. Results suggest that with respect to brain activity that covaries with memory load, probe N100 amplitude is associated with phonological coding and LPW amplitude is associated with semantic coding.

Acoustic Stimulation↗

PubMed2003

Passive transport disrupts directional path integration by rat head direction cells.

A subset of neurons in the rat limbic system encodes head direction (HD) by selectively discharging when the rat points its head in a preferred direction in the horizontal plane. The preferred firing direction is sensitive to the location of landmark cues, as well as idiothetic or self-motion cues (i.e., vestibular, motor efference copy, proprioception, and optic flow). Previous studies have shown that the preferred firing direction remains relatively stable (average shift +/- 18 degrees ) after the rat walks from a familiar environment into a novel one, suggesting that without familiar landmarks, the preferred firing direction can be maintained using idiothetic cues, a process called directional path integration. This study repeated this experiment and manipulated the idiothetic cues available to the rat as it moved between the familiar and novel environment. Motor efference copy/proprioceptive cues were disrupted by passively transporting the animal between the familiar and novel environment. Darkening the room as the animal moved to the novel environment eliminated optic flow cues. HD cell preferred firing directions shifted in the novel environment by an average of 30 degrees after locomotion from the familiar environment with the room lights off; by an average of 70 degrees after passive transport from the familiar environment with the room lights on; and by an average of 67 degrees after passive transport with the room lights off. These findings are consistent with the view that motor efference copy/proprioception cues are important for maintaining the preferred firing direction of HD cells under conditions requiring path integration.

Action Potentials↗

PubMed2002

Differences between appetitive and aversive reinforcement on reorientation in a spatial working memory task.

Tasks using appetitive reinforcers show that following disorientation rats use the shape of an arena to reorient, and cannot distinguish two geometrically similar corners to obtain a reward, despite the presence of a prominent visual cue that provides information to differentiate the two corners. Other studies show that disorientation impairs performance on certain appetitive, but not aversive, tasks. This study evaluated whether rats would make similar geometric errors in a working memory task that used aversive reinforcement. We hypothesized that in a task that used aversive reinforcement rats that were initially disoriented would not reorient by arena shape and thus make similar geometric errors. Tests were performed in a rectangular arena having one polarizing cue. In the appetitive condition water consumption was the reward. The aversive condition was a water maze task with reinforcement provided by escape to a hidden platform. In the aversive condition rats returned to the reinforced corner significantly more often than in the dry condition, and did not favor the diagonally opposite corner. Results show that rats can use cues besides arena shape to reorient in an aversive reinforcement condition. These findings may also reflect different strategies, with an escape/homing strategy in the wet condition and a foraging strategy in the dry condition.

Animals↗

PubMed2002

Auditory event-related potentials during target detection are abnormal in mild cognitive impairment.

OBJECTIVE: To define brain activity and behavioral changes in mild cognitive impairment (MCI), an isolated memory deficit in the elderly that is a major risk factor for Alzheimer's disease. METHODS: Brain potentials and reaction time were examined in elderly controls (n=12) and MCI (n=15) using a target detection paradigm. Subjects listened to a sequence of tones and responded to high-pitched target tones (P=0.20) that were randomly mixed with low-pitched tones (P=0.80). Measures were a pre-stimulus readiness potential (RP), post-stimulus potentials (P50, N100, P200, N200, P300), and reaction time. RESULTS: Accuracy was equivalent between groups, but there was a trend for longer reaction times in MCI (P=0.08). Two potentials differed between groups: (1) P50 amplitude and latency were significantly increased in MCI, and (2) P300 latency was significantly longer in MCI. Results from two MCI subjects that converted to Alzheimer's disease are also discussed. CONCLUSIONS: Brain potentials in MCI subjects during target detection have certain features similar to healthy aging (RP, N100, P200, N200), and other features similar to Alzheimer's disease (delayed P300 latency, slower reaction time). P50 differences in MCI may reflect pathophysiological changes in the modulation of auditory cortex by association cortical regions having neuropathological changes in early Alzheimer's disease.

Acoustic Stimulation↗

PubMedDate not supplied

Serial position effects in auditory event-related potentials during working memory retrieval.

It is established that recall of an item from a list of sequentially presented items is sensitive to the item's position in the memorized list. However, little is known about the brain mechanisms that mediate these serial position effects. Studies of working memory retrieval using event-related potentials report amplitude reductions during retrieval (auditory cortical N100, neocortical late positive wave [LPW]) as memory load increases. We tested the hypothesis that N100 and LPW amplitudes to probes are also affected by serial position. Event-related potentials were recorded from subjects performing an auditory working memory task. A set of one or five digits was memorized, then subjects classified a probe digit as either present or absent from the memory set. A control task was also given. Amplitudes of the N100 and LPW were reduced in the 5-item versus the 1-item set. In the 5-item set N100 amplitude was significantly larger for the initial (1st) serial position, relative to Positions 2-5, while linear increases in LPW amplitude were seen across serial positions (5th > 1st position). A control task without memorization showed no N100 or LPW amplitude changes with set size or serial position. The findings reveal that the N100 and LPW are influenced differently by serial position during working memory retrieval: N100 shows a primacy effect and LPW demonstrates a recency effect. The results suggest that primacy and recency effects may be mediated by different brain regions at different times during memory retrieval.

Adult↗