Biomedical subjects

T C Holmes

Publications and source records attributed to T C Holmes.

4 recordsLinked to original sources

PubMed1991

Interactions of 3,4-diaminopyridine and choline in stimulating acetylcholine release and protecting membrane phospholipids.

We investigated the effects of 3,4-DAP on ACh release from rat striatal slices superfused with or without choline, at rest and during electrical stimulation. In a choline-free medium, 3,4-DAP increased basal and stimulated ACh release while lowering the net efflux of choline; thus while the sum of ACh plus choline released remained constant, the ratio of released ACh to that of choline was increased. The drug failed to affect tissue ACh, choline or membrane phospholipid levels (including those of phosphatidylcholine). In a choline-containing medium, 3,4-DAP potentiated the enhancement by choline of both basal and electrically stimulated ACh release. Electrical stimulation alone increased ACh release from the slices without altering choline efflux or depleting tissue choline or ACh stores; however, this treatment did deplete membranes of phosphatidylcholine and of other major phospholipids. Superfusion of the slices with 3,4-DAP protected the slices from stimulation-induced phospholipid depletion. Calcium-dependent activation of high-affinity choline uptake may underlie the observed effects of 3,4-DAP.

4-Aminopyridine↗

PubMed1991

Intensity-amplitude relationships in monkey event-related potentials: parallels to human augmenting-reducing responses.

In human, the amplitudes of specific event-related potential (ERP) components can increase or decrease in response to increasing stimulus intensity depending on the location of the recording site. Large increases characterize components presumably generated by modality-specific sites, while smaller increases or even decreases are associated with those originating in associational areas. Comparable data from non-human primates, which would permit invasive studies of the neural substrates underlying these intensity-amplitude differences, are limited. To more fully characterize these relationships, auditory ERPs were recorded from chronically implanted epidural electrodes in 5 squirrel monkeys (Saimiri sciureus) in response to tones (500 Hz, 300 msec duration) of varying intensities (50, 60, 70, 80 dB SPL). Squirrel monkey ERPs recorded at Fz exhibited 3 peaks during the 200 msec post-stimulus interval. These peaks included a positivity (P1), followed by a negativity (N1), and then another positivity (P2). At posterior sites, the frontal P1-N1 configuration was recorded as an N1-P1 complex. At these sites, a small negativity (N2) preceded the last positive peak (P2). Changes in polarity were independent of reference site and posterior N1-P1 peaks exhibited latencies similar to those of the frontal P1-N1 components. Amplitudes at Fz, Cz, and Pz increased substantially with increasing stimulus intensity ('augmenting'). In contrast, only small increases or even decreases in amplitude ('reducing') were evident at T3 and T4. On the other hand, peak latencies decreased with higher stimulus intensities at most sites. The site-specific amplitude responses exhibited considerable temporal stability. In one subject, for example, similar 'augmenting' profiles were recorded at Fz in 8 sessions over a 6-month period. The topography of monkey intensity-amplitude response profiles, their temporal stability, and peak latency shifts resemble observations made in humans. The data show that 'augmenting' characterizes monkey vertex potentials, which, like the analogous human potentials, may originate in primary auditory cortex. In contrast, potentials recorded over temporal cortex, which may originate in auditory association cortex, exhibit 'reducing.' Thus, the data support the hypothesis that differences in amplitude with increasing intensity may reflect differences in cortical origin.

Acoustic Stimulation↗

PubMed1989

Brain-stem auditory evoked potentials in squirrel monkey (Saimiri sciureus).

To more fully characterize brain-stem auditory evoked potentials (BAEPs) in non-human primates, BAEPs were recorded from chronically implanted epidural electrodes in 10 squirrel monkeys (Saimiri sciureus). The effects of stimulus intensity, repetition rate, and anesthesia (ketamine 20 mg/kg i.m.) on peak latencies and inter-peak intervals were evaluated. Monkey wave forms consisted of approximately 7 peaks (I-VII), each exhibiting similar latencies across sessions, with later peaks exhibiting greater variability. In some subjects, additional peaks (IIa, IIIa) and slow potentials were recorded. The slow potentials provided a substratum for peaks IV through VII. As with human, monkey peaks exhibited systematic changes in latency with changes in stimulus intensity or repetition rate. These shifts included significant decreases in latency with increasing intensity for peaks I-IV and increases in latency with increases in repetition rate for peaks III, V, and VI. Inter-peak intervals were similar to those observed in human. Furthermore, ketamine anesthesia significantly delayed the latencies of most peaks (except I, V, and VII). Some differences between monkey and human BAEPs were evident in the relative amplitude of specific peaks. For example, peak V is typically most prominent in human, while this was true for peak III in monkey. The similarities between unanesthetized monkey and human inter-peak intervals suggest that the times required for impulses to reach particular brain-stem areas are conserved across primate species that vary in brain size. This supports the hypothesis that comparably numbered BAEP peaks in monkey and human index homologous processes. The data also suggest that the differences between animal and human BAEPs commonly reported may result from the use of anesthetics. In summary, unanesthetized monkey BAEPs resemble human BAEPs in morphology, number of peaks, polarity, latency variability, inter-peak intervals, slow potentials superimposed on the high-frequency peaks, and variations in morphology, amplitude, and resolution of peaks as a function of recording site. Thus, unanesthetized monkey BAEPs may be an excellent model for investigating the neural substrates of human BAEP or for determining species differences in acoustic processing among primates.

Anesthesia↗

PubMed1988

Endogenous event-related potentials in monkey: the role of task relevance, stimulus probability, and behavioral response.

Monkeys were trained in auditory discrimination tasks resembling human paradigms in which long-latency endogenous components, such as P300, are typically recorded. Morphological, topographical, and functional properties of the monkey event-related potentials (ERPs) were analyzed to determine similarities and differences with human ERPs reported in the literature. ERPs were recorded from epidural electrodes in monkeys trained to produce operant responses. In a conditional discrimination (CD) task, tone pips (2 kHz or 6 kHz, 40 msec duration, and 60 dB above nHL) were presented every 4-8 sec. Target tones presented during 'time-in' (TI) were rewarded when followed by a response in the correct post-stimulus interval (400-3000 msec). In contrast, tones presented during 'time-out' (TO) were not rewarded. Under both conditions, tones elicited an initial frontally dominant triphasic complex (P56-N92-P157). Additionally, TI target tones followed by a response elicited a large negativity (N358) having maximal amplitude over mid-frontal regions and followed by a parietally distributed positivity (P658). The scalp distribution and covariation with task requirements of N358 resemble those reported for the human 'O' wave. ERPs were also recorded in an auditory oddball paradigm in which tone pips (2 kHz and 6 kHz, 40 msec duration, and 60 dB above nHL) were presented in random order every second. Monkeys trained in the CD paradigm, along with additional subjects, were trained to make delayed responses following target tones embedded in a background of different-pitch tones. Tone probabilities were varied in different sessions from 90-10, 70-30, to 50-50 to assess the effects of probability. Background and target tones elicited a triphasic complex (P52-N110-P159) similar in latency and distribution to that recorded in the CD task. Additionally, target tones in this paradigm elicited a long-latency positive component (LPC) that exhibited an inverse relationship with stimulus probability. LPC had an onset latency of approximately 150-200 msec, a duration of approximately 300 msec, and multiple peaks (P244 and P376). These data indicate the importance of stimulus context in eliciting long-latency endogenous activity. It further suggests that strong analogies exist between monkey and human potentials recorded under similar paradigms. The effects of task relevance, stimulus probability, and the act of producing behavioral responses are similar to the effects of these variables on analogous human potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗