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Biomedical subjects

Michael E Goldberg

Publications and source records attributed to Michael E Goldberg.

At least 19 recordsLinked to original sources

LIP responses to a popout stimulus are reduced if it is overtly ignored.

Bright objects capture our attention by virtue of 'popping out' from their surroundings. This correlates with strong responses in cortical areas thought to be important in attentional allocation. Previous studies have suggested that with the right mindset or training, humans can ignore popout stimuli. We studied the activity of neurons in monkey lateral intraparietal area while monkeys performed a visual search task. The monkeys were free to move their eyes, and a distractor, but never the search target, popped out. On trials in which the monkeys made a saccade directly to the search target, the popout distractor evoked a smaller response than the non-popout distractors. The intensity of the response to the popout correlated inversely with the monkeys' ability to ignore it. We suggest that this modulation corresponds to a top-down mechanism that the brain uses to adjust the parietal representation of salience.

Animals↗

Activity in the lateral intraparietal area predicts the goal and latency of saccades in a free-viewing visual search task.

The purpose of saccadic eye movements is to facilitate vision, by placing the fovea on interesting objects in the environment. Eye movements are not made for reward, and they are rarely restricted. Despite this, most of our knowledge about the neural genesis of eye movements comes from experiments in which specific eye movements are rewarded or restricted. Such experiments have demonstrated that activity in the lateral intraparietal (LIP) area of the monkey correlates with the monkey's planning of a memory-guided saccade or deciding where, on the basis of motion information, to make a saccade. However, other experiments have shown that neural activity in LIP can easily be dissociated from the generation of saccadic eye movements, especially when sophisticated behavioral paradigms dissociate the monkey's locus of attention from the goal of an intended saccade. In this study, we trained monkeys to report the results of a visual search task by making a nontargeting hand movement. Once the task began, the monkeys were entirely free to move their eyes, and rewards were not contingent on the monkeys making specific eye movements. We found that neural activity in LIP predicted not only the goal of the monkey's saccades but also their saccadic latencies.

Action Potentials↗

Reaction times of manual responses to a visual stimulus at the goal of a planned memory-guided saccade in the monkey.

Monkeys demonstrate improved contrast sensitivity at the goal of a planned memory-guided saccade (Science 299:81-86, 2003). Such perceptual improvements have been ascribed to an endogenous attentional advantage induced by the saccade plan. Speeded reaction times have also been used as evidence for attention. We therefore asked whether the attentional advantage at the goal of a planned memory-guided saccade led to speeded manual reaction times following probes presented at the saccade goal in a simple detection task. We found that monkeys showed slower manual reaction times when the probe appeared at the memorized goal of the planned saccade when compared to manual reaction times following a probe that appeared opposite the saccade goal. Flashing a distractor at the saccade goal after target presentation appeared to slow reaction times further. Our data, combined with prior results, suggest that a spatially localized inhibition operates on the neural representation of the saccade goal. This inhibition may be closely related or identical to the processes underlying inhibition-of-return. We also found that if the same detection task was interleaved with a difficult perceptual discrimination task, manual reaction times became faster when the probe was at the saccade goal. We interpret these results as being an effect of task difficulty; the more difficult interleaved task may have engaged endogenous attentional resources more effectively, allowing it to override the inhibition at the saccade goal. We construct and discuss a simple working hypothesis for the relationship between the effects of prior attention on neural activity in salience maps and on performance in detection and discrimination tasks.

Animals↗

Saccades, salience and attention: the role of the lateral intraparietal area in visual behavior.

Neural activity in the lateral intraparietal area (LIP) has been associated with attention to a location in visual space, and with the intention to make saccadic eye movement. In this study we show that neurons in LIP respond to recently flashed task-irrelevant stimuli and saccade targets brought into the receptive field by a saccade, although they respond much to the same stimuli when they are stable in the environment. LIP neurons respond to the appearance of a flashed distractor even when a monkey is planning a memory-guided delayed saccade elsewhere. We then show that a monkey's attention, as defined by an increase in contrast sensitivity, is pinned to the goal of a memory-guided saccade throughout the delay period, unless a distractor appears, in which case attention transiently moves to the site of the distractor and then returns to the goal of the saccade. LIP neurons respond to both the saccade goal and the distractor, and this activity correlates with the monkey's locus of attention. In particular, the activity of LIP neurons predicts when attention migrates from the distractor back to the saccade goal. We suggest that the activity in LIP provides a salience map that is interpreted by the oculomotor system as a saccade goal when a saccade is appropriate, and simultaneously is used by the visual system to determine the locus of attention.

Animals↗

Neural correlates of attention and distractibility in the lateral intraparietal area.

We examined the activity of neurons in the lateral intraparietal area (LIP) during a task in which we measured attention in the monkey, using an advantage in contrast sensitivity as our definition of attention. The animals planned a memory-guided saccade but made or canceled it depending on the orientation of a briefly flashed probe stimulus. We measured the monkeys' contrast sensitivity by varying the contrast of the probe. Both subjects had better thresholds at the goal of the saccade than elsewhere. If a task-irrelevant distractor flashed elsewhere in the visual field, the attentional advantage transiently shifted to that site. The population response in LIP correlated with the allocation of attention; the attentional advantage lay at the location in the visual field whose representation in LIP had the greatest activity when the probe appeared. During a brief period in which there were two equally active regions in LIP, there was no attentional advantage at either location. This time, the crossing point, differed in the two animals, proving a strong correlation between the activity and behavior. The crossing point of each neuron depended on the relationship of three parameters: the visual response to the distractor, the saccade-related delay activity, and the rate of decay of the transient response to the distractor. Thus the time at which attention lingers on a distractor is set by the mechanism underlying these three biophysical properties. Finally, we showed that for a brief time LIP neurons showed a stronger response to signal canceling the planned saccade than to the confirmation signal.

Action Potentials↗

Effect of saccadic adaptation on localization of visual targets.

Objects flashed briefly around the time of a saccadic eye movement are grossly mislocalized by human subjects, so they appear to be compressed toward the endpoint of the saccade. In this study, we investigate spatial localization during saccadic adaptation to examine whether the focus of compression tends toward the intended saccadic target or at the endpoint of the actual (adapted) movement. We report two major results. First, that peri-saccadic focus of the compression did not occur at the site of the initial saccadic target, but tended toward the actual landing site of the saccade. Second, and more surprisingly, we observed a large long-term perceptual distortion of space, lasting for hundreds of milliseconds. This distortion did not occur over the whole visual field but was limited to a local region of visual space around the saccade target, suggesting that saccadic adaptation induces a visuo-topic remapping of space. The results imply that the mechanisms controlling saccadic adaptation also affect perception of space and point to a strong perceptual plasticity coordinated with the well-documented plasticity of the motor system.

Adaptation, Physiological↗

The number of injections does not influence absorption of bupivacaine after cervical plexus block for carotid endarterectomy.

STUDY OBJECTIVE: To investigate the efficacy and kinetics of bupivacaine when used for deep cervical plexus block (CPB), using either a single-injection or multiple-injections technique. DESIGN: Prospective, randomized, double-blind study. SETTING: Operating room of a university hospital. PATIENTS: Twenty-four adult patients (16 men, 8 women) scheduled for carotid endarterectomy. INTERVENTIONS: Patients were randomly assigned to receive CPB either by a single injection or after 3 injections. Patients in the multiple-injections group received a total dose of 15 mL of 0.5% bupivacaine (5 mL each deposited at C2, C3, and C4 over 2 minutes). Patients in the single-injection group received a single 15-mL injection of 0.5% bupivacaine. After the deep CPB, a superficial CPB was performed with 20 mL of 0.5% bupivacaine in all patients. MEASUREMENTS: An anesthesiologist and a surgeon graded the success of the block. Arterial plasma concentrations of bupivacaine were measured using liquid chromatography-mass spectroscopy. MAIN RESULTS: No significant differences were seen between the 2 groups with respect to the mean peak concentration of bupivacaine (single injection 2314 +/- 1385 ng/mL vs multiple injections 2255 +/- 1105 ng/mL) or time to reach the maximal concentration (time to maximum concentration [single injection 12.1 +/- 7.2 minutes vs multiple injections 12.5 +/- 3.9 minutes]). Furthermore, there were no significant differences in mean block scores between the single-injection and the multiple-injections groups, evaluated either by the anesthesiologists or the surgeon. CONCLUSIONS: The results of this study showed that the absorption of bupivacaine is independent of the number of injections after CPB, and that anesthesia for carotid endarterectomy may be accomplished successfully using either technique.

Absorption↗

Pain evaluation in patients receiving intravenous patient-controlled analgesia after surgery.

STUDY OBJECTIVE: To evaluate the effectiveness of intravenous patient-controlled analgesia (PCA) in patients after surgery. DESIGN: Prospective, observational study. SETTING: University teaching hospital. PATIENTS: Sixty patients with American Society of Anesthesiologists physical status I-III receiving intravenous PCA for postoperative pain. The PCA was programmed to deliver morphine 1 mg or hydromorphone 0.1-0.2 mg, with a lockout interval of 10 and 6 minutes for 80% and 20% of the patients, respectively. MEASUREMENTS AND MAIN RESULTS: Patients were asked, up to 4 times during PCA use and once within 4 hours after PCA use, to describe and rate their intensity of pain at rest and after activity. During the first 12 hours of intravenous PCA use, 75% of the patients reported moderate-to-severe pain > or = 5 on a verbal numeric rating scale) at rest, 80% after activity. Corresponding values, respectively, were 33% and 72% for the 12-24-hour period, 43% and 76% for the 24-36-hour period, and 36% and 64% for the 36-48-hour period of intravenous PCA use. Within 4 hours of stopping PCA, 30% and 58% of the patients had moderate-to-severe pain at rest and after activity, respectively. In approximately 50% of patients, presence of pain was described with words signifying sensory and affective dimensions of pain. Pain control was rated as good or very good by 54% of patients during the first 12 hours of intravenous PCA. Ratings of pain control tended to improve with time. CONCLUSION: Successful postoperative pain management using PCA is difficult to achieve on a consistent basis unless treatment is individualized. Our data support the hypothesis that small fixed doses fail to achieve adequate relief in many patients.

Analgesia, Patient-Controlled↗

Multi-day low dose ketamine infusion for the treatment of complex regional pain syndrome.

BACKGROUND: Complex regional pain syndrome (CRPS) is characterized by pain that is out of proportion to the injury and is regional in distribution. A large body of literature supports a dynamic change in the physiology and structure of central pain projecting neurons mediated through the N-methyl-D-aspartate (NMDA) receptor. A critical factor in central sensitization seems to be the release of the magnesium block on the NMDA receptor with influx of calcium and initiation of intracellular cascades. Current literature supports the effectiveness of ketamine in blocking central sensitization through its effects on the NMDA receptor. Recent treatment with anesthetic doses of ketamine in severely ill patients with generalized CRPS prompted our interest in a lower dose therapy. OBJECTIVE: To report on the efficacy of low dose outpatient ketamine infusion for the treatment of CRPS diagnosed by International Association for the Study of Pain (IASP) criteria in patients who have failed conservative treatment. DESIGN: Open label, prospective, pain journal evaluation of a 10-day infusion of intravenous ketamine in the CRPS patient. METHODS: Patients diagnosed with CRPS by a single neurologist were assigned to receive a 10-day outpatient infusion of ketamine supervised by an Anesthesiologist/Pain Management Specialist. The infusion was administered in a short procedure unit after each patient had been instructed on how to complete a pain questionnaire. Monitoring consisted of continuous ECG, pulse oximetry, and non-invasive blood pressure every 15 minutes. Patients made journal entries each day prior to the infusion of 40-80 mg of ketamine. The subjects were also asked to rate their pain intensity using a verbal analog pain scale of 0-10 and the affective component using a verbal scale of 0-4. RESULTS: There was a significant reduction in pain intensity from initiation of infusion (Day 1) to the 10th day, with a significant reduction in the percentage of patients experiencing pain by Day 10 as well as a reduction in the level of their "worst" pain. The nadirs of pain were lower by Day 10 with a significant reduction in the incidence of "punishing pain." Moreover, there was a significant improvement in the ability to initiate movement by the 10th day. CONCLUSION: A four-hour ketamine infusion escalated from 40-80 mg over a 10-day period can result in a significant reduction of pain with increased mobility and a tendency to decreased autonomic dysregulation.

Journal Article↗

Simultaneous representation of saccade targets and visual onsets in monkey lateral intraparietal area.

The monkey's lateral intraparietal area (LIP) has been associated with attention and saccades. LIP neurons have visual on-responses to objects abruptly appearing in their receptive fields (RFs) and sustained activity preceding saccades to the RF. We studied the relationship between the on-responses and delay activity in LIP using a 'stable-array' task. Monkeys viewed eight distinct, continuously illuminated objects, arranged in a circle with at least one object in the RF. A cue flashed instructing the monkey to make a saccade, after a delay, to the stable object physically matching the cue. The location of the cue was fixed in trial blocks, either in or out of the RF. If the cue was outside the RF, neurons developed delay-period activity tuned for the direction of the saccade target at approximately 190 ms after cue onset. If the cue appeared in the RF, neurons initially responded to cue onset and developed tuning for saccade direction only toward the end of the delay period, 390 ms after cue onset. The cue- and saccade-target responses coexisted throughout a significant portion of the delay period. The results show that visual-on responses and delay-period activity in LIP are functionally separable, and that, although highly selective, the salience representation in LIP can contain more than one object at a time.

Animals↗

Prefrontal neurons coding suppression of specific saccades.

The prefrontal cortex has been implicated in the suppression of unwanted behavior, based upon observations of humans and monkeys with prefrontal lesions. Despite this, there has been little direct neurophysiological evidence for a mechanism that suppresses specific behavior. In this study, we used an oculomotor delayed match/nonmatch-to-sample task in which monkeys had to remember a stimulus location either as a marker of where to look or as a marker of where not to look. We found a group of neurons in both the frontal eye field and the caudal prefrontal cortex that carried signals selective for the forbidden stimulus. The activity of these "don't look" neurons correlated with the monkeys' success or failure on the task. These results demonstrate a frontal signal that is related to the active suppression of one action while the subject performs another.

Action Potentials↗

Neurons in monkey prefrontal cortex whose activity tracks the progress of a three-step self-ordered task.

The self-ordered task is a powerful tool for the analysis of dorsal prefrontal deficits. Each trial consists of a number of steps, and subjects must remember their choices in previous steps. The task becomes more difficult as the number of objects to be remembered increases. We recorded the activity of 156 neurons in the mid-dorsal prefrontal cortex of two rhesus monkeys performing an oculomotor version of the task. Although the task requires working memory, there was no convincing evidence for activity selective for the working memory of the objects that the monkey had to remember. Instead, nearly one-half of neurons (47%, 74/156) showed activity that was modulated according to the step of the task in any one or more task periods. Although the monkey's reward also increased with step, the neurons exhibited little or no step modulation in a reward control task in which reward increased without a concurrent increase in task difficulty. The activity of some neurons was also selective for the location of saccade target that the monkey voluntarily chose. Neurons showed less step modulation in error trials, and there was no increase between the second and third step responses on trials in which the error was on the third step. These results suggest that the mid-dorsal prefrontal cortex contributes to the self-ordered task, not by providing an object working memory signal, but by regulating some general aspect of the performance in the difficult task.

Action Potentials↗

A rapid and precise on-response in posterior parietal cortex.

The activity of neurons in the lateral intraparietal area (LIP) of the monkey predicts the monkey's allocation of spatial attention. We show here that despite being relatively high within the visual hierarchy, neurons in LIP have extremely short and precise visual latencies. Mean latency was 45.2 msec; the timing precision of the onset response was usually better than 4 msec. The majority of neurons had a pause in response after an initial burst, followed by more sustained visual activity. Previous attention allocation had no effect on either the latency or magnitude of the initial burst, but produced clear effects on the magnitude of the later sustained activity. Together, these data indicate that the initial burst in LIP visual response reflects an uncontaminated sensory signal. Information about stimulus onset is transmitted rapidly through the visual system to LIP; the on-response has a higher speed and temporal precision than realized previously. This information could be used to orient attention to novel objects in the visual environment rapidly and reliably.

Animals↗

Art and the brain: the influence of art on Roger Shepard's studies of mental rotation.

This paper explores the influence of visual sources on Roger N. Shepard's 1971 mental rotation experiments and the centrality of ambiguity as one of his experimental and artistic concerns. Sources include Shepard's statements about ambiguity as expressed in the book, Mind Sights, and a recent interview. Parallel investigations of ambiguity by the contemporary artists Al Held and Robert Smithson are considered. Shepard utilized a wide range of visual sources while formulating his experimental design, namely Necker cube illusions, hypnopompic images, René Magritte, and M.C. Escher. In addition, he drew upon key art historical theses of the time, such as Ernst Gombrich's theories about schemas. For Shepard as for Gombrich, the world of appearances is a world of ambiguity.

Art↗

Modafinil improves recovery after general anesthesia.

UNLABELLED: Recovery from general anesthesia often involves residual sedation, drowsiness, fatigue, and lack of energy that may last hours to days. Modafinil is a wakefulness-promoting drug approved for patients with excessive daytime sleepiness associated with narcolepsy. We evaluated the effect of single doses of modafinil (200 mg) and placebo in patients recovering from general anesthesia. Thirty-four subjects participated in this prospective, randomized, double-blind study approved by our IRB. Preoperatively, patients were asked to rate various symptoms they had experienced over the previous 24-h using a verbal analog scale (VAS) of 0 to 10 as well as discrete scale when indicated. Postoperatively, once the patient was able to tolerate oral intake and met our institutional discharge criteria, the study drug (modafinil 200 mg or placebo) was administered with a sip of water. Patients were contacted 24 (1) hours after dosing to evaluate postdischarge symptoms. Patients in the placebo group reported significantly more postoperative fatigue (4.8 [3.3] versus 1.4 [1.8]), exhaustion (4.3 [3.3] versus 2.4 [3.1]), or degree of feeling worn out (4.7 [3.6] versus 2.9 [2.4]). Significantly more patients reported moderate to severe fatigue in the placebo group (65% versus 12%). Two major themes of "alertness" and "energy" were expressed by 71% of the patients receiving modafinil versus 18% of those receiving placebo. Patients recovering from general anesthesia can significantly benefit from modafinil. IMPLICATIONS: Modafinil significantly reduces fatigue and improves feelings of alertness and energy in postoperative patients. Patients recovering from general anesthesia can significantly benefit from modafinil administration.

Adolescent↗

Analgesic and hemodynamic effects of a single 7.5-mg intravenous dose of morphine in patients with moderate-to-severe postoperative pain.

STUDY OBJECTIVES: To evaluate the analgesic and hemodynamic effects of a single dose of intravenous morphine 7.5 mg in patients experiencing moderate-to-severe postoperative pain, and to determine any gender differences in analgesic response. DESIGN: Randomized, double-blind, parallel-group, multicenter study. SETTING: Postanesthesia care unit of a university teaching hospital. PATIENTS: Eighty-eight patients who underwent total abdominal hysterectomy or prostatectomy. INTERVENTION: Thirty-seven patients received a single dose of morphine sulfate 7.5 mg and 51 patients received placebo, both administered intravenously for 1 minute. MEASUREMENTS AND MAIN RESULTS: Overall, morphine had no significant effect on systolic or diastolic blood pressure, heart rate, oxygen saturation, or respiratory rate. Compared with baseline, morphine significantly reduced pain intensity at 2, 5, and 10 minutes after administration (p<0.05). The difference in pain intensity between patients who received morphine and those who received placebo, however, was significant only at the 5-minute time point (p<0.02). Patients receiving morphine also reported mild pain relief at 2 and 5 minutes after its administration. Peak analgesic effect was reported 2 minutes after its administration in three quarters of the patients. Significant gender differences also were observed in response to analgesic effect. In women, no significant differences in pain intensity were seen at any time between the morphine and placebo groups, whereas in men receiving morphine, pain intensity was significantly less at 2, 5, and 10 minutes compared with baseline and that seen in the placebo group. Women were generally more satisfied with their pain treatment than were men. CONCLUSION: A single 7.5-mg intravenous bolus dose of morphine did not appear to provide adequate reduction in perceived pain intensity in patients with moderate-to-severe postoperative pain. In addition, in contrast to the findings of other experimental pain studies, our data suggest that women are more tolerant of postoperative pain than are men.

Adult↗