Impact of repetitive mouse clicking on forearm muscle fatigue and mouse aiming performance.

Exercise induced performance fatigue has been shown to impair many aspects of fine motor function in the distal upper limb. However, most fatiguing protocols do not reflect the conditions experienced with computer use. The purpose of this study was to determine how a prolonged, low-force mouse clicking fatigue protocol impacts performance fatigue of the distal upper limb for gamers and non-gamers. Participants completed a total of 1 h of mouse clicking at 5 clicks per second. Muscle fatigue and performance were intermittently assessed. RMS amplitude increased for the forearm flexors throughout the fatigue protocol. Accuracy decreased following the first bout of clicking and returned to baseline values after 40-min. EDC and ECU displayed the greatest muscle activity while aiming, producing 11.4% and 12.9% of MVC, respectively. These findings indicate that mouse clicking may not result in performance fatigue, however, high levels of extensor activity may explain common injuries among gamers.

Sex Difference in Lower-limb Electromyography and Kinematics when Using Resistance Bands during a Barbell Back Squat.

The aim of this study was to compare the muscle activity of the gluteus medius (GMe), gluteus maximus (GMa), biceps femoris (BF), vastus lateralis (VL), vastus medialis (VM) and erector spinae (ES) as well as medial knee displacement (MKD) while using varying stiffness resistance bands (red: 1.68 kg; black: 3.31 kg; gold: 6.44 kg) during a barbell back squat (BBS) among males and females. A total of 23 (females: 11) resistance trained people were recruited for this study. Muscle activity was measured using electromyography, and motion capture cameras tracked lower-limb kinematics and MKD. Three resistance bands were placed at the distal end of the femur while performing a BBS at their 85% repetition maximum (RM). Parametric and non-parametric statistical analyses were conducted with the alpha level of 0.05. The gold resistance band resulted in a smaller knee-width-index value (i.e., greater MKD) compared to other bands (p < 0.01). Males exhibited less MKD compared to females during the BBS for each resistance band (p = 0.04). Males produced greater VL activity when using the black and gold resistance bands during the BBS (p = 0.03). When using a gold resistance band, the GMe muscle activation was higher compared to other resistance bands (p < 0.01). VM muscle activity was reduced when using a gold resistance band compared to no band condition (p < 0.01). BF (p = 0.39) and ES (p = 0.88) muscle activity did not change when using different resistance bands. As a result, females may be at a biomechanical disadvantage when using resistance bands compared to males while performing the BBS hindering them from optimal performance.

The effects of isometric hand grip force on wrist kinematics and forearm muscle activity during radial and ulnar wrist joint perturbations.

The purpose of this work was to investigate forearm muscle activity and wrist angular displacement during radial and ulnar wrist perturbations across various isometric hand grip demands. Surface electromyography (EMG) was recorded from eight muscles of the upper extremity. A robotic device delivered perturbations to the hand in the radial and ulnar directions across four pre-perturbation grip magnitudes. Angular displacement and time to peak displacement following perturbations were evaluated. Muscle activity was evaluated pre- and post-perturbation. Results showed an inverse relationship between grip force and angular displacement (p ≤ 0.001). Time to peak displacement decreased as grip force increased (p ≤ 0.001). There was an increase in muscle activity with higher grip forces across all muscles both pre-and post-perturbation (p ≤ 0.001) and a greater average muscle activity in ulnar as compared to radial deviation (p = 0.02). This work contributes to the wrist joint stiffness literature by relating wrist angular displacement to grip demands during novel radial/ulnar perturbations and provides insight into neuromuscular control strategies.

Influence of muscle fatigue on motor task performance of the hand and wrist: A systematic review.

Muscle fatigue is represented as a reduction in force production capability; however, fatigue does not necessarily result in performance impairments. As the distal upper limb serves as the end effector when interacting or manipulating objects, it is important to understand how muscle fatigue may impact motor functionality. The aim of this study was to systematically review the literature to identify how various aspects of motor performance of the distal upper limb are impaired following muscle fatigue. Four databases were searched using 23 search terms describing the distal upper limb, muscle fatigue, and various performance metrics. A total of 4561 articles were screened with a total of 28 articles extracted and critically appraised. Evidence extracted indicates that muscle fatigue results in unique impairments based on the type of motor performance being evaluated. Furthermore, much data suggests that muscle fatigue does not result in consistent, predictable performance impairments, particularly while performing submaximal tasks. Additionally, magnitude of fatigue does not directly correlate with reductions in performance outcomes at the hand and wrist. Fatiguing protocols used highlighted the importance of fatigue specificity. When fatiguing and performance tasks are similar, performance impairment is likely to be observed. The numerous muscles found in the hand and wrist, often considered redundant, play a critical role in maintaining task performance in the presence of muscle fatigue. The presence of motor abundance (e.g. multiple muscles with similar function) is shown to reduce the impairment in multiple performance metrics by compensating for reduced function of fatigued muscles. Continued exploration into various fatiguing protocols (i.e. maximal or submaximal) will provide greater insights into performance impairments in the distal upper limb.

Wrist extensor muscle activity is less task-dependent than wrist flexor muscle activity while simultaneously performing moderate-to-high handgrip and wrist forces.

The aim of this study was to characterise wrist extensor and flexor muscle activity during combinations of moderate-to-high handgrip and wrist forces that are similar to actions and intensities used in many workplace settings. Surface electromyography was recorded from three wrist flexors and three wrist extensors while participants performed simultaneous handgrip forces and wrist forces ranging in intensities from 15% to 60% of maximum. While the wrist flexors were highly task-dependent, in that their activity significantly changed between conditions, wrist extensor activity was consistently high throughout the experiment. Wrist joint co-contraction was also significantly higher when the wrist extensors were functioning as the antagonists. These findings suggest that the wrist extensors likely demonstrate consistently higher muscleactivity during most tasks of the hand and wrist, which is likely a leading mechanism behind why they develop chronic overuse injuries more frequently than the wrist flexors. Practitioner Summary: This study was conducted to identify forearm muscle activity patterns that might help explain why the wrist extensors develop overuse injuries more frequently than the flexors. Results demonstrated that the wrist extensors are consistently, highly active during combined handgrip and wrist forces and exhibit no periods of low muscle activity.Abbreviations: BB: biceps brachii; ECR: extensor carpi radialis; ECU: extensor carpi ulnaris; ED: extensor digitorum; EMG: electromyography; ES: effect size; FCR: flexor carpi radialis; FCU: flexor carpi ulnaris; FDS: flexor digitorum superficialis; MVC: maximal voluntary contraction; MVE: maximal voluntary excitation; SD: standard deviation; SE: standard error; TB: triceps brachii.

THERABAND® CLX gold reduces knee-width index and range of motion during overhead, barbell squatting.

This study examined the influence of the TherabandTM CLX gold band on lower-limb muscle activity and kinematics during an overhead barbell squat. Participants performed two sets (band and no-band) of 12 repetitions of overhead barbell squats at 25% bodyweight. Three-dimensional kinematics were measured using motion capture with rigid bodies placed bilaterally on the foot, shank, thigh and thorax. Electromyography was collected from seven, bilateral muscles of the lower-limb and was unchanged for all muscles between conditions. Medial knee collapse was calculated using a knee-width index (KWI) ratio of the distance between the lateral epicondyles of the femur and the lateral malleoli. Average KWI was smaller during the band condition for the concentric (No band: 0.99 ± 0.05, Band: 0.97 ± 0.06, p < 0.05) and eccentric phases (No band: 1.00 ± 0.06, Band: 0.97 ± 0.05, p < 0.05). KWI was significantly smaller with the use of the TherabandTM CLX. As the gold band is the strongest of the CLX offerings, any benefit of increased proprioception may have been lost due to the high resistance of the band. Further research examining the dose-response of elastic band resistance to knee alignment may be needed to inform proper exercise prescription.

Sustained Isometric Wrist Flexion and Extension Maximal Voluntary Contractions Similarly Impair Hand-Tracking Accuracy in Young Adults Using a Wrist Robot.

Due to their stabilizing role, the wrist extensor muscles demonstrate an earlier onset of performance fatigability and may impair movement accuracy more than the wrist flexors. However, minimal fatigue research has been conducted at the wrist. Thus, the purpose of this study was to examine how sustained isometric contractions of the wrist extensors/flexors influence hand-tracking accuracy. While gripping the handle of a three-degrees-of-freedom wrist manipulandum, 12 male participants tracked a 2:3 Lissajous curve (±32° wrist flexion/extension; ±18° radial/ulnar deviation). A blue, circular target moved about the trajectory and participants tracked the target with a yellow circle (corresponding to the handle's position). Five baseline tracking trials were performed prior to the fatiguing task. Participants then exerted either maximal wrist extension or flexion force (performed on separate days) against a force transducer until they were unable to maintain 25% of their pre-fatigue maximal voluntary contraction (MVC). Participants then performed 7 tracking trials from immediately post-fatigue to 10 min after. Performance fatigability was assessed using various metrics to account for errors in position-tracking, error tendencies, and movement smoothness. While there were no differences in tracking error between flexion/extension sessions, tracking error significantly increased immediately post-fatigue (Baseline: 1.40 ± 0.54°, Post-fatigue: 2.02 ± 0.51°, P < 0.05). However, error rapidly recovered, with no differences in error from baseline after 1-min post-fatigue. These findings demonstrate that sustained isometric extension/flexion contractions similarly impair tracking accuracy of the hand. This work serves as an important step to future research into workplace health and preventing injuries of the distal upper-limb.

Dynamic Wrist Flexion and Extension Fatigue Induced via Submaximal Contractions Similarly Impairs Hand Tracking Accuracy in Young Adult Males and Females.

We evaluated the effects of muscle fatigue on hand-tracking performance in young adults. Differences were quantified between wrist flexion and extension fatigability, and between males and females. Participants were evaluated on their ability to trace a pattern using a 3-degrees-of-freedom robotic manipulandum before (baseline) and after (0, 1, 2, 4, 6, 8, and 10 mins) a submaximal-intensity fatigue protocol performed to exhaustion that isolated the wrist flexors or extensors on separate days. Tracking tasks were performed at all time points, while maximal voluntary contractions (MVCs) were performed at baseline, and 2, 6-, and 10-mins post-task termination. We evaluated movement smoothness (jerk ratio, JR), shape reproduction (figural error, FE), and target tracking accuracy (tracking error, TE). MVC force was significantly lower in females (p < 0.05), lower than baseline for all timepoints after task termination (p < 0.05), with no muscle group-dependent differences. JR did not return to baseline until 10-mins post-task termination (most affected), while FE returned at 4-mins post-task termination, and TE at 1-min post-task termination. Males tracked the target with significantly lower JR (p < 0.05), less TE (p < 0.05), and less FE (p < 0.05) than females. No muscle group-dependent changes in hand-tracking performance were observed. Based on this work, hand tracking accuracy is similarly impaired following repetitive submaximal dynamic wrist flexion or extension. The differences between male and female fatigability was independent of the changes in our tracking metrics.

Sustained Isometric Wrist Flexion and Extension Maximal Voluntary Contractions on Corticospinal Excitability to Forearm Muscles during Low-Intensity Hand-Gripping.

The wrist extensors demonstrate an earlier fatigue onset than the wrist flexors. However, it is currently unclear whether fatigue induces unique changes in muscle activity or corticospinal excitability between these muscle groups. The purpose of this study was to examine how sustained isometric wrist extension/flexion maximal voluntary contractions (MVCs) influence muscle activity and corticospinal excitability of the forearm. Corticospinal excitability to three wrist flexors and three wrist extensors were measured using motor evoked potentials (MEPs) elicited via transcranial magnetic stimulation. Responses were elicited while participants exerted 10% of their maximal handgrip force, before and after a sustained wrist flexion or extension MVC (performed on separate sessions). Post-fatigue measures were collected up to 10-min post-fatigue. Immediately post-fatigue, extensor muscle activity was significantly greater following the wrist flexion fatigue session, although corticospinal excitability (normalized to muscle activity) was greater on the wrist extension day. Responses were largely unchanged in the wrist flexors. However, for the flexor carpi ulnaris, normalized MEP amplitudes were significantly larger following wrist extension fatigue. These findings demonstrate that sustained isometric flexion/extension MVCs result in a complex reorganization of forearm muscle recruitment strategies during hand-gripping. Based on these findings, previously observed corticospinal behaviour following fatigue may not apply when the fatiguing task and measurement task are different.

Characterizing forearm muscle activity in university-aged males during dynamic radial-ulnar deviation of the wrist using a wrist robot.

Functioning as wrist stabilizers, the wrist extensor muscles exhibit higher levels of muscle activity than the flexors in most distal upper-limb tasks. However, this finding has been derived mostly from isometric or wrist flexion-extension protocols, with little consideration for wrist dynamics or radial-ulnar wrist deviations. The purpose of this study was to assess forearm muscle activity during the execution of dynamic wrist radial-ulnar deviation in various forearm orientations (pronation/supination). In 12 healthy university-aged males, surface electromyography (EMG) was recorded from eight muscles of the dominant arm: flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), extensor carpi radialis (ECR), extensor carpi ulnaris (ECU), extensor digitorum (ED), biceps brachii (BB) and triceps brachii (TB). While grasping a handle, participants performed dynamic radial-ulnar deviation using a three-degrees-of-freedom wrist manipulandum. The robotic device applied torque to the handle, in either a radial or ulnar direction, and in one of three forearm postures (30° supinated/neutral/30° pronated). Results indicated that forearm posture influenced the muscles acting upon the hand (FDS/ED), whereas movement phase (concentric-eccentric) and torque direction influenced nearly every muscle. The ECR demonstrated the greatest task-dependency of all forearm muscles, which is possibly reflective of forearm muscle lines of action. Co-contraction ratios were much higher in radial trials than ulnar (Radial: 1.20 ± 0.78, Ulnar: 0.28 ± 0.18, P < 0.05), suggesting greater FCU and ECU contribution to wrist joint stability in radial-ulnar movement. These findings highlight a greater complexity of wrist extensor function than has previously been reported in isometric work.

Characterizing forearm muscle activity in young adults during dynamic wrist flexion-extension movement using a wrist robot.

Current research suggests that the wrist extensor muscles function as the primary stabilizers of the wrist-joint complex. However, most investigations have utilized isometric study designs, with little consideration for wrist dynamics or changes in posture. The purpose of the present study was to assess forearm muscle activity during the execution of dynamic wrist flexion/extension in multiple forearm orientations (pronation/supination). In 12 young adult males, surface electromyography (EMG) was recorded from eight muscles of the dominant arm: flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), extensor carpi radialis (ECR), extensor carpi ulnaris (ECU), extensor digitorum (ED), biceps brachii (BB) and triceps brachii (TB). While grasping a handle, participants performed dynamic wrist flexion/extension using a three-degrees-of-freedom wrist manipulandum. The robotic device applied torque to the handle, in either a flexion or extension direction, and in one of three forearm postures (30° supinated/neutral/30° pronated). Results indicated that forearm posture had minimal influence on forearm muscle activity, but significantly altered the activity of the biceps and triceps brachii. Movement phase (concentric-eccentric) dictated muscle activity in every muscle. Interestingly, muscle activity in the eccentric phase was equal between the two applied handle torques, regardless of whether the muscle acted as the agonist or antagonist. Co-contraction ratios were higher in the flexion conditions (flexion: 2.28 ± 2.04, extension: 0.32 ± 0.27), suggesting significantly greater wrist extensor activity-likely a contribution to wrist joint stability. This highlights the vulnerability of the wrist extensor muscles to overuse injuries in settings requiring prolonged use of dynamic wrist exertions.

Investigating the Muscular and Kinematic Responses to Sudden Wrist Perturbations During a Dynamic Tracking Task.

Sudden disturbances (perturbations) to the hand and wrist are commonplace in daily activities and workplaces when interacting with tools and the environment. It is important to understand how perturbations influence forearm musculature and task performance when identifying injury mechanisms. The purpose of this work was to evaluate changes in forearm muscle activity and co-contraction caused by wrist perturbations during a dynamic wrist tracking task. Surface electromyography was recorded from eight muscles of the upper-limb. Participants performed trials consisting of 17 repetitions of ±40° of wrist flexion/extension using a robotic device. During trials, participants received radial or ulnar perturbations that were delivered during flexion or extension, and with known or unknown timing. Co-contraction ratios for all muscle pairs showed significantly greater extensor activity across all experimental conditions. Of all antagonistic muscle pairs, the flexor carpi radialis (FCR)-extensor carpi radialis (ECR) muscle pair had the greatest change in co-contraction, producing 1602% greater co-contraction during flexion trials than during extensions trials. Expected perturbations produced greater anticipatory (immediately prior to the perturbation) muscle activity than unexpected, resulting in a 30% decrease in wrist displacement. While improving performance, this increase in anticipatory muscle activity may leave muscles susceptible to early-onset fatigue, which could lead to chronic overuse injuries in the workplace.

Upper extremity posture and muscle activity during IV pole interaction.

Background. The physical demands associated with patient handling activities have been well documented in healthcare. However, many activities contribute to the physical demands of caregivers. Our purpose was to evaluate upper extremity muscle activity and kinematics during intravenous (IV) pole interaction. Materials and methods. Muscle activity was measured from six muscles using surface electromyography and joint kinematics were measured using motion capture. Participants performed two IV pole tasks: loading an IV bag and a medical device onto the pole. Two poles were evaluated: a traditional IV pole and a redesigned pole with ergonomic considerations. Results. Cervical extensor activity was significantly greater for the bag task with the traditional pole (43.29 ± 5.10% maximal voluntary exertion) compared to the redesigned pole (28.55 ± 3.42% maximal voluntary exertion). Peak right shoulder flexion was reduced from 102.88° ± 32.42° with the traditional pole to 55.44° ± 19.59° with the redesigned pole. Conclusion. Interactions with a traditional pole are comparable to upper extremity muscle activity during manual patient handling transfers. The redesigned pole reduced shoulder flexion during bag attachment, leading to less time in an overhead posture. Caregivers frequently interact with IV poles and reducing the physical demands associated with pole use could aid in a reduction of musculoskeletal disorders.

The influence of simultaneous handgrip and wrist force on forearm muscle activity.

The purpose of this study was to examine forearm muscle activity during simultaneous execution of dual motor tasks; hand-gripping and wrist forces. Surface electromyography was recorded from eight muscles of the upper-limb: flexor carpi radialis, flexor carpi ulnaris, flexor digitorum superficialis, extensor carpi radialis, extensor carpi ulnaris, extensor digitorum, biceps brachii and triceps brachii. Participants were seated with their forearm supported in a neutral position with an adjustable force transducer placed on either the palmar or dorsal side of the hand (for palmar/dorsal forces). Participants performed trials of simultaneous handgrip and wrist forces of various magnitudes, ranging in intensity from 0 to 40% of their maximal voluntary contraction. Trials lasted 5 s and force and electromyography data were assessed. The wrist flexors provided greatest contributions to tasks dominated by palmar forces but exhibited very low muscle activity in dorsal dominant tasks. Wrist extensors were active at moderate-to-high levels across nearly all conditions and demonstrated greater activity than the wrist flexors during handgrip-dominant tasks. These findings suggest that the wrist extensors provide the greatest contribution to wrist stiffness in complex motor tasks, and highlight the importance of investigating forearm muscle recruitment strategies under dual task parameters.

Changes in Corticospinal and Spinal Excitability to the Biceps Brachii with a Neutral vs. Pronated Handgrip Position Differ between Arm Cycling and Tonic Elbow Flexion.

The purpose of this study was to examine the influence of neutral and pronated handgrip positions on corticospinal excitability to the biceps brachii during arm cycling. Corticospinal and spinal excitability were assessed using motor evoked potentials (MEPs) elicited via transcranial magnetic stimulation (TMS) and cervicomedullary-evoked potentials (CMEPs) elicited via transmastoid electrical stimulation (TMES), respectively. Participants were seated upright in front on arm cycle ergometer. Responses were recorded from the biceps brachii at two different crank positions (6 and 12 o'clock positions relative to a clock face) while arm cycling with neutral and pronated handgrip positions. Responses were also elicited during tonic elbow flexion to compare/contrast the results to a non-rhythmic motor output. MEP and CMEP amplitudes were significantly larger at the 6 o'clock position while arm cycling with a neutral handgrip position compared to pronated (45.6 and 29.9%, respectively). There were no differences in MEP and CMEP amplitudes at the 12 o'clock position for either handgrip position. For the tonic contractions, MEPs were significantly larger with a neutral vs. pronated handgrip position (32.6% greater) while there were no difference in CMEPs. Corticospinal excitability was higher with a neutral handgrip position for both arm cycling and tonic elbow flexion. While spinal excitability was also higher with a neutral handgrip position during arm cycling, no difference was observed during tonic elbow flexion. These findings suggest that not only is corticospinal excitability to the biceps brachii modulated at both the supraspinal and spinal level, but that it is influenced differently between rhythmic arm cycling and tonic elbow flexion.

Neuroscience findings in AIDS: a review of research sponsored by the National Institute of Mental Health.

1. The human immunodeficiency virus (HIV-1) infects cells in both the immune system and the brain, but these effects are not independent. 2. Research funded by the National Institute of Mental Health (NIMH) has been directed at identifying some of the mechanisms by which HIV-1 infects the brain, produces pathology, causes behavioral changes, and alters immune responses. 3. HIV-1-associated peptides have been shown to produce immunological changes without active virus present and there is also evidence that neurological damage may result not from direct viral action, by via excitotoxin production. 4. Rhesus macaque monkeys infected with simian immunodeficiency virus (SIV) are proving to be a useful model of the neurological and behavioral changes identified in human AIDS patients; behavioral changes observed in monkeys are similar to those seen in humans infected with HIV-1. 5. Studies examining the relationship between the brain and immune system are identifying the role that the macrophage cytokine interleukin-1 may play in suppressing T-lymphocyte activity by two pathways, both mediated by corticotropin releasing factor (CRF). 6. One pathway involves the pituitary-adrenal axis and release of glucocorticoids while the other involves direct interaction with the sympathetic noradrenergic nervous system, which has been shown to innervate T-lymphocytes in the spleen and thymus. 7. These observations are relevant because macrophages infected with HIV-1 infiltrate the brain and may release substances that damage the brain. 8. Stress may affect these pathways via the CRF-mediated release of glucocorticoids; a model of stress has also demonstrated that stress can suppress the cellular immune response.

Minipump clorgyline administration and CSF amine metabolites in unrestrained monkeys.

The irreversible MAO-A inhibitor clorgyline was administered in doses of 0.5 mg/kg (N = 1), 1 mg/kg (N = 3), and 2 mg/kg (N = 1) to 5 young (age 5.5 to 23.9 months) pigtail (M. nemestrina) monkeys using a 28-day (Alza 2ML4) osmotic minipump. CSF MHPG, 5-HIAA, HVA, and plasma MHPG were measured before and at approximately weekly intervals after pump implantation. Implants were well tolerated. CSF MHPG decreased about 75%, 5-HIAA 30%, and HVA from 30-50% with a tendency to plateau by the second week. Plasma MHPG decreased to undetectable levels. The findings demonstrate that long-term inhibition of MAO-A can be produced in unrestrained monkeys by minipump administered clorgyline. There is an apparently greater effect on the norepinephrine system relative to the serotonin and dopamine systems.

Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase.

Two individuals with an X-chromosomal deletion were recently found to lack the genes encoding monoamine oxidase type A (MAO-A) and MAO-B. This abnormality was associated with almost total (90%) reductions in the oxidatively deaminated urinary metabolites of the MAO-A substrate, norepinephrine, and with marked (100-fold) increases in an MAO-B substrate, phenylethylamine, confirming systemic functional consequences of the genetic enzyme deficiency. However, urinary concentrations of the deaminated metabolites of dopamine and serotonin (5-HT) were essentially normal. To investigate other deaminating systems besides MAO-A and MAO-B that might produce these metabolites of dopamine and 5-HT, we examined plasma amine oxidase (AO) activity in these two patients and two additional patients with the same X-chromosomal deletion. Normal plasma AO activity was found in all four Norrie disease-deletion patients, in four patients with classic Norrie disease without a chromosomal deletion, and in family members of patients from both groups. Marked plasma amine metabolite abnormalities and essentially absent platelet MAO-B activity were found in all four Norrie disease-deletion patients, but in none of the other subjects in the two comparison groups. These results indicate that plasma AO is encoded by gene(s) independent of those for MAO-A and MAO-B, and raise the possibility that plasma AO, and perhaps the closely related tissue AO, benzylamine oxidase, as well as other atypical AOs or MAOs encoded independently from MAO-A and MAO-B may contribute to the oxidative deamination of dopamine and 5-HT in humans.

Intravenous physostigmine increases cerebrospinal fluid neuropeptide-Y.

The ability to measure directly central nervous system (CNS) neurotransmitter changes after an acute pharmacological challenge would be a useful clinical tool in psychiatric research. As one approach to this possibility, we attempted to measure cerebrospinal fluid (CSF) neuropeptide changes produced by an intravenous infusion of the indirect cholinergic agonist physostigmine. Six rhesus monkeys, with indwelling CSF catheters, had serial CSF samples removed before and after a 15 micrograms/kg physostigmine infusion. Five of six monkeys studied showed at least a 50% increase in CSF neuropeptide-Y (NPY) levels. Normal human subjects (n = 27) had CSF sampled before and 15, 30, and 45 min after an acute intravenous infusion of physostigmine (either 0, 5, or 15 micrograms/kg). An Analysis of Variance revealed a significant (p = 0.04) dose-time interaction, suggesting that physostigmine increased CSF NPY at the 15 micrograms/kg dose. CSF levels of seven other neuropeptides remained unchanged. These results suggest that the pharmacological challenge paradigm can be adapted to CSF neuropeptides, providing new measures of CNS stimulus-induced response beyond the peripheral plasma determinations usually employed.

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the dog: effect of pargyline pretreatment.

Adult beagle dogs of either sex were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-HCl (2.5 mg/kg, i.v.) alone or after pretreatment with pargyline (5.0 mg/kg, s.c., twice), with pargyline alone, or were uninjected. Groups were killed 2 h, 3 weeks, or 3 months after injection, and several brain areas were assayed for biogenic amines and their synthetic and degradative enzymes. MPTP caused a massive and permanent loss of striatal dopamine, tyrosine hydroxylase, and 3,4-dihydroxyphenylalanine decarboxylase activities and the loss of cells within the substantia nigra pars compacta. Dopamine and norepinephrine also were depleted to various degrees in cortex, olfactory bulb, and hypothalamus; however, dopamine beta-hydroxylase activity in cortex was normal. There was no cell loss in the ventral tegmental area or locus ceruleus. The activities of monoamine oxidase (MAO)-A and MAO-B in cortex and caudate were not affected by MPTP. Despite a permanent loss of the nigrostriatal system, the dogs exhibited only a transient hypokinesia lasting 1-2 weeks. Pargyline pretreatment prevented the loss of striatal dopamine and cells from the substantia nigra, but did not prevent a prolonged but reversible decrease in the concentration of dopamine metabolites. It is argued that this apparent inhibition of MAO is due not to suicide inactivation of the enzyme by MPTP, but to reversible inhibition by accumulation of the pyridinium metabolite, 1-methyl-4-phenylpyridinium, selectivity in aminergic terminals.