Ron J. Balnave

The Midbrain Periaqueductal Gray Control of Respiration

The midbrain periaqueductal gray (PAG) organizes basic survival behavior, which includes respiration. How the PAG controls respiration is not known. We studied the PAG control of respiration by injecting d,l-homocysteic acid in the PAG in unanesthetized precollicularly decerebrated cats. Injections in different parts of the PAG caused different respiratory effects. Stimulation in the dorsomedial PAG induced slow and deep breathing and dyspnea. Stimulation in the dorsolateral PAG resulted in active breathing and tachypnea consistent with the respiratory changes during fright and flight. Stimulation in the medial part of lateral PAG caused inspiratory apneusis. Stimulation in lateral parts of the lateral and ventrolateral PAG produced respiratory changes associated with vocalization (mews, alternating mews and hisses, or hisses). d,l-Homocysteic acid injections in the caudal ventrolateral PAG induced irregular breathing. These results demonstrate that the PAG exerts a strong influence on respiration, suggesting that it serves as the behavioral modulator of breathing.

Roles of periaqueductal gray and nucleus tractus solitarius in cardiorespiratory function in the rat brainstem

Periaqueductal gray (PAG) and nucleus tractus solitarius (NTS) are important centres for regulation of cardiorespiratory function in cats. We aimed to study the effects of specific PAG stimulation on cardiorespiratory parameters in the rat. Microinjection of D, L-homocysteic acid (DLH) into dorsolateral PAG of anaesthetised rats, led to: marked increases in respiratory frequency (RF) and amplitude of diaphragmatic electromyogram, decreases in inspiratory and expiratory durations, and increased blood pressure and heart rate. Following injection of propranolol (150 pmol, 30 nl), a beta-adrenergic antagonist, into the commissural subnucleus of NTS, the DLH-induced increase in RF was markedly attenuated. Inspiratory neurones (late I cells) in NTS were excited upon stimulation of PAG and their increased activity was accompanied by increased RF. The changes in activity of the late I cells in response to stimulation of dorsolateral PAG provide physiological evidence of a link, possibly noradrenergic, between the two nuclei and involvement of the NTS in control of respiratory functions orchestrated by the PAG.

Variability of grip strength during isometric contraction

The use of measures of strength variability as a means of determining sincerity of effort is becoming a more common practice, particularly in medico-legal and rehabilitation settings. The stability of such variability measures, however, has not been documented. This research investigated, in two studies, the trial-to-trial variability of grip strength under maximal and submaximal effort conditions. In the first study, 63 subjects were asked to give 100% grip effort, and in the second study 40 subjects from the original group were asked to give 50% grip effort. The Jamar hand dynamometer was used to measure grip strength in both experiments, and a coefficient of variation (CV) was calculated for every three repeat measures at each handle position. Testing was conducted on two separate occasions for both experiments. Although the interoccasion reliability of grip strength was very high, in comparison, the CV was not stable over test occasions, with interoccasion reliability indices close to zero. Factors significantly influencing CV were effort level, with submaximal effort producing larger CVs, and gender, with females having greater strength variability. If the rule is applied that one or more CVs above the 7.5% cut-off value could indicate submaximal effort, then for this sample of subjects giving maximal effort, 97% of females and 64% of males would be misclassified. Applying a single CV classification cut-off value to a mixed sample of subjects appears to unfairly discriminate against the females. Further research into the factors associated with high CV values is essential before the CV can be used with any confidence in a clinical setting as a method for determining sincerity of effort.

Identification of different types of respiratory neurones in the dorsal brainstem nucleus tractus solitarius of the rat

In Nembutal anaesthetised, spontaneously breathing rats, stereotaxic mapping of the nucleus tractus solitarius (NTS) for respiratory neuronal activity was undertaken. Eight different types of respiratory cells were found between 0.25 and 1.5 mm lateral to midline, extending 0.5 mm caudal to 1.5 mm rostral to obex, and 0.4-1.5 mm below the dorsal surface. A study of the respiratory motor (diaphragm EMG) and neuronal responses to excitatory amino acid (EAA) stimulation of the NTS areas was undertaken. Electrical stimulation of the vagus nerve was employed to study the NTS cellular responses to activation of pulmonary afferents. The effects of chemical activation of the midbrain periaqueductal grey (PAG) on NTS respiratory neuronal activity were investigated. EAA microinjections into the ventrolateral NTS rostral to the obex resulted in an increase in respiratory motor frequency along with increases to inspiratory cell discharge, whilst microinjections into the medial NTS caudal to the obex caused respiratory depression. EAA stimulation of calamus scriptorius produced apnea. NTS inspiratory neurones were inhibited following stimulation of ipsilateral vagus nerve, suggesting their involvement in the Hering-Breuer reflex pathway. PAG stimulation caused excitation of the NTS inspiratory cells indicating the presence of an excitatory respiratory pathway between the two nuclei. Following beta-adrenergic antagonist pre-treatment of ventrolateral NTS, EAA microinjections into PAG did not evoke a cardiorespiratory effect. Based on the various findings the role of NTS in organising respiration in the rat is discussed.

Review of sincerity of effort testing

Occupational rehabilitation professionals have for many years recognised the need to develop methods to determine whether a genuinely maximal effort is being given during clinical strength testing. A number of different sincerity of effort tests have been devised in an attempt to satisfy this need, however, in most cases the accuracy and reliability of these tests have not been adequately researched. This article reviews three of the most commonly-used sincerity of effort tests.

Behavioural control of breathing in mammals: Role of the midbrain periaqueductal gray

Brainstem respiratory neurons play a critical role in the generation of basic breathing rhythm in mammals (Richter et al., 2001, Feldman et al., 2003). This basic respiratory rhythm is modified by neurons probably with behaviour roles to support development of emotional expressivity. Such modulatory neurons are thought to be hierarchically organised throughout the neuraxis from the cerebral cortex through to the brainstem and spinal cord (Holstege, 1991a,b). One area within this hierarchy, that has been shown to be involved in motor patterning of defensive behaviour (in rats and cats) and vocalization (in cats) is the midbrain periaqueductal gray (PAG) (Carrive et al., 1987, Zhang et al., 1994).

Responses of brainstem respiratory neurons to activation of midbrain periaqueductal gray in the rat.

Eupneic breathing has been shown to be affected by output from the midbrain periaqueductal gray matter (PAG) (Huang et al. 2000; Hayward et al. 2003; Subramanian et al. 2007). In the rat, anatomical tracing studies have demonstrated connections between the PAG and other brainstem areas. It is generally accepted that PAG efferents activate descending pathways that originate in the medulla (Holstege 1991b). The aims of our studies were to isolate and record from respiratory cells in the ventral respiratory group (VRG) and the nucleus tractus solitarius (NTS) regions of the rat brainstem and to examine the changes in firing patterns and timing of these cells following excitatory amino acid (EAA) stimulation of the PAG. We also investigated the effect of β-adrenergic blockade in the vlNTS on the PAG induced respiratory patterning.

Ventilation induced apnea and its effect on dorsal brainstem inspiratory neurones in the rat

The purpose of this study was to examine the effect of mechanical ventilation (MV) on inherent breathing and on dorsal brainstem nucleus tractus solitarius (NTS) respiratory cell function. In pentobarbitone-anaesthetised rats, application of MV at combined high frequencies and volumes (representing threshold levels) produced apnea. The apnea persisted as long as MV was maintained at or above the threshold frequency and volume. Following removal of MV, inherent breathing did not resume immediately, with the diaphragm exhibiting post-mechanical ventilation apnea. The fall in arterial P(CO2) (Pa(CO2)) levels evoked by MV-engendered hyperventilation was shown not to be the trigger for initiation of apnea. MV-induced apnea was immediately reversed by bilateral vagotomy. Further, MV-induced apnea could not be evoked in bilaterally vagotomized animals suggesting that vagal feedback is the critical pathway for its initiation. NTS inspiratory neurones were inhibited during both MV-induced apnea and post-mechanical ventilation apnea, implying the involvement of central neural mechanisms in mediating this effect.

The physiological motor patterns produced by neurons in the nucleus retroambiguus in the rat and their modulation by vagal, peripheral chemosensory and nociceptive stimulation.

The nucleus retroambiguus (NRA) is a neuronal cell group in the medullary ventrolateral tegmentum, rostrocaudally between the obex and the first cervical spinal segment. NRA neurons are premotor interneurons with direct projections to the motoneurons of soft palate, pharynx, and larynx in the nucleus ambiguus in the lateral medulla as well as to the motoneurons in the spinal cord innervating diaphragm, abdominal, and pelvic floor muscles and the lumbosacral motoneurons generating sexual posture. These NRA premotor interneurons receive very strong projections from the periaqueductal gray (PAG) in the context of basic survival mechanisms as fight, flight, freezing, sound production, and sexual behavior. In the present study in rat we investigated the physiological motor patterns generated by NRA neurons, as the result of vagal, peripheral chemosensory, and nociceptive stimulation. The results show that the NRA contains phasic respiratory modulated neurons, as well as nonphasic tonically modulated neurons. Stimulation in the various rostrocaudal levels of the NRA generates site‐specific laryngeal, respiratory, abdominal, and pelvic floor motor activities. Vagal and peripheral chemosensory stimulation induces both excitatory and inhibitory modulation of phasic NRA‐neurons, while peripheral chemosensory and nociceptive stimulation causes excitation and inhibition of nonphasic NRA‐neurons. These results are in agreement with the concept that the NRA represents a multifunctional group of neurons involved in the output of the emotional motor system, such as vomiting, vocalization, mating, and changes in respiration.