Biomedical subjects

Luke A Henderson

Publications and source records attributed to Luke A Henderson.

14 recordsLinked to original sources

PubMed2006

Discrete changes in cortical activation during experimentally induced referred muscle pain: a single-trial fMRI study.

Noxious stimulation of skeletal muscle evokes pain that is often referred into distal areas. Despite referred pain being of significant clinical importance, the brain regions responsible for the perception of referred pain remain unexplored. The aim of this investigation is to define these regions using functional magnetic resonance imaging. We induced muscle pain by hypertonic saline injections (0.5 ml) into the tibialis anterior (TA) or flexor carpi radialis (FCR) muscle. TA injections evoked pain that was referred to the ankle/foot in 10/17 subjects, whereas FCR injections evoked pain that was projected into the wrist/hand in 6/12 subjects. Regional brain responses were statistically tested by convolving the temporal profile of the subjective pain intensity rating with the hemodynamic response function. For all subjects, signal increased in the region of primary somatosensory cortex (SI), which represents the leg or arm, that is, the area corresponding to the injection site. However, for those subjects who reported referred pain, signal intensity increases also occurred in the SI region representing the foot or hand. Interestingly, differential signal changes also occurred in anterior cingulate, cerebellar, and insular cortices. This is the first study to provide evidence of cortical differentiation in the processing of primary and referred pain.

Adult↗

PubMed2006

Hypotensive but not normotensive haemorrhage increases tryptophan hydroxylase-2 mRNA in caudal midline medulla.

Severe blood loss triggers shock, a precipitous hypotension and bradycardia. The integrity of (i) neurons in the vasodepressor region of the caudal midline medulla and (ii) central 5-HT neurotransmission are critical for the expression of haemorrhagic shock. This study investigated whether progressive blood loss triggers altered synthesis of 5-HT in the vasodepressor region of the caudal midline medulla by measuring changes in relative expression levels of tryptophan hydroxylase 2 (TpH 2) mRNA, the rate-limiting enzyme in the synthesis of neuronal 5-HT. Hypotensive but not normotensive haemorrhage triggered a significant increase in TpH 2 mRNA in the vasodepressor region of the caudal midline medulla, identifying an important role for 5-HT-containing caudal midline medullary neurons in haemorrhagic shock.

Animals↗

PubMed2005

Regional brain response patterns to Cheyne-Stokes breathing.

Cheyne-Stokes breathing (CSB) results from impaired integration of sensory information with respiratory motor output; however, regions mediating the disturbed control are unknown. We examined functional magnetic resonance imaging signals during CSB within sleep to determine affected areas. Two male patients with severe obstructive sleep apnea were scanned while asleep over multiple sessions during which they exhibited CSB. Significant signal increases coincident with apneic periods emerged bilaterally in the cerebellar cortex, hippocampus, mediodorsal thalamus, frontal cortex and precentral gyrus. Signals declined bilaterally in the anterior cingulate cortex and postcentral gyrus. The reduced activation in primary sensory cortex and increased signals prior to breathing onset in the motor cortex are consistent with loss of sensory stimulation by airflow, and with anticipatory action of the motor cortex prior to initiation of breathing. Hippocampal and anterior cingulate cortex participation likely reflect previously-demonstrated roles for initiating inspiratory efforts and resolving sensory information and motor action, respectively.

Adult↗

PubMed2005

Inspiratory loading elicits aberrant fMRI signal changes in obstructive sleep apnea.

We hypothesized that neural processes mediating deficient sensory and autonomic regulatory mechanisms in obstructive sleep apnea (OSA) would be revealed by responses to inspiratory loading in brain regions regulating sensory and motor control. Functional magnetic resonance imaging (fMRI) signals and physiologic changes were assessed during baseline and inspiratory loading in 7 OSA patients and 11 controls, all male and medication-free. Heart rate increases to inspiratory loading began earlier and load pressures were achieved later in OSA patients. Comparable fMRI changes emerged in multiple brain regions in both groups, including limbic, cerebellar, midbrain, and primary motor cortex. However, in OSA subjects, altered signals appeared in primary sensory thalamus and sensory cortex, supplementary motor cortex, cerebellar cortex and deep nuclei, cingulate, medial temporal, and insular cortices, right hippocampus, and midbrain. Signal delays occurred in basal ganglia. We conclude that areas mediating sensory and autonomic processes, and motor timing, are affected in OSA; many of these areas overlap regions of previously demonstrated gray matter loss.

Adult↗

PubMed2004

Functional magnetic resonance imaging during hypotension in the developing animal.

Hypotension in adult animals recruits brain sites extending from cerebellar cortex to the midbrain and forebrain, suggesting a range of motor and endocrine reactions to maintain perfusion. We hypothesized that comparable neural actions during development rely more extensively on localized medullary processes. We used functional MRI to assess neural responses during sodium nitroprusside challenges in 14 isoflurane-anesthetized kittens, aged 14-25 days, and seven adult cats. Baseline arterial pressure increased with age in kittens, and basal heart rates were higher. The magnitude of depressor responses increased with age, while baroreceptor reflex sensitivity initially increased over those of adults. In contrast to a decline in adult cats, functional MRI signal intensity increased significantly in dorsal and ventrolateral medullary regions and the midline raphe in the kittens during the hypotensive challenges. In addition, significant signal intensity differences emerged in cerebellar cortex and deep nuclei, dorsolateral pons, midbrain tectum, hippocampus, thalamus, and insular cortex. The altered neural responses in medullary baroreceptor reflex sites may have resulted from disinhibitory or facilitatory influences from cerebellar and more rostral structures as a result of inadequately developed myelination or other neural processes. A comparable immaturity of blood pressure control mechanisms in humans would have significant clinical implications.

Age Factors↗

PubMed2003

Functional magnetic resonance signal changes in neural structures to baroreceptor reflex activation.

The sequence of neural responses to exogenous arterial pressure manipulation remains unclear, especially for extramedullary sites. We used functional magnetic resonance imaging procedures to visualize neural responses during pressor (phenylephrine) and depressor (sodium nitroprusside) challenges in seven isoflurane-anesthetized adult cats. Depressor challenges produced signal-intensity declines in multiple cardiovascular-related sites in the medulla, including the nucleus tractus solitarius, and caudal and rostral ventrolateral medulla. Signal decreases also emerged in the cerebellar vermis, inferior olive, dorsolateral pons, and right insula. Rostral sites, such as the amygdala and hypothalamus, increased signal intensity as arterial pressure declined. In contrast, arterial pressure elevation elicited smaller signal increases in medullary regions, the dorsolateral pons, and the right insula and signal declines in regions of the hypothalamus, with no change in deep cerebellar areas. Responses to both pressor and depressor challenges were typically lateralized. In a subset of animals, barodenervation resulted in rises and falls of blood pressure that were comparable to these resulting from the pharmacological challenges but different regional neural responses, indicating that the regional signal intensity responses did not derive from global perfusion effects but from baroreceptor mediation of central mechanisms. The findings demonstrate widespread lateralized distribution of neural sites responsive to blood pressure manipulation. The distribution and time course of neural responses follow patterns associated with early and late compensatory reactions.

Anesthesia↗

PubMed2003

fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects.

Obstructive sleep apnea (OSA) patients exhibit altered sympathetic outflow, which may reveal mechanisms underlying the syndrome. We used functional MRI (fMRI) in 16 control and 10 OSA subjects who were free of cardiovascular or mood-altering drugs to examine neural responses to a forehead cold pressor challenge, which elicits respiratory slowing, bradycardia, and enhanced sympathetic outflow. The magnitude of cold-induced bradycardia was smaller, and respiratory slowing showed greater intersubject variability and reached a nadir later in OSA patients. Both groups showed similar signal changes to cold stimulation in multiple brain sites. However, signal increases emerged in OSA over controls in anterior and posterior cingulate and cerebellar and frontal cortex, whereas signals markedly declined in the ventral thalamus, hippocampus, and insula rather than rising as in controls. Anomalous responses often paralleled changes in breathing and heart rate. Medullary, midbrain areas and lentiform and cerebellar dentate nuclei also showed lower signals in OSA cases. Cold pressor physiological responses are modified in OSA and may result from both diminished and exaggerated responses in multiple brain structures.

Adult↗

PubMed2003

Somatic and visceral afferents to the 'vasodepressor region' of the caudal midline medulla in the rat.

Previous research has found that the integrity of a restricted region of the caudal midline medulla (including caudal portions of nucleus raphé obscurus and nucleus raphé pallidus) was critical for vasodepression (hypotension, bradycardia, decreased cardiac contractility) evoked either by haemorrhage or deep pain. In this anatomical tracing study we found that the vasodepressor part of the caudal midline medulla (CMM) receives inputs arising from spinal cord, spinal trigeminal nucleus (SpV) and nucleus of the solitary tract (NTS). Specifically: (i) a spinal-CMM projection arises from neurons of the deep dorsal horn, medial ventral horn and lamina X at all spinal segmental levels, with approximately 60% of the projection originating from the upper cervical spinal cord (C1-C4); (ii) a SpV-CMM projection arises primarily from neurons at the transition between subnucleus caudalis and subnucleus interpolaris; (iii) a NTS-CMM projection arises primarily from neurons in ventrolateral and medial subnuclei. In combination, the specific spinal, SpV and NTS regions which project to the CMM receive the complete range of somatic and visceral afferents known to trigger vasodepression. The role(s) of each specific projection is discussed.

Afferent Pathways↗

PubMed2002

Brain morphology associated with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by repeated occurrences of hypoxic, hypercapnic, and transient blood pressure elevation episodes that may damage or alter neural structures. Underdeveloped structures or pre-existing damage in brain areas may also contribute to the genesis of the syndrome. Brain morphology in 21 patients with OSA and in 21 control subjects was assessed using high-resolution T1-weighted magnetic resonance imaging. Three-dimensional brain images were obtained with voxels of approximately 1 mm3. Images were spatially normalized and segmented into gray matter, white matter, and cerebrospinal fluid. For each segment, regional volumetric differences were determined relative to age, handedness, and group (patients with OSA versus control subjects), using voxel-based morphometry, with OSA effects weighted by disease severity. A significant age effect on total gray matter was found in control subjects but not in patients with OSA. Diminished regional and often unilateral gray matter loss was apparent in multiple sites of the brain in patients with OSA, including the frontal and parietal cortex, temporal lobe, anterior cingulate, hippocampus, and cerebellum. Unilateral loss in well-perfused structures suggests onset of neural deficits early in the OSA syndrome. The gray matter loss occurs within sites involved in motor regulation of the upper airway as well as in areas contributing to cognitive function.

Adult↗

PubMed2002

Neural responses during Valsalva maneuvers in obstructive sleep apnea syndrome.

The repetitive upper airway muscle atonic episodes and cardiovascular sequelae of obstructive sleep apnea (OSA) suggest dysfunction of specific neural sites that integrate afferent airway signals with autonomic and somatic outflow. We determined neural responses to the Valsalva maneuver by using functional magnetic resonance imaging. Images were collected during a baseline and three Valsalva maneuvers in 8 drug-free OSA patients and 15 controls. Multiple cortical, midbrain, pontine, and medullary regions in both groups showed intensity changes correlated to airway pressure. In OSA subjects, the left inferior parietal cortex, superior temporal gyrus, posterior insular cortex, cerebellar cortex, fastigial nucleus, and hippocampus showed attenuated signal changes compared with controls. Enhanced responses emerged in the left lateral precentral gyrus, left anterior cingulate, and superior frontal cortex of OSA patients. The anterior cingulate, cerebellar cortex, and posterior insula exhibited altered response timing patterns between control and OSA subjects. The response patterns in OSA subjects suggest deficits in particular neural pathways that normally mediate the Valsalva maneuver and compensatory actions in other structures.

Adult↗

PubMed2002

Delta- and kappa-opioid receptors in the caudal midline medulla mediate haemorrhage-evoked hypotension.

In mammals blood loss can trigger, shock, an abrupt, life-threatening hypotension and bradycardia. In the halothane-anaesthetised rat this response is blocked by inactivation of a discrete, vasodepressor area in the caudal midline medulla (CMM). Haemorrhagic shock is blocked also by systemic or ventricular injections of the opioid antagonist, naloxone. This study investigated, in the halothane anaesthetised rat, the contribution of delta-, kappa- and mu-opioid receptors in the CMM vasodepressor region to haemorrhage-evoked shock (i.e. hypotension and bradycardia) and its recovery. It was found that microinjections into the CMM of the delta-opioid receptor antagonist, naltrindole delayed and attenuated the hypotension and bradycardia evoked by haemorrhage, but did not promote recompensation. In contrast, CMM microinjections of the kappa-opioid receptor antagonist, nor-binaltorphamine, although it did not alter haemorrhage-evoked hypotension and bradycardia, did lead to a rapid restoration of AP, but not HR. CMM microinjections of the mu-opioid receptor antagonist, CTAP had no effect on haemorrhage-evoked shock or recompensation. These data indicate that delta- and kappa- (but not mu-) opioid receptor-mediated events within the CMM contribute to the hypotension and bradycardia evoked by haemorrhage and the effectiveness of naloxone in reversing shock.

Animals↗

PubMed2002

Structural mechanisms underlying autonomic reactions in pediatric arousal.

Arousal provides an essential means to restore homeostasis following a system perturbation during a quiescent state. The classic definition of 'arousal' includes a constellation of cardiovascular, respiratory and somatic muscle characteristics, together with activation of the electrocorticogram (ECoG). At least two ascending activating systems, a ventral cholinergic and a serotonergic ascending system, both interacting with other regional neurotransmitter processes, contribute to electrocortical activation, with separate behaviors mediated by each system. A number of 'arousal' processes essential for survival operate at local levels, and interact with the systems that mediate cortical activation. These processes include cerebellar compensatory mechanisms which respond to extreme cardiovascular challenges, and limbic structures which respond to hypoxia or hypercarbia and the resultant dyspnea. The local processes show exceptional cortical arousing properties upon recruitment of some structures, such as the amygdala, which has major projections to ascending arousal systems. Components of arousal can emerge without ECoG activation and can be mediated at local levels which interact with ascending systems.

Journal Article↗

PubMed2002

Neural responses to intravenous serotonin revealed by functional magnetic resonance imaging.

We examined the sequence of neural responses to the hypotension, bradycardia, and apnea evoked by intravenous administration of 5-hydroxytryptamine (serotonin). Functional magnetic resonance imaging signal changes were assessed in nine isoflurane-anesthetized cats during baseline and after a bolus intravenous low dose (10 microg/kg) or high dose (20-30 microg/kg) of 5-hydroxytryptamine. In all cats, high-dose challenges elicited rapid-onset, transient signal declines in the intermediate portion of the solitary tract nucleus, caudal midline and caudal and rostral ventrolateral medulla, and fastigial nucleus of the cerebellum. Slightly delayed phasic declines appeared in the dentate and interpositus nuclei and dorsolateral pons. Late-developing responses also emerged in the solitary tract nucleus, parapyramidal region, periaqueductal gray, spinal trigeminal nucleus, inferior olivary nucleus, cerebellar vermis, and fastigial nucleus. Amygdala and hypothalamic sites showed delayed and prolonged signal increases. Intravenous serotonin infusion recruits cerebellar, amygdala, and hypothalamic sites in addition to classic brain stem cardiopulmonary areas and exhibits site-specific temporal patterns.

Animals↗

PubMed2002

Brain responses associated with the Valsalva maneuver revealed by functional magnetic resonance imaging.

The Valsalva maneuver, a test frequently used to evaluate autonomic function, recruits discrete neural sites. The time courses of neural recruitment relative to accompanying cardiovascular and breathing patterns are unknown. We examined functional magnetic resonance imaging signal changes within the brain to repeated Valsalva maneuvers and correlated these changes with physiological trends. In 12 healthy subjects (age, 30-58 yr), a series of 25 volumes (20 gradient echo echo-planar image slices per volume) was collected using a 1.5-Tesla scanner during a 60-s baseline and 90-s challenge period consisting of three Valsalva maneuvers. Regions of interest were examined for signal intensity changes over baseline and challenge conditions in cardiorespiratory-related regions. In addition, whole brain correlations between signal intensity and heart rate and airway load pressure were performed on a voxel-by-voxel basis. Significant signal changes, correlated with the time course of load pressure and heart rate, emerged within multiple areas, including the amygdala and hippocampus, insular and lateral frontal cortices, dorsal pons, dorsal medulla, lentiform nucleus, and fastigial and dentate nuclei of the cerebellum. Signal intensities peaked early in the Valsalva maneuver within the hippocampus and amygdala, later within the dorsal medulla, pons and midbrain, and deep cerebellar nuclei, and last within the lentiform nuclei and the lateral prefrontal cortex. The ventral pontine signals increased during the challenge, but not in a fashion correlated to load pressure or heart rate. Sites showing little or no correlation included the vermis and medial prefrontal cortex. These data suggest an initiating component arising in rostral brain areas, a later contribution from cerebellar nuclei, basal ganglia, and lateral prefrontal cortex, and a role for the ventral pons in mediating longer term processes.

Adult↗