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Biomedical subjects

Richard D Lane

Publications and source records attributed to Richard D Lane.

14 recordsLinked to original sources

The role of vagal function in the risk for cardiovascular disease and mortality.

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The understanding of the risk factors for CVD may yield important insights into the prevention, etiology, course, and treatment of this major public health concern. We review the evidence for the role of vagal function in the risk for cardiovascular disease and mortality. Using a broad range of indicators of vagal function including resting heart rate, heart rate recovery, heart rate variability, and baroreflex sensitivity we show that decreased vagal function is associated with an increased risk for morbidity and mortality. These effects are independent of traditional risk factors. Moreover, we show that decreased vagal function is associated with both traditional and emerging risk factors as well as modifiable and non-modifiable risk factors. Most importantly, we provide evidence to support the notion that decreased vagal function precedes the development of a number of risk factors and that modification of risk profiles in the direction of lower risk is associated with increased vagal function. We close with a brief overview of the neural concomitants of vagal function and suggest that a model of neurovisceral integration may provide a unifying framework within which to investigate the impact of risk factors, including psychosocial factors, on cardiovascular disease.

Acetylcholine↗

Impaired self-awareness and theory of mind: an fMRI study of mentalizing in alexithymia.

Alexithymic individuals have difficulty in recognizing and describing emotions in themselves. We investigated the neuronal basis of mentalizing in alexithymia to determine whether there is a common neuronal substrate associated with knowing the mental states of the self and others. Individuals high in alexithymia (n = 16) and low in alexithymia (n = 14) were selected from a pool of 310 college students using a combination of the Toronto Alexithymia Scale (TAS-20) and the Structured Interview version of the Beth Israel Questionnaire (SIBIQ). We compared the two groups on psychological measures, including ratings of mentalizing and the Interpersonal Reactivity Index (IRI), and regional brain activation using functional magnetic resonance imaging (fMRI) during a mentalizing animation task. The results for both groups showed activation in regions associated with mentalizing: medial prefrontal cortices (MPFC), temporo-parietal junctions (TPJ), and the temporal pole (TP). Alexithymics had lower mentalizing and IRI perspective-taking scores and less activation in the right MPFC. Activity in the MPFC was positively correlated with the mentalizing score and the IRI perspective-taking score. Although there were no group differences in cerebral activity in the TPJ and the TP, the activity in the right TP had a positive correlation with mentalizing and IRI personal distress scores. These results suggest that alexithymic individuals have an impairment in mentalizing associated with an inability to take the perspective of others. Thus, the skills involved in comprehending the self and others are inter-related and play an important role in emotion regulation.

Adult↗

Boundary-limited serotonergic influences on pattern organization in rat sensory cortex.

In neonatal rodents, elevated levels of cortical serotonin (5-HT) blur the normally segmented vibrissae-related pattern of thalamocortical afferents (TCAs) in the posteromedial barrel subfield (PMBSF) of primary somatosensory cortex. We employed 5-HT immunocytochemistry or anterograde transport of 1'1'-dioctadecyl-3,3,3',3' tetramethyl-indocarbocyanin (Di-I) to label TCA arbors to study the effects of 5-HT manipulations on space occupied by TCAs within the PMBSF and the total area labeled. In rats treated to increase cortical 5-HT from birth to postnatal day (P) 6, the percentage of PMBSF area occupied by terminal labeling was significantly higher from that in controls (79.0% versus 23.7%, P < 0.05) for the highest levels of cortical 5-HT and was raised, although not significantly, for lower levels of 5-HT. The TCA coverage was significantly correlated with treatment dose. In animals exposed to a selective 5-HT1B agonist, 5-nonyloxytryptamine, or elevated endogenous 5-HT, the total areas of TCA aggregates in the PMBSF and those in visual cortex were similar to the controls. These results suggest that TCAs have a graded response to increasingly higher 5-HT concentrations. The lack of TCA expansion beyond normal cortical areas further implies that 5-HT-induced axon outgrowth is restricted at cortical boundaries.

Afferent Pathways↗

Reducing contralateral SI activity reveals hindlimb receptive fields in the SI forelimb-stump representation of neonatally amputated rats.

In adult rats that sustained forelimb amputation on the day of birth, >30% of multiunit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) also respond to cutaneous hindlimb stimulation when cortical GABA(A+B) receptors are blocked (GRB). This study examined whether hindlimb receptive fields could also be revealed in forelimb-stump sites by reducing one known source of excitatory input to SI GABAergic neurons, the contralateral SI cortex. Corpus callosum projection neurons connect homotopic SI regions, making excitatory contacts onto pyramidal cells and interneurons. Thus in addition to providing monosynaptic excitation in SI, callosal fibers can produce disynaptic inhibition through excitatory synapses with inhibitory interneurons. Based on the latter of these connections, we hypothesized that inactivating the contralateral (intact) SI forelimb region would "unmask" normally suppressed hindlimb responses by reducing the activity of SI GABAergic neurons. The SI forelimb-stump representation was first mapped under normal conditions and then during GRB to identify stump/hindlimb responsive sites. After GRB had dissipated, the contralateral (intact) SI forelimb region was mapped and reversibly inactivated with injections of 4% lidocaine, and selected forelimb-stump sites were retested. Contralateral SI inactivation revealed hindlimb responses in approximately 60% of sites that were stump/hindlimb responsive during GRB. These findings indicate that activity in the contralateral SI contributes to the suppression of reorganized hindlimb receptive fields in neonatally amputated rats.

Action Potentials↗

Local GABA receptor blockade reveals hindlimb responses in the SI forelimb-stump representation of neonatally amputated rats.

In adult rats that sustained forelimb amputation on the day of birth, there are numerous multi-unit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) that also respond to cutaneous stimulation of the hindlimb when cortical receptors for GABA are blocked. These normally suppressed hindlimb inputs originate in the SI hindlimb representation and synapse in the dysgranular cortex before exciting SI forelimb-stump neurons. In our previous studies, GABA (A + B) receptor blockade was achieved by topically applying a bicuculline methiodide/saclofen solution (BMI/SAC) to the cortical surface. This treatment blocks receptors throughout SI and does not allow determination of where along the above circuit the GABA-mediated suppression of hindlimb information occurs. In this study, focal injections of BMI/SAC were delivered to three distinct cortical regions that are involved in the hindlimb-to-forelimb-stump pathway. Blocking GABA receptors in the SI hindlimb representation and in the dysgranular cortex was largely ineffective in revealing hindlimb inputs ( approximately 10% of hindlimb inputs were revealed in both cases). In contrast, when the blockade was targeted at forelimb-stump recording sites, >80% of hindlimb inputs were revealed. Thus GABAergic interneurons within the forelimb-stump representation suppress the expression of reorganized hindlimb inputs to the region. A circuit model incorporating these and previous observations is presented and discussed.

Amputation Stumps↗

Comparison of reorganization of the somatosensory system in rats that sustained forelimb removal as neonates and as adults.

Studies of sensory pathways in several species indicate that the extent and form of reorganization resulting from deafferentation early in life vs. adulthood are not the same. The reasons for such differences are not well understood. To gain further insight into age-dependent mechanisms of reorganization, this study compared the consequences of neonatal vs. adult forelimb amputation in rats at multiple levels of the sensory pathway, including primary somatosensory cortex, brainstem, and dorsal root ganglia. At the cortical level, the average area of the functional forelimb-stump representation from rats amputated as adults was significantly smaller (P < 0.05) than that of neonatally amputated rats (4.3 +/- 1.3 mm(2) vs. 6.6 +/- 1.5 mm(2), respectively). At the brainstem level, neonatally amputated rat cuneate neurons possessed the following responsivities: 20% stump responsive, 40% responsive to both stump and hindlimb, 30% responsive to another body region, and 10% unresponsive. In contrast, cuneate neurons of adult amputated rats were 70% stump responsive, 2% responsive to both stump and hindlimb, and 30% unresponsive. A significantly (P < 0.001) greater percentage of the C(6)-C(8) dorsal root ganglia neurons of adult amputated rats were unresponsive to peripheral stimulation vs. neurons from neonatally amputated rats (48% vs. 16%, respectively). These results indicate that the reorganization that occurs in response to forelimb amputation at birth vs. adulthood is distinctly different at each of these levels of the dorsal column-medial lemniscal pathway. Possible mechanisms to account for these differences are considered.

Action Potentials↗

Role of development in reorganization of the SI forelimb-stump representation in fetally, neonatally, and adult amputated rats.

Rats that sustain forelimb removal on postnatal day (P) 0 exhibit numerous multi-unit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) that also respond to hindlimb stimulation when cortical GABAA+B receptors are blocked. Most of these hindlimb inputs originate in the medial SI hindlimb representation. Although many forelimb-stump sites in these animals respond to hindlimb stimulation, very few respond to stimulation of the face (vibrissae or lower jaw), which is represented in SI just lateral to the forelimb. The lateral to medial development of SI may influence the capacity of hindlimb (but not face) inputs to "invade" the forelimb-stump region in neonatal amputees. The SI forelimb-stump was mapped in adult (>60 days) rats that had sustained amputation on embryonic day (E) 16, on P0, or during adulthood. GABA receptors were blocked and subsequent mapping revealed increases in nonstump inputs in E16 and P0 amputees: fetal amputees exhibited forelimb-stump sites responsive to face (34%), hindlimb (10%), and both (22%); neonatal amputees exhibited 10% face, 39% hindlimb, and 5% both; adult amputees exhibited 10% face, 5% hindlimb, and 0% both, with approximately 80% stump-only sites. These results indicate age-dependent differences in receptive-field reorganization of the forelimb-stump representation, which may reflect the spatiotemporal development of SI. Results from cobalt chloride inactivation of the SI vibrissae region and electrolesioning of the dysgranular cortex suggest that normally suppressed vibrissae inputs to the SI forelimb-stump area originate in the SI vibrissae region and synapse in the dysgranular cortex.

Action Potentials↗

Functional neuroanatomy of grief: an FMRI study.

OBJECTIVE: In this study the authors examined the functional neuroanatomy of grief, which to their knowledge has not been studied previously in functional neuroimaging research. METHOD: Grief was elicited in eight bereaved women through photographs of the deceased versus a stranger, combined with words specific to the death event versus neutral words. Use of both pictures and words resulted in a 2x2 factorial design. RESULTS: Three brain regions were independently activated by the picture and word factors: posterior cingulate cortex, medial/superior frontal gyrus, and cerebellum. The two factors also activated distinct regions: for the picture factor, they were the cuneus, superior lingual gyrus, insula, dorsal anterior cingulate cortex, inferior temporal gyrus, and fusiform gyrus; and for the word factor, they were the precuneus, precentral gyrus, midbrain, and vermis. The interaction of the two factors showed significant activation in the cerebellar vermis. CONCLUSIONS: Grief is mediated by a distributed neural network that subserves affect processing, mentalizing, episodic memory retrieval, processing of familiar faces, visual imagery, autonomic regulation, and modulation/coordination of these functions. This neural network may account for the unique, subjective quality of grief and provide new leads in understanding the health consequences of grief and the neurobiology of attachment.

Adult↗

Effects of elevated serotonin levels on patterns of GAP-43 expression during barrel development in rat somatosensory cortex.

Elevating cortical serotonin (5-HT) in rats with clorgyline, a monoamine oxidase A (MAO(A)) inhibitor, from postnatal day (P-0) to P-6 delays the organization of thalamocortical afferent fibers into a vibrissae-related pattern in the somatosensory cortex (S-I). Despite continued elevation of cortical 5-HT through P-8, the thalamocortical fibers do form, albeit with some delay, a characteristic vibrissae pattern of barrels in layer IV of S-I by P-8. The growth-associated protein, GAP-43, is transiently expressed in developing S-I cortex of normal rats in a vibrissae related pattern until P-7. After P-7, GAP-43 expression is reduced in the barrel centers and increased in the septa. The present study evaluated the effect of elevated 5-HT levels on the distribution of GAP-43 immunoreactivity in S-I. We employed 5-HT immunocytochemistry and 1,1'-dioctadecyl-3,3,3",3'-tetramethylindocarbocyanine perchlorate (DiI) labeling of thalamic radiations to confirm a 'barrelless' phenotype in P-6 clorgyline-treated animals and a recovered barrel pattern in treated animals allowed to survive until P-8 and P-10. GAP-43 immunocytochemistry was used to evaluate the cortical distribution of this protein in similarly treated littermates. Continuous inhibition of MAO(A) from P-0 to P-6 resulted in a corresponding loss of the GAP-43 vibrissae-related pattern at P-6. Despite continued elevation of cortical 5-HT until P-8 and P-10, the characteristic vibrissae-complementary pattern of GAP-43 emerged with expression concentrated in the septa and rows. GAP-43 vibrissae-related thalamocortical axon pattern never appeared in the clorgyline-treated animals. Thus, while elevated 5-HT delays development of a vibrissae-related pattern of thalamocortical afferents, it does not appear to alter the time when a GAP-43 vibrissae-related complementary pattern emerges.

Animals↗

Effects of alterations of the vibrissae-related organization of thalamocortical axons upon the organization and outgrowth of intracortical connections in the barrelfield of the rat.

Previous studies have shown that intracortical projections in layer IV of the vibrissae representation of primary somatosensory cortex (S-I) are arrayed in a pattern complementary to that of thalamocortical axons (TCAs). Elevation of cortical serotonin (5-HT) in rats during the first postnatal week results in a transient disruption of the vibrissae-related pattern of TCAs and layer IV neurons in S-I. The present study examines the influence of elevated cortical 5-HT levels and the attendant loss of vibrissae-related TCA clusters on the organization of S-I intracortical connections. Cortical 5-HT was elevated in neonatal rats via chronic injections of clorgyline from birth until P-6. Animals were euthanized on P-6 or allowed to survive an additional 4 days without further clorgyline treatment. Distributions of TCAs and intracortical axons were assessed via application of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Di-I) and 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodide (Di-A) to the thalamic radiations and directly into the cortical barrelfield, respectively. Chronic administration of clorgyline resulted in a loss of the vibrissae-related organization of TCAs in layer IV of S-I. There was also a loss of the complementary pattern of intracortical projections in layer IV of this region. Discontinuation of clorgyline treatment resulted in a return of the vibrissae-related pattern of TCAs as well as the complementary pattern of intracortical projections. These results are consistent with the conclusion that the normal organization of intracortical projections in this region of S-I depends on the presence of the orderly array of TCAs.

Animals↗

Emotional awareness deficits in inpatients of a psychosomatic ward: a comparison of two different measures of alexithymia.

OBJECTIVE: The TAS 20 has demonstrated strong psychometric properties in a broad variety of studies in healthy populations. Much less work has been done in clinical contexts exploring the validity of the TAS 20 as a measure of the cognitive processing of emotions. The TAS 20, a self-report scale, tends to correlate with self-reported negative affect, but in a clinical context it is important to be able to differentiate between negative affect and the cognitive processing of emotion. We therefore used the TAS 20 and a performance measure, the Levels of Emotional Awareness Scale (LEAS), which in previous studies demonstrated no overlap with measures of negative affect, to explore the ability of the two measures to detect deficits in emotional awareness in a clinical sample. METHODS: Data from inpatients of a psychosomatic ward were collected at onset (N = 394) and at the end of multimodal psychodynamic treatment (N = 249). The sample consisted of six diagnostic groups (depression; anxiety and compulsive-obsessive disorders, adjustment disorders, somatoform disorders, psychological factors related to somatic disorders, eating disorders). Changes in the TAS 20 and LEAS were compared at the two time points controlling for the effects of gender, age, educational level, and associations with self-reported negative affect. RESULTS: In contrast to the LEAS, the TAS 20 correlated with negative affect at the onset and the end of treatment. The scores of the TAS 20 decreased with treatment in all diagnostic groups but the change in the TAS 20 was not statistically significant when negative affect was controlled. In contrast, LEAS scores increased with treatment in the groups with somatoform disorders and psychological factors related to somatic disorders, and this change was independent of negative affect. CONCLUSION: The LEAS captured a change in emotional awareness due to treatment, whereas the TAS 20 captured a change in negative affect. The LEAS appears to be a more specific measure of change in emotional awareness in clinical contexts than the TAS 20.

Adult↗

Psychological stress preceding idiopathic ventricular fibrillation.

OBJECTIVE: Emotional stress is well established as a trigger of sudden death in the context of coronary heart disease (CHD), but its role in patients experiencing cardiac arrest with apparently normal hearts is unknown. This study sought to determine the role of psychosocial stress as a precipitant of cardiac arrest in patients with apparently normal hearts, so-called idiopathic ventricular fibrillation (IVF). METHODS: We interviewed 25 IVF survivors (12 men, 13 women) and 25 matched comparison patients regarding life events during the 6 months and 24 hours preceding the cardiac event. The comparison group consisted of patients with an acute myocardial infarction or angina pectoris requiring angioplasty but without cardiac arrest. Judges independently rated written summaries of these interviews for psychosocial stress at each time point on a three-point scale (low, moderate, severe). RESULTS: During the 6 months before the cardiac event, 20 patients sustaining IVF had severe/moderate stress and five had low stress, whereas 10 comparison patients had severe/moderate stress and 15 had low stress (Fisher exact p = .008). During the preceding 24 hours, nine patients with IVF had severe/moderate stress and 16 had low stress, whereas two comparison patients had severe/moderate stress and 22 had low stress (Fisher exact p = .04) (one silent myocardial infarction could not be precisely dated). CONCLUSION: These data suggest that psychosocial stress is playing a role in otherwise unexplained cardiac arrest.

Depression↗