Lauren M. Salo

Human ability to scale and discriminate forces typical of those occurring during grasp and manipulation

When humans manipulate objects, the sensorimotor system coordinates three-dimensional forces to optimize and maintain grasp stability. To do this, the CNS requires precise information about the magnitude and direction of load force (tangential to skin surface) plus feedback about grip force (normal to skin). Previous studies have shown that there is rapid, precise coordination between grip and load forces that deteriorates with digital nerve block. Obviously, mechanoreceptive afferents innervating fingerpad skin contribute essential information. We quantify human capacity to scale tangential and normal forces using only cutaneous information. Our paradigm simulated natural manipulations (a force tangential to the skin superimposed on an indenting force normal to the skin). Precisely controlled forces were applied by a custom-built stimulator to an immobilized fingerpad. Using magnitude estimation, subjects (n = 8) scaled the magnitude of tangential force (0.25–2.8 N) in two experiments (normal force, 2.5 and 4 N, respectively). Performance was unaffected by normal force magnitude and tangential force direction. Moreover, when both normal (2–4 N) and tangential forces were varied in a randomized-block factorial design, the relationship between applied and perceived tangential force remained near linear, with a minor but statistically significant nonlinearity. Our subjects could also discriminate small differences in tangential force, and this was the case for two different reference stimuli. In both cases, the Weber fraction was 0.16. Finally, scaling functions for magnitude estimates of normal force (1–5 N) were also approximately linear. These data show that the cutaneous afferents provide a wealth of precise information about both normal and tangential force.

Processing of central and reflex vagal drives by rat cardiac ganglion neurones: an intracellular analysis

Non‐technical summary  The brain controls the heart through parasympathetic (vagal) and sympathetic nerves. Vagal control is integral to cardiac health and a loss of vagal tone is a poor prognostic sign in cardiovascular diseases such as heart failure and hypertension. The vagal drive to the heart is transmitted across synapses located in the cardiac ganglia on the heart. We have developed a novel methodology to make intracellular recordings from cardiac ganglion neurones on the surface of the beating heart in a preparation with intact functional drive from the brainstem. We show how these neurones process their synaptic inputs and demonstrate that the ganglion plays a key role in regulating the level of vagal tone reaching the heart. This identifies the cardiac ganglion as a viable target for interventions to restore the transmission of vagal tone in cardiovascular diseases.

Encoding of tangential torque in responses of tactile afferent fibres innervating the fingerpad of the monkey

Torsional loads are ubiquitous during everyday dextrous manipulations. We examined how information about torque is provided to the sensorimotor control system by populations of tactile afferents. Torsional loads of different magnitudes were applied in clockwise and anticlockwise directions to a standard central site on the fingertip. Three different background levels of contact (grip) force were used. The median nerve was exposed in anaesthetized monkeys and single unit responses recorded from 66 slowly adapting type‐I (SA‐I) and 31 fast adapting type‐I (FA‐I) afferents innervating the distal segments of the fingertips. Most afferents were excited by torque but some were suppressed. Responses of the majority of both afferent types were scaled by torque magnitude applied in one or other direction, with the majority of FA‐I afferent responses and about half of SA‐I afferent responses scaled in both directions. Torque direction affected responses in both afferent types, but more so for the SA‐I afferents. Latencies of the first spike in FA‐I afferent responses depended on the parameters of the torque. We used a Parzen window classifier to assess the capacity of the SA‐I and FA‐I afferent populations to discriminate, concurrently and in real‐time, the three stimulus parameters, namely background normal force, torque magnitude and direction. Despite the potentially confounding interactions between stimulus parameters, both the SA‐I and the FA‐I populations could extract torque magnitude accurately. The FA‐I afferents signalled torque magnitude earlier than did the SA‐I afferents, but torque direction was extracted more rapidly and more accurately by the SA‐I afferent population.

DIFFERENTIAL CONTROL OF CARDIAC FUNCTIONS BY THE BRAIN

1 The idea is introduced that cardiac rate, contractility or atrioventricular (A‐V) conduction spread may be controlled independently by the brain. Limited data from reflex studies are cited to support this view. 2 Evidence is presented that individual autonomic post‐ and preganglionic neurons have quite specific actions on the heart. Premotor and other central neurons can have preferential actions on heart rate, contractility or A‐V conduction. 3 The functional implications of selective cardiac control are discussed.

Cutaneous Afferents From the Monkeys Fingers: Responses to Tangential and Normal Forces

Control of tangential force plays a key role in everyday manipulations. In anesthetized monkeys, forces tangential to the skin were applied at a range of magnitudes comparable to those used in routine manipulations and in eight different directions. The paradigm used enabled separation of responses to tangential force from responses to the background normal force. For slowly adapting type I (SAI) afferents, tangential force responses ranged from excitatory through no response to suppression, with both a static and dynamic component. For fast adapting type I (FAI) afferents, responses were dynamic and excitatory only. Responses of both afferent types were scaled by tangential force magnitude, elucidating the neural basis for previous human psychophysical scaling data. Most afferents were direction selective with a range of preferred directions and a range in sharpness of tuning. Both the preferred direction and the degree of tuning were independent of the background normal force. Preferred directions were distributed uniformly over 360 degrees for SAI afferents, but for FAI afferents they were biased toward the proximo-ulnar direction. Afferents from all over the glabrous skin of the distal segment of the finger responded; there was no evident relationship between the position of an afferents receptive field on the finger and its preferred direction or its degree of tuning. Nor were preferred directions biased either toward or away from the receptive field center. In response to the relatively large normal forces, some afferents saturated and others did not, regardless of the positions of their receptive fields. Total afferent response matched human psychophysical scaling functions for normal force.

Restorative Effect of Atrial Natriuretic Peptide or Chronic Neutral Endopeptidase Inhibition on Blunted Cardiopulmonary Vagal Reflexes in Aged Rats

Arterial baroreflex function diminishes with age, but whether cardiopulmonary vagal reflexes are similarly altered with physiological aging has not been fully elucidated. In this study, predominantly cardiac high pressure mechanoreceptor-activated (ramp baroreflex) and cardiopulmonary chemoreceptor-activated (von Bezold-Jarisch reflex) vagal reflexes in conscious, instrumented rats were impaired by 30% to 40% (P<0.05) in 24-month-old (n=12) compared with 6-month-old rats (n=12). To determine whether this is a restorable deficit, the influence of atrial natriuretic peptide (ANP), either by infusion or blockade of its breakdown, was studied. ANP infusion was previously shown to enhance Bezold-Jarisch reflex and ramp baroreflex bradycardia in young adult rats. The present study confirmed that vagal reflex augmentation by ANP (50 pmol/kg per minute) also occurs in old rats (increased by 60±18% (Bezold-Jarisch reflex) and 91±15% (ramp baroreflex; P<0.05). Direct vagal stimulation in anesthetized animals showed that the target for ANP was not the cardiac vagus itself in old rats (n=7), although in young rats only, we confirmed the published finding that ANP enhances vagal bradycardia (by 58±14%, n=7). Neutral endopeptidase 24.11 degrades ANP and several other peptides. The neutral endopeptidase inhibitor candoxatrilat (5 mg/kg per day IV for 7 to 9 days) restored vagal reflex bradycardia in old rats (n=6) to levels similar to those in young neutral endopeptidase inhibitor-treated rats (n=6). Impaired cardiopulmonary vagal reflex control of heart rate is thus a feature of normal aging, and this deficit may be ameliorated by either ANP infusion or chronic neutral endopeptidase inhibition.

Control of cardiac rate, contractility, and atrioventricular conduction by medullary raphé neurons in anesthetized rats

The sympathetic actions of medullary raphé neurons on heart rate (HR), atrioventricular conduction, ventricular contractility, and rate of relaxation were examined in nine urethane-anesthetized (1-1.5 g/kg iv), artificially ventilated rats that had been adrenalectomized and given atropine methylnitrate (1 mg/kg iv). Mean arterial pressure (MAP), ECG, and left ventricular pressure were recorded. The peak rates of rise and fall in the first derivative of left ventricular (LV) pressure (dP/dtmax and dP/dtmin, respectively) and the stimulus-R (

85 INSIGHTS INTO VAGAL GANGLIONIC SYNAPTIC INTEGRATION FROM THE VON BEZOLD-JARISCH REFLEX

-R) interval were measured during brief periods of atrial pacing at 8.5 Hz before and after ventral medullary raphé neurons were activated by dl-homocysteic acid (DLH, 0.1 M) or inhibited by GABA (0.3 M) in local microinjections (90 nl). LV dP/dtmax values were corrected for the confounding effect of MAP, determined at the end of the experiments after giving propranolol (1 mg/kg iv) to block sympathetic actions on the heart. DLH microinjections into the ventral medullary raphé region increased HR by 44 +/- 2 beats/min, LV dP/dtmax by 1,055 +/- 156 mmHg/s, and the negative value of LV dP/dtmin by 729 +/- 204 mmHg/s (all, P < 0.001) while shortening the

Nonuniformity in the von Bezold-Jarisch reflex

-R interval by 2.8 +/- 0.8 ms (P < 0.01). GABA microinjections caused no significant change in HR, LV dP/dtmax, or

Anisotropy in the Fingerpad Afferents: Effects of Population Parameters and Tactile Discrimination of Gaps by Slowly Adapting

-R interval but reduced LV dP/dtmin from -5,974 +/- 93 to -5,548 +/- 171 mmHg/s and MAP from 115 +/- 4 to 105 +/- 5 mmHg (both, P < 0.01). Rises in tail skin temperature confirmed that GABA injections effectively inhibited raphé neurons. When activated, the neurons in the ventral medullary raphé region thus enhance atrioventricular conduction, ventricular contractility, and relaxation in parallel with HR, but they provide little or no tonic sympathetic drive to the heart.