What is the process by which stimulus energy is converted to electrical energy that the nervous system uses to transmit signals?

Abstract

Sensory systems have an old school ring to them, a very old school ring to them. In the 15th century Benedetti was able to write, “By means of nerves, the pathways of the senses are distributed like the roots and fibers of a tree” (Alessandro Benedetti, 1497). This is still a good place to start because it gives one a feel for the 3D structure of our sensory apparatus, but the challenge of understanding the senses has, of course, gone well beyond structure (which is not to imply that all structural descriptions are complete or that we have joined all the dots of structure–function relationships), and any serious scholar needs to have a working knowledge of the development, physiology, psychophysics (physiology without the blood), genetics, pathology, and computational models of the senses.

B Augmenting and Reducing Sensory Systems

Suppose that for a given system we study how the system reacts to stimuli with increasing intensities (Fig. 10.17). As one judge from Fig. 10.17 the response of the system will increase. However, the way of this increasing will depend on the state of the system. If the system is characterized by the initial low input and low overall activity (the point at the bottom of the curve), relative changes in the response will be higher than relative changes in the sensory input. These systems can be labeled as augmenting sensory systems (see insertion of Fig. 10.17). If the system has much higher overall activity, then relative changes in response will be lower than the relative increase in stimulus intensity. These systems can be labeled as reducing sensory systems.

In animal research the serotoninergic neurons of the brain stem were found to innervate the auditory cortex. The serotoninergic innervation in its turn leads to a strong dependence of overall activity of the auditory cortex with the level of serotonin. Auditory N1/P2 component serve as a good indicator of functioning of the auditory system. So, if the level of serotonin and correspondingly the input activity is increased the loudness dependence of auditory evoked potential reduces (i.e., the system shifts from the left point on the curve of Fig. 10.17 to the right point). In the studies of Gallinat et al. (2000) this property of the auditory system and N1/P2 component was used as a predictor of the acute response to serotonin reuptake inhibitors in depression.

Cellular Physiology (http://www.driesen.com/sensory_systems.htm ; http://isc.temple.edu/neuroanatomy/lab/neuexam/sensory.htm)

As far back as ancient times, sensory systems were divided into five modalities: hearing, smell, taste, touch, and vision. Others have been recognized and fall within the somatovisceral category that previously included touch (mechanoreception) and, more recently, position and movement (proprioception), heat and cold (thermoreception), and pain (nociception) Gebhart (1995). While sensation may be thought of as originating in the external world (exteroceptive), there are sensations that originate internally (interoceptive). This internal sensory information, which arises from the viscera, blood vessels, and muscles and is used to regulate body temperature, heart and respiratory rate, and blood pressure, may not be recognized at a conscious level.

Each sensory system begins with a receptor cell and its primary afferent neuron that makes specific connections with other nerve fibers. The groups of neuronal fibers, and the nuclei that relay this peripheral information into and throughout the central nervous system, define the sensory system. These neurons are essentially tuned to a specific sensory energy. It is this specificity that defines the sensation. For example, a peripheral sensory endorgan can be replaced with an artificial device such as a cochlear implant in a deaf patient. In this case, the implant electrically stimulates the peripheral ganglion cells that relay the electrical information to the central auditory system, producing the sensation of sound.

The initiation of a receptor response is dependent on an adequate stimulus, as defined by Sherrington Sherrington (1947), in which a specific stimulus is needed to initiate a response in a specific sensory receptor. The process whereby a stimulus energy is converted into the electrochemical energy occurs at the level of the receptor cell and is known as transduction. This conversion process allows for the coding of the sensory stimulus by the nervous system. For example, in hearing (bending of stereocilia) and touch (deformation of Pacinian corpuscles), mechanical energy is converted into the flow of ions (electrochemical) through ion channels in the membrane that generate cell membrane potentials known as receptor potentials. The initiation of a response is dependent on four factors: modality, intensity, location, and timing. As indicated above, in relation to specificity, the type of stimulus energy (sound, light, etc.), and the specificity of the receptors needed to sense that energy defines the modality. The intensity of a perceived stimulus at the cellular level is reflected in how long and fast the neurons fire, and how many neurons are firing. Thus, timing plays a role in this process, because an increase in stimulus rate results in an increase in firing rate, while an increase in stimulus amplitude results in an increase in receptor potential. For some sensory systems there is a close relationship between the subjective measurement of intensity, as defined by perception, and the objective measurement, as defined by the neuronal response; both types of responses are described by a power function, as proposed by Stevens Stevens (1957). However, this response is not strictly linear. For example, measurement of basilar membrane displacement in the cochlea Rhode and Robles (1974) in response to sound, or the measurement of an FA receptor response to touch on the skin Vallbo and Johansson (1984), shows a stimulus-response relationship that is nonlinear. Moreover, inherent in the response is the intensity threshold necessary to activate the receptor and, eventually, the sensation. For example, what is the lowest stimulus that an individual can perceive a specific sound? At the cellular level, the threshold is defined by the sensitivity of the receptor and the neuronal cells. Stimulation of the receptor cells occurs at a local level and is the result of a passive flow of current. Stimulation of the neurons is dependent on reaching the threshold necessary to generate an action potential in the many neurons that encode and relay a signal to and throughout the central nervous system. The generation of action potentials will generate a sensation depending on the strength of the stimulus.

Once a response is initiated, a change in stimulus is necessary to maintain a perceived sensation, as well as a receptor cell response. If a stimulus remains constant over time, the response of the receptor cell undergoes adaptation, resulting in a decrease in the receptor potential and, thus, a decrease in sensation. For example, there is evidence from the receptor cells (i.e., hair cells) of the auditory system that bending of the stereocilia (see record on Hearing) results in the stretching of tip links or filaments that open the ion channels of transduction, resulting in receptor cell depolarization or excitation. Bending of the stereocilia with a constant force results in a decrease in tip link tension by a mechanical mechanism involving actin and myosin molecules Hudspeth and Gillespie (1994). This interaction resets the tip link tension, causing a decrease that, in turn, resets the transduction channel to a resting state despite the bending of the stereocilia. The sensory cell, via the transduction channel, is now able to respond to any new change in stimulus. Adaptation can take place either slowly or rapidly, as demonstrated in touch receptors. Through the process of adaptation the receptors and neurons can encode and convey the ever-changing sensory environment to the brain.

A feature of sensory systems that contributes to their specificity is their spatial arrangement. This arrangement contributes to the localization of a stimulus and to the ability to discern the physical characteristics of that stimulus (e.g., size, shape, frequency, etc.). For example, touch receptors in the finger-tips and lips occur in clusters, offering a more stimulus sensitive arrangement than receptors in the back of the hand, which are less clustered and more randomly organized. Receptors for taste that are sensitive to salts, acids, bases, sugars, and proteins are arranged on different parts of the tongue, relaying this specific information to the central nervous system. The basilar membrane of the cochlea is tonotopically organized, responding in a low- to high-frequency arrangement along its length, from apex to base, respectively. This organization is the result of its physical characteristics, being thin and wide at the apex and thick and narrow at the base. Consequently, a low frequency tone of 20 Hz maximally stimulates the basilar membrane near the apical end, whereas a frequency of 20 kHz maximally stimulates the membrane at the basal end. In turn, the receptor cells that overlie these regions and transduce this mechanical energy into electrochemical energy are maximally stimulated as a result of this displacement. The spatial arrangement of receptor cells in their various sheets of epithelia defines the region whereby an adequate stimulus excites a particular receptor. For example, a touch receptor has a defined area, or receptive field, in the skin within which a stimulus excites the cell. In the cochlea, the basilar membrane and, thereby, the overlying receptor cell, are maximally stimulated or tuned to some specific frequency (best frequency) due to the tonotopic arrangement. The intensity threshold at the best frequency will be low for a receptor response. However, excitation still occurs at frequencies either above or below the best frequency, however, a greater stimulus energy (high threshold) is needed to activate the receptor (see Fig. 7 in Hearing).

The spatial arrangement at the sensory periphery is maintained by neurons as they relay information to the cerebral cortex. For example, in the auditory system, the first order neurons or ganglion cells innervate a specific receptor cell that overlies a specifically tuned region of the basilar membrane. As the auditory neuron leaves the cochlea, each one lies adjacent to nerves innervating neighboring regions, one with a higher and the other with a lower frequency specificity. Thus, each fiber relays information from a specific frequency region. This specificity can be seen in electrical recordings from individual neuronal fibers, which show that each one is tuned, or is most sensitive to, a specific or best frequency. As the relay neurons ascend through the system centrally, they maintain the tonotopic information. Electrical recordings from the different nuclei of the brain stem, midbrain, and cortex show regions with distinct frequency selectivities. Thus, the frequency map at the periphery is maintained centrally. Similar to the auditory system, each sensory system maintains a topographic map, whereby the strictly ordered relationship with neighboring neurons at the periphery is maintained throughout the system centrally. However, the information that is relayed to and integrated in the various sensory nuclei becomes more complex. Sensory signals are contrasted and refined through the divergence of fibers to multiple regions of a nucleus or through the convergence of multiple synapses on a single cell. Included in this process are inhibitory neurons that contribute to functions such as localizing a low-frequency stimulus in hearing or regulating selective attention in vision. In addition, fibers within a particular sensory pathway decussate so that information is shared with both sides of the brain. This sharing of signals can be a part of the integration process, as in sound localization, in which excitation is maintained on one side of the brain stem, while inhibition is activated on the other side. Also, the crossing over of fibers can provide redundancy in some systems so that damage in a part of the pathway may have less severe effects overall. Finally, the brain itself can contribute in the regulation and integration of sensory stimuli by sending signals back out to the periphery. Eye movements are regulated in response to different stimuli and in response to different sounds, using various muscles. At the cellular level, studies of the inner ear show that efferent projections, originating in the brain stem and synapsing on receptor cells of the cochlea, regulate and contribute to the dynamics of auditory signal processing. Thus, organisms are not passive receptors of sensation, but active interlopers in the processing of sensory information as perceptions and ideas on the basis of the external environment.

Table 1. Sensory Systems, Modalities, and Cell Types.

Adapted from Kandel et al. (2000) Principles of Neural Science, McGraw-Hill, New York, N Y. p. 414.

Antibacterial Drugs

Sensory Systems Consist of the Sense Organ, the Sensory Receptors, and the Pathways to the CNS

Sensory systems include receptors that respond to what is called an adequate stimulus, which is the kind of stimulus to which receptors respond preferentially. A sensory modality is an identifiable class of sensation. Sensory receptors respond to the adequate stimulus with the lowest threshold, referring to the lowest stimulus intensity that elicits a response from the sensor. For example, vision is a sensory modality whose adequate stimulus is light within the narrow band of wavelengths that we can see. The receptors for vision are the rods and cones in the retina that actually respond to light. However, rods and cones will also respond to pressure on the eyeballs, causing us to “see” light, called phosphenes. The proper sensing of light requires not just the rods and cones but all of the accessory structures that enables us to see. Table 4.3.1 shows the various modalities, their receptor cells, and their sense organs.

Table 4.3.1. Sensory Modalities, Their Receptors, and Their Organs

Mitiglinide

Sensory systems A randomised, open-label, two-period, two-treatment, single-dose, crossover study was conducted in 24 healthy male subjects. An FDC tablet of mitiglinide and metformin (10 mg/500 mg) was administered in one period, and corresponding doses of individual formulations concurrently in the other period. The most commonly reported adverse effect was feeling hot (n = 7), it is not specifically determined which drug, metformin or mitiglinide, was the main contributor of this adverse effect. [49c]

Isotretinoin [SEDA-32, 298; SEDA-33, 340; SEDA-34, 264]

Sensory systems Ocular surface changes and tear-film functions have been studied in 50 patients using oral isotretinoin 0.8 mg/kg in a prospective trial [104C]. There were no significant differences in average Schirmer test scores before, during, or after isotretinoin treatment, but mean anesthetized Schirmer test scores and tear breakup time fell significantly during treatment. Mean impression cytology scores, Ocular Surface Disease Index scores, and rose Bengal staining scores increased significantly during treatment. There was blepharitis 18 patients. All abnormal findings disappeared 1 month after withdrawal of treatment.

1 INTRODUCTION

The sensory systems of humans and animals achieve levels of performance that far exceed those of any artificial sensory system. The almost instantaneous processing by the brain of data from the five senses – sight, hearing, smell, touch and taste – remains well beyond the capability of artificial cognitive systems.

What we can describe as ‘conventional’ or ‘IT-centric’ systems pay little attention to the fundamental principles or mechanisms of information processing in biological sensory systems. Their implementation is within conventional computing architectures, using conventional algorithmic computation methods. While this approach has not been able to match natural sensory systems, it has achieved some impressive results, as this report will describe.

In contrast to these IT centric approaches, it is highly likely, and to some extent already apparent, that the brain uses an entirely different ‘computational paradigm’. The brain's processing involves flexible deployment of highly parallel, asynchronous, non-linear and adaptive dynamical systems.

This chapter reviews progress in building artificial systems that can process data from the first three senses; sight (computer vision), hearing (speech recognition) and smell (olfaction). We then go on to review the issue of ‘data fusion’, the ability to combine disparate sensory data, a task biological systems perform with great success. We consider systems built on the principles of deriving a probabilistic model of sensory data and applying essentially Bayesian methods of information processing (the IT-centric approach), and contrast these with the unique characteristics of biological sensory information processing.

This review is tailored to promote the objective of the Foresight Cognitive Systems project and hence is necessarily incomplete and intentionally selective. The aim of the project is to investigate ways in which the life sciences and physical sciences can learn from each other, either by working together or by greater understanding of recent progress in each others’ areas of research. For this reason, each section ends with a brief overview of ‘open questions’, which relates the state of the art in artificial cognitive systems to our current knowledge of the human brain, where appropriate. We also highlight fruitful areas for collaborative research.

Latanoprost (PGF2α analogue) [SED-15, 2002; SEDA-32, 729; SEDA-33, 847; SEDA-34, 660]

Cardiovascular Latanoprost ocular administration has been associated with second-degree heart block [38A].

Sensory systems Central serous chorioretinopathy occurred after treatment with topical latanoprost 0.005% for 1 month in a 65-year-old woman; withdrawal led to complete recovery [39A].

Immunologic Endothelial corneal graft rejection in one eye has been described in two patients with prior penetrating keratoplasties shortly after treatment with topical latanoprost for 15 days in one case and 1 month in the other [40A]. Latanoprost was immediately withdrawn and graft rejection was treated with glucocorticoids and ciclosporin. The temporal sequence of graft rejection immediately after starting latanoprost was suggestive of a cause-and-effect relation.

Anticholinergic drugs [SED-15, 264; SEDA-32, 290; SEDA-33, 324; SEDA-34, 246]

See also Chapter 16.

Systematic reviews A network meta-analysis of 69 trials of all currently used antimuscarinic drugs in 26 229 patients with an overactive bladder has shown similar efficacy, making the choice dependent on their adverse event profiles [100M]. There were similar overall adverse events profiles for darifenacin, fesoterodine, transdermal oxybutynin, propiverine, solifenacin, tolterodine, and trospium chloride, but not for oral oxybutynin when currently used starting dosages were compared. The authors concluded that most currently used antimuscarinic drugs seem to be equivalent first-choice drugs to use in treating an overactive bladder except for oral oxybutynin in dosages of 10 mg/day or more, which may have a more unfavorable adverse events profile.

Sensory systems Anticholinergic drugs cause bilateral mydriasis when they are taken systemically. However, unilateral mydriasis can occur after application of a transdermal patch [101A].

A 34-year-old man with a nasopharyngeal carcinoma used a hyoscine (scopolamine) patch to control drooling and the emetic effects of his anticancer treatment. After a few weeks, he complained of blurred vision in his right eye a few hours after applying a patch and had a unilaterally, dilated, non-responsive pupil. The patch was removed and the mydriasis disappeared in 72 hours, with quick restoration of vision.

The authors did not specify the site of application of the patch. Hyoscine patches are usually applied behind one or other ear, and mydriasis when it occurs usually affects the eye on the same side, presumably because of local spread. In some cases patients contaminate themselves when they rub their eyes after handling the patch without washing their hands.

Unilateral mydriasis also occurred in a 76-year-old woman during administration of nebulized ipratropium because of direct exposure [102A].