Cognition or higher brain activity is sometimes seen as a phenomenon greater than the sum of its parts. This viewpoint however is largely dependent on the state of the art of experimental techniques that endeavor to characterize morphology and its association to function. Retinal ganglion cells are readily accessible for this work and we discuss recent advances in computational techniques in identifying novel parameters that describe structural attributes possibly associated with specific function. These parameters are based on calculating wavelet (...) gradients from cell images followed by the extraction of meaningful measures including 2nd wavelet moment, entropy of orientation, and curvature. For the three cell types analyzed, the mean 2nd wavelet moment, which relates to the field of influence of the dendritic-tree segments was significantly different. cells had the highest mean 2nd wavelet moment, followed by the and cells (134 ± 22, 93 ± 19 and 63 ± 12, respectively). There was no significant difference between cells for entropy of orientation, indicating no class with a preferential orientation of their dendritic tree. Curvature provided similar results to the 2nd wavelet moment with cells having the highest curvature followed by and the cells (mean ± SD: 161 ± 15; 134 ± 22; 121 ± 15). Our feature space analysis also indicated a difference between these cell types. No difference was found between the and cell types and their physiological counterparts the Y and X cells based on wavelet analysis. Both the X and Y cells can be divided into two subtypes, the ON- and OFF-center cells based on the stratification level of the dendritic tree within the retina. Using 2nd wavelet moment, a difference in their morphological attributes, not reported previously, was noted for these subtypes. The 2nd wavelet moment and curvature are further discussed with respect to explaining regularity of spacing and coverage associated with retinal ganglion cell mosaics. (shrink)

This paper offers an overview of "the species problem", arguing for a view of species as homeostatic property cluster kinds, positioning the resulting form of realism about species as an alternative to the claim that species are individuals and pluralistic views of species. It draws on taxonomic practice in the neurosciences, especially of neural crest cells and retinal ganglion cells, to motivate both the rejection of the species-as-individuals thesis and species pluralism.

The idea that only complex brains can possess genuine representations is an important element in mainstream philosophical thinking. An alternative view, which I label ‘liberal representationalism’, holds that we should accept the existence of many more full-blown representations, from activity in retinal ganglion cells to the neural states produced by innate releasing mechanisms in cognitively unsophisticated organisms. A promising way of supporting liberal representationalism is to show it to be a consequence of our best naturalistic theories of representation. However, (...) several philosophers and scientists have recently argued against this strategy. In the paper I counter these objections in defense of liberal representationalism. (shrink)

Institutional Review Board decisions hinge on the availability and interpretation of information. This is demonstrated by the following well-known historical example. In 2001, 24-year-old Ellen Roche died from respiratory distress and organ failure as a result of her participation in a study at Johns Hopkins Asthma and Allergy Center. The non-therapeutic physiological study, “Mechanisms of Deep Inspiration-Induced Airway Relaxation,” was designed to examine airway hyperresponsiveness in healthy individuals in order to better understand the pathophysiology of asthma. Participants inhaled hexamethonium, a (...) chemical ganglionic blocker that was not FDA-approved for use as specified in the experimental protocol. Risks of inhaling hexamethonium, including lung damage, had been reported in the 1950s and ‘60s. An investigation conducted after Roche's death determined that the study's principal investigator had failed to adequately search the medical literature; the protocol submitted for IRB review cited articles indexed in online literature databases that went back only as far as the 1970s. (shrink)

The quantization error in a fixed-size Self-Organizing Map (SOM) with unsupervised winner-take-all learning has previously been used successfully to detect, in minimal computation time, highly meaningful changes across images in medical time series and in time series of satellite images. Here, the functional properties of the quantization error in SOM are explored further to show that the metric is capable of reliably discriminating between the finest differences in local contrast intensities and contrast signs. While this capability of the QE is (...) akin to functional characteristics of a specific class of retinal ganglion cells (the so-called Y-cells) in the visual systems of the primate and the cat, the sensitivity of the QE surpasses the capacity limits of human visual detection. Here, the quantization error in the SOM is found to reliably signal changes in contrast or colour when contrast information is removed from or added to the image, but not when the amount and relative weight of contrast information is constant and only the local spatial position of contrast elements in the pattern changes. While the RGB Mean reflects coarser changes in colour or contrast well enough, the SOM-QE is shown to outperform the RGB Mean in the detection of single-pixel changes in images with up to five million pixels. This could have important implications in the context of unsupervised image learning and computational building block approaches to large sets of image data (big data). (shrink)

Background: Primary open-angle glaucoma patients exhibit widespread white matter degeneration throughout their visual pathways. Whether this degeneration starts at the pre- or post-geniculate pathways remains unclear. In this longitudinal study, we assess the progression of WM degeneration exhibited by the pre-geniculate optic tracts and the post-geniculate optic radiations of POAG patients over time, aiming to determine the source and pattern of spread of this degeneration.Methods: Diffusion-weighted MRI scans were acquired for 12 POAG patients and 14 controls at (...) two time-points 5.4 ± 2.1 years apart. Fiber density, an estimate of WM axonal density, was computed for the OTs and ORs of all participants in an unbiased longitudinal population template space. First, FD was compared between POAG patients and the controls at time-point 1 and time-point 2 independently. Secondly, repeated measures analysis was performed for FD change in POAG patients between the two time-points. Finally, we compared the rate of FD change over time between the two groups.Results: Compared to the controls, POAG patients exhibited significantly lower FD in the left OT at TP1 and in both OTs and the left OR at TP2. POAG patients showed a significant loss of FD between the time-points in the right OT and both ORs, while the left OR showed a significantly higher rate of FD loss in POAG patients compared to the controls.Conclusions: We find longitudinal progression of neurodegenerative WM changes in both the pre- and post-geniculate visual pathways of POAG patients. The pattern of changes suggests that glaucomatous WM degeneration starts at the pre-geniculate pathways and then spreads to the post-geniculate pathways. Furthermore, we find evidence that the trans-synaptic spread of glaucomatous degeneration to the post-geniculate pathways is a prolonged process which continues in the absence of detectable pre-geniculate degenerative progression. This suggests the presence of a time window for salvaging intact post-geniculate pathways, which could prove to be a viable therapeutic target in the future. (shrink)

Every normally developing human infant solves the difficult problem of mapping their native-language phonology, but the neural mechanisms underpinning this behavior remain poorly understood. Here, motor constellation theory, an integrative neurophonological model, is presented, with the goal of explicating this issue. It is assumed that infants’ motor-auditory phonological mapping takes place through infants’ orosensory “reaching” for phonological elements observed in the language-specific ambient phonology, via reference to kinesthetic feedback from motor systems, and auditory feedback from resulting speech and speech-like sounds. (...) Attempts are regulated by basal ganglion–cerebellar speech neural circuitry, and successful attempts at reproduction are enforced through dopaminergic signaling. Early in life, the pace of anatomical development constrains mapping such that complete language-specific phonological mapping is prohibited by infants’ undeveloped supralaryngeal vocal tract and undescended larynx; constraints gradually dissolve with age, enabling adult phonology. Where appropriate, reference is made to findings from animal and clinical models. Some implications for future modeling and simulation efforts, as well as clinical settings, are also discussed. (shrink)

The processing of information within the retino-tectal visual system of amphibians is decomposed into five major operational stages, three of them taking place in the retina and two in the optic tectum. The stages in the retina involve (i) a spatially local high-pass filtering in connection to the perception of moving objects, (ii) separation of the receptor activity into ON- and OFF-channels regarding the distinction of objects on both light and dark backgrounds, (iii) spatial integration via near excitation and far-reaching (...) inhibition. Variation of the spatial range of excitation and inhibition allows to account for typical activities observed in a variety of classes of retina ganglion cells.Mathematical description of the operations in the tectum opticum include (i) spatial summation of retinal output (mainly of class-2 and class-3 retina ganglion cells), and (ii) direct or indirect lateral inhibition between tectal cells. In the computer simulation, first the output of the mathematical retina model is computed which, then, is used as the input to the tectum model. The full spatio-temporal dynamics is taken into account. (shrink)

The repeatedly noted absence of case-reports of individuals with schizophrenia and congenital/early developed blindness has led several authors to argue that the latter can confer protective effects against the former. In this work, we present a number of relevant case-reports from different syndromes that show comorbidity of congenital and early blindness with schizophrenia. On the basis of these reports, we argue that a distinction between different types of blindness in terms of the origin of the visual deficit, cortical or peripheral, (...) is crucial for understanding the observed patterns of comorbidity. We discuss the genetic underpinnings and the brain structures involved in schizophrenia and blindness, with insights from language processing, laying emphasis on the three structures that particularly stand out: the occipital cortex, the lateral geniculate nucleus and the pulvinar. Last, we build on previous literature on the nature of the protective effects in order to offer novel insights into the nature of the protection mechanism from the perspective of the brain structures involved in each type of blindness. (shrink)

Initial evaluation structures (IESs) currently proposed as the earliest detectors of affective stimuli (e.g., amygdala, orbitofrontal cortex, or insula) are high-order structures (a) whose response latency cannot account for the first visual cortex emotion-related response (~80 ms), and (b) lack the necessary infrastructure to locally analyze the visual features that define emotional stimuli. Several thalamic structures accomplish both criteria. The lateral geniculate nucleus (LGN), a first-order thalamic nucleus that actively processes visual information, with the complement of the thalamic reticular (...) nucleus (TRN) are proposed as core IESs. This LGN–TRN tandem could be supported by the pulvinar, a second-order thalamic structure, and by other extrathalamic nuclei. The visual thalamus, scarcely explored in affective neurosciences, seems crucial in early emotional evaluation. (shrink)

Studies on the snailMelampusreveal that connectivity is crucial to the survival of transplanted ganglia. Transplanted CNS ganglia can innervate targets or induce supernumerary structures. Neuron survival is optimized by the neural incorporation that occurs when a transplanted ganglion is substituted for an excised ganglion. Better provision for the trophic requirements of neurons will improve the success of mammalian fetal transplants.

Background: There is limited research on brain lesions in children with cerebral visual impairment of heterogeneous etiologies and according to associated subtyping and vision dysfunctions. This study was part of a larger project establishing data-driven subtypes of childhood CVI according to visual dysfunctions. Currently there is no consensus in relation to assessment, diagnosis and classification of CVI and more information about brain lesions may be of potential diagnostic value.Aim: This study aimed to investigate overall patterns of brain lesions and associations (...) with level of visual dysfunction and to compare the patterns between the classification subgroups in children with CVI.Methods: School-aged children with CVI received ophthalmological and neuro-psychological/developmental assessments to establish CVI-related subtyping. Other pediatric information was collected from medical records. MRI scans were coded according to a semi-quantitative template including brain regions and summed for total scores. Non-parametric analyses were conducted.Results: 28 children had clinical brain MRI scans available [44% of total sample, Group A n = 16, Group B n = 12]. Total brain scores ranged between 0 and 18 and were widespread across regions. 71 per cent had post-geniculate visual pathway damage. The median total brain and hemisphere scores of Group B were higher than subgroup A but differences did not reach statistical significance. No statistically significant associations were found between brain scores and vision variables.Conclusion: This study found a spread of lesions across all regions on the brain scans in children with congenital CVI. The majority had damage in the postgeniculate visual pathways and visual cortex region suggesting this is an area of interest and potentially informative for diagnosis. However the subtyping classification did not show differences in number or region of lesions though the trend was higher toward Group B. This study confirms the complex diffuse and variable nature of brain lesions in children with congenital CVI, many of whom have other neurological impairments. (shrink)

While recent studies have shed some light on the significance of the electrical activity of the nervous system, there has been no adequate explanation for the wave formation or synchronization of this electrical activity. Adrian sums up the problem. “The origin of the 10-a-second rhythm is still uncertain, though the evidence points to some widespread organization, probably involving the central masses as well as the cortex. There are abundant nervous connexions for coordinating the beat, and when the rhythm is well (...) developed it is possible to record impulse discharges in phase with it passing to and fro in the nerve fibers of the white matter below the cortex. But in some areas no impulse could be detected entering or leaving the cell layers, though the potential waves keep more or less in step with those elsewhere. There is no proof that the waves are kept in phase by some means which does not involve nervous signalling, for impulses in axons of small diameter might well be missed, but it is not altogether unlikely that the synchronization is due in part to a direct electrical influence of one group of nerve cells on another. Gerard and Libet have shown that synchronization can occur between the two halves of a frog's brain cut in two and then placed in contact, and more recently Arvanitaki has shown that individual nerve cells may influence one another if they are brought close together in a conducting medium. At all events there are many examples of synchronized rhythmic activity in large collections of nerve-or-muscle cells. In the optic ganglion of the water beetle, for instance, there may be both a slow rhythm when the eye is in darkness and a rapid one when the eye is exposed to a bright light. The change from a slow to a fast rhythm is curiously reminiscent of that in the cerebral cortex when a sensory stimulus abolishes the 10-a-second rhythm and substitutes one at 40–60 a second. Such resemblances in preparations of quite different structures may be quite fortuitous, but they make it difficult to resist the suggestion that the rhythms of the brain may be dependent on the general properties of cell masses rather than on any special anatomical arrangement of them. Whatever its origin, the 10-a-second rhythm of the cortex corresponds to the resting, drowsy, or inattentive state and there is no such uniform pulsation when the brain is alert.”. (shrink)

Eyesight is practically a main organ of senses for man orienting in the world. But it is also a result of evolutional development of nature from 600 to 450 mln. years according to evolutional scale and still it preserves its stable contradictory inner structure. The genesis of eyesight has been reconstructed in Arthropoda type. It was made possible by using a philosophical approach, namely, by considering this process from the dualism point of view. Two Laurence's concepts were used as basic (...) interrelated categories. They are intranspecific and interspecific aggressiveness. Development of the two interrelated opposites results in the formation of a new kind – eyesight (Hegelian not Marx’s), typical for all succeeding kinds of animals. The eye has become a unity consisting of on- and off-type ganglionic cells, that percept both fixed end non-fixed objects simultaneously. The two eyes of higher animals and man allow to orient in the world, and depending on outside conditions, they can fully enough demonstrate one of the stable contradictory inner tendencies. This is just one of the directions in studying philosophy of nature. (shrink)

Patients fit with cochlear implants commonly indicate at the time of device fitting and for some time after, that the speech signal sounds abnormal. A high pitch or timbre is one component of the abnormal percept. In this project, our aim was to determine whether a number of years of CI use reduced perceived upshifts in frequency spectrum and/or voice fundamental frequency. The participants were five individuals who were deaf in one ear and who had normal hearing in the other (...) ear. The deafened ears had been implanted with a 18.5 mm electrode array which resulted in signal input frequencies being directed to locations in the spiral ganglion that were between one and two octaves higher than the input frequencies. The patients judged the similarity of a clean signal presented to their implanted ear and candidate, implant-like, signals presented to their normal-hearing ear. Matches to implant sound quality were obtained, on average, at 8 months after device activation and at 35 months after activation. At Time 1, the matches to CI sound quality were characterized, most generally, by upshifts in the frequency spectrum and in voice pitch. At Time 2, for four of the five patients, frequency spectrum values remained elevated. For all five patients F0 values remained elevated. Overall, the data offer little support for the proposition that, for patients fit with shorter electrode arrays, cortical plasticity nudges the cortical representation of the CI voice toward more normal, or less upshifted, frequency values between 8 and 35 months after device activation. Cortical plasticity may be limited when there are large differences between frequencies in the input signal and the locations in the SG stimulated by those frequencies. (shrink)

With the advent of powerful parallel computers, efforts have commenced to simulate complete mammalian brains. However, so far none of these efforts has produced outcomes close to explaining even the behavioral complexities of animals. In this article, we suggest four challenges that ground this shortcoming. First, we discuss the connection between hypothesis testing and simulations. Typically, efforts to simulate complete mammalian brains lack a clear hypothesis. Second, we treat complications related to a lack of parameter constraints for large-scale simulations. To (...) demonstrate the severity of this issue, we review work on two small-scale neural systems, the crustacean stomatogastric ganglion and the Caenorhabditis elegans nervous system. Both of these small nervous systems are very thoroughly, but not completely understood, mainly due to issues with variable and plastic parameters. Third, we discuss the hierarchical structure of neural systems as a principled obstacle to whole-brain simulations. Different organizational levels imply qualitative differences not only in structure, but in choice and appropriateness of investigative technique and perspective. The challenge of reconciling different levels also undergirds the challenge of simulating and hypothesis testing, as modeling a system is not the same thing as simulating it. Fourth, we point out that animal brains are information processing systems tailored very specifically for the ecological niches the respective animals live in. (shrink)

Segregated neural circuits that effect particular domain-specific behaviors can be differentiated from neuroanatomical structures implicated in many different aspects of behavior. The basal ganglionic components of circuits regulating nonlinguistic motor behavior, speech, and syntax all function in a similar manner. Hence, it is unlikely that special properties and evolutionary mechanisms are associated with the neural bases of human language.

This paper reports on the investigation of the effects of neuronal shape, at both individual cell and network level, on the behavior of neuronal systems. More specifically, two-dimensional biologically realistic neuronal networks are obtained that take explicity into account the position and morphology of neuronal cells, with the respective behavior for associative recall being simulated through a diluted version of Hopfield's model. While a specific probability density function is used for the placement of the cell bodies, images of real neuronal (...) cells (namely alpha and beta ganglion cells from the cat retina) are used to obtain biologically realistic models. Several morphological measures – including fractal dimension, the excluded volume, and integral geometry functionals–are estimated for the considered cells, and their values are correlated with the potential of the network for associative recall, which is quantified in terms of the overlap between distorted version of the trained patterns and their original version. Such an approach allows the quantitative and objective characterization of the relationship between neuronal shape and function, an important issue in neuroscience. The obtained results substantiate interesting relationships between the neural morphology and function as determined by the performance of the network. (shrink)

Identification of the molecular mechanisms underlying axonal branching in vivo has begun in several neuronal systems, notably the projections formed by dorsal root ganglion (DRG) neurons or retinal ganglion cells (RGC). cGMP signalling is essential for sensory axon bifurcation at the spinal cord, whereas brain‐derived neurotrophic factor (BDNF) and ephrinA signalling establish position‐dependent branching of RGC axons. In the latter system, the degradation of specific signalling components, via the ubiquitin‐proteasome system, may provide an additional mechanism involved in axon (...) branching of RGC. The process of arborisation is essential for neurons to innervate multiple targets and to build topographic maps. The various forms of branching found in different types of neurons are regulated by distinct signalling pathways activated by multiple extracellular cues in addition to axonal guidance factors. These signalling cascades, together with transcriptional programs, most likely interact and trigger the polymerisation or depolymerisation of the actin and tubulin cytoskeleton to regulate branching. (shrink)

The processing of information within the retino-tectal visual system of amphibians is decomposed into five major operational stages, three of them taking place in the retina and two in the optic tectum. The stages in the retina involve a spatially local high-pass filtering in connection to the perception of moving objects, separation of the receptor activity into ON- and OFF-channels regarding the distinction of objects on both light and dark backgrounds, spatial integration via near excitation and far-reaching inhibition. Variation of (...) the spatial range of excitation and inhibition allows to account for typical activities observed in a variety of classes of retina ganglion cells.Mathematical description of the operations in the tectum opticum include spatial summation of retinal output, and direct or indirect lateral inhibition between tectal cells. In the computer simulation, first the output of the mathematical retina model is computed which, then, is used as the input to the tectum model. The full spatio-temporal dynamics is taken into account.The simulations show that different combinations of strength of lateral inhibition on the one side and the response properties of the retina ganglion cells on the other side determine the response properties of tectal cell types involved in object recognition. (shrink)

Injury to the central or peripheral nervous system is often associated with persistent pain. After ischemic injury to the spinal cord, rats develop severe mechanical allodynia-like symptoms, expressed as a pain-like response to innocuous stimuli. In its short-lasting phase the allodynia can be relieved with the [gamma]-aminobutyric acid (GABA)-B receptor agonist baclofen, which also reverses the hyperexcitability of dorsal horn interneurons to mechanical stimuli. Furthermore, there is a reduction in GABA immunoreactivity in the dorsal horn of allodynic rats. Clinical neuropathic (...) pain of peripheral and central origin often cannot be relieved by opiates at doses that do not cause side effects. The loss of sensitivity to opiates may be associated with the up-regulation of endogenous antiopioid substances, such as the neuropeptide cholecystokinin (CCK). CCK and its receptor (CCK-R) protein is normally not detectable in rat dorsal root ganglion cells. After peripheral nerve section, both CCK and CCK-R are up-regulated in the dorsal root ganglia. Furthermore, CI 988, an antagonist of the CCK-B receptor, chronically coadministered with morphine, reduces autotomy, a behavior that may be a sign of neuropathic pain following peripheral nerve section. Thus, opiate insensitivity may be due to the release of CCK from injured primary afferents. Similarly, in the chronic phase of the spinal ischemic model of central pain, the allodynia-like symptom is not relieved by systemic morphine, but is significantly reversed by the CCK-B antagonist. Consequently, up-regulation of CCK and CCK-R in the CNS may also underlie opiate drug insensitivity following CNS injury. Thus, dysfunction of central inhibition involving GABA and endogenous opioids may be a factor underlying the development of sensory abnormalities and/or pain following injury to neural tissue. (shrink)

This paper reports on the investigation of the effects of neuronal shape, at both individual cell and network level, on the behavior of neuronal systems. More specifically, two-dimensional biologically realistic neuronal networks are obtained that take explicity into account the position and morphology of neuronal cells, with the respective behavior for associative recall being simulated through a diluted version of Hopfield's model. While a specific probability density function is used for the placement of the cell bodies, images of real neuronal (...) cells (namely alpha and beta ganglion cells from the cat retina) are used to obtain biologically realistic models. Several morphological measures – including fractal dimension, the excluded volume, and integral geometry functionals–are estimated for the considered cells, and their values are correlated with the potential of the network for associative recall, which is quantified in terms of the overlap between distorted version of the trained patterns and their original version. Such an approach allows the quantitative and objective characterization of the relationship between neuronal shape and function, an important issue in neuroscience. The obtained results substantiate interesting relationships between the neural morphology and function as determined by the performance of the network. (shrink)

This commentary provides experimental data in support of the critical role of capsaicin-sensitive primary afferent fibers in the initiation and maintenance of pathological pain. The demonstration of capsaicin-induced, centrally-evoked cutaneous hyperalgesia, and of neuroplastic changes elicited by the degeneration of C-fiber primary afferent terminals following peripheral nerve damage, indicates a significant contribution of capsaicin-sensitive sensory ganglion neurons in the development of pathological pain conditions. [coderre & katz].

The peripheral nervous system has classically been separated into a somatic division composed of both afferent and efferent pathways and an autonomic division containing only efferents. J. N. Langley, who codified this asymmetrical plan at the beginning of the twentieth century, considered different afferents, including visceral ones, as candidates for inclusion in his concept of the “autonomic nervous system”, but he finally excluded all candidates for lack of any distinguishing histological markers. Langley's classification has been enormously influential in shaping modern (...) ideas about both the structure and the function of the PNS. We survey recent information about the PNS and argue that many of the sensory neurons designated as “visceral” and “somatic” are in fact part of a histologically distinct group of afferents concerned primarily autonomic function. These afferents have traditionally been known as “small dark” neurons or B-neurons. In this target article we outline an association between autonomic and B-neurons based on ontogeny, cell phenotype, and functional relations, grouping them together as part of a common reflex system involved in homeostasis. This more parsimonious classification of the PNS, made possible by the identification of a group of afferents associated primarily with the ANS, avoids a number of confusions produced by the classical orientation. It may also have practical implications for an understanding of nociception, homeostatic reflexes, and the evolution of the nervous system. (shrink)

Which roles are played by subcortical pathways in models of cortical streams for visual processing? Through their thalamic relays, magnocellular (M) and parvocellular (P) projecting ganglion cells send complementary signals to V1, where their outputs are combined in several different ways. The synergic role of M and P cells in vision can be understood by estimating cell response entropy in all domains of interest.

The processing of information within the retino-tectal visual system of amphibians is decomposed into five major operational stages, three of them taking place in the retina and two in the optic tectum. The stages in the retina involve a spatially local high-pass filtering in connection to the perception of moving objects, separation of the receptor activity into ON- and OFF-channels regarding the distinction of objects on both light and dark backgrounds, spatial integration via near excitation and far-reaching inhibition. Variation of (...) the spatial range of excitation and inhibition allows to account for typical activities observed in a variety of classes of retina ganglion cells.Mathematical description of the operations in the tectum opticum include spatial summation of retinal output , and direct or indirect lateral inhibition between tectal cells. In the computer simulation, first the output of the mathematical retina model is computed which, then, is used as the input to the tectum model. The full spatio-temporal dynamics is taken into account.The simulations show that different combinations of strength of lateral inhibition on the one side and the response properties of the retina ganglion cells on the other side determine the response properties of tectal cell types involved in object recognition. (shrink)