Alessandro E. P. Villa

Prediction of n-octanol/water partition coefficients from PHYSPROP database using artificial neural networks and E-state indices.

A new method, ALOGPS v 2.0 (http://www.lnh.unil.ch/~itetko/logp/), for the assessment of n-octanol/water partition coefficient, log P, was developed on the basis of neural network ensemble analysis of 12 908 organic compounds available from PHYSPROP database of Syracuse Research Corporation. The atom and bond-type E-state indices as well as the number of hydrogen and non-hydrogen atoms were used to represent the molecular structures. A preliminary selection of indices was performed by multiple linear regression analysis, and 75 input parameters were chosen. Some of the parameters combined several atom-type or bond-type indices with similar physicochemical properties. The neural network ensemble training was performed by efficient partition algorithm developed by the authors. The ensemble contained 50 neural networks, and each neural network had 10 neurons in one hidden layer. The prediction ability of the developed approach was estimated using both leave-one-out (LOO) technique and training/test protocol. In case of interseries predictions, i.e., when molecules in the test and in the training subsets were selected by chance from the same set of compounds, both approaches provided similar results. ALOGPS performance was significantly better than the results obtained by other tested methods. For a subset of 12 777 molecules the LOO results, namely correlation coefficient r(2)= 0.95, root mean squared error, RMSE = 0.39, and an absolute mean error, MAE = 0.29, were calculated. For two cross-series predictions, i.e., when molecules in the training and in the test sets belong to different series of compounds, all analyzed methods performed less efficiently. The decrease in the performance could be explained by a different diversity of molecules in the training and in the test sets. However, even for such difficult cases the ALOGPS method provided better prediction ability than the other tested methods. We have shown that the diversity of the training sets rather than the design of the methods is the main factor determining their prediction ability for new data. A comparative performance of the methods as well as a dependence on the number of non-hydrogen atoms in a molecule is also presented.

Estimation of Aqueous Solubility of Chemical Compounds Using E-State Indices

The molecular weight and electrotopological E-state indices were used to estimate by Artificial Neural Networks aqueous solubility for a diverse set of 1291 organic compounds. The neural network with 33-4-1 neurons provided highly predictive results with r(2) = 0.91 and RMS = 0.62. The used parameters included several combinations of E-state indices with similar properties. The calculated results were similar to those published for these data by Huuskonen (2000). However, in the current study only E-state indices were used without need of additional indices (the molecular connectivity, shape, flexibility and indicator indices) also considered in the previous study. In addition, the present neural network contained three times less hidden neurons. Smaller neural networks and use of one homogeneous set of parameters provides a more robust model for prediction of aqueous solubility of chemical compounds. Limitations of the developed method for prediction of large compounds are discussed. The developed approach is available online at http://www.lnh.unil.ch/~itetko/logp.

Auditory corticocortical interconnections in the cat: evidence for parallel and hierarchical arrangement of the auditory cortical areas

SummaryThe origin and laminar arrangement of the homolateral and callosal projections to the anterior (AAF), primary (AI), posterior (PAF) and secondary (AII) auditory cortical areas were studied in the cat by means of electrophysiological recording and WGA-HRP tracing techniques. The transcallosal projections to AAF, AI, PAF and AII were principally homotypic since the major source of input was their corresponding area in the contralateral cortex. Heterotypic transcallosal projections to AAF and AI were seen, originating from the contralateral AI and AAF, respectively. PAF received heterotypic commissural projections from the opposite ventroposterior auditory cortical field (VPAF). Heterotypic callosal inputs to AII were rare, originating from AAF and AI. The neurons of origin of the transcallosal connections were located mainly in layers II and III (70–92%), and less frequently in deep layers (V and VI, 8–30%). Single unit recordings provided evidence that both homotypic and heterotypic transcallosal projections connect corresponding frequency regions of the two hemispheres. The regional distribution of the anterogradely labeled terminals indicated that the homotypic and heterotypic auditory transcallosal projections are reciprocal. The present data suggest that the transcallosal auditory interconnections are segregated in 3 major parallel components (AAF-AI, PAF-VPAF and AII), maintaining a segregation between parallel functional channels already established for the thalamocortical auditory interconnections. For the intrahemispheric connections, the analysis of the retrograde tracing data revealed that AAF and AI receive projections from the homolateral cortical areas PAF, VPAF and AII, whose neurons of origin were located mainly in their deep (V and VI) cortical layers. The reciprocal interconnections between the homolateral AAF and AI did not show a preferential laminar arrangement since the neurons of origin were distributed almost evenly in both superficial (II and III) and deep (V and VI) cortical layers. On the contrary, PAF received inputs from the homolateral cortical fields AAF, AI, AII and VPAF, originating predominantly from their superficial (II and III) layers. The homolateral projections reaching AII originated mainly from the superficial layers of AAF and AI, but from the deep layers of VPAF and PAF. The laminar distribution of anterogradely labeled terminal fields, when they were dense enough for a confident identification, was systematically related to the laminar arrangement of neurons of origin of the reciprocal projection: a projection originating from deep layers was associated with a reciprocal projection terminating mainly in layer IV, whereas a projection originating from superficial layers was associated with a reciprocal projection terminating predominantly outside layer IV. This laminar distribution indicates that the homolateral auditory cortical interconnections have a feed-forward/feed-back organization, corresponding to a hierarchical arrangement of the auditory cortical areas, according to criteria previously established in the visual system of primates. The principal auditory cortical areas could be ranked into 4 distinct hierarchical levels. The tonotopically organized areas AAF and AI represent the lowest level. The second level corresponds to the non-tonotopically organized area AII. Higher, the tonotopically organized areas VPAF and PAF occupy the third and fourth hierarchical levels, respectively.

Corticofugal modulation of the information processing in the auditory thalamus of the cat

SummarySingle unit activity of 355 cells was recorded in the auditory thalamus of anesthetized cats before, during, and after the inactivation by cooling of the ipsilateral primary auditory cortex (AI). Most of the units (n = 288) showed similar functional characteristics of firing before and after the cryogenic blockade of AI. The spontaneous firing rate remained unchanged by cooling in 20% of the units and decreased in the majority of them (60%). In some regions, i.e. dorsal division of the medial geniculate body (MGB), lateral part of the posterior group of the thalamus, and auditory sector of the reticular nucleus of the thalamus, the maximum firing rate evoked by white noise bursts was generally affected by cooling in the same direction and to the same extent as the spontaneous activity. Units in the ventral division of MGB showed a characteristic increase of signal-to-noise ratio during cortical cooling. The corticofugal modulation led to the appearance or disappearance of the best frequency of tuning in 51 units and changed it by more than 0.5 octave in 34 units. The bandwidths of different response patterns to pure tones stimulation were used to define a set of functional properties. During cryogenic blockade of AI, two cortically modulated sub-populations of units were usually distinguished that exhibited changes for a given functional property. The complexity and diversity of the effects of cortical inactivation suggest that the corticothalamic projection may be the support for selective operations such as an adaptive filtering of the incoming acoustic signal at the thalamic level adjusted as a function of cortical activity.

Functional organization of the ventral division of the medial geniculate body of the cat: Evidence for a rostro-caudal gradient of response properties and cortical projections

The response properties to clicks, noise and tone bursts of 2152 single units located in the ventral division of the medial geniculate body were analysed as a function of their anatomical position. A particular spatial distribution of these properties was observed in the pars lateralis (LV) and ovoidea (OV). The distribution of different response characteristics changed along the rostro-caudal axis. Units located posteriorly were in majority either insensitive to simple acoustical stimuli or responded exclusively to pure tones, presenting generally a broad tuning and a loose tonotopic arrangement. Inhibitory response patterns were about as frequent as excitatory ones, response latencies were long on the average and widely distributed. Only a few units showed time-locking of their discharges in response to repetitive clicks. Most units had non-monotonic intensity functions. Going anteriorly, the distribution of response properties progressively changed: the number of units sensitive to various simple acoustical stimuli (pure tones and broad band stimuli together) increased, the tonotopic arrangement was more precise and more units were sharply tuned. Response patterns were in majority of the excitatory type, and latencies were shorter on the average and less dispersed. More units were precisely time-locked to repetitive clicks. The proportion of units with monotonic intensity functions increased. The origin of thalamo-cortical projections was studied with focal injections of wheat-germ agglutinin labeled with horseradish peroxidase in functionally defined loci of the various auditory cortical fields. An evolution of the density of labeled cells in LV and OV was observed along the same rostro-caudal axis for which a gradient of functional properties is described above. Thalamo-cortical projections to the primary auditory area and the anterior auditory field originated predominantly from the anterior half of LV, whereas the posterior auditory field received inputs from a wider rostro-caudal extend of LV including its posterior half.

Functional organization of the medial division of the medial geniculate body of the cat: Tonotopic organization, spatial distribution of response properties and cortical connections

The discharge properties of 735 single units located in the pars magnocellularis (M) of the medial division of the medial geniculate body (MGB) were studied in 23 nitrous oxide anesthetized cats in response to simple acoustic stimuli (clicks, noise and tone bursts). A systematic decrease of single unit characteristic frequencies (CF) was observed along electrode track portions crossing M from dorso-medial to ventro-lateral. These data indicate that M is tonotopically organized with an arrangement of low CF units latero-ventrally and high CF units dorso-medially. This preferential arrangement of single units as a function of their CF was consistent with the location and orientation of clusters of labeled cells in M resulting from wheat-germ agglutinin labeled with horseradish peroxidase (WGA-HRP) injections in CF defined loci in the anterior (AAF) or primary (AI) auditory cortical fields. The quality of the tonotopic arrangement was low caudally and increased in the rostral direction, indicating that this tonotopicity concerns mainly the anterior half of M. Response latencies to clicks, noise and tone bursts were on average longer in the posterior part of M than in its anterior part. Time-locking of discharges in response to repetitive acoustic pulses was more frequent anteriorly than posteriorly and the upper limiting rate of locking was on average higher rostrally (up to 200-300 Hz). In contrast, other response properties such as responsiveness to the various combinations of simple acoustic stimuli, response patterns and tuning were more randomly distributed in M, showing the whole range of response properties seen in the MGB. Data derived from several injections of WGA-HRP performed in distinct auditory cortical fields in several animals indicated that M projects to the tonotopic cortical fields (AAF, AI and PAF) as well as to the non-tonotopically organized secondary auditory cortex (AII). The contribution of M to the total thalamic input reaching each field of the auditory cortex was quantitatively more important for AAF (30%) and PAF (20%) than for AI and AII (about 10% each).

Morphology and spatial distribution of corticothalamic terminals originating from the cat auditory cortex.

In this paper we studied the morphology and spatial distribution of corticothalamic axons and terminals originating from the auditory cortical fields of the cat. The anterograde tracer biocytin was injected at electrophysiologically characterized loci in the primary (AI) (N = 2), anterior (AAF) (N = 1), posterior (PAF) (N = 1) and secondary (AII) (N = 2) auditory fields. In all cases, two different types of labeled terminals were found in the auditory thalamus: small spherical endings (1-2 microns) and giant, finger-like endings (5-10 microns). After biocytin injections in AI and AAF, the majority of anterogradely labeled axons terminated in the rostral half of the pars lateralis (LV) of the ventral division of the medial geniculate body (vMGB). In LV, the corticothalamic axons ramified profusely, giving rise to dense terminal fields forming well delineated curved stripes, with small spherical endings. Additional terminal fields formed by small endings were observed in the medial division of the medial geniculate body (mMGB). Giant endings were observed in a small area in the dorsal nucleus (D) of the dorsal division of the medial geniculate body (dMGB), near its border with the vMGB. PAF projections were located in the caudal half of vMGB and in mMGB, where only small terminals were found. Giant endings were seen in the superficial part of dMGB emerging from labeled corticothalamic axons oriented in parallel to the dorsal surface of the MGB. Projections from AII gave rise to a main terminal field of small endings in D; a second terminal field consisting of giant endings intermingled with small endings was found in the deep dorsal nucleus (DD) of dMGB. We conclude that small terminals serve the feedback projection to the thalamic nucleus from which the injected cortical field receives its main input, whereas giant terminals cross the borders between the parallel ascending auditory pathways.

Artificial Neural Networks and Machine Learning – ICANN 2012

A complex-valued multilayer perceptron (MLP) can approximate a periodic or unbounded function, which cannot be easily realized by a real-valued MLP. Its search space is full of crevasse-like forms having huge condition numbers; thus, it is very hard for existing methods to perform efficient search in such a space. The space also includes the structure of reducibility mapping. The paper proposes a new search method for a complex-valued MLP, which employs both eigen vector descent and reducibility mapping, aiming to stably find excellent solutions in such a space. Our experiments showed the proposed method worked well.

Evidence for spatiotemporal firing patterns within the auditory thalamus of the cat

Multiple spike trains were recorded in the auditory thalamus of cats. Each unit was studied before, during and after cooling of the ipsilateral primary auditory cortex, during spontaneous activity and acoustically evoked activity. The search for spatiotemporal firing patterns provided evidence that excess of patterns does exist and that the acoustical stimulation increased their number. Cortical cooling did not affect the probability of finding the firing pattern.

Physiological differentiation within the auditory part of the thalamic reticular nucleus of the cat

Spike trains of 153 single units were recorded in the caudoventral part of the thalamic reticular nucleus (RE) of 7 nitrous oxide anaesthetized cats. Functional properties defined by spontaneous activity pattern, studied by mean of auto renewal density histograms, were used to subdivide the units into 4 groups. Types I (18%), II (56%) and III (15%) were defined by an increasing bursting activity and Type IV (11%) by firing no bursts spontaneously. The responses to auditory stimuli confirmed that the caudoventral part of RE is tightly related to central auditory pathways. Responses to white noise bursts (200 ms duration) significantly let appear that Type I units responded in a high proportion (greater than 70%) until 80 ms after the stimulus onset, Type II units where mostly affected during the entire stimulus duration, and Type III units showed preferentially late responses. The units responsive to high frequencies (greater than 8 kHz) were mostly located in the dorsal and the units responsive to low frequencies (less than 2 kHz) in the anteroventral sector of auditory RE. However, only a loosely tonotopy is supported by this study. The neuronal circuitry within RE was shown to be stable when white noise bursts were delivered. Cross-correlograms indicated a large proportion of interconnected units (64%) and signs of mutual inhibition between neighboring RE units (11%). The hypothesis is discussed that the auditory RE exerts a fine control on the time-dependent analysis of the incoming auditory input to the cerebral cortex. The complex intranuclear connectivity suggests that the cell types correspond to distinct patterns of functional connections.