Frank W. Ohl

Change in pattern of ongoing cortical activity with auditory category learning

Humans are able to classify novel items correctly by category; some other animals have also been shown to do this. During category learning, humans group perceptual stimuli by abstracting qualities from similarity relationships of their physical properties. Forming categories is fundamental to cognition and can be independent of a ‘memory store’ of information about the items or a prototype. The neurophysiological mechanisms underlying the formation of categories are unknown. Using an animal model of category learning, in which frequency-modulated tones are distinguished into the categories of ‘rising’ and ‘falling’ modulation, we demonstrate here that the sorting of stimuli into these categories emerges as a sudden change in an animals learning strategy. Electro-corticographical recording from the auditory cortex shows that the transition is accompanied by a change in the dynamics of cortical stimulus representation. We suggest that this dynamic change represents a mechanism underlying the recognition of the abstract quality (or qualities) that defines the categories.

Learning-induced plasticity in animal and human auditory cortex

Recent data on learning-related changes in animal and human auditory cortex indicate functions beyond mere stimulus representation and simple recognition memory for stimuli. Rather, auditory cortex seems to process and represent stimuli in a task-dependent fashion. This implies plasticity in neural processing, which can be observed at the level of single neuron firing and the level of spatiotemporal activity patterns in cortical areas. Auditory cortex is a structure in which behaviorally relevant aspects of stimulus processing are highly developed because of the fugitive nature of auditory stimuli.

Differential Frequency Conditioning Enhances Spectral Contrast Sensitivity of Units in Auditory Cortex (Field Al) of the Alert Mongolian Gerbil

Differential aversive auditory conditioning in the awake Mongolian gerbil was performed during single‐ and multi‐unit recording in field Al of the primary auditory cortex. Presentations of pure tone stimuli of a given frequency (reinforced conditioned stimulus; CS+) paired with electrocutaneous stimulation (unconditioned stimulus) were combined with several other non‐reinforced tone stimuli (non‐reinforced conditioned stimulus; CS‐). Stimulus presentation during training and testing was optimized for constancy of the probability of occurrence of both the CS+ and the CS‐ stimulus. The paradigm led to a reorganization of both the spectral and temporal response characteristics of auditory cortical neurons with the following basic results. First, tone‐evoked responses of Al neurons recorded after multiple acoustic stimulation under these conditions varied statistically around a mean value (stationarity). Conditioning produced a shift in mean values of evoked responses. The altered tone responses were also stationary (stability of the plastic effects). Second, the frequency‐receptive fields (FRFs) of neurons were reorganized in a frequency‐specific way such that the CS+ frequency became located in a local minimum of the FRF after training. This resulted from a training‐induced increase in the responses to frequencies adjacent to the CS+ frequency in the FRF relative to the CS+ response. The effect can be interpreted as an enhancement of the ‘spectral contrast’ sensitivity of the unit in the CS+ neighbourhood. Third, apart from this frequency‐specific plastic effect, responses to other frequencies also underwent changes during training. The non‐frequency‐specific changes were not generally predictable but the post‐trial responses were stationary. Fourth, the analysis of the long‐term behaviour of FRF reorganization revealed the stability of plastic effects under retention training and the gradual re‐establishment of the pretrial FRF during extinction training. Fifth, not only the spectral characteristics but also the temporal structure of the tone‐evoked responses could be affected by the training. In most cases the training‐induced changes measured within the first tens of milliseconds of the response corresponded to the response changes obtained by integration over the total response period. There were some cases, however, in which the direction of the response change varied with time, indicating that excitatory and inhibitory influences on the temporal response pattern were differently affected by training.

Spectral Integration in Primary Auditory Cortex Attributable to Temporally Precise Convergence of Thalamocortical and Intracortical Input

Primary sensory cortex integrates sensory information from afferent feedforward thalamocortical projection systems and convergent intracortical microcircuits. Both input systems have been demonstrated to provide different aspects of sensory information. Here we have used high-density recordings of laminar current source density (CSD) distributions in primary auditory cortex of Mongolian gerbils in combination with pharmacological silencing of cortical activity and analysis of the residual CSD, to dissociate the feedforward thalamocortical contribution and the intracortical contribution to spectral integration. We found a temporally highly precise integration of both types of inputs when the stimulation frequency was in close spectral neighborhood of the best frequency of the measurement site, in which the overlap between both inputs is maximal. Local intracortical connections provide both directly feedforward excitatory and modulatory input from adjacent cortical sites, which determine how concurrent afferent inputs are integrated. Through separate excitatory horizontal projections, terminating in cortical layers II/III, information about stimulus energy in greater spectral distance is provided even over long cortical distances. These projections effectively broaden spectral tuning width. Based on these data, we suggest a mechanism of spectral integration in primary auditory cortex that is based on temporally precise interactions of afferent thalamocortical inputs and different short- and long-range intracortical networks. The proposed conceptual framework allows integration of different and partly controversial anatomical and physiological models of spectral integration in the literature.

Singular perturbation analysis of competitive neural networks with different time scales

The dynamics of complex neural networks must include the aspects of long- and short-term memory. The behavior of the network is characterized by an equation of neural activity as a fast phenomenon and an equation of synaptic modification as a slow part of the neural system. The main idea of this paper is to apply a stability analysis method of fixed points of the combined activity and weight dynamics for a special class of competitive neural networks. We present a quadratic-type Lyapunov function for the flow of a competitive neural system with fast and slow dynamic variables as a global stability method and a modality of detecting the local stability behavior around individual equilibrium points.

Non-sensory cortical and subcortical connections of the primary auditory cortex in Mongolian gerbils : Bottom-up and top-down processing of neuronal information via field AI

In the present study, we will provide further anatomical evidence that the primary auditory cortex (field AI) is not only involved in sensory processing of its own modality, but also in complex bottom-up and top-down processing of multimodal information. We have recently shown that AI in the Mongolian gerbil (Meriones unguiculatus) has substantial connections with non-auditory sensory and multisensory brain structures [Budinger, E., Heil, P., Hess, A., Scheich, H., 2006. Multisensory processing via early cortical stages: Connections of the primary auditory cortical field with other sensory systems. Neuroscience 143, 1065-1083]. Here we will report about the direct connections of AI with non-sensory cortical areas and subcortical structures. We approached this issue by means of the axonal transport of the sensitive bidirectional neuronal tracers fluorescein-labelled (FD) and tetramethylrhodamine-labelled dextran (TMRD), which were simultaneously injected into different frequency regions of the gerbils AI. Of the total number of retrogradely labelled cell bodies found in non-sensory brain areas, which identify cells of origin of direct projections to AI, approximately 24% were in cortical areas and 76% in subcortical structures. Of the cell bodies in the cortical areas, about 4.4% were located in the orbital, 11.1% in the infralimbic medial prefrontal (areas DPC, IL), 18.2% in the cingulate (3.2% in CG1, 2.9% in CG2, 12.1% in CG3), 9.5% in the frontal association (area Fr2), 12.0% in the insular (areas AI, DI), 10.8% in the retrosplenial, and 34.0% in the perirhinal cortex. The cortical regions with retrogradely labelled cells, as well as the entorhinal cortex, also contained anterogradely labelled axons and their terminations, which means that they are also target areas of direct projections from AI. The laminar pattern of corticocortical connections indicates that AI receives primarily cortical feedback-type inputs and projects in a feedforward manner to its target areas. The high number of double-labelled somata, the non-topographic distribution of single FD- and TMRD-labelled somata, and the overlapping spatial distribution of FD- and TMRD-labelled axonal elements suggest rather non-tonotopic connections between AI and the multimodal cortices. Of the labelled cell bodies in the subcortical structures, about 38.8% were located in the ipsilateral basal forebrain (10.6% in the lateral amygdala LA, 11.5% in the globus pallidus GP, 3.7% in the ventral pallidum VPa, 13.0% in the nucleus basalis NB), 13.1% in the ipsi- and contralateral diencephalon (6.4% in the posterior paraventricular thalamic nuclei, 6.7% in the hypothalamic area), and 48.1% in the midbrain (20.0% in the ipsilateral substantia nigra, 9.8% in the ipsi- and contralateral ventral tegmental area, 5.0% in the ipsi- and contralateral locus coeruleus, 13.3% the ipsi- and contralateral dorsal raphe nuclei). Thus, the majority of subcortical inputs to AI was related to different neurotransmitter systems. Anterograde labelling was only found in some ipsilateral basal forebrain structures, namely, the LA, basolateral amygdala, GP, VPa, and NB. As for the cortex, the proportion and spatial distribution of single FD-, TMRD-, and double-labelled neuronal elements suggests rather non-tonotopic connections between AI and the neuromodulatory subcortical structures.

The cognitive auditory cortex: task-specificity of stimulus representations.

Auditory cortex (AC), like subcortical auditory nuclei, represents properties of auditory stimuli by spatiotemporal activation patterns across neurons. A tacit assumption of AC research has been that the multiplicity of functional maps in primary and secondary areas serves a refined continuation of subcortical stimulus processing, i.e. a parallel orderly analysis of distinct properties of a complex sound. This view, which was mainly derived from exposure to parametric sound variation, may not fully capture the essence of cortical processing. Neocortex, in spite of its parcellation into diverse sensory, motor, associative, and cognitive areas, exhibits a rather stereotyped local architecture. The columnar arrangement of the neocortex and the quantitatively dominant connectivity with numerous other cortical areas are two of its key features. This suggests that cortex has a rather common function which lies beyond those usually leading to the distinction of functional areas. We propose that task-relatedness of the way, how any information can be represented in cortex, is one general consequence of the architecture and corticocortical connectivity. Specifically, this hypothesis predicts different spatiotemporal representations of auditory stimuli when concepts and strategies how these stimuli are analysed do change. We will describe, in an exemplary fashion, cortical patterns of local field potentials in gerbil, of unit spiking activity in monkey, and of fMRI signals in human AC during the execution of different tasks mainly in the realm of category formation of sounds. We demonstrate that the representations reflect context- and memory-related, conceptual and executional aspects of a task and that they can predict the behavioural outcome.

Right auditory cortex lesion in Mongolian gerbils impairs discrimination of rising and falling frequency-modulated tones

Mongolian gerbils (Meriones unguiculatus) were trained in a shuttle box to discriminate the direction in frequency-modulated tones (FM). Whereas control animals easily acquired FM discrimination, animals with auditory cortex lesion on the right side showed considerable difficulties in learning this task. The discrimination performance of gerbils with left auditory cortex lesion, however, was not different from controls. This study, suggesting that the right auditory cortex plays a dominant role in FM discrimination learning in gerbils, describes a useful animal model for investigation of the basic mechanisms underlying hemispheric asymmetries in auditory perception.

Superposition of horseshoe-like periodicity and linear tonotopic maps in auditory cortex of the Mongolian gerbil.

The segregation of an individual sound from a mixture of concurrent sounds, the so‐called cocktail‐party phenomenon, is a fundamental and largely unexplained capability of the auditory system. Speaker recognition involves grouping of the various spectral (frequency) components of an individuals voice and segregating them from other competing voices. The important parameter for grouping may be the periodicity of sound waves because the spectral components of a given voice have one periodicity, viz. fundamental frequency, as their common denominator. To determine the relationship between the representations of spectral content and periodicity in the primary auditory cortex (AI), we used optical recording of intrinsic signals and electrophysiological mapping in Mongolian gerbils (Meriones unguiculatus). We found that periodicity maps as an almost circular gradient superimposed on the linear tonotopic gradient in the low frequency part of AI. This geometry of the periodicity map may imply competitive signal processing in support of the theory of ‘winner‐takes‐all’.

Enhanced cognitive flexibility in reversal learning induced by removal of the extracellular matrix in auditory cortex

Significance The brain’s extracellular matrix (ECM) mediates structural stability by enwrapping synaptic contacts fundamental for long-term memory storage. Whether the ECM in the adult brain might thereby govern learning-related plasticity, lifelong memory reformation, and higher cognitive functions is largely unknown. Here, we enzymatically degraded the ECM in the auditory cortex of adult Mongolian gerbils during a reversal learning task. Such local weakening of the structurally rigid ECM specifically accelerated strategy changes required for reversal learning. It neither affected general sensory learning nor erased already established, learned memory traces. Thus, ECM modulation might promote the cognitive flexibility that can build on learned behaviors, and has further implications to develop new tools for guided neuroplasticity with therapeutic potential. During brain maturation, the occurrence of the extracellular matrix (ECM) terminates juvenile plasticity by mediating structural stability. Interestingly, enzymatic removal of the ECM restores juvenile forms of plasticity, as for instance demonstrated by topographical reconnectivity in sensory pathways. However, to which degree the mature ECM is a compromise between stability and flexibility in the adult brain impacting synaptic plasticity as a fundamental basis for learning, lifelong memory formation, and higher cognitive functions is largely unknown. In this study, we removed the ECM in the auditory cortex of adult Mongolian gerbils during specific phases of cortex-dependent auditory relearning, which was induced by the contingency reversal of a frequency-modulated tone discrimination, a task requiring high behavioral flexibility. We found that ECM removal promoted a significant increase in relearning performance, without erasing already established—that is, learned—capacities when continuing discrimination training. The cognitive flexibility required for reversal learning of previously acquired behavioral habits, commonly understood to mainly rely on frontostriatal circuits, was enhanced by promoting synaptic plasticity via ECM removal within the sensory cortex. Our findings further suggest experimental modulation of the cortical ECM as a tool to open short-term windows of enhanced activity-dependent reorganization allowing for guided neuroplasticity.