Disrupted cross-laminar cortical processing in ß amyloid pathology precedes cell death.

Disruption of neuronal networks in the Alzheimer-afflicted brain is increasingly recognized as a key correlate of cognitive and memory decline in Alzheimer patients. We hypothesized that functional synaptic disconnections within cortical columnar microcircuits by pathological ß-amyloid accumulation, rather than cell death, initially causes the cognitive impairments. During development of cortical ß-amyloidosis with still few plaques in the transgenic 5xFAD mouse model single cell resolution mapping of neuronal thallium uptake revealed that electrical activity of pyramidal cells breaks down throughout infragranular cortical layer V long before cell death occurs. Treatment of 5xFAD mice with the glutaminyl cyclase inhibitor, PQ 529, partially prevented the decline of pyramidal cell activity, indicating pyroglutamate-modified forms, potentially mixed oligomers of Aß are contributing to neuronal impairment. Laminar investigation of cortical circuit dysfunction with current source density analysis identified an early loss of excitatory synaptic input in infragranular layers, linked to pathological recurrent activations in supragranular layers. This specific disruption of normal cross-laminar cortical processing coincided with a decline of contextual fear learning.

Neuronal analysis of wave form in the time domain: midbrain units in electric fish during social behavior.

A fish of the genus Eigenmannia responds differently to a neighboring conspecific fish with a slightly higher frequency of the electric organ discharge than its own than to one with a slightly lower such frequency than its own. When the two frequencies are beating against each other the special wave shape of the electric organ discharge leads to asymmetries of the beat pattern which are distinct for the two cases. Midbrain neurons, called "deltaF recoders," sign and magnitude of the frequency difference on the basis of these patterns. that is, in the time rather than the frequency domain.

Click train encoding in primary and non-primary auditory cortex of anesthetized macaque monkeys.

We studied encoding of temporally modulated sounds in 28 multiunits in the primary auditory cortical field (AI) and in 35 multiunits in the secondary auditory cortical field (caudomedial auditory cortical field, CM) by presenting periodic click trains with click rates between 1 and 300 Hz lasting for 2-4 s. We found that all multiunits increased or decreased their firing rate during the steady state portion of the click train and that all except two multiunits synchronized their firing to individual clicks in the train. Rate increases and synchronized responses were most prevalent and strongest at low click rates, as expressed by best modulation frequency, limiting frequency, percentage of responsive multiunits, and average rate response and vector strength. Synchronized responses occurred up to 100 Hz; rate response occurred up to 300 Hz. Both auditory fields responded similarly to low click rates but differed at click rates above approximately 12 Hz at which more multiunits in AI than in CM exhibited synchronized responses and increased rate responses and more multiunits in CM exhibited decreased rate responses. These findings suggest that the auditory cortex of macaque monkeys encodes temporally modulated sounds similar to the auditory cortex of other mammals. Together with other observations presented in this and other reports, our findings also suggest that AI and CM have largely overlapping sensitivities for acoustic stimulus features but encode these features differently.

Dynamics of cortical theta activity correlates with stages of auditory avoidance strategy formation in a shuttle-box.

By comparing behavioral performance and cortical theta activity (4-8 Hz) on a trial by trial basis we examined how the different behavioral stages of tone-induced avoidance learning in the shuttle-box may be distinguishable by theta power as a potential correlate of changing strategies of information processing. Electrocorticograms with pronounced theta content were recorded across the cortical surface of gerbils during avoidance learning and analyzed in each trial in conjunction with reaction times and unconditioned and conditioned responses. The focus of theta analysis in this paradigm with a 5-s delay between tone and foot-shock onsets was on the 14-s periods after hurdle crossing where feedback information from a trial is available. The strongest theta activity occurred in stage 1 of initial tone conditioning which was sharply reduced to a minimum during stage 2 of optimization of unconditioned escape responses from the foot shock. A few initial successful avoidance responses gave rise to a reversal of the decline of theta activity that later reached a second maximum. A systematic increase of theta activity during this stage 3 of avoidance conditioning was found for the occasional trials with unconditioned responses and not for the increasing number of conditioned responses suggesting that error processing is a major correlate of this new increase of theta power. After the second maximum the theta power slowly declined together with a further improvement of behavioral performance indicating that stage 4 of retrieval of the consolidated avoidance response was reached. The results suggest that behind a previously reported general trend of decreasing theta power with increasing performance in this paradigm there is a hidden microstructure of theta activity across trials which separates stages of avoidance conditioning and is partially mirrored by known changes of prefrontal dopamine release.

False recognition of emotional stimuli is lateralised in the brain: An fMRI study.

We have investigated whether the left (LH) and right (RH) hemisphere play a different role in eliciting false recognition (FR) and whether their involvement in this memory illusion depends on the emotional content of stimuli. Negative and neutral pictures (taken from IAPS) were presented in the divided-visual field paradigm. Subjects task was to indicate whether the pictures had already been presented or not during the preceding study phase. FR rate was much higher for the RH than the LH presentations. In line, FR resulted in activations mainly in the right prefrontal cortex (PFC) for either RH or LH presentations. Emotional content of stimuli facilitated the formation of false memories and strengthened the involvement of the right PFC in FR induction.

Comparing brain activity patterns during spontaneous exploratory and cue-instructed learning using single photon-emission computed tomography (SPECT) imaging of regional cerebral blood flow in freely behaving rats.

Learning can be categorized into cue-instructed and spontaneous learning types; however, so far, there is no detailed comparative analysis of specific brain pathways involved in these learning types. The aim of this study was to compare brain activity patterns during these learning tasks using the in vivo imaging technique of single photon-emission computed tomography (SPECT) of regional cerebral blood flow (rCBF). During spontaneous exploratory learning, higher levels of rCBF compared to cue-instructed learning were observed in motor control regions, including specific subregions of the motor cortex and the striatum, as well as in regions of sensory pathways including olfactory, somatosensory, and visual modalities. In addition, elevated activity was found in limbic areas, including specific subregions of the hippocampal formation, the amygdala, and the insula. The main difference between the two learning paradigms analyzed in this study was the higher rCBF observed in prefrontal cortical regions during cue-instructed learning when compared to spontaneous learning. Higher rCBF during cue-instructed learning was also observed in the anterior insular cortex and in limbic areas, including the ectorhinal and entorhinal cortexes, subregions of the hippocampus, subnuclei of the amygdala, and the septum. Many of the rCBF changes showed hemispheric lateralization. Taken together, our study is the first to compare partly lateralized brain activity patterns during two different types of learning.

Auditory cortex: comparative aspects of maps and plasticity.

Much recent work in the field of auditory cortex analysis consists of an intensified search for complex sound representation and sound localization mechanisms using tonotopic maps as a frame of reference. Mammalian species rely on parallel processing in multiple tonotopic and non-tonotopic maps but show different degrees of unit complexity, and orderly representation of acoustic dimensions in such maps depending on the predictability of sounds in their environment. Birds appear to rely chiefly on one tonotopic map which harbours multidimensional complex representations. During development and after partial hearing loss, tonotopic organization changes in a predictable manner. Learning also modifies the spatial representation of sounds and even modifies tonotopic organization, but the spatial rules involved in this process have not yet emerged.

Multisensory processing via early cortical stages: Connections of the primary auditory cortical field with other sensory systems.

It is still a popular view that primary sensory cortices are unimodal, but recent physiological studies have shown that under certain behavioral conditions primary sensory cortices can also be activated by multiple other modalities. Here, we investigate the anatomical substrate, which may underlie multisensory processes at the level of the primary auditory cortex (field AI), and which may, in turn, enable AI to influence other sensory systems. We approached this issue by means of the axonal transport of the sensitive bidirectional neuronal tracer fluorescein-labeled dextran which was injected into AI of Mongolian gerbils (Meriones unguiculatus). Of the total number of retrogradely labeled cell bodies (i.e. cells of origin of direct projections to AI) found in non-auditory sensory and multisensory brain areas, approximately 40% were in cortical areas and 60% in subcortical structures. Of the cell bodies in the cortical areas about 82% were located in multisensory cortex, viz., the dorsoposterior and ventroposterior, posterior parietal cortex, the claustrum, and the endopiriform nucleus, 10% were located in the primary somatosensory cortex (hindlimb and trunk region), and 8% in secondary visual cortex. The cortical regions with retrogradely labeled cells also contained anterogradely labeled axons and their terminations, i.e. they are also target areas of direct projections from AI. In addition, the primary olfactory cortex was identified as a target area of projections from AI. The laminar pattern of corticocortical connections suggests that AI receives primarily cortical feedback-type inputs and projects in a feedforward manner to its target areas. Of the labeled cell bodies in the subcortical structures, approximately 90% were located in multisensory thalamic, 4% in visual thalamic, and 6% in multisensory lower brainstem structures. At subcortical levels, we observed a similar correspondence of retrogradely labeled cells and anterogradely labeled axons and terminals in visual (posterior limitans thalamic nucleus) and multisensory thalamic nuclei (dorsal and medial division of the medial geniculate body, suprageniculate nucleus, posterior thalamic cell group, zona incerta), and in the multisensory nucleus of the brachium of the inferior colliculus. Retrograde, but not anterograde, labeling was found in the multisensory pontine reticular formation, particularly in the reticulotegmental nucleus of the pons. Conversely, anterograde, but no retrograde, labeling was found in the visual laterodorsal and lateroposterior thalamic nuclei, in the multisensory peripeduncular, posterior intralaminar, and reticular thalamic nuclei, as well as in the multisensory superior and pericentral inferior colliculi (including cuneiform and sagulum nucleus), pontine nuclei, and periaqueductal gray. Our study supports the notion that AI is not merely involved in the analysis of auditory stimulus properties but also in processing of other sensory and multisensory information. Since AI is directly connected to other primary sensory cortices (viz. the somatosensory and olfactory ones) multisensory information is probably also processed in these cortices. This suggests more generally, that primary sensory cortices may not be unimodal.

New insights into the hemodynamic blood oxygenation level-dependent response through combination of functional magnetic resonance imaging and optical recording in gerbil barrel cortex.

Fast, low-angle shoot functional magnetic resonance imaging (fMRI), based on the blood oxygenation level-dependent (BOLD) effect, was combined with optical recording of intrinsic signals (ORIS) and 2-deoxyglucose labeling in gerbil barrel cortex. We observed over the activated barrel a positive BOLD signal and increased levels of deoxyhemoglobin and total hemoglobin during each period of prolonged (30 sec) D2 vibrissal stimulation. These data show that the hemodynamic basis of this fMRI signal is not necessarily a washout of deoxyhemoglobin, as generally assumed. Instead, they suggest that a positive BOLD signal can also be caused by a local increase of blood volume, even if deoxyhemoglobin levels are persistently elevated. We also show that this alternative interpretation is consistent with theoretical models of the BOLD signal. The changes in BOLD signal and blood volume, which are most tightly correlated with the periodic stimulation, peak at the site of neuronal activation. These results contribute to the understanding of the hemodynamic mechanisms underlying the BOLD signal and also suggest analysis methods, which improve the spatial localization of neuronal activation with both fMRI and ORIS.

Effects of unilateral and bilateral cochlea removal on 2-deoxyglucose patterns in the chick auditory system.

The 2-deoxyglucose (2DG) method was used to map functional activity in the auditory system of chicks that had been subjected to unilateral or bilateral cochlea removal. Following survival times of 1 day to 4 weeks, chicks were exposed to continuous white noise in the 2DG experiments. In monaural subjects nucleus angularis and nucleus magnocellularis showed faint 2DG uptake on the side contralateral to the intact ear. In the binaural nucleus laminaris, the asymmetrical and almost mirror-imaged labeling pattern (Lippe, Stewart, and Rubel: Brain Res. 196:43-58, '80) was produced. The superior olive (OS) was strongly labeled on the ipsilateral side, whereas the contralateral OS showed only a slight 2DG uptake at its medial border. The lateral lemniscus and nucleus lemnisci lateralis, pars ventralis (LLv) showed stronger activation on the contralateral side. Both Nissl stains and 2DG patterns provide evidence that nucleus ventralis lemnisci lateralis (VLV) can be subdivided into an anterior (VLVa) and a posterior (VLVp) part. Whereas VLVp is labeled only contralaterally, VLVa is labeled on both sides with similar intensity. Nucleus mesencephalicus lateralis, pars dorsalis (MLD) is strongly labeled throughout contralaterally. The ipsilateral MLD shows a defined ventral portion of high 2DG uptake. Intensity of labeling here is symmetrical to the corresponding area of the contralateral MLD. These symmetrical patterns were related to the tonotopic organization of MLD, which was mapped in intact animals by using tone stimuli. Assuming that symmetrical 2DG uptake in monaural animals indicates excitatory input from both ears (EE-cells), it appears that these EE-cells occupy a sector of each isofrequency plane in MLD. Nucleus ovoidalis (Ov) generally was stronger labeled on the contralateral side. The columnar organization of field L as seen in monaural chicks has already been described (Scheich, Exp. Brain Res. 51:199-205, '83). In bilaterally deafened chicks, MLD, Ov, and layer L2 of field L showed strong but spatially restricted 2DG accumulation in contrast to absence of labeling in peripheral nuclei. The 2DG patterns in monaural chicks are likely to reflect excitatory input within the auditory system. In addition they reveal new insights into the functional organization of some of its nuclei. In particular, they support the notion that MLD contains maps of several interaural integration mechanisms similar to field L. Labeling in the auditory system of bilaterally deafened chicks may result from descending projections or from other than auditory inputs.

Spatial representation of frequency-modulated signals in the tonotopically organized auditory cortex analogue of the chick.

For auditory communication, many birds, including domestic chicks, use a variety of frequency-modulated (FM) sounds. As a first approach to the spatial representation of such sounds in the central auditory system, we have analyzed 2-deoxyglucose (2DG) patterns that were produced by FM stimuli in the tonotopic map of the auditory forebrain area (field L/hyperstriatum ventrale complex) of domestic chicks. Linear FM signals, varying in the depth and range of modulation, and in the direction and rate of the frequency change, were tested. Also included were signals designed to mimic species-specific FM calls. All FM stimuli activated those regions of the map in which frequencies contained in the stimulus spectra were tonotopically represented. However, frequency and amplitude of the FM spectra were not faithfully reproduced by activation of the complete corresponding tonotopic space. FM signals that differed only in the direction of modulation, and therefore had identical long-term spectra, induced maximum 2DG activation at different locations of the tonotopic gradient. FM signals that differed in the rate of change of frequency produced maxima of 2DG uptake at different positions along an isofrequency dimension of the map. These results suggest that the direction of modulation may be represented in a complex fashion along the tonotopic axis of the structure, whereas the rate of change of frequency may be represented along an isofrequency dimension. None of the experiments provided evidence of FM-selective regions within the auditory forebrain complex. However, numerous telencephalic areas, in addition to the primary auditory area, were strongly activated in chicks stimulated with artificial "species-specific" FM signals. These areas could be involved in the processing of biologically relevant stimuli, requiring attention, recognition, and interpretation of the signals.

Auditory pathway and auditory activation of primary visual targets in the blind mole rat (Spalax ehrenbergi): I. 2-deoxyglucose study of subcortical centers.

The blind mole rat Spalax ehrenbergi is a subterranean rodent that shows striking behavioral, structural, and physiological adaptations to fossorial life including highly degenerated eyes and optic nerves and a behavioral audiogram that indicates high specialization for low-frequency hearing. A 2-deoxyglucose functional mapping of acoustically activated structures, in conjunction with Nissl/Klüver-Barrera-stained material, revealed a typical mammalian auditory pathway with some indications for specialized low-frequency hearing such as a poorly differentiated lateral nucleus and a well-developed medial nucleus in the superior olive complex. The most striking finding was a marked 2-deoxyglucose labeling of the dorsal lateral geniculate body and of cortical regions that correspond to visual areas in sighted rodents. The results render the blind mole rat a good model system for studying natural neural plasticity and intermodal compensation. In this report, we confine ourselves to the subcortical levels. The cortical level will be dealt comprehensively in a following paper.

Presynaptic cytomatrix protein bassoon is localized at both excitatory and inhibitory synapses of rat brain.

Bassoon is a 420-kDa protein specifically localized at the active zone of presynaptic nerve terminals. It is thought to be involved in the structural organization of the neurotransmitter release site. We studied the distribution of Bassoon transcripts and protein in rat brain and assessed which types of presynaptic terminals contain the protein. As shown by in situ hybridization, Bassoon transcripts are widely distributed in the brain and occur primarily in excitatory neurons. In addition, examples of gamma-aminobutyric acid (GABA)-ergic neurons expressing Bassoon are detected. At the light microscopic level, Bassoon immunoreactivity is found in synaptic neuropil regions throughout the brain, with the strongest expression in the hippocampus, the cerebellar cortex, and the olfactory bulb. Immunoelectron microscopy showed that Bassoon immunoreactivity is found in both asymmetric type 1 and symmetric type 2 synapses. Immunopositive asymmetric synapses include mossy fiber boutons and various spine and shaft synapses in the hippocampus and mossy fiber terminals and parallel fiber terminals in the cerebellum. Bassoon-containing symmetric synapses are observed, e.g., between basket and granule cells in the hippocampus, between Golgi cells and granule cells, and between basket cells and Purkinje cells in the cerebellum. Within synaptic terminals, Bassoon appears highly concentrated at sites opposite to postsynaptic densities. In cultured hippocampal neurons, Bassoon was found to colocalize with GABA(A) and glutamate (GluR1) receptors. These data indicate that Bassoon is a component of the presynaptic apparatus of both excitatory glutamatergic and inhibitory GABAergic synapses.

Analysis of evoked and emergent patterns of stimulus-related auditory cortical activity.

Cortical activity contains both evoked patterns and emergent patterns of stimulus-related activity. Here we compared evoked and emergent patterns in the primary auditory cortex, field AI, of the gerbil by studying the differential effects of diluting spatial information about the patterns on their geometric dissimilarity by randomly removing channels from the recording data. This identified the sets of most relevant channels for the discrimination of stimuli in both types of patterns. In the evoked patterns the sets of most discriminative channels were found to be focally organized at locations corresponding to the thalamically relayed input into the cortical tonotopic map. In the emergent patterns the sets of most discriminative channels were broadly distributed and held no apparent relationship to the tonotopic map. The results indicate the coexistence in the same neuronal tissue of a topographic mapping principle for the evoked activity and a holographic mapping principle for the emergent activity.

Synaptic potentiation and depression in slices of mediorostral neostriatum-hyperstriatum complex, an auditory imprinting-relevant area in chick forebrain.

Long-term potentiation, a tetanic stimulation-evoked, persistent increase in synaptic efficiency, is the most extensively studied form of synaptic plasticity. Intracellular correlates of long-term potentiation have been analysed in mammalian hippocampus and cortex, but not in bird cortical analogues. We present here studies on long-term potentiation in slices of the chick forebrain area mediorostral neostriatum-hyperstriatum complex which receives thalamic afferents and is relevant for auditory filial imprinting. Following afferent tetanic stimulation, population spike potentiation was extracellularly recorded in 25% of the tested neurons for longer than 40 min. Using intracellular recordings, the membrane potential, the amplitude of excitatory postsynaptic potentials, the latency between the test stimulus and the evoked action potentials, and the cellular excitability (excitatory postsynaptic potential-spike relationship) were found to change after the tetanus. A long-term depression following the tetanus was also seen in some units in this area. Furthermore, the mechanisms underlying long-term potentiation were investigated. A large depolarization of resting membrane potential (approx. 36 mV) was characteristic after the tetanic stimulation. N-methyl-D-aspartate receptor channels are necessary for induction of this depolarization, as well as for long-term potentiation, as demonstrated by the effect of DL-2-amino-5-phosphonovaleric acid. After intracellular recordings, the cells were injected with Lucifer Yellow. The combination of electrophysiological characterization and morphological identification suggested that the potentiation came chiefly from type I neurons, which have the largest soma among the neuron types in this area and up to eight dendrites. The results demonstrate that the recognized major phenomena of long-term potentiation are found in an auditory imprinting-relevant area of the chick forebrain, and that this potentiation is dependent on N-methyl-D-aspartate receptor channels. It is noteworthy that behavioural imprinting was previously shown to induce a reduction of up to 47% of the spine frequency of type I neurons and a growth of the remaining spine synapses, all resembling a synaptic selection process. Therefore, the intriguing possibility emerges that mechanisms underlying long-term potentiation are instrumental for this selection process, which involves regressive and proliferative morphological changes.

Learning a new behavioral strategy in the shuttle-box increases prefrontal dopamine.

Using microdialysis from medial prefrontal cortex of gerbils during aversive auditory conditioning in the shuttle-box we have previously shown a transient increase of dopamine efflux correlated with the establishment of avoidance behavior. We hypothesized that the acquisition of a new behavioral strategy is generally accompanied by this extra prefrontal dopamine release. The present experiment aimed at further testing this hypothesis. In a pre-training period in the shuttle-box the gerbils acquired an active avoidance response by generalizing two different tone signals to a GO-meaning (change of shuttle-box compartment). Thereafter, they were subjected in relearning sessions to differentially associate the known tone stimuli with GO- and NOGO- (no change of shuttle-box compartment) conditions, respectively. The following formation of discrimination behavior led to a similar extra dopamine increase as found during establishment of the avoidance strategy. This significant enhancement was limited to rapidly relearning individuals. Furthermore, the dopamine increase attenuated in these animals with increasing performance during the course of the discrimination training, similar to the retrieval stage of the avoidance strategy. Therefore, the dopamine system seems to be critically involved in the initial formation of associations for new behavioral strategies, i.e. learning. We assume that the prefrontal dopamine increase during initial learning of the complex discrimination behavior indicates an involvement of working memory principles and a goal-directed formation of a behavioral strategy.

Parvalbumin and calbindin-D28K immunoreactivity as developmental markers of auditory and vocal motor nuclei of the zebra finch.

The posthatch developmental profiles of parvalbumin and calbindin-D28K immunoreactivity were compared for the auditory nucleus mesencephalicus lateralis pars caudalis in the midbrain, n. ovoidalis in the thalamus, and telencephalic field L, as well as for the telencephalic vocal motor nuclei hyperstriatum ventrale pars caudalis and n. robustus archistriatalis. The two calcium-binding proteins showed specific temporal patterns of expression in each nucleus, without following an ascending or descending sequence. Calbindin-D28K immunoreactivity usually preceded parvalbumin immunoreactivity. Onset of expression, especially of parvalbumin-immunostaining, was earlier in auditory nuclei than in vocal motor nuclei. The developmental order of appearance of immunoreactivity in somata, dendrites and axons was different in various brain regions. In some structures parvalbumin or calbindin-D28K immunoreactivity occurred only transiently. The two antibodies bound to separate but spatially complementary groups of cells in the nucleus mesencephalicus lateralis pars dorsalis and n. ovoidalis, as has previously been described in visual nuclei. This pattern was maintained into adulthood. These hitherto unknown subcompartments may reflect internal functional organization in these nuclei. A transitory neostriatal zone containing parvalbumin-positive neurons and fibres was observed between the immature field L and the emerging hyperstriatum ventrale pars caudalis. Some comparative aspects are discussed as to the way in which neurons distinguished by the two Ca-binding proteins may differ in energy metabolism, activity pattern and other functional mechanisms.

Neuronal and behavioral discrimination between upward and downward pulse interval modulation in cochlea implanted gerbils.

Speech coding strategies for cochlear implants commonly use amplitude modulations of constant high rate pulses to differentially stimulate separate frequency channels in the cochlea. Thereby, time domain information in the fine structure of speech sounds, especially on transients, is largely lost. In gerbils with a single electrode cochlear implant was explored, whether upward and downward interval modulation of pulse trains can carry discriminable information. This question was pursued with unit recordings in primary auditory cortex (AI) and with behavioral discrimination training in a shuttle box. Units in AI showed multiple differences in the dynamic responses to the two directions of interval modulation and notably ON-response dominated patterns with increasing intervals and OFF-response dominated patterns with decreasing intervals of stimulation. In accordance with these neuronal correlates gerbils learned to distinguish the directions of interval modulation within 3 days, but only with certain specifications.

Auditory perception of laughing and crying activates human amygdala regardless of attentional state.

Adequate behavioral responses to socially relevant stimuli are often impaired after lesions of the amygdala. Such lesions concern especially the recognition of facial and sometimes of vocal expression of emotions. Using low-noise functional magnetic resonance imaging (fMRI), we investigated in which way the amygdala, auditory cortex and insula are involved in the processing of affective nonverbal vocalizations (Laughing and Crying) in healthy humans. The same samples of male and female Laughing and Crying were presented in different experimental conditions: Simply listening to the stimuli, self-induction of the corresponding emotions while listening, and detection of artificial pitch shifts in the same stimuli. All conditions activated the amygdala similarly and bilaterally, whereby the amount of activation was larger in the right amygdala. The auditory cortex was more strongly activated by Laughing than by Crying with a slight right-hemisphere advantage for Laughing, both likely due to acoustic stimulus features. The insula was bilaterally activated in all conditions. The mean signal intensity change with stimulation was much larger in the amygdala than in auditory cortex and insula. The amygdala results seem to be in accordance with the right-hemisphere hypothesis of emotion processing which may not be applicable as strongly to the level of auditory cortex or insula.

Short-term functional plasticity in the human auditory cortex: an fMRI study.

Applying functional magnetic resonance imaging (fMRI) techniques, hemodynamic responses elicited by sequences of pure tones of 950 Hz (standard) and deviant tones of 952, 954, and 958 Hz were measured before and 1 week after subjects had been trained at frequency discrimination for five sessions (over 1 week) using an oddball procedure. The task of the subject was to detect deviants differing from the standard stimulus. Frequency discrimination improved during the training session for three subjects (performance gain: T+) but not for three other subjects (no performance gain: T-). Hemodynamic responses in the auditory cortex comprising the planum temporale, planum polare and sulcus temporalis superior significantly decreased during training only for the T+ group. These activation changes were strongest for those stimuli accompanied by the strongest performance gain (958 and 954 Hz). There was no difference with respect to the hemodynamic responses in the auditory cortex for the T- group and the control group (CO) who did not received any pitch discrimination training. The results suggest a plastic reorganization of the cortical representation for the trained frequencies which can be best explained on the basis of 'fast learning' theories.