Pavlovian conditioning-induced hallucinations reduce MMN amplitudes for duration but not frequency deviants.

The mismatch negativity (MMN) is an evoked potential that indexes auditory regularity violations. Since the 90's, a reduced amplitude of this brain activity in patients with schizophrenia has been consistently reported. Recently, this alteration has been related to the presence of auditory hallucinations (AHs) rather than the schizophrenia diagnostic per se. However, making this attribution is rather problematic due to the high heterogeneity of symptoms in schizophrenia. In an attempt to isolate the AHs influence on the MMN amplitude from other cofounding variables, we artificially induced AHs in a non-clinical population by Pavlovian conditioning. Before and after conditioning, volunteers (N = 31) participated in an oddball paradigm that elicited an MMN. Two different types of deviants were presented: a frequency and a duration deviant, as the MMN alteration seems to be especially present in schizophrenia with the latter type of deviant. Hence, this pre-post design allowed us to compare whether experiencing conditioning-induced AHs exert any influence on MMN amplitudes. Our results show that duration-deviant related MMN reductions significantly correlate with the number of AHs experienced. Moreover, we found a significant correlation between AHs proneness (measured with the Launay-Slade Hallucination Extended Scale) and the number of AHs experienced during the paradigm. In sum, our study shows that AHs can be conditioned and exert similar effects on MMN modulation in healthy participants as has been reported for patients with schizophrenia. Thus, conditioning paradigms offer the possibility to study the association between hallucinations and MMN reductions without the confounding variables present in schizophrenia patients.

Conditioned up and down modulations of short latency gamma band oscillations in visual cortex during fear learning in humans.

Over the course of evolution, the human brain has been shaped to prioritize cues that signal potential danger. Thereby, the brain does not only favor species-specific prepared stimulus sets such as snakes or spiders but can learn associations between new cues and aversive outcomes. One important mechanism to achieve this is associated with learning induced plasticity changes in sensory cortex that optimizes the representation of motivationally relevant sensory stimuli. Animal studies have shown that the modulation of gamma band oscillations predicts plasticity changes in sensory cortices by shifting neurons' responses to fear relevant features as acquired by Pavlovian fear conditioning. Here, we report conditioned gamma band modulations in humans during fear conditioning of orthogonally oriented sine gratings representing fear relevant and irrelevant conditioned cues. Thereby, pairing of a sine grating with an aversive loud noise not only increased short latency (during the first 180 ms) evoked visual gamma band responses, but was also accompanied by strong gamma power reductions for the fear irrelevant control grating. The current findings will be discussed in the light of recent neurobiological models of plasticity changes in sensory cortices and classic learning models such as the Rescorla-Wagner framework.

A Model of the Early Visual System Based on Parallel Spike-Sequence Detection, Showing Orientation Selectivity.

Since the first half of the twentieth century, numerous studies have been conducted on how the visual cortex encodes basic image features. One of the hallmarks of basic feature extraction is the phenomenon of orientation selectivity, of which the underlying neuronal-level computational mechanisms remain partially unclear despite being intensively investigated. In this work we present a reduced visual system model (RVSM) of the first level of scene analysis, involving the retina, the lateral geniculate nucleus and the primary visual cortex (V1), showing orientation selectivity. The detection core of the RVSM is the neuromorphic spike-decoding structure MNSD, which is able to learn and recognize parallel spike sequences and considerably resembles the neuronal microcircuits of V1 in both topology and operation. This structure is equipped with plasticity of intrinsic excitability to embed recent findings about V1 operation. The RVSM, which embeds 81 groups of MNSD arranged in 4 oriented columns, is tested using sets of rotated Gabor patches as input. Finally, synthetic visual evoked activity generated by the RVSM is compared with real neurophysiological signal from V1 area: (1) postsynaptic activity of human subjects obtained by magnetoencephalography and (2) spiking activity of macaques obtained by multi-tetrode arrays. The system is implemented using the NEST simulator. The results attest to a good level of resemblance between the model response and real neurophysiological recordings. As the RVSM is available online, and the model parameters can be customized by the user, we propose it as a tool to elucidate the computational mechanisms underlying orientation selectivity.

Spatial analysis of thickness changes in ten retinal layers of Alzheimer's disease patients based on optical coherence tomography.

The retina is an attractive source of biomarkers since it shares many features with the brain. Thickness differences in 10 retinal layers between 19 patients with mild Alzheimer's disease (AD) and a control group of 24 volunteers were investigated. Retinal layers were automatically segmented and their thickness at each scanned point was measured, corrected for tilt and spatially normalized. When the mean thickness of entire layers was compared between patients and controls, only the outer segment layer of patients showed statistically significant thinning. However, when the layers were compared point-by point, patients showed statistically significant thinning in irregular regions of total retina and nerve fiber, ganglion cell, inner plexiform, inner nuclear and outer segment layers. Our method, based on random field theory, provides a precise delimitation of regions where total retina and each of its layers show a statistically significant thinning in AD patients. All layers, except inner nuclear and outer segments, showed thickened regions. New analytic methods have shown that thinned regions are interspersed with thickened ones in all layers, except inner nuclear and outer segments. Across different layers we found a statistically significant trend of the thinned regions to overlap and of the thickened ones to avoid overlapping.