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.

Human amygdala response to unisensory and multisensory emotion input: No evidence for superadditivity from intracranial recordings.

The amygdala is crucially implicated in processing emotional information from various sensory modalities. However, there is dearth of knowledge concerning the integration and relative time-course of its responses across different channels, i.e., for auditory, visual, and audiovisual input. Functional neuroimaging data in humans point to a possible role of this region in the multimodal integration of emotional signals, but direct evidence for anatomical and temporal overlap of unisensory and multisensory-evoked responses in amygdala is still lacking. We recorded event-related potentials (ERPs) and oscillatory activity from 9 amygdalae using intracranial electroencephalography (iEEG) in patients prior to epilepsy surgery, and compared electrophysiological responses to fearful, happy, or neutral stimuli presented either in voices alone, faces alone, or voices and faces simultaneously delivered. Results showed differential amygdala responses to fearful stimuli, in comparison to neutral, reaching significance 100-200 ms post-onset for auditory, visual and audiovisual stimuli. At later latencies, ∼400 ms post-onset, amygdala response to audiovisual information was also amplified in comparison to auditory or visual stimuli alone. Importantly, however, we found no evidence for either super- or subadditivity effects in any of the bimodal responses. These results suggest, first, that emotion processing in amygdala occurs at globally similar early stages of perceptual processing for auditory, visual, and audiovisual inputs; second, that overall larger responses to multisensory information occur at later stages only; and third, that the underlying mechanisms of this multisensory gain may reflect a purely additive response to concomitant visual and auditory inputs. Our findings provide novel insights on emotion processing across the sensory pathways, and their convergence within the limbic system.

Thalamocortical interactions underlying visual fear conditioning in humans.

Despite a strong focus on the role of the amygdala in fear conditioning, recent works point to a more distributed network supporting fear conditioning. We aimed to elucidate interactions between subcortical and cortical regions in fear conditioning in humans. To do this, we used two fearful faces as conditioned stimuli (CS) and an electrical stimulation at the left hand, paired with one of the CS, as unconditioned stimulus (US). The luminance of the CS was rhythmically modulated leading to "entrainment" of brain oscillations at a predefined modulation frequency. Steady-state responses (SSR) were recorded by MEG. In addition to occipital regions, spectral analysis of SSR revealed increased power during fear conditioning particularly for thalamus and cerebellum contralateral to the upcoming US. Using thalamus and amygdala as seed-regions, directed functional connectivity was calculated to capture the modulation of interactions that underlie fear conditioning. Importantly, this analysis showed that the thalamus drives the fusiform area during fear conditioning, while amygdala captures the more general effect of fearful faces perception. This study confirms ideas from the animal literature, and demonstrates for the first time the central role of the thalamus in fear conditioning in humans.

Source distribution of neuromagnetic slow-wave activity in schizophrenic patients--effects of activation.

When slow waves in the EEG delta and theta frequency range appear in the waking state, they may indicate pathological conditions including psychopathology. The generators of focal slow waves can be mapped using magnetic source imaging. The resulting brain maps may possibly characterize dysfunctional brain areas. The present study examined the stability of the density and distribution of MEG slow waves during three conditions-rest, mental arithmetic and imagery-in 30 schizophrenic patients and 17 healthy controls. Schizophrenic patients displayed a higher density of delta and theta generators primarily in temporal and parietal areas. The group difference was not affected by the particular conditions. The focal concentration of delta and theta slow waves did not differ between patients with and without neuroleptic medication, whereas the prominence of theta dipoles in the temporal area correlated with neuroleptic dosage. The relative amount of temporal slow waves was correlated with the negative symptoms score (PANSS-N) suggesting that temporal dysfunction may be related to negative symptomatology.Results suggest that the distribution of slow-wave activity, measured in a standardized setting, might add diagnostic information about brain abnormalities in schizophrenia.