Bistability of prefrontal states gates access to consciousness.

Access of sensory information to consciousness has been linked to the ignition of content-specific representations in association cortices. How does ignition interact with intrinsic cortical state fluctuations to give rise to conscious perception? We addressed this question in the prefrontal cortex (PFC) by combining multi-electrode recordings with a binocular rivalry (BR) paradigm inducing spontaneously driven changes in the content of consciousness, inferred from the reflexive optokinetic nystagmus (OKN) pattern. We find that fluctuations between low-frequency (LF, 1-9 Hz) and beta (∼20-40 Hz) local field potentials (LFPs) reflect competition between spontaneous updates and stability of conscious contents, respectively. Both LF and beta events were locally modulated. The phase of the former locked differentially to the competing populations just before a spontaneous transition while the latter synchronized the neuronal ensemble coding the consciously perceived content. These results suggest that prefrontal state fluctuations gate conscious perception by mediating internal states that facilitate perceptual update and stability.

Decoding internally generated transitions of conscious contents in the prefrontal cortex without subjective reports.

A major debate about the neural correlates of conscious perception concerns its cortical organization, namely, whether it includes the prefrontal cortex (PFC), which mediates executive functions, or it is constrained within posterior cortices. It has been suggested that PFC activity during paradigms investigating conscious perception is conflated with post-perceptual processes associated with reporting the contents of consciousness or feedforward signals originating from exogenous stimulus manipulations and relayed via posterior cortical areas. We addressed this debate by simultaneously probing neuronal populations in the rhesus macaque (Macaca mulatta) PFC during a no-report paradigm, capable of instigating internally generated transitions in conscious perception, without changes in visual stimulation. We find that feature-selective prefrontal neurons are modulated concomitantly with subjective perception and perceptual suppression of their preferred stimulus during both externally induced and internally generated changes in conscious perception. Importantly, this enables reliable single-trial, population decoding of conscious contents. Control experiments confirm significant decoding of stimulus contents, even when oculomotor responses, used for inferring perception, are suppressed. These findings suggest that internally generated changes in the contents of conscious visual perception are reliably reflected within the activity of prefrontal populations in the absence of volitional reports or changes in sensory input.

Decoding rapidly presented visual stimuli from prefrontal ensembles without report nor post-perceptual processing.

The role of the primate prefrontal cortex (PFC) in conscious perception is debated. The global neuronal workspace theory of consciousness predicts that PFC neurons should contain a detailed code of the current conscious contents. Previous research showed that PFC is indeed activated in paradigms of conscious visual perception, including no-report paradigms where no voluntary behavioral report of the percept is given, thus avoiding a conflation of signals related to visual consciousness with signals related to the report. Still, it has been argued that prefrontal modulation could reflect post-perceptual processes that may be present even in the absence of report, such as thinking about the perceived stimulus, therefore reflecting a consequence rather than a direct correlate of conscious experience. Here, we investigate these issues by recording neuronal ensemble activity from the macaque ventrolateral PFC during briefly presented visual stimuli, either in isolated trials in which stimuli were clearly perceived or in sequences of rapid serial visual presentation (RSVP) in which perception and post-perceptual processing were challenged. We report that the identity of each stimulus could be decoded from PFC population activity even in the RSVP condition. The first visual signals could be detected at 60 ms after stimulus onset and information was maximal at 150 ms. However, in the RSVP condition, 200 ms after the onset of a stimulus, the decoding accuracy quickly dropped to chance level and the next stimulus started to be decodable. Interestingly, decoding in the ventrolateral PFC was stronger compared to posterior parietal cortex for both isolated and RSVP stimuli. These results indicate that neuronal populations in the macaque PFC reliably encode visual stimuli even under conditions that have been shown to challenge conscious perception and/or substantially reduce the probability of post-perceptual processing in humans. We discuss whether the observed activation reflects conscious access, phenomenal consciousness, or merely a preconscious bottom-up wave.

Nonmonotonic spatial structure of interneuronal correlations in prefrontal microcircuits.

Correlated fluctuations of single neuron discharges, on a mesoscopic scale, decrease as a function of lateral distance in early sensory cortices, reflecting a rapid spatial decay of lateral connection probability and excitation. However, spatial periodicities in horizontal connectivity and associational input as well as an enhanced probability of lateral excitatory connections in the association cortex could theoretically result in nonmonotonic correlation structures. Here, we show such a spatially nonmonotonic correlation structure, characterized by significantly positive long-range correlations, in the inferior convexity of the macaque prefrontal cortex. This functional connectivity kernel was more pronounced during wakefulness than anesthesia and could be largely attributed to the spatial pattern of correlated variability between functionally similar neurons during structured visual stimulation. These results suggest that the spatial decay of lateral functional connectivity is not a common organizational principle of neocortical microcircuits. A nonmonotonic correlation structure could reflect a critical topological feature of prefrontal microcircuits, facilitating their role in integrative processes.

Testing the perceptual equivalence hypothesis in mental rotation of 3D stimuli with visual and tactile input.

Previous studies on mental rotation (i.e., the ability to imagine objects undergoing rotation; MR) have mainly focused on visual input, with comparatively less information about tactile input. In this study, we examined whether the processes subtending MR of 3D stimuli with both input modalities are perceptually equivalent (i.e., when learning within-modalities is equal to transfers-of-learning between modalities). We compared participants' performances in two consecutive task sessions either in no-switch conditions (Visual→Visual or Tactile→Tactile) or in switch conditions (Visual→Tactile or Tactile→Visual). Across both task sessions, we observed MR response differences with visual and tactile inputs, as well as difficult transfer-of-learning. In no-switch conditions, participants showed significant improvements on all dependent measures. In switch conditions, however, we only observed significant improvements in response speeds with tactile input (RTs, intercepts, slopes: Visual→Tactile) and close to significant improvement in response accuracy with visual input (Tactile→Visual). Model fit analyses (of the rotation angle effect on RTs) also suggested different specification in learning with tactile and visual input. In "Session 1", the RTs fitted similarly well to the rotation angles, for both types of perceptual responses. However, in "Session 2", trend lines in the fitting analyses changed in a stark way, in the switch and tactile no-switch conditions. These results suggest that MR with 3D objects is not necessarily a perceptually equivalent process. Specialization (and priming) in the exploration strategies (i.e., speed-accuracy trade-offs) might, however, be the main factor at play in these results-and not MR differences in and of themselves.

Calcium regulation by thermo- and osmosensing transient receptor potential vanilloid channels (TRPVs) in human conjunctival epithelial cells.

Transient receptor potential vanilloid (TRPV) channels respond to polymodal stresses to induce pain, inflammation and tissue fibrosis. In this study, we probed for their functional expression in human conjunctival epithelial (HCjE) cells and ex vivo human conjunctivas. Notably, patients suffering from dry eye syndrome experience the same type of symptomology induced by TRPV channel activation in other ocular tissues. TRPV gene and protein expression were determined by RT-PCR and immunohistochemistry in HCjE cells and human conjunctivas (body donors). The planar patch-clamp technique was used to record nonselective cation channel currents. Ca(2+) transients were monitored in fura-2 loaded cells. Cultivated HCjE cells and human conjunctiva express TRPV1, TRPV2, and TRPV4 mRNA. TRPV1 and TRPV4 localization was identified in human conjunctiva. Whereas the TRPV1 agonist capsaicin (CAP) (5-20 µM) -induced Ca(2+) transients were blocked by capsazepine (CPZ) (10 µM), the TRPV4 activator 4α-PDD (10 µM) -induced Ca(2+) increases were reduced by ruthenium-red (RuR) (20 µM). Different heating (<40°C or >43°C) led to Ca(2+) increases, which were also reduced by RuR. Hypotonic challenges of either 25 or 50% induced Ca(2+) transients and nonselective cation channel currents. In conclusion, conjunctiva express TRPV1, TRPV2, and TRPV4 channels which may provide novel drug targets for dry eye therapeutics. Their usage may have fewer side effects than those currently encountered with less selective drugs.

Altered calcium regulation by thermosensitive transient receptor potential channels in etoposide-resistant WERI-Rb1 retinoblastoma cells.

Differences in transient receptor potential (TRP) and cannabinoid receptor type 1 (CB1) expression levels can serve as prognostic factors for retinoblastoma (RB) tumor progression. We hypothesized in RB tissue that such differences are also indicators of whether or not they are sensitive to etoposide. Accordingly, we compared in malignant etoposide-sensitive and etoposide-resistant WERI-Rb1 cells TRPV1, TRPM8 and TRPA1 subtype and CB1 gene expression pattern levels and accompanying functional activity using quantitative real-time RT-PCR, immunohistochemistry, immunofluorescence microscopy, calcium imaging as well as patch-clamp technology. Gene expression patterns were evaluated in enucleated human RB tissues (n = 4). Both etoposide-resistant and etoposide-sensitive WERI-Rb1 cells expressed all of the aforementioned channels based on responses to known activators and thermal challenges. However, TRPA1 was absent in the etoposide-resistant counterpart. Even though both types of RB cells express TRPV1 as well as TRPM8 and CB1, the capsaicin (50 µM) (CAP)-induced Ca(2+) rise caused by TRPV1 activation was prompt and transient only in etoposide-resistant RB cells (n = 8). In this cell type, the inability of CB1 activation (10 µM WIN) to suppress Ca(2+) responses to CAP (50 µM; n = 4) may be attributable to the absence of TRPA1 gene expression. Therefore, using genetic approaches to upregulate TRPA1 expression could provide a means to induce etoposide sensitivity and suppress RB cell tumorigenesis.