Assessing the commensurability of theories of consciousness: On the usefulness of common denominators in differentiating, integrating and testing hypotheses.

How deep is the current diversity in the panoply of theories to define consciousness, and to what extent do these theories share common denominators? Here we first examine to what extent different theories are commensurable (or comparable) along particular dimensions. We posit logical (and, when applicable, empirical) commensurability as a necessary condition for identifying common denominators among different theories. By consequence, dimensions for inclusion in a set of logically and empirically commensurable theories of consciousness can be proposed. Next, we compare a limited subset of neuroscience-based theories in terms of commensurability. This analysis does not yield a denominator that might serve to define a minimally unifying model of consciousness. Theories that seem to be akin by one denominator can be remote by another. We suggest a methodology of comparing different theories via multiple probing questions, allowing to discern overall (dis)similarities between theories. Despite very different background definitions of consciousness, we conclude that, if attention is paid to the search for a common methological approach to brain-consciousness relationships, it should be possible in principle to overcome the current Babylonian confusion of tongues and eventually integrate and merge different theories.

Functional (ir)relevance of posterior parietal cortex during audiovisual change detection.

The posterior parietal cortex (PPC) plays a key role in integrating sensory inputs from different modalities to support adaptive behavior. Neuronal activity in PPC reflects perceptual decision making across behavioral tasks, but the mechanistic involvement of PPC is unclear. In an audiovisual change detection task, we tested the hypothesis that PPC is required to arbitrate between the noisy inputs from the two different modalities and help decide in which modality a sensory change occurred. In trained male mice, we found extensive single-neuron and population-level encoding of task-relevant visual and auditory stimuli, trial history, as well as upcoming behavioral responses. However, despite these rich neural correlates, which would theoretically be sufficient to solve the task, optogenetic inactivation of PPC did not affect visual or auditory performance. Thus, in spite of neural correlates faithfully tracking sensory variables and predicting behavioral responses, PPC was not relevant for audiovisual change detection. This functional dissociation questions the role of sensory- and task-related activity in parietal associative circuits during audiovisual change detection. Furthermore, our results highlight the necessity to dissociate functional correlates from mechanistic involvement when exploring the neural basis of perception and behavior.SIGNIFICANCE STATEMENTThe Posterior Parietal Cortex (PPC) is active during many daily tasks, but capturing its function has remained challenging. Specifically, it is proposed to function as an integration hub for multisensory inputs. Here, we tested the hypothesis that, rather than classical cue integration, mouse PPC is involved in the segregation and discrimination of sensory modalities. Surprisingly, even though neural activity tracked current and past sensory stimuli and reflected the ongoing decision-making process, optogenetic inactivation did not affect task performance. Thus, we show an apparent redundancy of sensory and task-related activity in mouse PPC. These results narrow down the function of parietal circuits, as well as direct the search for those neural dynamics that causally drive perceptual decision making.

The hippocampal-striatal axis in learning, prediction and goal-directed behavior.

The hippocampal formation and striatum subserve declarative and procedural memory, respectively. However, experimental evidence suggests that the ventral striatum, as opposed to the dorsal striatum, does not lend itself to being part of either system. Instead, it may constitute a system integrating inputs from the amygdala, prefrontal cortex and hippocampus to generate motivational, outcome-predicting signals that invigorate goal-directed behaviors. Inspired by reinforcement learning models, we suggest an alternative scheme for computational functions of the striatum. Dorsal and ventral striatum are proposed to compute outcome predictions largely in parallel, using different types of information as input. The nature of the inputs to striatum is furthermore combinatorial, and the specificity of predictions transcends the level of scalar value signals, incorporating episodic information.

Experience-dependent alterations in conscious resting state activity following perceptuomotor learning.

In monkeys and rats, neural activity patterns during learning are reactivated during subsequent periods of rest or sleep. According to the reactivation-consolidation account, this process underlies the consolidation of memories. Brain imaging studies have extended these findings to humans during sleep, but not yet, during rest. Here, we show that learning-related reactivation also occurs in humans during rest. During functional MRI-scanning, participants trained on a perceptuomotor task flanked by rest periods. During training, we found robust activity in the superior parietal cortex. During post-training rest, this same area reactivated. We also found a link between parietal reactivation and learning. Activity in superior parietal cortex was associated with learning during training, and a control group that did not train on the perceptuomotor task did not show any difference between the pre- and post-training rest blocks in this region. These findings indicate that, during rest, reactivation also occurs in humans. This process may contribute to consolidation of perceptuomotor memories.

Dissociating the "retrieval success" regions of the brain: effects of retrieval delay.

There is abundant evidence that the hippocampal formation critically supports episodic memory retrieval, the remembering of episodes including contextual details. Yet, a group of other brain regions has also been consistently implicated in successful episodic retrieval. This retrieval success network (RSN) includes the posterior midline region, medial prefrontal cortex (mPFC), and posterior parietal cortex (PPC). Despite these consistent findings, the functional roles of the RSN regions remain poorly understood. Given that vivid remembering leads to high-confidence retrieval decisions, it is unclear whether activity in these regions reflects episodic long-term memory, or is merely associated with retrieval confidence. In order to distinguish between these alternatives, we manipulated study-test delays within the context of a continuous recognition task during fMRI-scanning. The design was based on previous evidence indicating that retrieval at short delays is easier leading to high-evidence mnemonic decisions, whereas retrieval at longer delays is more difficult but also more hippocampus-dependent. Confirming previous findings, we found that retrieval decisions at short delays were more accurate and faster, and that the hippocampus showed greater activity at longer delays. Within the other RSN regions, we found three distinct activation patterns as a function of delay. Similar to the hippocampus, the retrosplenial cortex showed increased activity as a function of retrieval delay. Dorsal PPC and the precuneus showed decreased activity. Finally, the posterior cingulate, medial PFC and ventral PPC showed a V-shaped pattern. These findings support the idea that dorsal PPC and the precuneus are involved in decision-related retrieval processes rather than successful remembering.

Expression of amphetamine sensitization is associated with recruitment of a reactive neuronal population in the nucleus accumbens core.

RATIONALE: Repeated exposure to psychostimulant drugs causes a long-lasting increase in the psychomotor and reinforcing effects of these drugs and an array of neuroadaptations. One such alteration is a hypersensitivity of striatal activity such that a low dose of amphetamine in sensitized animals produces dorsal striatal activation patterns similar to acute treatment with a high dose of amphetamine. OBJECTIVES: To extend previous findings of striatal hypersensitivity with behavioral observations and with cellular activity in the nucleus accumbens and prefrontal cortex in sensitized animals. MATERIALS AND METHODS: Rats treated acutely with 0, 1, 2.5, or 5 mg/kg i.p. amphetamine and sensitized rats challenged with 1 mg/kg i.p. amphetamine were scored for stereotypy, rearing, and grooming, and locomotor activity recorded. c-fos positive nuclei were quantified in the nucleus accumbens and prefrontal cortex after expression of sensitization with 1 mg/kg i.p. amphetamine. RESULTS: Intense stereotypy was seen in animals treated acutely with 5 mg/kg amphetamine, but not in the sensitized group treated with 1 mg/kg amphetamine. The c-fos response to amphetamine in the accumbens core was augmented in amphetamine-pretreated animals with a shift in the distribution of optical density, while no effect of sensitization was seen in the nucleus accumbens shell or prefrontal cortex. CONCLUSIONS: A lack of stereotypy in the sensitized group indicates a dissociation of behavioral responses to amphetamine and striatal immediate-early gene activation patterns. The increase in c-fos positive nuclei and shift in the distribution of optical density observed in the nucleus accumbens core suggests recruitment of a new population of neurons during expression of sensitization.

Pharmacological manipulation of neuronal ensemble activity by reverse microdialysis in freely moving rats: a comparative study of the effects of tetrodotoxin, lidocaine, and muscimol.

To be able to address the question how neurotransmitters or pharmacological agents influence activity of neuronal populations in freely moving animals, the combidrive was developed. The combidrive combines an array of 12 tetrodes to perform ensemble recordings with a moveable and replaceable microdialysis probe to locally administer pharmacological agents. In this study, the effects of cumulative concentrations of tetrodotoxin, lidocaine, and muscimol on neuronal firing activity in the prefrontal cortex were examined and compared. These drugs are widely used in behavioral studies to transiently inactivate brain areas, but little is known about their effects on ensemble activity and the possible differences between them. The results show that the combidrive allows ensemble recordings simultaneously with reverse microdialysis in freely moving rats for periods at least up to 2 wk. All drugs reduced neuronal firing in a concentration dependent manner, but they differed in the extent to which firing activity of the population was decreased and the in speed and extent of recovery. At the highest concentration used, both muscimol and tetrodotoxin (TTX) caused an almost complete reduction of firing activity. Lidocaine showed the fastest recovery, but it resulted in a smaller reduction of firing activity of the population. From these results, it can be concluded that whenever during a behavioral experiment a longer lasting, reversible inactivation is required, muscimol is the drug of choice, because it inactivates neurons to a similar degree as TTX, but it does not, in contrast to TTX, affect fibers of passage. For a short-lasting but partial inactivation, lidocaine would be most suitable.

Augmented reinforcer value and accelerated habit formation after repeated amphetamine treatment.

Various processes might explain the progression from casual to compulsive drug use underlying the development of drug addiction. Two of these, accelerated stimulus-response (S-R) habit learning and augmented assignment of motivational value to reinforcers, could be mediated via neuroadaptations associated with long-lasting sensitization to psychostimulant drugs, i.e. augmented dopaminergic neurotransmission in the striatum. Here, we tested the hypothesis that both processes, which are often regarded as mutually exclusive alternatives, are present in amphetamine-sensitized rats. Amphetamine-sensitized rats showed increased responding for food under a random ratio schedule of reinforcement, indicating increased incentive motivational value of food. In addition, satiety-specific devaluation experiments under a random interval schedule of reinforcement showed that amphetamine-sensitized animals exhibit accelerated development of S-R habits. These data show that both habit formation and motivational value of reinforcers are augmented in amphetamine-sensitized rats, and suggest that the task demands determine which behavioral alteration is most prominently expressed.

Anatomical evidence for direct connections between the shell and core subregions of the rat nucleus accumbens.

The nucleus accumbens is thought to subserve different aspects of adaptive and emotional behaviors. The anatomical substrates for such actions are multiple, parallel ventral striatopallidal output circuits originating in the nucleus accumbens shell and core subregions. Several indirect ways of interaction between the two subregions and their associated circuitry have been proposed, in particular through striato-pallido-thalamic and dopaminergic pathways. In this study, using anterograde neuroanatomical tracing with Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine as well as single-cell juxtacellular filling with neurobiotin, we investigated the intra-accumbens distribution of local axon collaterals for the identification of possible direct connections between the shell and core subregions. Our results show widespread intra-accumbens projection patterns, including reciprocal projections between specific parts of the shell and core. However, fibers originating in the core reach more distant areas of the shell, including the rostral pole (i.e. the calbindin-poor part of the shell anterior to the core) and striatal parts of the olfactory tubercle, than those arising in the shell and projecting to the core. The latter projections are more restricted to the border region between the shell and core. The density of the fiber labeling within both the shell and core was very similar. Moreover, specific intrinsic projections within shell and core were identified, including a relatively strong projection from the rostral pole to the rostral shell, reciprocal projections between the rostral and caudal shell, as well as projections within the core that have a caudal-to-rostral predominance. The results of the juxtacellular filling experiments show that medium-sized spiny projection neurons and medium-sized aspiny neurons (most likely fast-spiking) contribute to these intra-accumbens projections. While such neurons are GABAergic, the intrastriatal projection patterns indicate the existence of lateral inhibitory interactions within, as well as between, shell and core subregions of the nucleus accumbens.

The ventral striatum in off-line processing: ensemble reactivation during sleep and modulation by hippocampal ripples.

Previously it has been shown that the hippocampus and neocortex can spontaneously reactivate ensemble activity patterns during post-behavioral sleep and rest periods. Here we examined whether such reactivation also occurs in a subcortical structure, the ventral striatum, which receives a direct input from the hippocampal formation and has been implicated in guidance of consummatory and conditioned behaviors. During a reward-searching task on a T-maze, flanked by sleep and rest periods, parallel recordings were made from ventral striatal ensembles while EEG signals were derived from the hippocampus. Statistical measures indicated a significant amount of reactivation in the ventral striatum. In line with hippocampal data, reactivation was especially prominent during post-behavioral slow-wave sleep, but unlike the hippocampus, no decay in pattern recurrence was visible in the ventral striatum across the first 40 min of post-behavioral rest. We next studied the relationship between ensemble firing patterns in ventral striatum and hippocampal ripples-sharp waves, which have been implicated in pattern replay. Firing rates were significantly modulated in close temporal association with hippocampal ripples in 25% of the units, showing a marked transient enhancement in the average response profile. Strikingly, ripple-modulated neurons in ventral striatum showed a clear reactivation, whereas nonmodulated cells did not. These data suggest, first, the occurrence of pattern replay in a subcortical structure implied in the processing and prediction of reward and, second, a functional linkage between ventral striatal reactivation and a specific type of high-frequency population activity associated with hippocampal replay.

C-fos activation patterns in rat prefrontal cortex during acquisition of a cued classical conditioning task.

The prefrontal cortex (PFC) is known to be involved in associative learning; however, its specific role in acquisition of cued classical conditioning has not yet been determined. Furthermore, the role of regional differences within the PFC in the acquisition of cued conditioning is not well described. These issues were addressed by exposing rats to either one or four sessions of a cued classical conditioning task, and subsequently examining c-fos immunoreactivity in various areas of the PFC. Differences in patterns of c-fos immunopositive nuclei were found when comparing the PFC areas examined. No significant differences were found between rats presented with a temporally contingent conditioned stimulus (CS) light and food (paired groups) and those presented with the same stimuli temporally non-contingently (unpaired groups). In lateral and orbital PFC, both the paired and unpaired groups showed more c-fos immunopositive nuclei than control groups exposed only to the behavioral setup (context exposed groups), and all groups showed a drop in c-fos immunopositive nuclei from session 1 to session 4. In dorsal medial PFC, no differences were seen between the paired, unpaired and context exposed groups. These groups did, however, differ from naive animals, an effect that was not seen in the ventral medial PFC. The results of this study do not support a role for the PFC in the acquisition of a cued classical conditioning task. The differences seen between paired, unpaired and context exposed groups in orbital and lateral PFC could be due to contextual conditioning or reward-related effects.