The claustrum and consciousness: An update

The seminal paper of Crick and Koch (2005) proposed that the claustrum, an enigmatic and thin grey matter structure that lies beside the insular cortex, may be involved in the processing of consciousness. As a result, this otherwise obscure structure has received ever-increasing interest in the search for neural correlates of consciousness. Here we review theories of consciousness and discuss the possible relationship between the claustrum and consciousness. We review relevant experimental evidence collected since the Crick and Koch (2005) paper and consider whether these findings support or contradict their hypothesis. We also explore how future experimental work can be designed to clarify how consciousness emerges from neural activity and to understand the role of the claustrum in consciousness.

Annotations for: The claustrum and consciousness: An update

CLA salience & CLA attention

“Salience and attention - Attention is categorized into 2 distinct pathways: bottom-up and top-down. Bottom-up attention is passive guidance of involuntary awareness driven by perceptual salience (i.e., salient stimuli that possess novel or prominent properties relative to the background). Top-down attention is a voluntary process that directs awareness onto information based on internally guided contexts (Katsuki & Constantinidis, 2014).” (Liaw and Augustine, 2023, p. 4)

CLA salience & CLA Change Detection: “is hypothesized to detect salient sensory changes and then recruit the attentional network to process the salient signal”

“Proposed roles of the claustrum include perceptual salience (Smith et al., 2019) and attentional modulation (Goll et al., 2015). The claustrum is hypothesized to detect salient sensory changes and then recruit the attentional network to process the salient signal. Given the quiescent nature of claustral neurons and how these neurons respond transiently to sudden stimuli (Remedios et al., 2014), the claustrum could serve as a salience detector. Day-Brown et al. (2017) proposed that local GABAergic circuits normally inhibit claustral activity, which is overcome transiently by excitatory cortico-claustral circuits to signal a salient stimulus. Such GABAergic circuitry, as well as claustral connectivity with sensory and frontal cortices (Goll et al., 2015; Mathur, 2014; Chia et al., 2020), fit with a possible role for the claustrum in gating attention” (Liaw and Augustine, 2023, p. 4)

CLA salience: evidence is missing

“To date, empirical evidence of a salience detection function for the claustrum is lacking. The most relevant evidence comes from measurement of responses of the macaque claustrum to acoustic stimulation: the claustrum responds to the onset of sound (Remedios et al., 2014). Claustrum responses are stronger, with shorter latencies, to novel sound stimuli with higher signal-to-noise ratio. Claustral neurons are also more active when rats explore a novel object in the environment and are significantly less active when the object is removed (Jankowski & O’Mara, 2015). Claustral activity dynamically follows the introduction, removal, repositioning, and location change of the novel object. These neurons are active in both light and dark conditions, suggesting that the claustrum is co-activated by both somato-sensory and visual inputs.” (Liaw and Augustine, 2023, p. 4)

Claustrum and Anterior Cingulate Cortex (ACC)

“Because the claustrum preferentially projects to the ACC (Smith & Alloway, 2010; Chia et al., 2017; Chia et al., 2020), an area known to be involved in selective attention (Pardo et al., 1990; Weissman et al., 2005; Totah et al., 2009; Schneider et al., 2020), the claustrum could receive top-down attentional influences from the ACC. Indeed, claus- trum neurons can transiently amplify inputs from the ACC (White & Mathur, 2018). During successful completion of an attentional task, the activity of ACC neurons projecting to the claustrum is elevated (White et al., 2018), while optogenetic inhibition of these neurons disrupts performance accuracy during attentional tasks (White & Mathur, 2018). In addition, extensive functional connectivity is observed between the claustrum and the ACC during cognitive tasks (Krimmel et al., 2019). Therefore, it is plausible that the claustrum and the ACC work together during an attention-requiring cognitive task.” (Liaw and Augustine, 2023, p. 4)

“(Atlan et al., 2018). This suggests that a subset of claustral neurons may suppress auditory distractions during attentional tasks.” (Liaw and Augustine, 2023, p. 4)

CLA attention necessary for “set-shifting”

“In addition, the claustrum is apparently involved in the formation of mPFC cell assemblies required for attentional set-shifting. Chemo-genetic inhibition of the claustrum disrupts this formation and subsequent behavioral task accuracy, suggesting that the claustrum-mPFC network is important for attentional set-shifting (Fodoulian et al., 2020). On the other hand, chemogenetic activation of the claustrum is reported to disrupt attention and significantly attenuate task accuracy (Liu et al., 2019). This could indicate that the claustrum modulates attention negatively, though it is also possible that the disruption of attention results from an abnormal pattern of claustrum activity induced by the chemogenetic activation.” (Liaw and Augustine, 2023, p. 5)

Consciousness: Wakefulness & Awareness

“Although there are diverse perspectives and approaches to neurological studies of human consciousness, most consider similar components: (1) waking is the first component in the generation of consciousness, and (2) being aware of the external environment is the second component associated with being conscious.” (Liaw and Augustine, 2023, p. 2)

“In “The feeling of life itself”, Christof Koch (2019) wrote, “Consciousness materializes out of the nervous system and endows us with the ability to be aware, have self-knowledge, and hold beliefs about the environment and ourselves.”” (Liaw and Augustine, 2023, p. 2)

Global workspace theory (GWT) (Baars, 2005)

“Global Workspace Theory – The Global Workspace Theory (GWT) was proposed by Baars (2005). He likened the consciousness contents to a brightly lit spot on the theater stage, while the rest of the dark theater remains unconscious.” (Liaw and Augustine, 2023, p. 2)

[[Integrated information theory (IIF)]]

“Integrated Information Theory - The Integrated Information Theory (IIT) posits that the realization of consciousness relies on the physical and functional integration of information within the related neuronal circuitry (Tononi, 2004).” (Liaw and Augustine, 2023, p. 2)

“One of the primary motivations behind their proposal is the extensive and reciprocal interconnectivity of the claustrum with most of the neocortex, as well as subcortical structures (Sherk, 1986; Torgerson et al., 2015; Wang et al., 2017; Zingg et al., 2018; Ham & Augustine, 2022).” (Liaw and Augustine, 2023, p. 2)

[[Loss of Consciousness (LOC)]]

“Clinically, the loss of consciousness (LOC) is defined as an interruption in wakefulness and can often be caused by 3 main reasons: anesthesia, brain lesion, or sleep.” (Liaw and Augustine, 2023, p. 3)

Anesthesia: interrupt consciousness

“Thus, anesthetics are believed to interrupt consciousness by blocking structures that integrate inter-cortical information (Alkire et al., 2008).” (Liaw and Augustine, 2023, p. 3)

CLA consciousness: anesthesia

“Taken together, these findings identify functional networks involving the claustrum that are modified in the anesthetized state, suggesting – but not proving - a role for the claustrum in anesthesiainduced unconsciousness.” (Liaw and Augustine, 2023, p. 3)

“In contrast to the findings above, several other clinical studies report no causal relationship between claustrum lesions and LOC.” (Liaw and Augustine, 2023, p. 3)

Claustrum could serve as intermediary between Anterior Cingulate Cortex (ACC) and Anterior Insula (?)

“Because the AI is only sparsely connected to the ACC (Chia et al., 2017), the claustrum could serve as an intermediary between these two structures.” (Liaw and Augustine, 2023, p. 3)

[[CLA sleep]]

“Given the enriched connectivity between the claustrum and both the prefrontal cortex (PFC) and the cingulate cortex (Zingg et al., 2018) where slow-wave oscillations originate (Massimini et al., 2004; Murphy et al., 2009; Nir et al., 2011) - the claustrum is a promising candidate for regulating slow-wave sleep (SWS). Indeed, recent animal studies provide strong support for claustral involvement in sleep processing: the claustrum has been found to be important for regulation of SWS in reptiles (Norimoto et al., 2020) and in rodents (Narikiyo et al., 2020). Narikiyo et al. (2020) also demonstrated that optogenetic activation of the mouse claustrum induces global silencing of the neocortex. This suggests that a global synchronization of silent and active states across the neocortex, via slow-wave activity, could regulate the state of consciousness.” (Liaw and Augustine, 2023, p. 3)

Claustrum & Serotonin

“The claustrum also expresses many serotonin receptors (Gehlert et al., 1991; Koyama et al., 2017; Morales et al., 1998; Norimoto et al., 2020; Wong et al., 2021). Results from genetic, neurochemical, electrophysiological, and neuropharmacological studies have suggested that serotonin is involved in regulation of sleep-wake cycles (Monti, 2011; Ursin, 2002; Watson et al., 2010). Electrophysiological results have shown that serotonin exerts a net inhibitory effect on the claustrum (Wong, 2021; Wong et al., 2021). Taken together, it is plausible that the claustrum regulates sleep-wake states via serotonergic inhibitory inputs from the DRN.” (Liaw and Augustine, 2023, p. 4)

[[CLA psychadelics]]

“Inhibition of the claustrum, by activating κ-opioid receptors (KOR), has been proposed to underlie the mind-altering effects of Salvia divinorum, which is a potent dissociative hallucinogen (Stiefel et al., 2014).” (Liaw and Augustine, 2023, p. 5)

“The claustrum also densely expresses serotonin receptors (Wong et al., 2021). Claustral neurons are activated by a psychedelic compound, 2,5-Dimethoxy-4-iodoamphet- amine (DOI), which is an agonist of serotonin receptors (Martin & Nichols, 2016).” (Liaw and Augustine, 2023, p. 5)

Schizophrenia: “hypersensitivity to non-salient stimuli”

“Schizophrenia is associated with hypersensitivity to non-salient stimuli (Roiser et al., 2012; Shitij Kapur, 2003) and deficits in sensory gating (Hall et al., 2010). Supporting the salience-processing role of the claustrum, Bak et al. (2011) found that activity in the claustrum is linked to normal sensory gating. It is possible that claustral disruption impairs normal sensory gating in the brain to filter out irrelevant, non-salient stimuli to minimize sensory overload. In the case of schizophrenia, this constant sensory overload may contribute to the psychotic symptoms (Braff & Geyer, 1990; Patterson et al., 2008).” (Liaw and Augustine, 2023, p. 5)

Consciousness: perception trough experience of memory

“Recently, Budson et al. (2022) proposed an alternative theory based on the concept that we do not experience our perceptions directly, but instead experience them by recalling a memory of our perceptions. According to this theory, a majority of our decisions and actions happen unconsciously; our awareness of these decisions and actions only occurs later, in the form of recalling a memory. This aligns with observations of sensorimotor systems in the primate brain that function in the absence of consciousness, termed the “zombie mode” by Koch and Crick (2001).” (Liaw and Augustine, 2023, p. 6)

“In order to understand the role of claustrum in awareness, future research could aim to clarify how the claustrum mediates sensory gating and modulates attentional switching, to prevent sensory overload in schizophrenic patients versus healthy subjects.” (Liaw and Augustine, 2023, p. 7)

“To circumvent such complications, future behavioral analyses of claustrum function should be based on tasks with higher cognitive workload (e.g., involving multisensory stimuli within or across modalities).” (Liaw and Augustine, 2023, p. 8)

“We hope that this review will inspire future research that explores claustral function from a perspective that clarifies the relationship between the claustrum and brain structures typically involved in memory formation, retrieval, and consolidation, as well as the relationship between the claustrum and structures involved in sleep, arousal, and wakefulness” (Liaw and Augustine, 2023, p. 8)