The brain is not mental! coupling neuronal and immune cellular processing in human organisms
Second, as Levin (2019) notes, traditional brain sciences operate with the built-in assumption that the body structure is tacitly taken to be fixed, determined by the genome and thus a reliable and stable machine for which appropriate control policies (i.e., behaviors) are implemented. Within this view, individual neurons coordinate to implement a higher-order entity, a “self” with coherent memories, beliefs, emotions, and plans. In short, brains are considered to be a stable, fixed structure in which the individuality of the immobile cells (very much like the bricks of a wall) disappears in the service of the adult body (despite the well-established turnover rate of neurons in adult human brains, which does not seem to alter self-continuity nor memory) (Spalding et al., 2013), and data on a variety of models in which memory appears to be not confined to brain tissues (Blackiston et al., 2015).
However, in healthy humans, successful survival of the organism cannot be done by neuronal processing alone, or in isolation of other key cellular processing. Rather, multiple cellular processing (e.g., immune system processing) must coordinate with the neural processing to achieve self-maintenance, and self-regulation of the biological system. For example, as illustrated earlier, immune and neural systems are intricate systems both composed from cells, communicating with each other, depending on each other and pursuing a common goal: self-preservation of the human body/organism (Varela and Coutinho, 1991a,b; Bhat et al., 2021).
Recently, several theorists joined voices to call for a reconceptualization of the fundamental basis of brain-body-behavior structural dynamics (Pessoa et al., 2021). For example, it has been argued that the vertebrate neuroarchitecture does not respect the boundaries of standard mental terms. Rather neuroscience should aim to address the dynamic coupling between large-scale brain circuits and complex, naturalistic behaviors” (Dennis et al., 2021; Pessoa et al., 2021; Branchi, 2022). These authors suggest that “brain evolution is better understood in terms of (i) modification in neuronal populations with the brain’s fundamental units (building blocks) and (ii) the reorganization of large-scale connectional systems in which they are engaged” (Pessoa et al., 2021:3; see also Pessoa et al., 2019).
Moreover, the neuroarchitecture is not additive, in the sense that new components are “added on atop an ancestral organization” (Pessoa et al., 2021:7). Rather, distributed brain circuits help solve challenging behavioral problems. Hence, standard mental properties (e.g., “decision-making”) are deeply intertwined with others (e.g., “affective processing”)” (Pessoa et al., 2021:7). The radical approach here is that standard mental categories such as perception, memory, perception and emotion may be ill-suited to investigating not only unconventional examples, such as slime mold memory (Vogel and Dussutour, 2016; Boussard et al., 2019), but also even the brain basis of behavior. This shift in focus invites neuroscience to consider the coupling between large-scale circuits and complex naturalistic behaviors by taking into account how the temporal evolution of behavior is linked to dynamic brain changes (Pessoa et al., 2021; Branchi, 2022).
Our proposal, although compatible with this approach, takes a step further and questions the very distinction between i) cognitive processes, supported by neural cells in the brain; ii) and bodily processes, supported by non-neural cells in the body. Rather, we suggest, all cells process information, make decisions, interact with each other, and as such, actively contribute to the survival of the biological organism as a whole.
This view echoes the enactive approach outlining that the interaction process itself constitutes an irreducible domain of dynamics which can be constitutive of individual agency and social cognition (De Jaegher and Froese, 2009). Importantly, it is possible to retrace the impact of such irreducible interactions between autonomous systems “all the way from cell to society” (Thompson, 2007; Levin and Dennett, 2020).
This paper proposed a shift in perspective from neuronal to cellular (i.e., immune) processing as an essential step to understand the fundamental nature of human mental processes and cognition. This approach is in line with previous seminal embodied cognition views reframing cognition to reflect its fundamental biological organismic basis (Maturana and Varela, 1980; Lyon et al., 2021). The embodied and enactive approaches seminally claim that cognition (brain processes) necessarily requires interactions with the body and the environment to get off the ground.
Our suggestion is subtly yet importantly different: cognition is the result of information processing distributed across all cellular systems in the body, including the brain, which is, in our view, (part of) the body. Speaking about brain-body-environment interactions in constituting cognition may be misleading because it tacitly inherits the distinction between mind (brain) and body. Cognitive processing however, does not require brain plus body plus environment. Rather, cognitive processing takes place in every single cell of our bodies, among which neuronal cells play a key part, but only a part. Hence, one may say that we literally think with all the cells of our bodies, and not just our heads.
Our paper thus paper invites to a nuanced understanding of cognitive processing as cut across multiple levels of bodily systems and cellular processing (e.g., neuronal and immune). Cognition may be thus better understood as “multi-scale continuum of organizational levels of capabilities” (Levin, 2019) designed to subserve the self-organization and adaptation of the human organism as a whole, rather than a process restrictively confined to the brain and the neural system.
The ideas mentioned here may have the potential to open new avenues of investigation in several important ways. For example, as we mentioned earlier, it invites to reconsider the prevailing differentiation between the brain and the body as two distinct organismic categories. Rather, the brain is (part of) the body, and as such both neuronal and non-neuronal bodily cells and complex network systems should be explored as constitutive parts of one single self-organizing biological system, the human organism. Unless one endorses explicitly a brain (mind)-body dualistic stance–stipulating that the brain is fundamentally different from the rest of the other human organs, and hence, conceptually and ontologically separable from the body itself–the dichotomy between brain and body remains unwarranted from a purely neurobiological perspective.
Another interesting field in which the approach proposed here could have an impact is developmental cognitive neuroscience. The human brain is a critically a developmental system responding to perturbations in a manner that yields flexible yet robust behaviors, constantly adjusting to stressful and unforeseen conditions throughout the lifespan. For example, one important yet overlooked idea in current discussions in philosophy and cognitive neuroscience is that human brains and bodies first develop within another human body (Ciaunica, 2016; Ciaunica and Crucianelli, 2019; Ciaunica et al., 2021a,b).
Future work needs to address the fascinating bridge linking neural and immunological information processing occurring between two developing “co-embodied’ self-organizing systems, e.g., in pregnancy (Ciaunica et al., 2021b). Without a systematic investigation of the intricate, context sensitive processes that actively generate and shape the development of neurons and other bodily cells and systems throughout the lifespan in relation to others’ bodies, any efforts at present to understand the fundamental basis of human cognition will remain patchwork at best. Research focused on these flexibly co-emerging processes and developmental systems may provide substantial new causal insights into the nature of mental and cognitive processing in humans.
The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.
AC wrote the full draft. ML provided substantial feedback. ES provided additional substantial feedback and wrote the section on the immune system. All authors contributed to the article and approved the submitted version.
This work was generously supported by the Fundação para a Ciência e a Tecnologia (FCT) grant PTDC/FER- FIL/4802/2020 and the Fundação para a Ciência e a Tecnologia (FCT) grant 2020-02773 CEECIND to AC. ML gratefully acknowledges support via Grant 62212 from the John Templeton Foundation.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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The opinions expressed in this publication are those of the author(s) and do not necessarily reflect the views of the John Templeton Foundation.
The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.