@article{Schoeller_Jain_Adrien_Maes_Reggente_2024c, title={Aesthetic chills mitigate maladaptive cognition in depression}, volume={24}, url={https://doi.org/10.1186/s12888-023-05476-3}, DOI={10.1186/s12888-023-05476-3}, number={1}, journal={BMC Psychiatry}, author={Schoeller, Félix and Jain, Abhinandan and Adrien, Vladimir and Maes, Pattie and Reggente, Nicco}, year={2024}, month=jan }
Using peak positive affect (aesthetic chills) to help with depression
In our recent collaboration with Pattie Maes’s Fluid Interfaces group at MIT Media Lab and Dr. Vladimir Adrien from Assistance Publique Hôpitaux de Paris (APHP) in France, we investigated the potential for aesthetic chills to serve as an innovative intervention for major depressive disorder. This effort is a considerable advancement towards the notion of promoting positive affect in depression, which stands in contrast to standard care which is mostly focused on mitigating negative affect.
Instead of focusing on how to help individuals with depression not feel so bad, this work suggests the potential of helping those individuals by presenting them with content so they can feel good.
Aesthetic chills are characterized by sensations like shivers, goosebumps, and tingling that arise in response to emotional experiences with art, music, or nature. We hypothesized that by eliciting chills through validated multimedia stimuli, we could positively influence the core beliefs and self-schemas of individuals with depression. Across two studies with 96 participants diagnosed with major depressive disorder, we engaged participants in randomized sessions involving chill-inducing and neutral control stimuli across visual, auditory, and written modalities. Our results demonstrated that aesthetic chills induced a notable increase in self-acceptance among depressed participants. Chill-inducing stimuli appeared to facilitate positive emotional breakthroughs and shifts in self-perception that could address cognitive distortions related to depression. The data further suggest that aesthetic chills may engage reward-related neural pathways similarly to interventions like psychedelic-assisted therapy.
Individuals with major depressive disorder reported more emotional breakthroughs in their maladaptive cognition (e.g., lack of self-acceptance) when they reported getting chills compared to individuals who viewed the same content, but didn’t get chills. This also scaled as a function of the intensity of those chills.
While preliminary, these findings bring much-needed attention to the potential for aesthetic chills to positively influence core beliefs and schemas related to the self and one’s place in the world. For individuals with depression stemming from early adverse experiences, chill-inducing stimuli could foster emotional catharsis and lasting change to maladaptive self-narratives developed as coping mechanisms. Our research provides initial evidence that the biological processes involved in aesthetic chills can be harnessed for therapeutic ends. Chill-based interventions offer a promising avenue for large-scale study given the ease of dissemination through multimedia experiences.
Looking forward, further research should explore the neurophysiological mechanisms of aesthetic chills and biomarkers that may predict individual responses. Larger clinical trials are needed to investigate optimal protocols and delivery methods for chill-based therapy. We believe aesthetic chills represent an innovative non-pharmacological intervention that warrants greater attention from the psychiatry, psychology, and human-computer interaction communities.
Schoeller, F., Horowitz, A. H., Jain, A., Maes, P., Reggente, N., Christov-Moore, L., . . . Friston, K. J. (2024). Interoceptive technologies for psychiatric interventions: From diagnosis to clinical applications. Neuroscience & Biobehavioral Reviews, 156, 105478. https://doi.org/10.1016/j.neubiorev.2023.105478
Schoeller, Félix, Adam Haar Horowitz, et al. “Interoceptive Technologies for Psychiatric Interventions: From Diagnosis to Clinical Applications.” Neuroscience & Biobehavioral Reviews, vol. 156, Jan. 2024, p. 105478. https://doi.org/10.1016/j.neubiorev.2023.105478.
@article{Schoeller_Horowitz_Jain_Maes_Reggente_Christov-Moore_Pezzulo_Barca_Allen_Salomon_et al._2024, title={Interoceptive technologies for psychiatric interventions: From diagnosis to clinical applications}, volume={156}, url={https://doi.org/10.1016/j.neubiorev.2023.105478}, DOI={10.1016/j.neubiorev.2023.105478}, journal={Neuroscience & Biobehavioral Reviews}, author={Schoeller, Félix and Horowitz, Adam Haar and Jain, Abhinandan and Maes, Pattie and Reggente, Nicco and Christov-Moore, Leonardo and Pezzulo, Giovanni and Barca, Laura and Allen, Micah and Salomon, Roy and Miller, Mark and Di Lernia, Daniele and Riva, Giuseppe and Tsakiris, Manos and Chalah, Moussa A. and Klein, Arno and Zhang, Ben and Garcia, Teresa and Pollack, Ursula and Trousselard, Marion and Verdonk, Charles and Dumas, Guillaume and Adrien, Vladimir and Friston, Karl J.}, year={2024}, month=jan, pages={105478} }
What Is Interoception?
Interoception refers to our awareness of internal bodily signals like heartbeat, breathing, and digestion. While often overlooked, emerging research is revealing interoception as a fundamental process underlying emotion, cognition, and mental health. A new multidisciplinary review led by IACS senior research scientist Felix Schoeller and published in Neuroscience & Biobehavioral Reviews explores the profound significance of interoception and its potential applications in psychiatric diagnosis and treatment.
Directly manipulating interoceptive signals in experiments has proven challenging due to the highly invasive techniques currently used, like esophageal balloon distension. There is also a lack of standardized, validated measures of interoceptive function across research disciplines as “the lack of correlation across unimodal tests underscores the need for multimodal approaches that assess integration of interoceptive information across bodily systems.” Drawing from fields like psychology, physiology, psychiatry, engineering, and neuroscience, the article provides a detailed account of the neurobiology of interoception, describing it as a hierarchical predictive processing system in the brain, and emphasizing the key role of dysfunctional interoceptive processing in disorders like anxiety, depression, and eating disorders.
What are Interoceptive Technologies?
The review also explores in details existing paradigms for modulating interoception, like interoceptive conditioning. This involves pairing internal bodily sensations with aversive stimuli to reshape emotional and physiological responses through a form of classical conditioning. The authors discuss clinical applications of these approaches, such as interoceptive exposure therapy for anxiety disorders. They also propose a new classification system for interoceptive technologies, dividing them into three categories: artificial sensations that induce novel bodily perceptions, interoceptive illusions that manipulate the precision of predictions, and emotional augmentation systems that facilitate beneficial changes in beliefs or behaviors.
Figure 1. Overview of interoceptive technologies: A) the breath-holding test as an artificial sensation, whereby some bodily signal is directly manipulated, B) false heart feedback as an interoceptive illusion, where contextual cues generate a perceptual drift (here the illusion that the heart beats faster at a faster-than-expected rate), C) the therapeutic alliance as entrainment, where the patient’s heart rate slows down as the therapist’s is increasing, leading both to tend towards some average value, D) augmented exposure therapy as emotional augmentation, similar to B but with additional exteroceptive cues having personal significance to the individual (e.g. eliciting the trauma-related memory) favoring an emotional explanation for the interoceptive drift.
Such technologies could have powerful implications. Artificially inducing bodily sensations could help diagnose psychiatric conditions by testing patients’ susceptibility to developing skewed predictions about their internal state. More advanced emotional augmentation systems could precisely modulate predictive processes to reshape maladaptive cognitions and behaviors. While acknowledging that much remains unknown, the review shows the vast potential for interoceptive interventions to improve diagnosis and treatment of mental health disorders. Developing standardized measures and new technologies to precisely manipulate interoceptive signaling may open transformative frontiers in biological psychiatry and psychology.
Bayne, T., Frohlich, J., Cusack, R., Moser, J., & Naci, L. (2023). Consciousness in the cradle: on the emergence of infant experience. Trends in Cognitive Sciences.
Bayne, Tim, et al. “Consciousness in the cradle: on the emergence of infant experience.” Trends in Cognitive Sciences (2023).
@article{bayne2023consciousness, title={Consciousness in the cradle: on the emergence of infant experience}, author={Bayne, Tim and Frohlich, Joel and Cusack, Rhodri and Moser, Julia and Naci, Lorina}, journal={Trends in Cognitive Sciences}, year={2023}, publisher={Elsevier} }
New research sheds fresh light on mystery of infant consciousness
When does consciousness begin? There is evidence that some form of conscious experience is present by birth, and perhaps even in late pregnancy, an international team of researchers led by Tim Bayne of Monash University in Melbourne, Australia and Joel Frohlich of the University of Tuebingen in Germany and the US-based Institute for Advanced Consciousness Studies in Santa Monica, California has concluded in a new review manuscript. The findings, just published in the peer-reviewed journal ‘Trends in Cognitive Science’, have important clinical, ethical, and potentially legal implications, according to the authors.
In the study, entitled ‘Consciousness in the cradle: on the emergence of infant experience’, the researchers argue that, by birth, the infant’s developing brain is likely capable of conscious experiences. Although each of us was once a baby, infant consciousness remains mysterious, because infants cannot tell us what they think or feel, explains one of the two lead authors of the paper Dr. Tim Bayne, Professor of Philosophy at Monash University.
“Nearly everyone who has held a newborn infant has wondered what, if anything, it is like to be a baby. But of course we cannot remember our infancy, and consciousness researchers have disagreed on whether consciousness arises ‘early’ (at birth or shortly after) or ‘late’ – by one year of age, or even much later.”
To provide a new perspective on when consciousness first emerges, the team reviewed recent advances in consciousness science. In adults, some markers from brain imaging have been found to reliably differentiate consciousness from its absence, and are increasingly applied in science and medicine. This is the first time that these advances, as translated to infants, have been reviewed in detail.
Co-author of the study, Dr. Lorina Naci, Associate Professor at Trinity College Dublin in Ireland, who leads the ‘Consciousness and Cognition Group’, explained: “Our findings suggest that newborns can integrate sensory and developing cognitive responses into coherent conscious experiences to understand the actions of others and plan their own responses.”
It is even possible that birth itself triggers the onset of consciousness. “Probably the first thing the newborn infant realizes is that the outside world is very unpredictable relative to the womb environment,” explained co-lead author and postdoctoral researcher Dr. Joel Frohlich. “Things are constantly changing, and so the newborn must build a mental model of the world to adapt and predict things.”
However, the authors don’t rule out the possibility that consciousness might already start some weeks beforehand. “Julia Moser’s work shows that third-trimester fetuses appear to be capable of learning sequences of auditory beeps,” said Dr. Frohlich, referring to his co-author Dr. Moser at the University of Minnesota. “When an auditory tone deviates from a pattern established earlier in the experiment, the fetus shows this ‘surprise’ response in its magnetic brain activity. The neural activity shows a field deflection as if the fetus is saying ‘huh?’.”
The paper also sheds light into ‘what it is like’ to be a baby. We know that seeing is much more immature in babies than hearing, for example (see the image below for a theoretical depiction). Furthermore, this work suggests that, at any point in time, infants are aware of fewer items than adults, and can take longer to grasp what’s in front of them, but they can easily process more diverse information, such as sounds from other languages, than their older selves.
“Infants can perceive many things which adults cannot, like the differences between vowel sounds in a foreign language,” explained Dr. Joel Frohlich. “By 10 months or so, we lose this ability as the brain decides these perceptual differences are no longer relevant and discards them.”
This blog post is based on a recent book chapter “VR for Cognition and Memory” in Current Topics in Behavioral Neuroscience: Virtual Reality in Behavioral Neuroscience: New Insights and Methods. This work presents a review of research on VR’s ability to provide ecologically valid environments to study memory and cognition and discusses how features like interactivity, locomotion, and contextual control engage the brain’s memory systems more naturally than lab studies.
Reggente N. (2023). VR for Cognition and Memory. Current topics in behavioral neurosciences, 10.1007/7854_2023_425. Advance online publication. https://doi.org/10.1007/7854_2023_425
Reggente N. VR for Cognition and Memory [published online ahead of print, 2023 Jul 14]. Curr Top Behav Neurosci. 2023;10.1007/7854_2023_425. doi:10.1007/7854_2023_425
Reggente, Nicco. “VR for Cognition and Memory.” Current topics in behavioral neurosciences, 10.1007/7854_2023_425. 14 Jul. 2023, doi:10.1007/7854_2023_425
Revolutionizing Cognition Research with Virtual Reality
For decades, scientists have worked tirelessly to elucidate the intricate neural machinery supporting human cognition. This endeavor is certainly not for the faint of heart, as formidable challenges present themselves at every turn.
“To study cognition holistically means investigating interconnections between its rich repertoire of functions, including attention, reasoning, language, and memory. Memory is a particularly crucial facet, as it supports and subserves all other aspects of cognition; no cognitive task can be accomplished without memory.”
A holistic understanding demands that we study cognition as it operates in its natural habitat – the real world. Otherwise, as the parable of the blind men and the elephant warns, we risk gross mischaracterizations. Researchers must therefore conduct experiments in “verisimilar contexts (i.e. contexts appearing as the RW)” to achieve ecological validity.
Virtual reality (VR) presents an unprecedented opportunity in this regard. By simulating the real world, we can now study memory and cognition with enhanced veridicality.
“The environmental customization afforded by VR makes it an ideal tool for studying cognition in an ecologically valid fashion. Through the lens of memory studies, this chapter showcases the ways in which VR has advanced a meaningful and applicable understanding of cognition.”
The article presents a thorough review of research that showcases how VR is revolutionizing the study of cognition and memory.
Bridging the Gap Between Lab and Real-World Cognition
Traditional lab experiments often possess limited generalizability, whereas VR can provide naturalistic environments and tasks that echo real-world demands, easily bolstering ecological validity. Previous work has made a compelling case for how VR enhances the ecological validity of fMRI memory research.
VR experiences engage recollection-based memory retrieval akin to real events, unlike lab stimuli which rely more on familiarity. Indeed, VR experiences appear to be retrieved via recollection-based processes similar to those that support autobiographical/recollection memory, whereas retrieval of conventional screen experiences seems more similar to familiarity. This makes VR apt for integrated cognition and memory research.
VR Permits for Information to be Situation in Space
Most importantly, VR permits realistic navigation around virtual environments (c.f.), affording users with a sense of space (the scaffolding of memory). Both philosophers and psychologists alike postulate that brains have evolved solely to support purposeful and predictable movement. Many posit that the ontogeny of episodic memory relates to the onset of locomotion during infancy that scales with Hippocampal development (which also provides a mechanism for infantile amnesia and age-related episodic memory loss). One source of evidence to support this proposition is in the life cycle of the bluebell tunicate. This filter feeder begins to digest a substantial chunk of its cerebral ganglion once identifying a suitable undersea perch to spend the rest of its existence. This phenomenon suggests that once it has served its purpose as a neural network supporting movement, the cerebral ganglion yields greater utility to the organism as nutrition.
From chemotaxis to cognitive maps, a representation of space is necessary for meaningful movement. A neural instantiation of a map that provides spatial bookmarks of an organism’s experiences, demarcating the locations of nutrition and enemies within an environment, is a fundamental component of brains. Indeed, there is a primacy of spatial content in the neural representation of events. Spatial information is often recalled earliest in the retrieval process, and the degree to which individuals report confidence in their autobiographical memories is predicted by their knowledge of the spatial layout of the setting in which the memory occurred. The Method of Loci (a.k.a. Memory Palace) mnemonic has long been appreciated for its ability to increase memory by imagining to-be-remembered information placed at familiar locations. Past work used a VR implantation of this technique to suggest that the principal component behind mnemonic efficacy is the explicit binding of the objects to a spatial location and revealed a tight relationship between spatial memory (SM) and free recall of encoded objects. These observations showcase that space and memory are inextricably linked at conceptual and neuronal levels – a notion that has become entrenched in popular culture; the phrase “out of space” is often used when indicating a computer’s memory is full.
If space is the inescapable wallpaper that serves as the backdrop for all experience, then it follows that as our spatial or environmental context changes, so should the neural activity underlying diverse cognitive processes. Given that VR can easily change environments, it provides an unparalleled landscape with which to study the intersection of space, memory, and cognition.
Additionally, VR enables human analogs of spatial memory research previously limited to animal models, like virtual radial arm mazes. This facilitates powerful translational research from rodents to humans.
Key Features of VR That Facilitate Cognition Research
Below are some features highlighted by the chapter that are exclusive to VR. Such features permit real-world scenarios with increased experimental control and significantly less costs.
VR provides absolute control over the environment. This permits isolation and systematic manipulation of spatial contexts, immersion, emotions, embodiment, etc.
Rapid teleportation between environments induces robust context-dependent learning, a fundamental principle in memory encoding.
Interactivity and locomotion increase embodiment and navigational involvement, enhancing hippocampal memory systems.
Implicit metrics like gaze, paths, and object interactions generate objective measures of memory and attention unbiased by subjective reporting.
Brain imaging during VR reveals in vivo neural correlates of cognition impossible with real-world navigation.
VR spatial mnemonics such as the Method of Loci can provide performance improvements over just imagination by standardizing and controlling the environments.
Applications of VR for Assessing and Enhancing Cognition
Conventional measures of memory typically focus on core content (i.e., the “what”) instead of the true binding that happens in actual episodes (i.e., “what,” where,” and “when”). They also often use verbal materials, which makes the test sensitive to performance in non-memory domains, permitting for compensatory strategies which could erroneously reveal normal “memory.” Subjective reports rarely scale with performance on traditional memory tests, warranting criticism that such measures wrongly estimate memory capacities for everyday situations. For example, patients reporting topographical memory deficits have preserved ability in tabletop tests of spatial or geographical knowledge. Additionally, cognitive complaints in amnesiacs typically show little correlation with verbal memory tests used in clinical settings.
VR tasks, however, have been more reliable in tracking self and caregiver reports of deficits that impact quality of life. The points below highlight other aspects of VR that can increase the ecological validity of both the detection and amelioration of memory deficits.
VR scenarios like virtual stores and routes enable sensitive, ecologically valid tools to identify mild cognitive impairment early.
VR spatial navigation paradigms can differentiate Alzheimer’s from milder impairment based on hippocampal recruitment patterns.
VR enables safe exposure therapy for memory deficits induced by trauma and realistic training for brain injury rehabilitation.
Spatial mnemonic techniques adapted to VR boost memory beyond baseline abilities in healthy individuals.
VR puzzles engage aging minds, increasing motivation. Long-term regimes may prevent decline. As one study found, “6 months of VR training powerfully increased long-term recall.”
VR training could augment real-world cognition and rehabilitate deficits, with proven memory transfer effects.
In conclusion, VR enables an unprecedented ability to understand real-world cognition, precisely diagnose impairments, and develop interventions that enhance memory and cognition. The immersive, interactive nature of VR environments engages our brains’ memory systems far more naturally than traditional lab studies.
The inherently engaging qualities of VR, coupled with its ability to implicitly quantify and enhance memory, make it a powerful tool in populations spanning from pediatrics to the elderly.
Indeed, VR may catalyze discoveries about the very mechanisms underlying human consciousness itself, which intimately relies on episodic memory. By augmenting these processes, VR could profoundly transform our experience and understanding of consciousness. The future of cognition research has never looked more exciting.
Schoeller, Felix, et al. “Aesthetic Chills Foster Self-Acceptance and Emotional Breakthrough in Depression.” 2022, https://doi.org/10.31234/osf.io/rhftq.
Schoeller, F., Jain, A., Adrien, V., & Maes, P. (2022). Aesthetic chills foster self-acceptance and emotional breakthrough in depression. https://doi.org/10.31234/osf.io/rhftq
Schoeller, Felix, Abhinandan Jain, Vladimir Adrien, and Pattie Maes. “Aesthetic Chills Foster Self-Acceptance and Emotional Breakthrough in Depression,” 2022. https://doi.org/10.31234/osf.io/rhftq.
Schoeller F, Jain A, Adrien V, Maes P. Aesthetic chills foster self-acceptance and emotional breakthrough in depression. 2022 Dec 21;https://www.frontiersin.org/articles/10.3389/fnins.2022.1013117/full
Schoeller, F., Jain, A., Adrien, V. and Maes, P. (2022). Aesthetic chills foster self-acceptance and emotional breakthrough in depression. doi:https://doi.org/10.31234/osf.io/rhftq.
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Chills Foster Emotional Breakthrough In Depression
Chills are a common emotional response to stimuli, whether it's from listening to your favorite music or engaging with deeply moving films. But did you know that this bodily response may hold potential for therapeutic intervention for individuals diagnosed with depression?
A recent exploratory study examined the effects of chills stimulation on subjects clinically diagnosed with depression. The study found that chill-inducing stimuli may have the potential to affect the core schema of depressed patients, specifically in terms of shame and self-acceptance. The results suggest that the mechanism of action during the chills response may resemble the form of problem resolution induced by the psychedelic and psychotherapeutic experience, leading to similar positive outcomes for the subject.
This study sheds light on the potential therapeutic value of aesthetic chills for reward-related or dopaminergic illnesses. Further research is needed to fully understand the effects of chills on mental health and to determine the feasibility and safety of using aesthetic chills as a therapeutic intervention.
It's exciting to think about the potential of aesthetic chills as a novel form of body-based experience to draw people out of anhedonia and depression and help them find meaning in life again. As research in this field progresses, we may see more developments in the use of chills stimulation as a therapeutic intervention for mental health.
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Abstract
Aesthetic chills, a strong emotional reaction characterized by a specific bodily response of thermoregulatory mechanisms such as shivers and goosebumps, may hold scientific and clinical potential for reward-related or dopaminergic illnesses. In this first exploratory study, we examined the effects of chills stimulation on subjects clinically diagnosed with depression. Our results suggest that chill-inducing stimuli may have the potential to affect the core schema of depressed patients, specifically in terms of shame and self-acceptance. These results suggest that the mechanism of action during the chills response may resemble the form of problem resolution induced by the psychedelic and psychotherapeutic experience, leading to similar positive outcomes for the subject. Further research is needed to fully understand the effects of chills on mental health and to determine the feasibility and safety of using aesthetic chills as a therapeutic intervention.
Christov‐Moore, L., Jinich‐Diamant, A., Safron, A., Lynch, C., & Reggente, N. (2023). Cognitive science below the neck: Toward an integrative account of consciousness in the body. Cognitive Science, 47(3). https://doi.org/10.1111/cogs.13264
Christov‐Moore, Leonardo, et al. “Cognitive Science below the Neck: Toward an Integrative Account of Consciousness in the Body.” Cognitive Science, vol. 47, no. 3, 2023, https://doi.org/10.1111/cogs.13264.
Christov‐Moore, Leonardo, Alex Jinich‐Diamant, Adam Safron, Caitlin Lynch, and Nicco Reggente. “Cognitive Science below the Neck: Toward an Integrative Account of Consciousness in the Body.” Cognitive Science 47, no. 3 (2023). https://doi.org/10.1111/cogs.13264.
Christov‐Moore, L. et al. (2023) “Cognitive science below the neck: Toward an integrative account of consciousness in the body,” Cognitive Science, 47(3). Available at: https://doi.org/10.1111/cogs.13264.
Christov‐Moore L, Jinich‐Diamant A, Safron A, Lynch C, Reggente N. Cognitive Science Below the Neck: Toward an Integrative Account of Consciousness in the Body. Cognitive Science. 2023 Mar;47(3).
Text Body
Cognitive Science Below the Neck: Toward an Integrative Account of Consciousness in the Body
Despite historic and recent evidence that our beliefs can have drastic effects on bodily function, we seem to lack a model of how this might work. We believe this is due in large part to a failure to consider that computational processes we attribute to cognition may be occurring below the neck, and to a lack of a language by which we could describe beliefs as something that can be instantiated within the body.
In a recent paper, we proposed that we expand the scope of cognitive science to include the body and develop a formal language to describe the relationship between cognitive and bodily systems. To do so, we propose to integrate the best parts of three contemporary accounts that deal with mind and body.
Firstly, parametrically deep allostasis (PDA), a two-level Bayesian inference model, can help us understand how affective valence (the positivity or negativity of a feeling) arises from our bodily experiences. At the surface level, the model uses sensory information to anticipate our homeostatic needs. At the deep level, it continuously tracks the fitness of the surface-level models, indexing fitness as affective valence. This model frames the role of our slow, deep feelings in statistical language that can allow us to possibly speak of beliefs in terms of signaling and computation in interoceptive systems.
Secondly, embodied predictive interoception coding (EPIC) provides a biologically plausible implementation of PDA. EPIC describes a predictive system in the central nervous system that takes inputs from the body via the interoceptive nervous system. It senses precision-weighted ascending homeostatic/metabolic and exteroceptive signals in highly laminated sensory "rich club" hubs and issues allostatic predictions that drive descending allostatic control signals.
Finally, Carvalho and Damasio's functional/anatomical account of the interoceptive nervous system (INS) provides a crucial, holistic field of view that permits for unique forms of computation in systems below the neck. They frame the spatiotemporally diffuse properties of interoception and affect (described in PDA) as products of INS physiology, with a neurobiological framing that “matches up” well with the cortical field of view of the EPIC model.
Combined, these complementary accounts can expand the scope of cognitive science below the neck, using a formal language that allows us to speak of beliefs in terms of signaling that can be studied within CNS/INS interactions. Beliefs can be enacted in bodily function and influence declarative awareness, while “beliefs” in bodily signaling can emerge to impact conscious thought. This approach can deepen our understanding of belief, ritual, and set/setting in research and clinical outcomes, with potential implications for treating psychopathology and effecting therapeutic change. Novel methodological developments will be needed to trace signaling in the transition from CNS to INS as beliefs translate into bodily change, and vice versa. A field of view that encompasses cortical and interoceptive anatomy and computational processes, along with a formal language for belief transmission and enactment, can transform mind-body mysteries into novel science and therapy.
Published in Frontiers in Human Neuroscience in 2022, this review intended to answer how ultrasound for neuromodulation works
Our review titled, Current state of potential mechanisms supporting low intensity focused ultrasound for neuromodulation, attempts to address the following questions: 1) How can we alter the amount of mechanical energy or other properties of the mechanical energy using the sonication parameters available with each device, 2) How are neuronal tissue affected by mechanical energy, and 3) How do those sonication parameters change the type of neuromodulation (i.e., excitatory or suppressive)? We reviewed the theoretical mechanisms of action for neuromodulation and the empirical findings tracking all the sonication parameters used to elucidate the possible link between the proposed mechanisms of action and the choice of sonication parameters. This is still an emerging field, but a tabulation of the empirical findings and theoretical models is needed to help clinicians and researchers choose the best paradigm to use.
DellItalia, John, et al. “Current state of potential mechanisms supporting low intensity focused ultrasound for neuromodulation.” Frontiers in Human Neuroscience: 228.
DellItalia, J., Sanguinetti, J. L., Monti, M. M., Bystritsky, A., & Reggente, N. Current state of potential mechanisms supporting low intensity focused ultrasound for neuromodulation. Frontiers in Human Neuroscience, 228.
DellItalia, John, Joseph L. Sanguinetti, Martin M. Monti, Alexander Bystritsky, and Nicco Reggente. “Current state of potential mechanisms supporting low intensity focused ultrasound for neuromodulation.” Frontiers in Human Neuroscience: 228
DellItalia, J., Sanguinetti, J.L., Monti, M.M., Bystritsky, A. and Reggente, N., Current state of potential mechanisms supporting low intensity focused ultrasound for neuromodulation. Frontiers in Human Neuroscience, p.228.
DellItalia J, Sanguinetti JL, Monti MM, Bystritsky A, Reggente N. Current state of potential mechanisms supporting low intensity focused ultrasound for neuromodulation. Frontiers in Human Neuroscience.:228.
Science Without Jargon
Science should be accessible to everyone. However, dense jargon-filled articles can make it difficult for non-experts to engage with research. Making science accessible promotes scientific literacy and informed decision-making. In this post, we summarize our recent article for a lay audience.
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How ultrasound for neuromodulation works
Non-invasive brain stimulation has been used to modulate the activity of neural tissue without the need for surgical procedures to implant devices or permanently alter the neural tissue. Non-invasive brain stimulation has been used for neuromodulation across empirical research and clinical practices using transcranial electrical stimulation and transcranial magnetic stimulation. These types of neural modulation use electric (i.e., transcranial electrical stimulation) or magnetic (i.e., transcranial magnetic stimulation) fields applied outside the skull to induce changes in the electrochemical activity underneath the device within and around neurons. These fields tend to affect larger areas and affect all the neural tissue that the fields pass through. Thus, this limits which brain regions can be targeted precisely or individually.
An alternative to the putative non-invasive brain stimulation is devices using ultrasound. Ultrasound has been used for decades by clinicians to image various parts of the body, but recently ultrasound devices have begun to be used for neuromodulation. Ultrasound doesn’t use electric or magnetic fields, rather it generates acoustic waves that are a mechanical force. This mechanical force can be focused on a precise area with only the maximal mechanical energy converging on millimeter-sized region. This allows for deeper and/or smaller brain regions to be targeted compared to transcranial electrical stimulation and transcranial magnetic stimulation. However, the different energy source compared to electric or magnetic fields requires a different understanding of how neuromodulation occurs. Without this understanding, effective uses of ultrasound in empirical research and clinical practices will be limited.
Ultrasound’s acoustic waves have the characteristic properties of wavelength, amplitude, and frequency. Wavelength is the distance between two peaks within the wave, the amplitude is the height of the wave, and frequency is the number of peaks in a second. Each of these properties affects the total amount of mechanical energy delivered by the ultrasound device and other sonication parameters. The total energy can be measured by either the average amount in a spatial region or the average amount delivered over time typically converted into the units of watts per centimeter squared. In addition to the intensity, the total energy delivered over time is affected by the duty cycle, which is the percentage of time the sonication occurs. The duty cycle also determines if a paradigm is pulsed or continuous. Pulsed paradigms are any duty cycle below 100 percent, which allows for breaks between the sonication, compared to a continuous application of ultrasound. The frequency of the ultrasound’s acoustic waves is related to the sonication parameters of center frequency and pulse repetition frequency. The center frequency is set by the device manufacturer, which is the frequency delivered by the device and this frequency is related to the spatial precision of the acoustic wave delivered. The pulse repetition frequency is the frequency of the acoustic wave delivered by the pulsed paradigm. The final commonly adjusted sonication parameter is sonication duration (i.e., total time of acoustic wave delivered).
The mechanical energy delivered by the ultrasound device has seven proposed mechanisms to affect the activity of groups of neurons. Neurons are connected and each neuron’s activity either helps to excite other neurons connected to it or suppresses the activity of the neurons connected to it. These signals involve both electrical and chemical signaling. Since ultrasound is mechanical, the mechanisms of action proposed describes: 1) effects of mechanical energy on the temperature., 2) how the neurons detect and transform that mechanical energy to electrical or chemical signaling (i.e., mechanosensitive ion channels), or 3) how mechanical energy interacts with the elasticity of neurons to change the electrical properties or structure of neurons (e.g., direct flexoelectricity, change of membrane conformational states, or sonoporation).
Ultrasound has been used for decades to destroy malignant tissue by using enough intensity to generate larger changes in temperature. These large changes in temperature are not seen in the intensity ranges used in non-invasive brain stimulation. Despite the lower intensity used, there is still a mechanical force acting on the neurons. Some neurons have specific mechanisms for detecting external mechanical forces. These are most well understood in our tactile sensations. When our hand presses against a surface, specialized neurons detect the mechanical force by getting stretched which allows for chemical and electrical signaling to occur. The amount and distribution of neurons with similar properties in the brain is an active area of research. In addition to these specialized neurons, the mechanical energy from ultrasound can change the electrical properties of neurons by distorting the shape. The specific configuration of the membrane allows for electrical signals (i.e., direct flexoelectricity) to be produced as the mechanical energy changes the alignment of the interior and exterior parts of the membrane. On top of these alignment changes, there are pressure changes which can also generate both chemical and electrical changes from the changes in membrane conformational states.
Additionally, the neuron’s membranes can have changes to their permeability called sonoporation allowing for electrical changes that can elicit the neuron to fire. This process was investigated how the ultrasound’s pulse repetition frequency, intensity, or duty cycle could produce excitatory or suppressive effects. The key sonication parameter that best predicted differences in neuronal activity was duty cycle. Higher duty cycles between 10% to 70%, typically excited neurons, while lower duty below 10% created suppressive effects. Unfortunately, this one parameter did not predict the suppressive findings well, but the excitatory findings were almost all exclusively found between 10% to 70% duty cycle.
While duty cycle was predictive of some results found in the literature, it left most of the results unexplained. More models and theories are needed to expand the understanding of the mechanisms of action. Hopefully, this review gives a basic knowledge base to clinicians and researchers to use in their treatments or experiments. As the understanding of the mechanisms of action expand, more nuanced treatments and experiments can be used.
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Figures & Captions
Feel free to use these figures in your articles, blogs, and presentations. If you do, please cite this work.
Figure 1.
Low intensity focused ultrasound general principles. (A) A depiction of a typical LIFU experimental setup. A participant is seated (2) with an US device (5) firmly pressed against their head held in place by an arm (3). The US device is controlled by a computer system (4) and targeted using infrared system (1). (B) Depiction of the mechanical wave properties (amplitude, wavelength, and frequency) used in US stimulation. (C) Spatial intensities of the mechanical wave. (D) Temporal intensities of the mechanical wave. (E) Two exemplary pulsation schemes: pulsed (in yellow) and continuous (in teal). Both the pulsing schemes have a customizable sonication duration with inter stimulation interval with the DC parameter (i.e., the ratio of tone burst duration over pulse repetition period) determining the pulsing scheme.
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Figure 2.
Proposed ultrasonic stimulation’s mechanisms for neuromodulation. Depicted in column 1 are six neuronal membranes (four with an ion channel [rows A,C,D,E] and two neuronal membranes [rows B,F] with polar lipid bilayer) and a neuron with the microtubules highlighted (row G). Depicted in column 2, these membranes have four types of electrophysiological-mechanical coupling during an action potential: change in membrane conformation state, thermodynamic waves, direct flexoelectricity, and opening of mechanosensitive ion channels (see Section above). Column 3 depicts these same four electrophysiological-mechanical coupling during US stimulation along with three other possible mechanisms of US’s neuromodulation: thermal modulation, sonoporation and cavitation, and microtubule resonance (see Section above).
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Figure 3.
Neuronal intramembrane cavitation excitation model. Plaksin et al. (2014, 2016) proposed the NICE model hypothesizing sonoporation (see Figure 2F) as US’s mechanism of neuromodulation. The US’s DC (see Figure 1E) determines the polarity of neuromodulation. A low DC (i.e., below 5%) during a stimulation’s off-periods will preferentially activate thalamic reticular neurons (TRN), thalamocortical neurons (TCN), and low-threshold spiking (LTS) interneurons via T-type voltage-gated calcium channels (see Section above for full description) producing an inhibitory effect. A high DC (i.e., over 20%) during the on-periods will preferentially activate regular spiking (RS) pyramidal cells and fast spiking (FS) interneurons while suppressing the LTS interneurons producing an overall excitatory effect. This excitatory effect is simulated using a basic network model of LTS, FS, and RS neurons connected with excitatory and inhibitory synapses and thalamic inputs. The network model predicts an optimum excitation of 70% DC.
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Figure 4.
Excitatory and suppressive empirical findings’ relationships to DC, PRF, ISPPA, fc, and SD. DC, PRF, ISPPA, fc, and SD are used as grouping factors for excitatory and suppressive findings. We used density plots for each study, but studies with multiple sonication parameters have each one plotted. In the top panel, high DC, above 10%, has the vast majority of the excitatory findings. While ow DC, less than 10%, contains the majority of the suppressive findings, there are still approximately 30% of the suppressive findings above 10% DC. The top panel is highlighted in red because DC is the one sonication parameter that has any distinction between excitatory and suppressive findings. In the four bottom panels, PRF, ISPPA, fc, and SD has no clear distinction between excitatory and suppressive findings.
