Hyperneuroplasticity, Nitric Oxide, and Dynamic Brain-Body States

By Dr. Patty Gently on September 12, 2025

Pomegranate, high in nitric oxide

Bright Insight Support Network founder and president Dr. Patricia Gently supports gifted and twice-exceptional adults in their own autopsychotherapy through identity exploration, structured reflection, and alignment with inner values. A writer, educator, and 2e adult, Dr. Patty centers depth, integrity, and complexity in all aspects of her work.

Enjoy this and other posts by @thegentleheretic on Substack!

Hyperneuroplasticity as Systemic Responsiveness

While researching and reading about the plasticity of octopuses, I found that they, like humans, utilize nitric oxide and benefit from dynamic brain states. Of course, this sent me down yet another rabbit hole (octopus den?) of exploration that allowed for additional understanding about hyperneuroplasticity and systemic responsiveness. To me, the octopus illustrates how distributed responsiveness can serve as a model for understanding how human hyperneuroplastic systems operate: both embody rapid, adaptive reconfiguration across different domains of functioning.

Hyperneuroplasticity reflects a trait-like systemic orientation toward rapid, deep, and whole-system neural reconfiguration. Unlike localized forms of plasticity confined to specific synapses or cortical regions, hyperneuroplasticity denotes an amplified capacity for reorganization across circuits, networks, and brain–body systems. This orientation creates both opportunity through enhanced learning, creativity, and adaptation, and risk, including destabilization, sensory flooding, and vulnerability to trauma-related dysregulation (Abraham & Bear, 1996; Kluger et al., 2024). To build on this foundation, the next sections explain how nitric oxide (NO) functions as a key mediator of plasticity and how dynamic brain and brain-body states emerge from these mechanisms.

Nitric Oxide (NO) as a Plasticity Mediator

Nitric oxide (NO) is a gaseous neuromodulator central to linking hyperneuroplastic processes to systemic brain and body states. Unlike typical neurotransmitters stored in vesicles and released at synapses, NO is synthesized on demand by nitric oxide synthases and diffuses freely across cell membranes. It can move bidirectionally between cells and often acts as a retrograde transmitter, traveling from postsynaptic neurons back to presynaptic terminals to regulate neurotransmitter release. This unusual signaling makes NO more like a broadcast signal than a letter passed hand-to-hand as a single sealed message. That is, NO communicates widely and rapidly, modulating synaptic plasticity and vascular responses in ways not restricted to conventional point-to-point transmission (Garthwaite, 2008; Picón-Pagés et al., 2019; Böhme et al., 1991).

To understand its synaptic, vascular, and immune roles, it is important to note that NO exerts multifaceted effects across neural and systemic domains. In synapses, it acts as a retrograde messenger in long-term potentiation (LTP) (a persistent strengthening of synapses) and long-term depression (LTD) (a long-lasting decrease in synaptic strength), helping to regulate presynaptic neurotransmitter release (Böhme et al., 1991; Hardingham et al., 2013; Picón-Pagés et al., 2019). Beyond synapses, NO mediates neurovascular coupling by dilating cerebral blood vessels to increase glucose and oxygen delivery during heightened demand (Attwell & Iadecola, 2002). It also participates in microglial signaling and broader inflammatory cascades, where dysregulated activity can promote oxidative stress while balanced signaling supports repair and resilience (Calabrese et al., 2007). This integrated profile illustrates why NO is central to hyperneuroplasticity: by adjusting the flow of information through neural circuits, it functions as a key dial on the brain’s learning and memory machinery, shaping how experience is encoded and how adaptive or destabilizing responses unfold.

Dynamic Brain States

Hyperneuroplastic systems tend toward heightened responsiveness across oscillatory and network levels. In practical terms, this means that the brain does not operate in a single steady state but shifts between different patterns of activity depending on context and need. While NO plays a central role, it is not the only factor: other neuromodulators such as dopamine, serotonin, and acetylcholine also contribute to these dynamic couplings, and hormones like cortisol or adrenaline can amplify or dampen systemic responses. Together, these molecules create a complex chemical orchestra that tunes this dynamic system exchange.

Oscillatory Modulation refers to how rhythmic patterns such as theta (linked to memory and navigation) and gamma (associated with attention and information binding) rise and fall. NO influences the balance between excitatory and inhibitory signals, helping coordinate these rhythms so that learning and working memory can occur smoothly (Garthwaite, 2008). These oscillations are like the tempo of music, setting the pace for how thoughts and perceptions are processed.

Metastability describes how the brain operates in a flexible zone between stability and chaos. It hovers near a critical point where small changes, such as a thought, emotion, or external stimulus, can trigger larger reconfigurations in activity. Hyperneuroplastic systems amplify this responsiveness, with NO acting like a volume knob that can determine whether shifts remain balanced or tip toward overload (Tognoli & Kelso, 2014; Baek et al., 2025). This is comparable to a flock of birds: each bird adjusts to its neighbors, allowing the whole flock to change direction rapidly while still holding together.

Other dynamic brain states include synchronization and desynchronization, where large populations of neurons briefly align their activity before breaking apart, and phase transitions, sudden shifts where the brain reorganizes from one stable pattern to another. For lay understanding, these can be thought of as the brain’s way of “changing gears,” adapting its mode of processing much like a car switching speeds depending on the road ahead. Together, these dynamics illustrate why hyperneuroplastic systems feel especially fluid and responsive, yet sometimes precarious. Building on Kluger et al. (2024), these shifts also unfold across nested timescales, meaning that past states influence which future states are accessible. This framing emphasizes that brain dynamics are not isolated moments but evolving trajectories that shape both opportunities for adaptation and risks of overload.

These states are not just theoretical, either. They appear in everyday life. Flow states, for example, arise when rhythms align to support deep immersion in a task, while sleep-wake cycles demonstrate shifting oscillatory patterns across REM and deep sleep. Moments of focused attention show transient synchronization across brain regions, whereas mind-wandering involves desynchronization and reconfiguration. Emotional arousal can push the system toward instability, making it highly responsive to small triggers, while sudden insights or “aha” moments illustrate phase transitions where the brain rapidly reorganizes around new associations. Trauma responses, such as hypervigilance or dissociation, also represent dynamic states, showing how this responsiveness can support adaptation yet risk becoming precarious.

Dynamic Brain-Body States

NO links hyperneuroplasticity to systemic bodily processes through its effects on cardiovascular, immune, and metabolic systems. Put more simply, what happens in the brain reverberates into the body, and what happens in the body feeds back to shape brain activity. A dynamic brain-body state is the shifting configuration of neural, physiological, and cognitive processes that continuously adapt to both internal and external demands. This ongoing coordination gives rise to recognizable modes, such as executive, emotional, or survival states, that influence thoughts, feelings, and behaviors in real time. It mirrors the broader chemical orchestra noted earlier, where other neuromodulators and hormones join NO in tuning this intricate interplay.

Autonomic Regulation: By modulating vascular tone and smooth muscle function, NO contributes to cardiovascular and gastrointestinal dynamics, embedding brain states in broader bodily responsiveness (Förstermann & Sessa, 2012; Picón-Pagés et al., 2019). Beyond circulation and digestion, autonomic regulation also encompasses heart rate variability, breathing rhythms, and stress responses, all of which can be tipped toward balance or instability by NO signaling. In hyperneuroplastic systems, this sensitivity means that everyday shifts, like posture changes, emotional arousal, or metabolic demand, can cascade into broad systemic effects, helping explain why autonomic regulation is such a key link between neural plasticity and bodily states.

Blood-Brain Barrier Dynamics. NO also plays a direct role in regulating the blood-brain barrier (BBB), the selective interface that governs exchange between the brain and bloodstream that was discussed in a previous post titled: The Shared Terrain of Hyperneuroplasticity, the Blood-Brain Barrier, and Functional Neurological Disorder. At healthy levels, NO derived from endothelial nitric oxide synthase (eNOS) helps maintain vascular tone, supports neurovascular coupling, and preserves BBB stability by facilitating nutrient and oxygen delivery (Brown, 2010; Förstermann & Sessa, 2012). In this sense, NO acts as a gatekeeper balancing circulation and metabolic supply with neural demand.

Yet in inflammatory or oxidative states, inducible nitric oxide synthase (iNOS) can produce excess NO, which reacts with superoxide to form peroxynitrite. This damages tight junction proteins such as claudins and occludins, increasing BBB permeability and allowing immune cells, toxins, or inflammatory molecules to enter brain tissue (Ballabh, Braun, & Nedergaard, 2004; Gu, Dee, & Shen, 2011). The result is a leaky barrier linked to conditions such as multiple sclerosis, stroke, Alzheimer’s disease, and traumatic brain injury. Importantly, emerging research also connects BBB dysregulation to functional neurological disorder (FND), where stress-related NO signaling and barrier vulnerability may contribute to altered sensorimotor integration and symptom expression (Perez et al., 2021). This dual role illustrates why hyperneuroplastic systems are so sensitive to barrier dynamics: too little NO disrupts vascular responsiveness, while too much destabilizes protective boundaries.

Trauma and Neurodivergence: In conditions such as autism, ADHD, gifted neurodivergence, and cPTSD, heightened responsiveness may reflect both adaptive hyperneuroplastic capacity and dysregulated NO signaling. These dynamics can produce intense sensory experience, heightened emotional lability, and systemic vulnerability to stress, while also supporting rapid learning and innovation (Kluger et al., 2024). Put differently, the same mechanism that allows for quick adaptation can also lead to overload, much like a car engine that revs quickly but risks overheating.

Taken together, these brain-body dynamics show how NO acts as a bridge between neural plasticity and whole‑body states, making it central to understanding why hyperneuroplasticity feels both expansive and precarious. Building on Kluger et al. (2024), these dynamics can also be understood as transient, high‑dimensional brain-body states shaped by both internal cues (like interoception, cardiovascular tone, and metabolic needs) and external context (such as environment and social setting). These states unfold across multiple timescales, from moment‑to‑moment fluctuations in arousal to daily or seasonal rhythms, creating trajectories that are sensitive to prior state history. This framing also helps explain chronic health situations such as dysautonomia, Ehlers‑Danlos syndrome (EDS), mast cell activation syndrome (MCAS), and related conditions, where the coupling of brain and body regulation can be especially fragile or easily tipped toward instability. In lay terms, it is as if the brain and body are constantly improvising within a musical score: past notes shape what comes next, and small shifts can redirect the entire piece toward harmony or discord.

Integrative Implications

Bringing all these seemingly random threads of dynamic brain states, nitric oxide, and neurodivergence together highlights how hyperneuroplasticity involves the intimate coupling of brain and body. And please understand, this is not about fixing neurodivergent brains or making them conform. Rather, it is about expanding access to the full range of dynamic responsiveness. Stabilizing interventions such as vagus nerve stimulation, breathwork, EMDR, and other therapies may support regulation without erasing difference, honoring the dual nature of hyperneuroplastic systems as both barrier and brilliance (Janssen et al., 2021; Kluger et al., 2024). However, framed through the hyperneuroplastic lens, the point is less about prescribing treatments and more about deepening understanding. Recognizing these patterns of hyperneuroplasticity and NO helps us accept that fluidity and sensitivity are inherent features of the system. Rather than aiming to correct or normalize, the focus becomes embracing these dynamics as part of the lived reality of neurodivergence and health, fostering acceptance and insight into why experience can feel both expansive and precarious.

References

Abraham, W. C., & Bear, M. F. (1996). Metaplasticity: The plasticity of synaptic plasticity. Trends in Neurosciences, 19(4), 126–130. https://doi.org/10.1016/S0166-2236(96)80018-X

Attwell, D., & Iadecola, C. (2002). The neural basis of functional brain imaging signals. Trends in Neurosciences, 25(12), 621–625. https://doi.org/10.1016/S0166-2236(02)02264-6

Baek, I., Lee, W., Lee, Y., Kim, J., Lee, J., Kim, H., & Lee, S. (2025). Identification of functional dynamic brain states based on graph attention networks. NeuroImage, 290, 120643. https://doi.org/10.1016/j.neuroimage.2025.120643

Ballabh, P., Braun, A., & Nedergaard, M. (2004). The blood–brain barrier: An overview. Neurobiology of Disease, 16(1), 1–13. https://doi.org/10.1016/j.nbd.2003.12.016

Böhme, G. A., Bon, C., Lemaire, M., Reibaud, M., Piot, O., Stutzmann, J. M., … & Blanchard, J. C. (1991). Evidence for a role of nitric oxide in long-term potentiation in hippocampal slices. European Journal of Pharmacology, 199(2), 379–381. https://doi.org/10.1016/0014-2999(91)90558-N

Brown, G. C. (2010). Nitric oxide and neuronal death. Nitric Oxide, 23(3), 153–165. https://doi.org/10.1016/j.niox.2010.06.001

Calabrese, V., Mancuso, C., Calvani, M., Rizzarelli, E., Butterfield, D. A., & Stella, A. M. (2007). Nitric oxide in the central nervous system: Neuroprotection versus neurotoxicity. Nature Reviews Neuroscience, 8(10), 766–775. https://doi.org/10.1038/nrn2214

Förstermann, U., & Sessa, W. C. (2012). Nitric oxide synthases: Regulation and function. European Heart Journal, 33(7), 829–837. https://doi.org/10.1093/eurheartj/ehr304

Garthwaite, J. (2008). Concepts of neural nitric oxide-mediated transmission. European Journal of Neuroscience, 27(11), 2783–2802. https://doi.org/10.1111/j.1460-9568.2008.06285.x

Gu, Y., Dee, C. M., & Shen, J. (2011). Interaction of free radicals, matrix metalloproteinases and caveolin-1 impacts blood–brain barrier permeability. Frontiers in Bioscience, 16, 1954–1969. https://doi.org/10.2741/222

Hardingham, N., Fox, K., & Jack, J. J. B. (2013). Presynaptic efficacy directs normalization of synaptic strength in layer 2/3 rat neocortex after paired activity. The Journal of Neuroscience, 33(6), 2293–2303. https://doi.org/10.1523/JNEUROSCI.3872-12.2013

Janssen, T. W. P., et al. (2021). Repetitive transcranial magnetic stimulation: Exploring plasticity in autism spectrum disorder. Neuroscience & Biobehavioral Reviews, 125, 146–159. https://doi.org/10.1016/j.neubiorev.2021.02.029

Kluger, D. S., Allen, M. G., & Gross, J. (2024). Brain–body states embody complex temporal dynamics. Trends in Cognitive Sciences, 28(9), 691–705. https://doi.org/10.1016/j.tics.2024.05.005

Perez, D. L., Edwards, M. J., Nielsen, G., Kozlowska, K., Hallett, M., & LaFrance, W. C. Jr. (2021). Decade of progress in motor functional neurological disorder: Continuing the momentum. Journal of Neurology, Neurosurgery & Psychiatry, 92(6), 668–677. https://doi.org/10.1136/jnnp-2021-326214

Picón-Pagés, P., Garcia-Buendia, J., & Muñoz, F. J. (2019). Functions and dysfunctions of nitric oxide in brain. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, 1865(8), 1949–1967. https://doi.org/10.1016/j.bbadis.2018.12.013

Tognoli, E., & Kelso, J. A. S. (2014). The metastable brain. Neuron, 81(1), 35–48. https://doi.org/10.1016/j.neuron.2013.12.022