The study, led by Yujie Sun and colleagues at the Shengli Clinical Medical College of Fujian Medical University and the Affiliated Hospital of Qingdao University, focused on patients with symptomatic non-acute middle cerebral artery occlusion, or MCAO—a condition in which the major artery supplying blood to large portions of the brain has been blocked for more than two weeks, yet patients continue to experience symptoms. Unlike the frantic timelines of acute stroke care, where clot-busting drugs and thrombectomy dominate, non-acute occlusions present a more ambiguous clinical landscape. The brain has had time to adapt, collateral vessels may have sprouted, and the question of whether restoring flow through the blocked artery will actually help becomes far less straightforward.

At the heart of the research lies a delicate vascular architecture known as the lenticulostriate arteries, or LSAs. These are small, thin perforating vessels that branch directly off the M1 segment of the middle cerebral artery and plunge deep into the brain to nourish critical structures, including the internal capsule and portions of the basal ganglia—regions responsible for movement, sensation, and the relay of motor signals. The LSAs are traditionally divided into two groups: the medial lenticulostriate arteries, which arise more proximally and tend to be larger, and the lateral lenticulostriate arteries, which arise slightly further along the vessel and fan out laterally. Because these vessels are end arteries—meaning they have virtually no backup supply from neighboring vessels—damage or hypoperfusion in their territories can cause devastating, often permanent deficits.

What makes the new study compelling is its territory-specific approach. Rather than treating the deep brain as a uniform block of tissue, the researchers used CT perfusion imaging to separately quantify blood flow dynamics in the medial and lateral LSA territories, comparing the affected side of the brain with the healthy contralateral side. CT perfusion works by rapidly injecting iodinated contrast while the CT scanner repeatedly images the same brain region, tracking how the contrast washes in and out of tissue. From these dynamics, four key parameters are derived: cerebral blood volume (CBV), the amount of blood present in a given volume of tissue; cerebral blood flow (CBF), the rate at which blood moves through the tissue; mean transit time (MTT), the average time blood takes to pass through the capillary bed; and time to peak (TTP), how long it takes contrast concentration to reach its maximum.

To account for natural side-to-side variation, the team calculated relative indices—rCBV, rCBF, rMTT, and rTTP—by comparing each territory on the affected side with its mirror image on the healthy side. This normalization strategy is crucial in perfusion imaging, because absolute values can vary between individuals and between scanners, while relative asymmetries often reveal pathology more reliably. Eighteen patients who underwent successful endovascular recanalization, confirmed by the modified Thrombolysis in Cerebral Infarction (mTICI) grading on digital subtraction angiography, and who had perioperative CT perfusion scans, were retrospectively analyzed with paired statistical comparisons pre-specified before the analysis.

The pre-treatment findings painted a picture of two territories living very different realities under the same arterial occlusion. The lateral LSA territory showed the more severe insult: its cerebral blood volume and cerebral blood flow were significantly reduced compared with the healthy side, while its mean transit time and time to peak were markedly prolonged. In plain terms, less blood was arriving, and what did arrive moved sluggishly through the tissue. The medial territory, by contrast, told a subtler story. Although its blood flow was reduced and its transit times delayed—clear signs of compromised supply—its cerebral blood volume remained preserved. Blood was arriving slowly, but the tissue was still holding a near-normal quantity of blood within its vessels.

This dissociation between preserved volume and reduced flow is physiologically meaningful, and it points to compensatory vasodilation. When perfusion pressure drops, the cerebral vasculature has a first line of defense: the small arterioles dilate to reduce resistance and maintain flow. As pressure falls further, flow declines, but the dilated vessels still hold blood, keeping CBV relatively stable even as CBF falls and transit times lengthen. In this framework, the medial territory appeared to be sitting in a state of exhausted-but-active compensation—its reserve mobilized, its vessels maximally widened, its blood volume defended even as delivery faltered. The lateral territory, having lost ground on all fronts, suggested a deeper stage of hemodynamic compromise, where even the compensatory mechanisms were no longer sufficient to defend tissue perfusion.

Why would the lateral territory fare worse than the medial one? The authors note that the two groups of perforators may possess different hemodynamic vulnerabilities. The medial lenticulostriate arteries arise more proximally on the M1 segment, potentially closer to collateral inflow and at a different angle relative to the direction of occlusive flow, while the lateral branches, arising slightly downstream and oriented differently, may be more sensitive to pressure drops across the occluded segment. Anatomical differences in vessel caliber, branching pattern, and the territory each group supplies may compound these pressures. Whatever the precise anatomical basis, the imaging data demonstrate that deep perforator territories cannot be treated as a single hemodynamic unit in chronic MCA occlusion.

Then came the intervention: endovascular recanalization, in which physicians reopen the blocked artery—typically using a combination of catheter navigation, stent placement, and balloon angioplasty—to restore antegrade flow through the previously occluded vessel. After successful reopening, the follow-up CT perfusion scans documented meaningful changes in both territories, but with distinct signatures. The lateral LSA territory showed the more classical pattern of successful reperfusion: relative cerebral blood flow increased, and relative mean transit time and time to peak shortened, indicating that blood was once again arriving briskly. This is the profile clinicians hope to see when they reopen an occluded artery—faster flow, faster transit, restored supply.

The medial territory also showed improved flow and shortened transit times, confirming that recanalization benefited it as well. But one parameter moved in the opposite direction: relative cerebral blood volume decreased after treatment. Rather than indicating deterioration, this decrease is consistent with the resolution of compensatory vasodilation. Once the occlusion is lifted and perfusion pressure is restored, the chronically dilated arterioles no longer need to remain maximally open; vascular tone returns toward normal, vessel caliber narrows, and blood volume within the tissue falls accordingly. In this reading, the drop in rCBV is not a warning sign but a physiological sigh of relief—a measurable marker that the brain’s emergency adaptations are being stood down.

The clinical implications of these differential patterns are potentially significant. First, they suggest that territory-based CT perfusion analysis could become a more precise tool for assessing hemodynamic vulnerability before deciding on intervention in non-acute MCAO. Patients whose lateral LSA territories show severe hypoperfusion with exhausted reserve may represent those most likely to benefit from recanalization, while the state of the medial territory’s compensatory response might inform expectations about recovery. Second, the post-treatment profiles offer a template for evaluating whether a procedure has genuinely improved deep perforator hemodynamics—something conventional angiography, which shows the parent vessel, cannot directly assess. Recanalizing the artery is one thing; confirming that blood flow dynamics in the vulnerable deep territories have actually normalized is another, and CT perfusion provides that window.

The study also carries a broader conceptual message: the deep brain is not monolithic. Perforator territories that sit side by side, supplied by branches of the same parent artery, can occupy different positions along the spectrum of hemodynamic compensation. This territory-specific framing may prove relevant not only to chronic MCA occlusion but also to other conditions involving perforator vessels, including small-vessel disease and the notorious risk of periprocedural complications during endovascular interventions, where reperfusion injury or hemorrhage in perforator territories remains a feared event.

The researchers are appropriately measured about the scope of their conclusions. With eighteen patients analyzed retrospectively, the findings are best viewed as hypothesis-generating, laying the groundwork for larger prospective studies that could validate territory-specific perfusion metrics as predictors of outcome. The authors also emphasize that their paired, pre-specified comparison design strengthens the internal validity of the observed changes, since each patient served as their own anatomical control before and after treatment. The work was funded by grants from the Fujian Province Joint Funds for the Innovation of Science and Technology, and the study was conducted under the approval of the Ethics Committee of the Affiliated Hospital of Qingdao University in accordance with the Declaration of Helsinki.

For now, the message for the field is clear. When a major brain artery has been quietly blocked for weeks, the tiny territories it once fed are not merely surviving or dying as one. The medial lenticulostriate territory may be straining under compensatory vasodilation, its vessels dilated to their limits, while the lateral territory slips toward more profound hypoperfusion. And when flow is restored, the brain’s recovery writes itself in perfusion numbers—flow rising, transit quickening, and blood volume gently falling as the machinery of compensation powers down. Territory-specific CT perfusion, the study suggests, can read both the struggle and the relief, opening a path toward more individualized decisions in the treatment of chronic cerebral arterial occlusion.

Breathwork, an ancient practice gaining rapid popularity in mental health circles, involves controlled modifications of breathing patterns. When executed at high ventilation rates—with fast, deep breaths—in concert with music, practitioners report achieving states of bliss, insight, and emotional release. These subjective experiences bear remarkable resemblance to those elicited by psychedelic substances, such as psilocybin. However, until now, the neural correlates of breathwork-induced ASCs have remained poorly understood.

Led by Amy Amla Kartar and her colleagues in the Clinical Neuroscience Department, the study employed a multimodal experimental approach involving 15 online participants, 8 laboratory-based individuals, and 19 participants undergoing functional magnetic resonance imaging (fMRI). These participants engaged in a 20- to 30-minute continuous cyclic breathing protocol accompanied by curated music tracks designed to enhance the breathwork experience. Immediately following the session, they completed detailed questionnaires assessing their subjective states.

The neuroimaging revealed striking patterns of cerebral blood flow alterations accompanying the breathwork-induced ASCs. Although HVB generally led to widespread cerebral hypoperfusion—an overall decrease in blood flow—the researchers identified key exceptions. Notably, increases were observed in the right amygdala and anterior hippocampus, regions deeply implicated in emotional memory processing and affective regulation. This localized hyperperfusion correlated with participants’ reports of profound emotional catharsis and psychedelic-type experiences.

Simultaneously, blood flow to the left operculum and posterior insula diminished significantly. These brain areas are central hubs in interoception, the brain’s awareness of internal bodily states such as respiration. The suppression of activity here may facilitate a decoupling from the usual bodily self-awareness, a hallmark of altered consciousness. This neurovascular pattern hints at a complex, region-specific modulation of brain networks during breathwork, whereby internal bodily signals are attenuated while emotional and mnemonic circuits become hyperactive.

Physiological data corroborated these findings. Heart rate variability, a proxy for autonomic nervous system activity, decreased in tandem with increasing ASC intensity, suggesting sympathetic nervous system activation—often associated with stress responses. Intriguingly, this sympathetic activation did not translate into negative subjective outcomes. On the contrary, participants consistently reported reductions in fear and negative emotions, underscoring a potential paradox where physiological stress might coexist with, or even facilitate, therapeutic emotional breakthroughs.

One of the most captivating aspects of the study was the reliable induction of Oceanic Boundlessness (OBN) through HVB. First coined by Sigmund Freud in 1920 and popularized in psychedelic research, OBN encompasses experiences of spiritual unity, bliss, deep insight, and self-transcendence. The researchers found that breathwork elicited these states across diverse settings and participant groups without adverse effects, suggesting a safe and accessible path to profound altered consciousness.

The authors emphasize the novelty of their approach as the first to integrate neuroimaging with breathwork protocols, thereby bridging a critical gap in the understanding of non-pharmacological methods to induce ASC. They propose that changes in specific brain regions related to self-awareness, fear modulation, and emotional memory are key mechanistic substrates underlying the observed phenomenology of breath-induced psychedelic states.

Future work, the authors caution, should include larger sample sizes and rigorous control conditions to disentangle the independent contributions of music and breathing patterns. Nevertheless, these preliminary findings illuminate the transdiagnostic therapeutic potential of HVB, particularly as a legally and ethically unrestricted alternative to psychedelic-assisted therapies, which often face logistical and regulatory hurdles.

Lead author Amy Kartar reflects on the journey, highlighting the excitement of scientifically validating a practice embraced anecdotally by many. Her team’s findings represent an important step towards harnessing breathwork’s neuromodulatory effects for clinical interventions, especially in mental health conditions characterized by emotional dysregulation and trauma.

Principal investigator Dr. Alessandro Colasanti underscores the clinical implications, describing breathwork as a powerful, natural tool for neuromodulation. By orchestrating systemic metabolic shifts and modulating neurovascular function, HVB holds immense promise as an accessible, effective, and non-invasive therapeutic approach. As the field moves forward, breathwork could become a cornerstone modality within integrative psychiatry.

Together, these findings catalyze a paradigm shift in understanding consciousness alteration absent pharmacology. The neurovascular signatures and subjective phenomena elucidated here illuminate how simple, rhythmically modulated breathing intertwined with music powerfully recalibrates brain dynamics, evoking states historically confined to psychedelics. This nexus of respiratory physiology, emotion, and consciousness illuminates new frontiers in mind-body science and therapeutic innovation.

The intersection between breath and brain unearthed by Kartar and colleagues opens exciting avenues for translational research and clinical application. Beyond mental health, HVB’s potential to enhance wellbeing, cognitive flexibility, and emotional resilience positions it as a versatile tool for a wider population. As science peels back layers of the mind’s mysteries, breathwork emerges as an elegant key—rooted in biology, amplified by culture, and ripe for exploration.

Subject of Research: People

Article Title: Neurobiological substrates of altered states of consciousness induced by high ventilation breathwork accompanied by music

News Publication Date: 27-Aug-2025

Web References: http://dx.doi.org/10.1371/journal.pone.0329411

References: Kartar AA, Horinouchi T, Örzsik B, Anderson B, Hall L, Bailey D, et al. (2025) Neurobiological substrates of altered states of consciousness induced by high ventilation breathwork accompanied by music. PLoS One 20(8): e0329411.

Image Credits: Air Hunger, directed by Bob van de Gronde, CC-BY 4.0

Keywords: high ventilation breathwork, altered states of consciousness, psychedelic-like experience, neuroimaging, cerebral blood flow, emotional memory, oceanic boundlessness, autonomic nervous system, respiratory modulation, non-pharmacological therapy