In, Myung‐Ho

Abstract Hypoxia constrains cerebral oxygen availability and challenges brain function and stability. Although hypoxia-responsive functional connectivity (HR-FC) reorganizes rapidly with declining arterial oxygen partial pressure, its relationship to local neurovascular activity remains unclear. We examined time-resolved amplitude of low-frequency fluctuations (ALFF) in blood-oxygenation-level dependent (BOLD) fMRI during graded acute hypoxia in healthy adults, performing a continuous cognitive test (Go/No-go task) with concurrent physiological monitoring. Dynamic ALFF and functional connectivity were estimated using a sliding-window approach and analyzed across large-scale brain networks defined by Schaefer’s 17-network parcellation. Severe hypoxia elicited temporally dissociated responses across modalities. Functional connectivity increased monotonically, whereas ALFF exhibited pronounced nonlinear modulation, including phase-dependent divergence across networks. During hypoxic decompensation, the default mode network (DefaultA) showed marked ALFF suppression, whereas a ventral secondary somatosensory-dominant network (SomMotB) exhibited preferential preservation despite similar engagement in HR-FC. Together, these findings indicate that network-level ALFF captures a distinct yet complementary layer of functional dynamics, with a temporal profile distinct from functional connectivity. Spontaneous BOLD dynamics during acute hypoxia reflect structured network-level modulation rather than a uniform suppression attributable solely to reduced oxygen availability. These findings support a conceptual framework of cerebral oxygen budgeting , in which metabolic constraints reshape functional dynamics across brain networks.

OBJECTIVE Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established neurosurgical treatment for the motor symptoms of Parkinson’s disease (PD). While often highly effective, DBS does not always yield optimal therapeutic outcomes, and stimulation-induced adverse effects, including paresthesia, muscle contractions, and nausea/lightheadedness, commonly occur and can limit the efficacy of stimulation. Currently, objective metrics do not exist for monitoring neural changes associated with stimulation-induced therapeutic and adverse effects. METHODS In the present study, the authors combined intraoperative functional MRI (fMRI) with STN DBS in 20 patients with PD to test the hypothesis that stimulation-induced blood oxygen level–dependent signals contained predictive information concerning the therapeutic and adverse effects of stimulation. RESULTS As expected, DBS resulted in blood oxygen level–dependent activation in myriad motor regions, including the primary motor cortex, caudate, putamen, thalamus, midbrain, and cerebellum. Across the patients, DBS-induced improvements in contralateral Unified Parkinson’s Disease Rating Scale tremor subscores correlated with activation of thalamic, brainstem, and cerebellar regions. In addition, improvements in rigidity and bradykinesia subscores correlated with activation of the primary motor cortex. Finally, activation of specific sensorimotor-related subregions correlated with the presence of DBS-induced adverse effects, including paresthesia and nausea (cerebellar cortex, sensorimotor cortex) and unwanted muscle contractions (caudate and putamen). CONCLUSIONS These results suggest that DBS-induced activation patterns revealed by fMRI contain predictive information with respect to the therapeutic and adverse effects of DBS. The use of fMRI in combination with DBS therefore may hold translational potential to guide and improve clinical stimulator optimization in patients.

Abstract Introduction While the clinical efficacy of deep brain stimulation (DBS) the treatment of motor‐related symptoms is well established, the mechanism of action of the resulting cognitive and behavioral effects has been elusive. Methods By combining functional magnetic resonance imaging (fMRI) and DBS, we investigated the pattern of blood‐oxygenation‐level‐dependent (BOLD) signal changes induced by stimulating the nucleus accumbens in a large animal model. Results We found that diffused BOLD activation across multiple functional networks, including the prefrontal, limbic, and thalamic regions during the stimulation, resulted in a significant change in inter‐regional functional connectivity. More importantly, the magnitude of the modulation was closely related to the strength of the inter‐regional resting‐state functional connectivity. Conclusions Nucleus accumbens stimulation affects the functional activity in networks that underlie cognition and behavior. Our study provides an insight into the nature of the functional connectivity, which mediates activation effect via brain networks.