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• Journal article
  Rintoul J, Butler C, Cleveland R, Grossman Net al., 2026,

  Non-invasive in vivo acoustoelectric neuromodulation and its contribution to ultrasound stimulation

  , Nature Communications, ISSN: 2041-1723

  Non-invasive brain stimulation offers therapeutic potential without surgery, yet existing electrical approaches lack spatial precision due to the long wavelengths of electric fields. Here we demonstrate acoustoelectric neuromodulation, a nonlinear interaction between applied acoustic and electric fields that generates spatially localized, low-frequency electric fields at the ultrasound focus. Using in vitro and in vivo mouse electrophysiology, we show motor evoked responses that depend on both the amplitude and frequency of the acoustoelectric field, with controls excluding purely acoustic or electrical origins. In vivo measurements show acoustoelectric potentials of ≈9 mV, corresponding to estimated focal electric fields of ~6 V/m at 500 kHz and 1 MPa acoustic pressure, with ~1.5 mm extrema spacing demonstrated in phantom experiments. Importantly, we identify an acoustoelectric contribution to conventional ultrasound stimulation, arising from interactions between ultrasound-induced electrical signals and propagating acoustic waves, establishing acoustoelectric neuromodulation as a distinct mechanism influencing ultrasound-based brain stimulation.

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• Journal article
  David MCB, Mallas E-J, Kolanko MA, Del Giovane M, Kurtin DL, Nilforooshan R, Zimmerman KA, Bonet Olivares C, Lally PJ, CR&T Group of UKDRI, Sharp DJ, Malhotra PA, Scott Get al., 2026,
  , Alzheimers Dement, Vol: 22

  INTRODUCTION: The brain is a complex dynamical system, influenced by arousal state. Cortical synchrony supports information processing and is disrupted in Alzheimer's disease (AD). Locus coeruleus (LC) integrity and pupillometry index arousal system structure and function. METHODS: Sixty-four AD and 26 controls underwent resting-state pupillometry-fMRI. Neuromelanin MRI and Addenbrooke's Cognitive Examination were conducted. Mean and standard deviation of blood oxygen level dependent (BOLD) phase coherence yielded synchrony and metastability, respectively. Leading Eigenvector Dynamics Analysis (LEiDA) produced coherence-based states. RESULTS: AD had reduced global synchrony [b = -0.90, p < 0.001], metastability [b = -0.61, p < 0.01], LEiDA "global coherence state" occupancy [b = -0.06, p < 0.01], and LC integrity [b = -0.37, p = 0.01]. Synchrony [b = 0.19, p = 0.01] and LC integrity [b = 0.17, p < 0.01] related to cognition and one another [b = 0.27, p = 0.01]. Pupil-linked arousal correlated with synchrony and global coherence state maintenance. DISCUSSION: In health, cortical activity shows widespread but dynamic synchrony across regions to meet changing demands. In AD, arousal dysfunction appears to disrupt these dynamics, impacting cognition.

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• Journal article
  Katz DI, Bodien YG, Faerman A, Schwertfeger J, Bogdanova Y, Blum S, Dwyer B, Gilmore N, Goncalves JV, Hays K, Graf MJP, Marino M, Mallas E-J, Shapiro-Rosenbaum A, Sherer M, Williams MW, Zhang Bet al., 2026,
  , J Neurotrauma, Vol: 43, Pages: 835-849

  The post-traumatic confusional state (PTCS) is a period of recovery that follows traumatic brain injury (TBI), characterized by post-traumatic amnesia (PTA), impairments in attention, and behavioral dysregulation, among other clinical symptoms. The pathophysiology of PTCS is unknown, contributing to the absence of neurobiologically based diagnostic criteria, prognostic models, and treatments. The workgroup conducted a scoping review of the literature in MEDLINE/PubMed database and manual searches of references to synthesize the existing knowledge on structural, functional, electroencephalographic (EEG), molecular, and genetic biomarkers underlying PTCS diagnosis and prognosis through five Population, Intervention, Comparison, and Outcome (PICO) questions. The search yielded 3,333 abstracts of which 69 were retained and included. Teams of two workgroup members independently reviewed abstracts and articles. Most articles addressed whether biomarkers differentiated patients with PTCS/PTA from those not in PTCS/PTA, and whether biomarkers were associated with severity or duration of PTCS/PTA. Our findings suggest that transition through PTCS/PTA from lower to higher states of consciousness involves increased thalamic function, restoration of default mode network dynamics, and normalizing of excessive slow wave activity on quantitative EEG. For patients with mild TBI, PTCS/PTA was associated with greater TBI lesion burden on structural imaging. PTCS/PTA severity and duration were associated with lesion burden, reduced white matter integrity, and electrophysiological signatures. Results across studies were variable with many finding no relationship between PTCS/PTA and biomarkers. In summary, while it is premature to include biomarkers in the definition of PTCS/PTA, our findings provide avenues for future research that is designed specifically to address the pathophysiology of this condition.

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• Journal article
  Carhart-Harris R, 2026,
  , Nature Communications, Vol: 17, ISSN: 2041-1723

  Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown. In an exploratory, placebo-controlled, within-subjects, electroencephalography (EEG), and magnetic resonance imaging (MRI) study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes are detected from one-hour to one-month after a single high-dose (25 mg) of psilocybin. Increases in cognitive flexibility, psychological insight, and well-being are seen at one-month. Diffusion tensor imaging (DTI) done before and one-month after 25mg psilocybin reveals decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlate with decreases in brain network modularity (fMRI) over the same month. Enduring functional brain changes are largely absent, but network modularity change (numerical decrease) negatively correlates with well-being change (significant increase), in line with previous findings in depression. Increased cortical signal entropy (EEG) at 1- and 2-hours post-dosing predicts improved psychological well-being at one-month. Next-day psychological insight mediates the entropy to well-being relationship. All effects are exclusive to 25mg psilocybin; no effects occur with a 1mg psilocybin placebo.

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• Journal article
  Agnorelli C, Peill J, Sawicka G, Kurtin D, Shatalina E, Ahmad K, Wall MB, Rua C, Godfrey K, Ertl N, Searle G, Zhou K, Osugo M, Weiss B, Greenway KT, Fagiolini A, Carhart-Harris R, Matthews PM, Rabiner EA, Nutt D, Erritzoe Det al., 2026,
  , J Cereb Blood Flow Metab

  We investigated ketamine's neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1-8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven male participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (glutamate and GABA) and resting-state fMRI (intrinsic brain activity, functional connectivity), before and after ketamine. While group-level analyses showed no significant increases in PET synaptic markers, ketamine administration resulted in significantly elevated glutamate levels within the anterior cingulate cortex (ACC). Functional connectivity analyses revealed reduced coupling between the ACC and the dorsolateral prefrontal cortex (dlPFC) and increased coupling between the ACC and the amygdala in the days following ketamine administration. Our multimodal analysis revealed that participants showing an increase in [11C]-UCBJ volume distribution (VT), a putative index of synaptic plasticity, showed a correlated reduction in intrinsic activity within regions belonging to the default mode network (DMN). By linking molecular, cellular and network-level changes, our results point to the DMN as a central hub where ketamine may reshape brain hierarchies in the long term, providing new directions for understanding its therapeutic mechanisms and developing targeted treatments.

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