Charlotte Luff

All Publications

• Pulse-width modulated temporal interference (PWM-TI) brain stimulation. Brain stimulation Luff, C. E., Dzialecka, P., Acerbo, E., Williamson, A., Grossman, N. 2024; 17 (1): 92-103

  Abstract

  Electrical stimulation involving temporal interference of two different kHz frequency sinusoidal electric fields (temporal interference (TI)) enables non-invasive deep brain stimulation, by creating an electric field that is amplitude modulated at the slow difference frequency (within the neural range), at the target brain region.Here, we investigate temporal interference neural stimulation using square, rather than sinusoidal, electric fields that create an electric field that is pulse-width, but not amplitude, modulated at the difference frequency (pulse-width modulated temporal interference, (PWM-TI)).We show, using ex-vivo single-cell recordings and in-vivo calcium imaging, that PWM-TI effectively stimulates neural activity at the difference frequency at a similar efficiency to traditional TI. We then demonstrate, using computational modelling, that the PWM stimulation waveform induces amplitude-modulated membrane potential depolarization due to the membrane's intrinsic low-pass filtering property.PWM-TI can effectively drive neural activity at the difference frequency. The PWM-TI mechanism involves converting an envelope amplitude-fixed PWM field to an amplitude-modulated membrane potential via the low-pass filtering of the passive neural membrane. Unveiling the biophysics underpinning the neural response to complex electric fields may facilitate the development of new brain stimulation strategies with improved precision and efficiency.

  View details for DOI 10.1016/j.brs.2023.12.010

  View details for PubMedID 38145754

• Can Neuromodulation Improve Sleep and Psychiatric Symptoms? Current psychiatry reports Luff, C. E., de Lecea, L. 2024

  Abstract

  In this review, we evaluate recent studies that employ neuromodulation, in the form of non-invasive brain stimulation, to improve sleep in both healthy participants, and patients with psychiatric disorders. We review studies using transcranial electrical stimulation, transcranial magnetic stimulation, and closed-loop auditory stimulation, and consider both subjective and objective measures of sleep improvement.Neuromodulation can alter neuronal activity underlying sleep. However, few studies utilizing neuromodulation report improvements in objective measures of sleep. Enhancements in subjective measures of sleep quality are replicable, however, many studies conducted in this field suffer from methodological limitations, and the placebo effect is robust. Currently, evidence that neuromodulation can effectively enhance sleep is lacking. For the field to advance, methodological issues must be resolved, and the full range of objective measures of sleep architecture, alongside subjective measures of sleep quality, must be reported. Additionally, validation of effective modulation of neuronal activity should be done with neuroimaging.

  View details for DOI 10.1007/s11920-024-01540-1

  View details for PubMedID 39352645

  View details for PubMedCentralID 1991337

• Optimized ultrasound neuromodulation for non-invasive control of behavior and physiology. Neuron Murphy, K. R., Farrell, J. S., Bendig, J., Mitra, A., Luff, C., Stelzer, I. A., Yamaguchi, H., Angelakos, C. C., Choi, M., Bian, W., DiIanni, T., Pujol, E. M., Matosevich, N., Airan, R., Gaudillière, B., Konofagou, E. E., Butts-Pauly, K., Soltesz, I., de Lecea, L. 2024

  Abstract

  Focused ultrasound can non-invasively modulate neural activity, but whether effective stimulation parameters generalize across brain regions and cell types remains unknown. We used focused ultrasound coupled with fiber photometry to identify optimal neuromodulation parameters for four different arousal centers of the brain in an effort to yield overt changes in behavior. Applying coordinate descent, we found that optimal parameters for excitation or inhibition are highly distinct, the effects of which are generally conserved across brain regions and cell types. Optimized stimulations induced clear, target-specific behavioral effects, whereas non-optimized protocols of equivalent energy resulted in substantially less or no change in behavior. These outcomes were independent of auditory confounds and, contrary to expectation, accompanied by a cyclooxygenase-dependent and prolonged reduction in local blood flow and temperature with brain-region-specific scaling. These findings demonstrate that carefully tuned and targeted ultrasound can exhibit powerful effects on complex behavior and physiology.

  View details for DOI 10.1016/j.neuron.2024.07.002

  View details for PubMedID 39079529

• The neuron mixer and its impact on human brain dynamics. Cell reports Luff, C. E., Peach, R., Mallas, E. J., Rhodes, E., Laumann, F., Boyden, E. S., Sharp, D. J., Barahona, M., Grossman, N. 2024; 43 (6): 114274

  Abstract

  A signal mixer facilitates rich computation, which has been the building block of modern telecommunication. This frequency mixing produces new signals at the sum and difference frequencies of input signals, enabling powerful operations such as heterodyning and multiplexing. Here, we report that a neuron is a signal mixer. We found through ex vivo and in vivo whole-cell measurements that neurons mix exogenous (controlled) and endogenous (spontaneous) subthreshold membrane potential oscillations, producing new oscillation frequencies, and that neural mixing originates in voltage-gated ion channels. Furthermore, we demonstrate that mixing is evident in human brain activity and is associated with cognitive functions. We found that the human electroencephalogram displays distinct clusters of local and inter-region mixing and that conversion of the salient posterior alpha-beta oscillations into gamma-band oscillations regulates visual attention. Signal mixing may enable individual neurons to sculpt the spectrum of neural circuit oscillations and utilize them for computational operations.

  View details for DOI 10.1016/j.celrep.2024.114274

  View details for PubMedID 38796852

• The neuron frequency mixer Peach, R., Rhodes, E., Grossman, N., Luff, C. SPRINGER. 2024: S84-S85

  View details for Web of Science ID 001414215700149

• Characteristics of motor evoked potentials in patients with peripheral vascular disease. PloS one Sarai, P., Luff, C., Rohani-Shukla, C., Strutton, P. H. 2024; 19 (4): e0290491

  Abstract

  With an aging population, it is common to encounter people diagnosed with peripheral vascular disease (PVD). Some will undergo surgeries during which the spinal cord may be compromised and intraoperative neuromonitoring with motor evoked potentials (MEPs) is employed to help mitigate paralysis. No data exist on characteristics of MEPs in older, PVD patients, which would be valuable for patients undergoing spinal cord at-risk surgery or participating in neurophysiological research. Transcranial magnetic stimulation, which can be delivered to the awake patient, was used to stimulate the motor cortex of 20 patients (mean (±SD)) age 63.2yrs (±11.5) with confirmed PVD, every 10 minutes for one hour with MEPs recorded from selected upper and lower limb muscles. Data were compared to that from 20 healthy volunteers recruited for a protocol development study (28yrs (±7.6)). MEPs did not differ between patient's symptomatic and asymptomatic legs. MEP amplitudes were not different for a given muscle between patients and healthy participants. Except for vastus lateralis, disease severity did not correlate with MEP amplitude. There were no differences over time in the coefficient of variation of MEP amplitude at each time point for any muscle in patients or in healthy participants. Although latencies of MEPs were not different between patients and healthy participants for a given muscle, they were longer in older participants. The results obtained suggest PVD alone does not impact MEPs; there were no differences between more symptomatic and less symptomatic legs. Further, in general, disease severity did not corelate with MEP characteristics. With an aging population, more patients with PVD and cardiovascular risk factors will be participating in neurophysiological studies or undergoing surgery where spinal cord integrity is monitored. Our data show that MEPs from these patients can be easily evoked and interpreted.

  View details for DOI 10.1371/journal.pone.0290491

  View details for PubMedID 38662756

  View details for PubMedCentralID PMC11045072