GoKawiilPatient recruitment
Experiments were conducted according to protocol guidelines approved by the Institutional Review Board for Baylor College of Medicine and Affiliated Hospitals (H-50885 for the Neuropixels recordings and H-18112 for the EMU recordings). All of the recruited patients for the Neuropixels recordings were diagnosed with drug-resistant temporal lobe epilepsy and were scheduled to undergo an anteromesial temporal lobectomy for seizure control. All of the patients provided written informed consent to participate in the study and were aware that participation was voluntary and would not affect their clinical course. Included patients’ age ranged from 25–54 years old (average, 39.6 ± 11.8), with three female and four male patients. Four resections were on the left side, and three were on the right. In one individual (p3), recordings were performed in the middle temporal lobe before resection. None of the patients reported explicit memory of intraoperative events after the case when discussed in the post-operative care unit or while recovering in the hospital the next day.
Note that we include for comparison purposes a cohort of awake patients listening to podcast stimuli. These patients were recruited from patients undergoing invasive recordings in the EMU at Baylor St Luke’s Hospital. Details on methods for this group of patients were reported previously21,34,52,53,54.
Neuropixels data acquisition set-up and intraoperative recordings
Neuropixels 1.0-S probes (IMEC) with 384 recording channels (total recording contacts = 960, usable recording contacts = 384) were used for recordings (dimensions: 70 μm width, 100 μm thickness, 10 mm length). The Neuropixels probe, consisting of both the recording shank and the headstage, were individually sterilized with ethylene oxide (Bioseal)6. Our intraoperative data acquisition system included a custom-built rig including a PXI chassis affixed with an IMEC/Neuropixels PXIe Acquisition module (PXIe-1071) and National Instruments DAQ (PXI-6133) for acquiring neuronal signals and any other task-relevant analogue/digital signals respectively. Our recording rig was certified by the Biomedical Engineering at Baylor St Luke’s Medical Center, where the intraoperative recording experiments were conducted. A high-performance computer (10-core processor) was used for neural data acquisition using open-source software such as SpikeGLX 3.0 and OpenEphys v.0.6x for data acquisition (the action potential (AP) band was band-pass filtered from 0.3 kHz to 10 kHz and acquired at 30 kHz sampling rate; the LFP band was band-pass filtered from 0.5 Hz to 500 Hz and acquired at a 2,500 Hz sampling rate). We used a short-map probe channel configuration for recording, selecting the 384 contacts located along the bottom third of the recording shank.
Audio was played through a separate computer using pregenerated .wav files and captured at 30 kHz or 1,000 kHz on the NIDAQ through a coaxial cable splitter that sent the same signal to speakers adjacent to the patient. MATLAB (MathWorks) in conjunction with a LabJack (LabJack U6) was used to generate a continuous TTL pulse of which the width was modulated by the current timestamp and recorded on both the neural and audio datafiles. Online synchronization of the AP and LFP files was performed by the OpenEphys recording software. Offline synchronization of the neural and audio data was performed by calculating a scale and offset factor via a linear regression between the time stamps of the reconstructed TTL pulses and confirmed with visual inspection of the aligned traces.
Acute intraoperative recordings were conducted in brain tissue designated for resection based on purely clinical considerations. The probe was positioned using a ROSA ONE Brain (Zimmer Biomet) robotic arm and lowered into the brain 5–6 mm from the ependymal surface using an AlphaOmega (Alpha Omega Engineering). The penetration was monitored through online visualization of the neuronal data and through direct visualization with the operating microscope (Kinevo 900). Reference and ground signals on the Neuropixels probe were acquired by connecting to sterile needles placed in the scalp (separate needles inserted at distinct scalp locations for ground and reference respectively).
For all patients (n = 7), we conducted neuronal recordings under general anaesthesia for at most 30 min as per the experimental protocol. All of the patients were under total intravenous anaesthesia, with propofol as the main anaesthetic for each experimental protocol (Extended Data Table 1). Inhaled anaesthetics were only used for induction and stopped at least 1 h before recordings. The anaesthesiologist titrated the anaesthetic drug infusion rates so that the BIS monitor (Medtronic) value was between 45 and 60 for the duration of the surgical case55. Notably, BIS values range between 0 (completely comatose) and 100 (fully awake), with standard intraoperative values between 40 and 60. Specific anaesthesia depth was flat across the brief time of the experiment. First, recordings took place several hours after anaesthesia induction and several hours before the end of the procedure, so patients were well into the stable portion of the surgery. Second, the anaesthesiologist was maintaining active monitoring and stably controlled anaesthesia levels.
For patients p4, p5 and p6, we recorded neuronal activity during passive auditory stimuli presentation. For p4, a sequence of auditory stimuli (pure tones; f1 = 1 kHz, f2 = 3 kHz) was presented with an 80–20 probability distribution, with the less frequent auditory stimulus serving as an auditory oddball stimulus (n = 300 trials). For p5 and p6 we counterbalanced the tones. A sequence of auditory stimuli (pure tones; f 1 = 200 Hz, f 2 = 5 kHz) were presented with an 80–20 probability distribution, while switching the tone frequency designated as the auditory oddball stimulus halfway through (first half, n = 150 trials, f 2 is auditory oddball; second half, n = 150 trials, f 1 is auditory oddball). We interleaved a washout period (30 trials) using the same auditory stimuli but presented at a 50–50 probability distribution in between the two counterbalanced tasks. The auditory pure tone stimuli were presented for a 100 ms duration, and the intertrial interval for the auditory oddball task was randomly drawn from between 1 and 3 s.
Sound stimuli for the auditory oddball task consisted of high- and low-pitched tones. The low-pitched tone was 100 ms duration and 200 Hz, approximating a square wave. The high-pitched tone was 100 ms duration and 5 kHz frequency, also approximating a square wave. These stimuli were constructed to have distinct perceived pitch and salient onset structure. Stimulus waveforms were matched in amplitude. Sounds were delivered in stereo, using a sound delivery system that was calibrated in the testing suite (B&K type 4939-A-011 calibration mic and NEXUS 4939-A-011 conditioning amplifier). Both speakers had a relatively flat frequency response (±5 dB) across the used frequency range (200–6,000 Hz) and no high- or low-frequency roll-off.
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