Comb-like, silicon-based NeuroProbes array with four 10-mm-long probe shafts separated by 400 µm.

<p>Each shank is comprised of eight IrOx electrode sites. The array is interconnected to a highly flexible polyimide ribbon cable interfacing with a zero insertion force (ZIF) connector on a printed circuit board (PCB) that was connected to the stimulator. For probe insertion, the probe comb is fixed adhesively to the insertion plate and attached to a micromanipulator. The 100-µm-thick probe shanks proved to be stiff enough for insertion into deep brain structures.</p

Modeled safe stimulation parameters.

<p>Stimulation above the solid black line (k = 2) has been shown to induce tissue damage and co-varies with total charge and charge density per pulse phase. The curves with different symbols reflect how charge density changes with increasing charge per phase for either the NP or AMI sites, i.e., for different site areas, for three different pulse widths each. The local field potential (LFP, red dot, 200 µs/phase) and spike (Spk, blue dot, 200 µs/phase) thresholds obtained from animal studies are labeled on the plot for direct comparison.</p

Rate growth curves recorded from A1 and pooled from all 12 stimulated NP sites.

<p>A) Growth rate of LFP peak magnitude versus stimulus level (in dB relative to 1 µA). B) Growth rate of LFP area versus stimulus level. C) Growth rate for multi-unit spikes versus stimulus level.</p

Raw data and PSTH plots.

<p>A) Averaged unfiltered raw data (20 sweeps) showing LFP in response to stimulation with an NP site from 20 to 52 dB relative to 1 µA (actual stimuli were 12–52 dB in 2-dB steps). The monotonic increase in LFP size with stimulation amplitude is evident. The LFP threshold is 28 dB in this example. B) PSTHs corresponding to the different stimulation levels indicated in each plot. PSTH bars represent 1 ms bins. The dotted line indicates stimulus onset at 0 ms. Bottom right trace is a single trial filtered for spikes with the artifact removed and showing multi-unit activity in response to a stimulation at 52 dB. Each detected spike is marked by an * with the red line indicating threshold for spike detection. The MUA threshold is 34 dB, which is higher than the LFP threshold.</p

Wireless recording of single unit activity from the rat dorsal striatum during operant conditioning.

<p><b>A.</b> Coronal sections of a rat brain showing the striatum and the placement of the microwire arrays. A 16-channel, 2×8 microwire array was used. <b>B.</b> Rat performing operant task of pressing a small protrusion in order to receive a reward. The lever measures the force that is exerted upon it, and the reward is contingent upon the duration and force of the press. Use of the wireless telemetry system for this facilitates task acquisition and prevents the rat from chewing removing the headstage and chewing the wires. <b>C.</b> Raster plot and peri-stimulus time histogram of a putative tonically active cholinergic neuron recorded from the rat striatum. Bin size for the PSTH is 20 ms. The X-axis shows time from the delivery of a food pellet reward following a successfully completed lever press. The neuron showed burst firing immediately after reward delivery. <b>D.</b> Action potential waveform of the neuron shown in C.</p

Corticostriatal gamma60-delta PAC during 5-CSRTT performance.

<p>A) Example of raw and filtered LFP data showing PAC. Vertical dashed purple lines indicate local gamma60 power maxima; vertical green lines indicate local delta peaks and troughs. B) Phase-amplitude coupling between low (phase giving) and high frequency (amplitude giving) oscillations in PFC and NAcb calculated over whole 30 minute recordings. PAC peaked between gamma60 oscillations and a 2–3 Hz delta oscillation, and was weaker in PRL than other regions. Note that PAC was calculated with amplitude and phase data taken from the same electrode. C) PAC between 30–80 Hz high frequency oscillations and a 2.75 Hz delta oscillation around wait-start for all correct, previously rewarded trials recorded from NAcbC electrodes. D) PAC between 30–80 Hz and 2.75 Hz delta oscillations around nose-poking for all correct, previously rewarded trials recorded from the NAcbC. E) Gamma60-delta PAC around wait-start. Solid lines represent the mean of all trials. Shaded areas represent the SEM. F) Model statistics for the effect of upcoming trial outcome, previous reward, velocity and brain region on instantaneous gamma60-delta PAC around the wait-start alignment event. G) Gamma60-delta PAC around nose-poking. Solid lines represent the mean of all trials. Shaded areas represent the SEM. H) Model statistics for the effect of upcoming trial outcome, previous reward, velocity, and brain region on instantaneous gamma60-delta PAC around nose-poking.</p

Wireless recording of single-unit activity from the mouse dorsal striatum during rotarod running.

<p><b>A.</b> Coronal section of a mouse brain showing superimposed electrode placement targeting the dorsal striatum. This experiment used a 2 by 8, 16 channel microwire electrode array. <b>B.</b> Photo of a mouse during a rotarod task. The wireless telemetry system allows the animal to fall and rest between trials without getting wires tangled up in the testing apparatus, yet is small and light enough that it minimally interferes in the task itself. <b>C.</b> Raster plot and peri-event time histogram of a putative medium spiny projection neuron from the dorsal striatum. The start and end of each trial are marked by triangles. Notice the clear difference in firing rates between the trial state and the resting state. The histogram bin size is 4 seconds. <b>D.</b> Action potential waveform of the neuron shown in C.</p

Side-by-side comparison between wireless and tethered recording systems.

<p><b>A.</b> Simultaneously recorded action potentials from the substantia nigra using wireless and tethered recording systems in an awake, behaving mouse. The gain of both the tethered and the wireless system were set at 2×. <b>B.</b> Principal component analysis (PCA) of 30 seconds of neural data from the same recording session. The cluster on the left is the spike, while the cluster on the right is noise. <b>C.</b> Comparison of 20 ms of raw analog data, recorded from the same recording session. Asterisks mark neuron action potentials.</p

Electrode placements and behavioural data.

<p>A) Representative histology of silicon probe placement in the medial prefrontal cortex and nucleus accumbens. B) Reconstructed placements of all electrode contacts in prelimbic and infralimbic prefrontal cortex and nucleus accumbens core and shell. C) Scheme of 5-Choice Serial Reaction Time Task (5-CSRTT). Trials start with a nose-poke in the food magazine. After a 5 second delay a 0.5 second light stimulus is presented pseudorandomly in one of 5 nose-poke ports. A response to the illuminated hole within 5 seconds is rewarded with a food pellet. Responses during the waiting period, to the wrong hole, or the absence of a response within 5 seconds of stimulus presentation are punished with a 5 second lights-off timeout. D) Distribution of behavioural latencies for rats to move from entering the food magazine, starting a new trial, to leaving the magazine to start waiting, split by the outcome of the previous trial (either ending in a correct response, and being rewarded, or ending in an incorrect or premature error response). Boxes show the range from 1^st to 3^rd quartile of responses, black lines show the median, and whiskers extend to the furthest value from the hinge within 1.5 times the inter-quartile range. Values outside this range are represented as black dots.</p

Predicting upcoming impulsive responses.

<p>A) Stacked distribution of premature and non-premature (i.e. correct and incorrect) responses as a function of latency of rats to move to wait-start, divided into trials where the previous trials was rewarded (+), or non-rewarded (−). Time zero is the start of the trial, a vertical grey line represents the time of stimulus light presentation (or in the case of premature responses, the time the stimulus light would have been presented). B) Distribution of premature and non-premature responses as depicted in A, represented as a proportion of all responses. C) Receiver-operator characteristic curve for models predicting upcoming premature responses based on leave-one-out cross-validation results. The diagonal grey line represents an uninformative classifier. D) Plot of model accuracy ([number of true positives] + [number of true negatives]/[number of true positives] + [number of false positives] + [number of true negatives] + [number of false negatives]) against threshold predicted probability value. E) Distribution of predicted probabilities for true premature and non-premature trials from the full (behaviour plus LFP) model. The area under each curve is equal to the total number of trials.</p