Canada

The diagnosis of concussion remains challenging, particularly in cases where several months have passed between a head injury and clinical assessment. Tracking multiple moving objects in three-dimensional (3D) space engages many of the same cognitive processes that are affected by concussion, a form of mild traumatic brain injury (mTBI), suggesting that tests of 3D multiple object tracking (3D-MOT) may be sensitive to post-concussion syndrome after a brain injury has occurred. To test this, we evaluated 3D-MOT performance (using NeuroTrackerTM) against Sports Concussion Assessment Tool results for cognition, balance, and symptom severity in a large sample (N = 457) of male and female participants between the ages of 6 to 73. 3D-MOT performance in subjects under age 13 was not impaired by a history of concussion, but was positively associated with cognition and balance. 3D-MOT performance in those 13 and older was negatively associated with concussion symptom severity, and positively associated with cognition and balance. 3D-MOT was selectively impaired in subjects with probable post-concussion syndrome (pPCS), defined using the 95th percentile of symptom severity for subjects with no history of concussion. A decision tree predicted concussion status with 95.2% overall test accuracy (91.1% sensitivity, 97.8% specificity) using concussion history, age, and 3D-MOT score. Individuals with a history of concussion in the past 37 days were predicted to have pPCS if they were age 35 or older, or if they were under age 35 but achieved scores below 1.2 on the 3D-MOT. These results demonstrate the potential of 3D-MOT for pPCS diagnosis, and highlight the increased vulnerability to concussion symptoms that comes with age.

CAN-ACN 2021

Multiple object tracking scores predict post-concussion status years after mild traumatic brain injury

concussion

cognition

machine learning

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I am very happy to welcome you to the 14th annual Canadian Neuroscience Meeting, and to the first virtual edition of our meeting. I want to highlight the important work the CAN meeting chair, **Roger Thompson** and co-chair, **Alyson Fournier**, did to put together the great program we are offering this year. Moving to a virtual format required a complete re-design of the program, and both Roger and Alyson did a splendid job in providing us with an appealing and well adapted program for our first virtual event. I wish to thank them for this very important effort.

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14th Canadian Neuroscience Meeting from August 23rd-25th

Our research group has recently reported that nicotine, cocaine, and their conditioned contextual stimuli (CS), enhance object memory consolidation via noradrenergic and dopaminergic receptors. This suggests the hypothesis that the neuropharmacology of unconditioned and conditioned memory modulation is not influenced by drug class. To test the hypothesis, male Sprague-Dailey rats received infusions of the nicotinic receptor antagonist mecamylamine (MEC) within the perirhinal cortex (PRh); a cortical region well known to be involved in consolidation object memory. To establish the drug CSs, rats were confined for 2 h in a chamber (the CS+) after injections of 0.4 mg/kg nicotine or 20 mg/kg cocaine, and in another chamber (the CS−) after injections of vehicle. This was repeated over 10 d (5 drug/CS+ and 5 vehicle/CS− pairings in total). Surprisingly, it was found that the memory enhancing action of post-sample 0.4 mg/kg nicotine, but not 20 mg/kg cocaine, was blocked by intra-PRh infusions of 10 and 30 μg/side MEC. Moreover, the memory enhancing effects of the nicotine CS, but not cocaine CS, were also blocked by 30 μg/side MEC. Overall, these data indicate that a nicotine CS promotes memory consolidation by enhancing PRh cholinergic activity similar to the central effects of nicotine itself, but this is not the case for cocaine and cocaine CSs. These results suggest that in addition to mimicking the behavioural effects of drugs, drug CSs also possess the ability to mimic the neurochemical effects of the drugs themselves on object memory consolidation. Supported by NSERC.

Role of nicotinic receptors in the perirhinal cortex in memory modulation by nicotine, cocaine, and their conditioned stimuli

Functional Magnetic Resonance Imaging (fMRI) and functional Near Infrared Spectroscopy (fNIRS) are neuroimaging techniques that can measure changes in blood flow in response to external stimuli. fNIRS is a portable imaging device and considered to be the optical equivalent of fMRI. The objective of this preliminary work is to investigate the ability of fNIRS to detect brain activity during a median nerve stimulation task in healthy controls and to compare the results to fMRI findings. To date, 25 healthy controls have been recruited to the fMRI task, of which 10 have also participated in the fNIRS task. Median nerve stimulation was conducted while brain activity was recorded with fMRI and fNIRS (tests done sequentially). Both the left and right hand were stimulated, successively, at a current that sustained thumb abduction (8-35 mA). A block design with eight cycles of stimulation 'on' and seven cycles of 'rest' was used. At the group level, for both fMRI and fNIRS, significant brain activity was observed in the contralateral primary and bilateral secondary somatosensory areas for each hand being stimulated. At the single subject level, the results demonstrate an 80% agreement between fMRI and fNIRS results where fMRI is considered ground truth. The overall good agreement between the two techniques is promising, and future work will focus on recruiting additional participants to better assess the sensitivity between modalities. Ultimately, this work adds to the growing body of research highlighting fNIRS as a suitable alternative to fMRI, as it affords the advantage of being portable and low-cost to maintain.

A quantitative comparison of fMRI and fNIRS activity to a median nerve stimulation task

The role of the hippocampus in representing space is widely supported. Neurons that increase their firing rate when an animal occupies a certain region, 'Place Cells,' have been thoroughly identified and studied in multiple species. This unique population of neurons has been thought to support a cognitive-map like representation of space in the brain; however, little is known about how these representations are formed in the common marmoset during free navigation in a 3D environment. Moreover, whether these representations are modulated by spatial view or movement kinematic has yet to be determined. In this work, we sought to identify the firing properties of neurons in the CA fields of the hippocampus while we register spatial and view information of freely navigating marmosets as they engage in a variety of foraging behaviors in 3D space. For this purpose, we habituated the experimental subjects to freely move inside a plexiglass recording chamber with four vertical levels while wearing affixed infrared reflective markers on top of skull implants that allowed for 6 degrees of freedom position and head direction camera tracking (Optitrack, Natural Point Inc, USA). Using MRI-guided neuro-navigation techniques, we chronically implanted 32ch microwire arrays in the hippocampus, and we were able to record single-unit activity during the aforementioned behaviors wirelessly. We analyzed data from 2 animals; spatial view and occupancy rate maps were constructed using 20cm3 bins. Spatial Information Content (SIC) was calculated independently for place and view for 200 total cells. SIC was higher for the spatial view than body position. We also found cells whose firing rate was highly correlated for both body velocity and head angular velocity.

Representation of 3D space in the hippocampus of freely moving marmosets

While the SARS-CoV-2 virus is well known for its impact on the respiratory system, neurological symptoms such as headache, anosmia, and cognitive impairments have been observed. Most strikingly, anosmia is reported in around 50% of COVID-19 cases. Male golden hamsters are used to study the outcomes of SARS-CoV-2 infection and therefore may also be used to model the neurological and behavioural effects of following virus challenge. To this end, we are developing a behavioural battery that could easily be run by any scientific group in containment level 3 to assess behavioral changes in hamsters following SARS-CoV-2 infection. All tasks rely on rodents' innate preference for novelty and are conducted without extensive training or rule learning. Briefly, hamsters are exposed to two copies of a stimulus (odour or object) in a training trial. Following a brief delay, the hamsters are re-exposed to a third copy of the now familiar stimulus, and a novel stimulus. Results indicate that hamsters show a preference for novel odours; however, they are unable to perform the object-based task. In a sociability task, male hamsters were found to preferentially explore a novel hamster more than a novel object, as well as discriminate between a novel and familiar hamster in a similar paradigm. Experiments to refine these tasks are ongoing, with a goal of incorporating them into SARS-CoV-2 vaccine trials at the Vaccine and Infectious Disease Organization/Intervac in the fall of 2021.

Development of spontaneous tests of olfactory, object, and social discrimination behaviour in male golden hamsters: use in rodent models of SARS-CoV-2 infection?

Perineuronal nets (PNNs) are extracellular matrices that preferentially surround parvalbumin-positive (PV+) interneurons. Since PV+ neurons shape neural dynamics and plasticity, PNNs surrounding PV+ neurons have been proposed to regulate neural function. Much of the research on PNNs has centered on their role in sensory circuits, and little is known about how PNNs in sensorimotor structures affect behavioral expression. Here, we analyze the relationship between PNN and PV expression in sensorimotor systems and vocal performance in songbirds. Because songbirds, like humans, learn their vocalizations and use auditory feedback for vocal learning and control, songbirds are powerful animal models to reveal neural mechanisms of sensorimotor plasticity and function. We specifically relate PNN expression around PV+ neurons in forebrain and basal ganglia circuitry to the performance of learned vocalizations in the zebra finch. We hypothesize that, just as PNNs in sensory processing areas consolidate the sensory representations, PNNs in sensorimotor structures could consolidate sensorimotor commands for vocalizations. In this respect, we propose that more PV+ neurons are surrounded by PNNs in birds that produce more stereotyped vocalizations. Given that developmental exposure to song and age affect song stereotypy, we investigate this relationship in juvenile and adult birds that are either reared normally or deprived of song exposure throughout development. Our studies hope to provide further insight into the influence of PNNs on behavioral control and plasticity.

Investigating the influence of perineuronal nets surrounding parvalbumin-positive neurons in sensorimotor circuitry on motor performance

With the recent legalization of cannabis in Canada, there is concern that its use may perpetuate negative outcomes in mental health and impact executive brain functions like working memory (WM). The endocannabinoid (eCB) system regulates the homeostasis of the circuitry underlying memory processes. We were interested in investigating the effects of acute cannabis smoke (Mohawk strain, high-THC; Treasure Island strain, low-THC) exposure on adult male Long-Evans rats' WM capacity. We used a validated object paradigm to evaluate visuospatial WM capacity. Then, we developed a novel odour-based paradigm for assessing olfactory WM capacity as it is rodents' primary sense. An identical (IOT) and differential (DOT) version of the paradigms allowed us to evaluate various cognitive loads on WM capacity using 3 and 6 items. The spontaneous WM tasks used capitalize on rodents' innate preference for novelty and the time spent exploring familiar stimuli in the sample phase, and novel stimuli introduced in the test phase, was analyzed. In both the object and odour paradigms, a load-dependent effect on memory was found whereby more stimuli notably decreased WM function in the DOT, but not IOT, versions. Following acute smoke exposure, no overall disruption in WM function was observed in the object paradigm. However, WM deficits were observed in the odour paradigm after acute exposure to Mohawk, but not Treasure Island, smoke in both the IOT and DOT task. Due to this olfaction-based WM disruption, the task shows promise to model the cognitive impacts of cannabis consumption in humans.

Use of spontaneous object- and odour-based working memory (WM) tasks to evaluate the effects of acute cannabis smoke exposure on WM capacity in male rats

It has been hypothesized that cell assemblies represent mental or perceptual entities, forming the basis of neural coding and computation. We investigated how the number of cell assemblies was related to the age of the rats and spontaneous remapping, using unit recordings of CA1 pyramidal cells in six young and six old rats while they learned a place-dependent eyeblink conditioning task (Schimanski et al., 2013). To control the dependence of cell assembly detection on different number of recorded neurons, we selected 30 pyramidal cells randomly from each recording session and repeated the procedure 25 times. This generated >8000 data sets. The number of cell assemblies was estimated by a recently proposed method (Russo and Durstewitz, 2017). We found that young rats had significantly more cell assemblies than old ones (median for young = 166.7, median for old = 87.4, Mann-Whitney test, p = 3.1 x 10-8). Significantly more cell assemblies were also detected in non-remapping rats than remapping ones (median for non-remapping = 192.1, median for remapping = 90.9, Mann-Whitney test, p = 8.4 x 10-13). Interestingly, cell assemblies were most abundant in the first few days of recording if rats were grouped into non-remapping, young or old, but not in remapping. Taken together, we showed that significantly more cell assemblies were detected in young and non-remapping rats. Reduction of cell assemblies over training in non-remapping rats suggests that efficient neural codes may be generated by learning and hence a reduced number of cell assemblies is sufficient.

Hippocampal CA1 network supports more cell assemblies in young and non-remapping rats

Behavioural neuroscience researchers continue to seek relevant rodent paradigms that mimic human patterns of cannabis use. Injected Δ9-tetrahydrocannabinol (THC) is commonly used to assess acute cannabis effects in rodents despite pharmacokinetics varying greatly between injection and inhalation. In addition, tasks used to assess behaviour following cannabis exposure often lack strong translational relevance to human tasks. Therefore, in the present experiment, we investigated cognitive effects of acute exposure to cannabis smoke in two rodent tasks highly translatable to human tasks for measuring working memory, attention, and impulsivity. Male Long-Evans rats were trained in two cognitive tasks using touchscreen-equipped operant conditioning chambers: (1) the trial-unique, delayed nonmatching-to-location (TUNL; n=16); (2) the five-choice serial-reaction time task (5CH; n=16). Trained rats received: (i) combusted cannabis smoke (two strains: Mohawk, high-THC; Treasure Island: low-THC) using a 4-chamber pump-driven system; or (ii) injected THC (3.0mg/kg; i.p.) and behaviour was immediately assessed on the tasks. Interestingly, we failed to observe any effects of cannabis smoke on performance of TUNL or 5CH; however, injected THC significantly reduced accuracy and number of trials completed during TUNL, plus a notable (albeit insignificant) increase in omissions during 5CH. These data support a growing literature showing distinct differences between cannabis strain and method of administration, highlighting a continued need to investigate cannabinoid effects on cognition.

Effects of smoked cannabis and injected Δ9-tetrahydrocannabinol on touchscreen-based tasks for measuring working memory, attention, and impulsivity in male Long Evans rats

The functioning of timbre and other form-bearing dimensions in music depends on the acoustic generation of sound, as well as physiological responses and the psychological organization of the information carried by sound. Human hearing can be reshaped by individual experience and can even be affected by cultural circumstances. To understand how hearing loss can affect the perception of timbre, we adopted noise maskers of varying kinds into a one-interval 2AFC task measuring the performance of timbre identification. Stimuli were presented using participant's personal laptop over headphones/earphones. In each trial, either a 300-ms trumpet or clarinet note at 440-Hz fundamental (target) with the same pitch was embedded in the middle of a 1-second Gaussian noise (masker). Three types of noise were used: broad-band noise, low-pass noise filtered at 4 kHz, and band-pass noise filtered between 5 kHz and 9 kHz. The target was fixed at one sound level, while the maskers of each kind were attenuated to 3 different levels. Our preliminary results show that (1) performance on the timbre identification task can be undermined by increasing the masker level and (2) noise maskers through a low-pass filter are as effective as broadband noise maskers but not those through a band-pass filter, suggesting that lower frequencies contribute more to identification. In future studies, we will further refine the composition of the noise masker, in both spectral and temporal domains, to explore how acoustic features contribute to timbre perception.

Identification of musical instrument sounds under noise masking

The cortical mechanisms for presaccadic signal processing remain poorly understood at the network level, in particular how they interact with simultaneously presented visual stimuli. Here, we used graph theory analysis (GTA) to construct and evaluate functional brain networks based on EEG data collected in the perisaccadic interval. EEG was recorded via 64 channels in two behavioral conditions (fixation or saccade). Participants (N=21) were pre-cued with a series 1-3 grids (three horizontal lines, 10° by 10°) located 5° below the central fixation-point. 100ms later, a stimulus (three vertical lines; same size/location) was briefly presented (for 70ms). In the saccade condition, a left/right shift of the fixation-point during the interstimulus interval triggered a saccade after the second stimulus. Source localization (SL) was performed on the 200ms period following the saccade cue, or the equivalent time during fixation trials. Lagged coherences were calculated between all pairs of 84 Brodmann areas. SL/GTA identified major network hubs near the frontal and parietal eye fields, with widespread cortical connectivity. Other GTA measures (clustering coefficient, global efficiency, energy, entropy) showed that network segregation, integration, synchronizability, and complexity were enhanced during the perisaccadic interval. Further, these network properties significantly interacted with stimulus repetition, altering both hubs and network topography. These data suggest a network mechanism for enhanced visual information processing and propagation in the presaccadic interval. Acknowledgements: Grant Support: an NSERC Discovery Grant and VISTA Fellowship, funded by CFREF.

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