Decoding cerebro-spinal signatures of human behavior: Application to motor sequence learning.

Mapping the neural patterns that drive human behavior is a key challenge in neuroscience. Even the simplest of our everyday actions stem from the dynamic and complex interplay of multiple neural structures across the central nervous system (CNS). Yet, most neuroimaging research has focused on investigating cerebral mechanisms, while the way the spinal cord accompanies the brain in shaping human behavior has been largely overlooked. Although the recent advent of functional magnetic resonance imaging (fMRI) sequences that can simultaneously target the brain and spinal cord has opened up new avenues for studying these mechanisms at multiple levels of the CNS, research to date has been limited to inferential univariate techniques that cannot fully unveil the intricacies of the underlying neural states. To address this, we propose to go beyond traditional analyses and instead use a data-driven multivariate approach leveraging the dynamic content of cerebro-spinal signals using innovation-driven coactivation patterns (iCAPs). We demonstrate the relevance of this approach in a simultaneous brain-spinal cord fMRI dataset acquired during motor sequence learning (MSL), to highlight how large-scale CNS plasticity underpins rapid improvements in early skill acquisition and slower consolidation after extended practice. Specifically, we uncovered cortical, subcortical and spinal functional networks, which were used to decode the different stages of learning with a high accuracy and, thus, delineate meaningful cerebro-spinal signatures of learning progression. Our results provide compelling evidence that the dynamics of neural signals, paired with a data-driven approach, can be used to disentangle the modular organization of the CNS. While we outline the potential of this framework to probe the neural correlates of motor learning, its versatility makes it broadly applicable to explore the functioning of cerebro-spinal networks in other experimental or pathological conditions.

Early stages of sensorimotor map acquisition: neurochemical signature in primary motor cortex and its relation to functional connectivity.

The earliest stages of sensorimotor learning involve learning the correspondence between movements and sensory results-a sensorimotor map. The present exploratory study investigated the neurochemical underpinnings of map acquisition by monitoring 25 participants as they acquired a new association between movements and sounds. Functional magnetic resonance spectroscopy was used to measure neurochemical concentrations in the left primary motor cortex during learning. Resting-state functional magnetic resonance imaging data were also collected before and after training to assess learning-related changes in functional connectivity. There were monotonic increases in γ-aminobutyric acid (GABA) and decreases in glucose during training, which extended into the subsequent rest period and, importantly, in the case of GABA correlated with the amount of learning: participants who showed greater behavioral learning showed greater GABA increase. The GABA change was furthermore correlated with changes in functional connectivity between the primary motor cortex and a cluster of voxels in the right intraparietal sulcus: greater increases in GABA were associated with greater strengthening of connectivity. Transiently, there were increases in lactate and reductions in aspartate, which returned to baseline at the end of training, but only lactate showed a statistical trend to correlate with the amount of learning. In summary, during the earliest stages of sensorimotor learning, GABA levels are linked on a subject-level basis to both behavioral learning and a strengthening of functional connections that persists beyond the training period. The findings are consistent with the idea that GABA-mediated inhibition is linked to maintenance of newly learned information.NEW & NOTEWORTHY Learning the mapping between movements and their sensory effects is a necessary step in the early stages of sensorimotor learning. There is evidence showing which brain areas are involved in early motor learning, but their role remains uncertain. Here, we show that GABA, a neurotransmitter linked to inhibitory processing, rises during and after learning and is involved in ongoing changes in resting-state networks.

Brown tumor of the iliac crest initially misdiagnosed as a giant cell tumor of the bone.

SUMMARY: Brown tumors (BTs) are expansile osteolytic lesions complicating severe primary hyperparathyroidism (PHPT). Clinical, radiological and histological features of BTs share many similarities with other giant cell-containing lesions of the bone, which can make their diagnosis challenging. We report the case of a 32-year-old man in whom an aggressive osteolytic lesion of the iliac crest was initially diagnosed as a giant cell tumor by biopsy. The patient was scheduled for surgical curettage, with a course of neoadjuvant denosumab. Routine biochemical workup prior to denosumab administration incidentally revealed high serum calcium levels. The patient was diagnosed with PHPT and a parathyroid adenoma was identified. In light of these findings, histological slices of the iliac lesion were reviewed and diagnosis of a BT was confirmed. Follow-up CT-scans performed 2 and 7 months after parathyroidectomy showed regression and re-ossification of the bone lesion. The aim of this case report is to underline the importance of distinguishing BTs from other giant cell-containing lesions of the bone and to highlight the relevance of measuring serum calcium as part of the initial evaluation of osteolytic bone lesions. This can have a major impact on patients' management and can prevent unnecessary invasive surgical interventions. LEARNING POINTS: Although rare, brown tumors should always be considered in the differential diagnosis of osteolytic giant cell-containing bone lesions. Among giant cell-containing lesions of the bone, the main differential diagnoses of brown tumors are giant cell tumors and aneurysmal bone cysts. Clinical, radiological and histological characteristics can be non-discriminating between brown tumors and giant cell tumors. One of the best ways to distinguish these two diagnoses appears to be through biochemical workup. Differentiating brown tumors from giant cell tumors and aneurysmal bone cysts is crucial in order to ensure better patient care and prevent unnecessary morbid surgical interventions.

The use of dorsal distraction plating for severely comminuted distal radius fractures: A review and comparison to volar plate fixation.

INTRODUCTION: Optimal fixation for highly comminuted distal radius fractures remains a major treatment challenge for orthopaedic surgeons. Dorsal distraction plating can serve as an improved fixation technique by allowing reduction under ligamentotaxis, providing a dorsal buttress, addressing proximal comminution, and allowing for early weightbearing in polytrauma patients. The aim of this study was to review current literature regarding treatment of distal radius fractures treated with dorsal distraction plating. METHODS: We performed a literature search in Pubmed and EMBASE databases to identify all studies analyzing use of dorsal distraction plating. Case reports, biomechanical and anatomic cadaver studies were excluded from analysis. Primary outcome measures were range of motion (ROM) at final follow up, grip strength, and radiographic parameters. RESULTS: Eight studies were included in the final analysis. Pooled mean ROM after dorsal distraction plating was found to be 47.6° of flexion, 50.5° of extension, 76.0° of pronation, and 74.2° of supination. Pooled mean grip strength was 79.1% compared to the uninjured contralateral limb. Pooled mean volar tilt was 3.6°. Overall radial height was maintained at an average of 10.5 mm with a pooled mean loss of only 3.8 mm in length. Mean radial inclination was found to be 19.4 mm with patients having a mean ulnar variance of 0.5 mm. DISCUSSION & CONCLUSION: Treatment of comminuted intra-articular distal radius fractures with dorsal distraction plating yielded excellent outcomes with very low complication rates, and has several advantages over volar plating and/or external fixation for these fractures. Necessity of plate removal remains a negative feature of this technique.

Influence of aerobic exercise training on the neural correlates of motor learning in Parkinson's disease individuals.

BACKGROUND: Aerobic exercise training (AET) has been shown to provide general health benefits, and to improve motor behaviours in particular, in individuals with Parkinson's disease (PD). However, the influence of AET on their motor learning capacities, as well as the change in neural substrates mediating this effect remains to be explored. OBJECTIVE: In the current study, we employed functional Magnetic Resonance Imaging (fMRI) to assess the effect of a 3-month AET program on the neural correlates of implicit motor sequence learning (MSL). METHODS: 20 healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+ 5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after the AET program, participants' brain was scanned while performing an implicit version of the serial reaction time task. RESULTS: Brain data revealed pre-post MSL-related increases in functional activity in the hippocampus, striatum and cerebellum in PD patients, as well as in the striatum in HC individuals. Importantly, the functional brain changes in PD individuals correlated with changes in aerobic fitness: a positive relationship was found with increased activity in the hippocampus and striatum, while a negative relationship was observed with the cerebellar activity. CONCLUSION: Our results reveal, for the first time, that exercise training produces functional changes in known motor learning related brain structures that are consistent with improved behavioural performance observed in PD patients. As such, AET can be a valuable non-pharmacological intervention to promote, not only physical fitness in early PD, but also better motor learning capacity useful in day-to-day activities through increased plasticity in motor related structures.

Multisession Anodal tDCS Protocol Improves Motor System Function in an Aging Population.

OBJECTIVES: The primary objective of this study was to investigate the effects of five consecutive, daily 20-minute sessions of M1 a-tDCS on motor learning in healthy, cognitively intact, aging adults. DESIGN: A total of 23 participants (51 to 69 years old) performed five consecutive, daily 20-minute sessions of a serial reaction time task (SRT task) concomitant with either anodal (n = 12) or sham (n = 11) M1 a-tDCS. RESULTS: We found a significant group × training sessions interaction, indicating that whereas aging adults in the sham group exhibited little-to-no sequence-specific learning improvements beyond the first day of training, reproducible improvements in the ability to learn new motor sequences over 5 consecutive sessions were the net result in age-equivalent participants from the M1 a-tDCS group. A significant main effect of group on sequence-specific learning revealed greater motor learning for the M1 a-tDCS group when the five learning sessions were averaged. CONCLUSION: These findings raise into prominence the utility of multisession anodal TDCS protocols in combination with motor training to help prevent/alleviate age-associated motor function decline.

Enhancing both motor and cognitive functioning in Parkinson's disease: Aerobic exercise as a rehabilitative intervention.

BACKGROUND: Aerobic exercise training (AET) has been shown to provide health benefits in individuals with Parkinson's disease (PD). However, it is yet unknown to what extent AET also improves cognitive and procedural learning capacities, which ensure an optimal daily functioning. OBJECTIVE: In the current study, we assessed the effects of a 3-month AET program on executive functions (EF), implicit motor sequence learning (MSL) capacity, as well as on different health-related outcome indicators. METHODS: Twenty healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike-training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after AET, EF tests assessed participants' inhibition and flexibility functions, whereas implicit MSL capacity was evaluated using a version of the Serial Reaction Time Task. RESULTS: The AET program was effective as indicated by significant improvement in aerobic capacity in all participants. Most importantly, AET improved inhibition but not flexibility, and motor learning skill, in both groups. CONCLUSION: Our results suggest that AET can be a valuable non-pharmacological intervention to promote physical fitness in early PD, but also better cognitive and procedural functioning.

Increased cortico-striatal connectivity during motor practice contributes to the consolidation of motor memory in writer's cramp patients.

Sensorimotor representations of movements are created in the sensorimotor network through repeated practice to support successful and effortless performance. Writer's cramp (WC) is a disorder acquired through extensive practice of finger movements, and it is likely associated with the abnormal acquisition of sensorimotor representations. We investigated (i) the activation and connectivity changes in the brain network supporting the acquisition of sensorimotor representations of finger sequences in patients with WC and (ii) the link between these changes and consolidation of motor performance 24 h after the initial practice. Twenty-two patients with WC and 22 age-matched healthy volunteers practiced a complex sequence with the right (pathological) hand during functional MRI recording. Speed and accuracy were measured immediately before and after practice (day 1) and 24 h after practice (day 2). The two groups reached equivalent motor performance on day 1 and day 2. During motor practice, patients with WC had (i) reduced hippocampal activation and hippocampal-striatal functional connectivity; and (ii) overactivation of premotor-striatal areas, whose connectivity correlated with motor performance after consolidation. These results suggest that patients with WC use alternative networks to reach equiperformance in the acquisition of new motor memories.

Speech acquisition predicts regions of enhanced cortical response to auditory stimulation in autism spectrum individuals.

A continuum of phenotypes makes up the autism spectrum (AS). In particular, individuals show large differences in language acquisition, ranging from precocious speech to severe speech onset delay. However, the neurological origin of this heterogeneity remains unknown. Here, we sought to determine whether AS individuals differing in speech acquisition show different cortical responses to auditory stimulation and morphometric brain differences. Whole-brain activity following exposure to non-social sounds was investigated. Individuals in the AS were classified according to the presence or absence of Speech Onset Delay (AS-SOD and AS-NoSOD, respectively) and were compared with IQ-matched typically developing individuals (TYP). AS-NoSOD participants displayed greater task-related activity than TYP in the inferior frontal gyrus and peri-auditory middle and superior temporal gyri, which are associated with language processing. Conversely, the AS-SOD group only showed enhanced activity in the vicinity of the auditory cortex. We detected no differences in brain structure between groups. This is the first study to demonstrate the existence of differences in functional brain activity between AS individuals divided according to their pattern of speech development. These findings support the Trigger-threshold-target model and indicate that the occurrence of speech onset delay in AS individuals depends on the location of cortical functional reallocation, which favors perception in AS-SOD and language in AS-NoSOD.

Host behaviour manipulation as an evolutionary route towards attenuation of parasitoid virulence.

By definition, insect parasitoids kill their host during their development. Data are presented showing that ladybirds not only can survive parasitism by Dinocampus coccinellae, but also can retain their capacity to reproduce following parasitoid emergence. We hypothesize that host behaviour manipulation constitutes a preadaptation leading to the attenuation of parasitoid virulence. Following larval development, the parasitoid egresses from the host and spins a cocoon between the ladybird's legs. Throughout parasitoid pupation, the manipulated host acts as a bodyguard to protect the parasitoid cocoon from predation. The parasitoid has evolved mechanisms to avoid killing the host prematurely so that its own survival is not compromised. Bodyguard manipulation may thus constitute a selective trait for the evolution of true parasitism in some host-parasitoid associations.

Prey DNA detection success following digestion by intraguild predators: influence of prey and predator species.

Intraguild predation (IGP) has been increasingly recognized as an important interaction in ecological systems over the past two decades, and remarkable insights have been gained into its nature and prevalence. We have developed a technique using molecular gut-content analysis to compare the rate of IGP between closely related species of coccinellid beetles (lady beetles or ladybirds), which had been previously known to prey upon one another. We first developed PCR primers for each of four lady beetle species: Harmonia axyridis, Coccinella septempunctata, Coleomegilla maculata and Propylea quatuordecimpunctata. We next determined the prey DNA detection success over time (DS(50) ) for each combination of interacting species following a meal. We found that DS(50) values varied greatly between predator-prey combinations, ranging from 5.2 to 19.3 h. As a result, general patterns of detection times based upon predator or prey species alone are not discernable. We used the DS(50) values to correct field data to demonstrate the importance of compensation for detection times that are specific to particular predator-prey combinations.

Functional neuroanatomy associated with the expression of distinct movement kinematics in motor sequence learning.

A broad range of motor skills, such as speech and writing, evolves with the ability to articulate elementary motor movements into novel sequences that come to be performed smoothly through practice. Neuroimaging studies in humans have demonstrated the involvement of the cerebello-cortical and striato-cortical motor loops in the course of motor sequence learning. Nonetheless, the nature of the improvement and brain mechanisms underlying different parameters of movement kinematics are not yet fully ascertained. We aimed at dissociating the cerebral substrates related to the increase in performance on two kinematic indices: velocity, that is the speed with which each single movement in the sequence is produced, and transitions, that is the duration of the gap between these individual movements. In this event-related fMRI experiment, participants practiced an eight-element sequence of finger presses on a keypad which allowed to record those kinematic movement parameters. Velocity was associated with activations in the ipsilateral spinocerebellum (lobules 4-5, 8 and medial lobule 6) and in the contralateral primary motor cortex. Transitions were associated with increased activity in the neocerebellum (lobules 6 bilaterally and lobule 4-5 ipsilaterally), as well as with activations within the right and left putamen and a broader bilateral network of motor cortical areas. These findings indicate that, rather than being the product of a single mechanism, the general improvement in motor performance associated with early motor sequence learning arises from at least two distinct kinematic processes, whose behavioral expressions are supported by partially overlapping and segregated brain networks.

Fast and slow spindle involvement in the consolidation of a new motor sequence.

This study aimed to determine the distinct contribution of slow (11-13 Hz) and fast (13-15 Hz) spindles in the consolidation process of a motor sequence learning task (MSL). Young subjects (n = 12) were trained on both a finger MSL task and a control (CTRL) condition, which were administered one week apart in a counterbalanced order. Subjects were asked to practice the MSL or CTRL task in the evening (approximately 9:00 p.m.) and their performance was retested on the same task 12h later (approximately 9:00 a.m.). Polysomnographic (PSG) recordings were performed during the night following training on either task, and an automatic algorithm was used to detect fast and slow spindles and to quantify their characteristics (i.e., density, amplitude, and duration). Statistical analyses revealed higher fast (but not slow) spindle density after training on the MSL than after practice of the CTRL task. The increase in fast spindle density on the MSL task correlated positively with overnight performance gains on the MSL task and with difference in performance gain between the MSL and CTRL tasks. Together, these results suggest that fast sleep spindles help activate the cerebral network involved in overnight MSL consolidation, while slow spindles do not appear to play a role in this mnemonic process.

Perspectives of Canadian researchers on ethics review of neuroimaging research.

The current and potential uses of neuroimaging in healthcare and beyond have spurred discussion about the ethical issues related to neuroimaging and neuroimaging research. This study examined the perspectives of neuroimagers on ethical issues in their research and on the ethics review process. One hundred neuroimagers from 13 Canadian neuroscience centers completed an online survey and 35 semi-structured interviews were conducted. Neuroimagers felt that most ethical and social issues identified in the literature were dealt with adequately, well, and even very well by research ethics boards (REBs), but some issues such as incidental findings and transfer of knowledge were problematic. Neuroimagers reported a range of practical problems in the ethics review process. We aimed to gather perspectives from REB on the ethics review process, but insufficient participation by REBs prevented us from reporting their perspectives. Given shortcomings identified by neuroimagers as well as longstanding issues in Canadian ethics governance, we believe that substantial challenges exist in Canadian research ethics governance that jeopardize trust, communication, and the overall soundness of research ethics governance. Neuroimagers and REBs should consider their shared responsibilities in developing guidance to handle issues such as incidental findings, risk assessment, and knowledge transfer.

Effect of motor imagery in the rehabilitation of burn patients.

Although there is ample evidence that motor imagery (MI) improves motor performance after CNS injury, it is still unknown whether MI may enhance motor recovery after peripheral injury and most especially in the rehabilitation of burn patients. This study aimed to investigate the effects of a 2-week MI training program combined with conventional rehabilitation on the recovery of motor functions in handed burn patients. Fourteen patients admitted to the Medical Burn Center were requested to take part in the study and were randomly assigned to the imagery or the control group. Behavioral data related to the ability to perform each successive step of three manual motor sequences were collected at five intervals during the medical procedure. The results provided evidence that MI may facilitate motor recovery, and the belief in the effectiveness of MI was strong in all patients. MI may substantially contribute to improve the efficacy of conventional rehabilitation programs. Hence, this technique should be considered as a reliable alternative method to help burn patients to recover motor functions.

Investigations on spinal cord fMRI of cats under ketamine.

Functional magnetic resonance imaging (fMRI) of the spinal cord has been the subject of intense research for the last ten years. An important motivation for this technique is its ability to detect non-invasively neuronal activity in the spinal cord related to sensorimotor functions in various conditions, such as after spinal cord lesions. Although promising results of spinal cord fMRI have arisen from previous studies, the poor reproducibility of BOLD activations and their characteristics remain a major drawback. In the present study we investigated the reproducibility of BOLD fMRI in the spinal cord of cats (N=9) by repeating the same stimulation protocol over a long period (approximately 2 h). Cats were anaesthetized with ketamine, and spinal cord activity was induced by electrical stimulation of cutaneous nerves of the hind limbs. As a result, task-related signals were detected in most cats with relatively good spatial specificity. However, BOLD response significantly varied within and between cats. This variability was notably attributed to the moderate intensity of the stimulus producing a low amplitude haemodynamic response, variation in end-tidal CO(2) during the session, low signal-to-noise ratio (SNR) in spinal fMRI time series and animal-specific vascular anatomy. Original contributions of the present study are: (i) first spinal fMRI experiment in ketamine-anaesthetized animals, (ii) extensive study of intra- and inter-subject variability of activation, (iii) characterisation of static and temporal SNR in the spinal cord and (iv) investigation on the impact of CO(2) end-tidal level on the amplitude of BOLD response.

Large-scale neural model validation of partial correlation analysis for effective connectivity investigation in functional MRI.

Recent studies of functional connectivity based upon blood oxygen level dependent functional magnetic resonance imaging have shown that this technique allows one to investigate large-scale functional brain networks. In a previous study, we advocated that data-driven measures of effective connectivity should be developed to bridge the gap between functional and effective connectivity. To attain this goal, we proposed a novel approach based on the partial correlation matrix. In this study, we further validate the use of partial correlation analysis by employing a large-scale, neurobiologically realistic neural network model to generate simulated data that we analyze with both structural equation modeling (SEM) and the partial correlation approach. Unlike real experimental data, where the interregional anatomical links are not necessarily known, the links between the nodes of the network model are fully specified, and thus provide a standard against which to judge the results of SEM and partial correlation analyses. Our results show that partial correlation analysis from the data alone exhibits patterns of effective connectivity that are similar to those found using SEM, and both are in agreement with respect to the underlying neuroarchitecture. Our findings thus provide a strong validation for the partial correlation method.

Neural substrates of cognitive skill learning in Parkinson's disease.

While cognitive skill learning is normally acquired implicitly through frontostriatal circuitry in healthy individuals, neuroimaging studies suggest that patients with Parkinson's disease (PD) do so by activating alternate, intact brain areas associated with explicit memory processing. To further test this hypothesis, 10 patients with PD and 12 healthy controls were tested on a modified, learning version of the Tower of London task while undergoing positron emission tomography at four different time points over the course of learning. Despite having less accurate problem solving abilities than controls, PD patients were able to acquire the skill learning task. However, as compared to controls, they maintained higher levels of cerebral blood flow activity in the dorsolateral prefrontal cortex and hippocampus and showed an increase in activity in the frontopolar cortex and posterior cingulate over the course of learning. These findings reflect a shift to the explicit memory system in PD patients, enabling them to learn this cognitive skill, which is normally acquired by control subjects using implicit learning strategies and frontostriatal circuitry.

REM sleep behavior disorder predicts cognitive impairment in Parkinson disease without dementia.

OBJECTIVE: To assess the relationship between the presence of REM sleep behavior disorder (RBD) and the cognitive profile of nondemented patients with Parkinson disease (PD). BACKGROUND: Cognitive impairment is an important nonmotor symptom in PD. Waking EEG slowing in nondemented PD has been related to the presence of RBD, a parasomnia affecting brainstem structures and frequently reported in PD. For this reason, RBD may be associated with cognitive impairment in PD. METHODS: Thirty-four patients with PD (18 patients with polysomnographic-confirmed RBD and 16 patients without RBD) and 25 healthy control subjects matched for age and educational level underwent sleep laboratory recordings and a comprehensive neuropsychological assessment. RESULTS: Patients with PD and concomitant RBD showed significantly poorer performance on standardized tests measuring episodic verbal memory, executive functions, as well as visuospatial and visuoperceptual processing compared to both patients with PD without RBD and control subjects. Patients with PD without RBD had no detectable cognitive impairment compared to controls. CONCLUSIONS: This study shows that cognitive impairment in nondemented patients with Parkinson disease (PD) is closely related to the presence of REM sleep behavior disorder, a sleep disturbance that was not controlled for in previous studies assessing cognitive deficits in PD.

Activation detection in diffuse optical imaging by means of the general linear model.

Due to its non-invasive nature and low cost, diffuse optical imaging (DOI) is becoming a commonly used technique to assess functional activation in the brain. When imaging with DOI, two major issues arise in the data analysis: (i) the separation of noise of physiological origin and the recovery of the functional response; (ii) the tomographic image reconstruction problem. This paper focuses on the first issue. Although the general linear model (GLM) has been extensively used in functional magnetic resonance imaging (fMRI), DOI has mostly relied on filtering and averaging of raw data to recover brain functional activation. This is mainly due to the high temporal resolution of DOI which implies a new design of the drift basis modelling physiology. In this paper, we provide (i) a filtering method based on cosine functions that is more adapted than standard averaging techniques for DOI specifically; (ii) a new mode-locking technique to recover small signals and locate them temporally with high precision (shift method). Results on real data show the capability of the shift method to retrieve HbR and HbO(2) peak locations.