Motor Activity Research Articles

Miniature battery-free epidural cortical stimulators.

Miniaturized neuromodulation systems could improve the safety and reduce the invasiveness of bioelectronic neuromodulation. However, as implantable bioelectronic devices are made smaller, it becomes difficult to store enough power for long-term operation in batteries. Here, we present a battery-free epidural cortical stimulator that is only 9 millimeters in width yet can safely receive enough wireless power using magnetoelectric antennas to deliver 14.5-volt stimulation bursts, which enables it to stimulate cortical activity on-demand through the dura. The device has digitally programmable stimulation output and centimeter-scale alignment tolerances when powered by an external transmitter. We demonstrate that this device has enough power and reliability for real-world operation by showing acute motor cortex activation in human patients and reliable chronic motor cortex activation for 30 days in a porcine model. This platform opens the possibility of simple surgical procedures for precise neuromodulation.

Intravenous administration of recombinant Phα1β: Antinociceptive properties and morphine tolerance reversal in a cancer-associated pain model

Cancer-related pain is considered one of the most prevalent symptoms for those affected by cancer, significantly influencing quality of life and treatment outcomes. Morphine is currently employed for analgesic treatment in this case, however, chronic use of this opioid is limited by the development of analgesic tolerance and adverse effects, such as digestive and neurological disorders. Alternative therapies, such as ion channel blockade, are explored. The toxin Phα1β has demonstrated efficacy in blocking calcium channels, making it a potential candidate for alleviating cancer-related pain. This study aims to assess the antinociceptive effects resulting from intravenous administration of the recombinant form of Phα1β (r-Phα1β) in an experimental model of cancer-related pain in mice, tolerant or not to morphine. The model of cancer-induced pain was used to evaluate these effects, with the injection of B16F10 cells, followed by the administration of the r-Phα1β, and evaluation of the mechanical threshold by the von Frey test. Also, adverse effects were assessed using a score scale, the rotarod, and open field tests. Results indicate that the administration of r-Phα1β provoked antinociception in animals with cancer-induced mechanical hyperalgesia, with or without morphine tolerance. Previous administration of r-Phα1β was able to recover the analgesic activity of morphine in animals tolerant to this opioid. r-Phα1β was proved safe for these parameters, as no adverse effects related to motor and behavioral activity were observed following intravenous administration. This study suggests that the concomitant use of morphine and r-Phα1β could be a viable strategy for pain modulation in cancer patients.

Role of Coriolis flow measurement technology in validation of model of syringe driver performance

The development of a flow/pressure measurement system in association with Bronkhorst High-Tech B.V. incorporating a Coriolis flow transducer, provided an opportunity to observe the flow/pressure dynamics of syringe drivers. A model of flow/pressure performance of syringe drivers was established where key variable factors included the compliance of the connected system and the associated line resistance. It was identified that the flow/pressure dynamics observed with the flow measurement system incorporating the Coriolis transducer matched that of the model. In this consideration the dominant compliance contribution related to that of the syringe. The model operates by considering the notional volume change in the residual fluid volume in the syringe with inflow from stepper motor action and outflow in the interval between sequential pulses. While many of the observations in the literature of syringe driver function are qualitative, the model allows a more precise prediction of associated device performance.

Postural balance in the comprehensive rehabilitation of adolescents with cleft lip and palate and maxillofacial anomalies: A literature review

BACKGROUND: Patients with cleft lip and palate experience significant jaw relationship disorders and pathological bite formation, leading to changes in the motor activity of chewing muscles and postural balance disturbances. Most studies on postural control are conducted on patients with skeletal dentofacial anomalies and deformities without cleft lip and palate. The state of postural balance in children with cleft lip and palate requiring long-term complex medical rehabilitation, including bone-reconstructive operations on the jaw bones, remains poorly understood.
 AIM: To analyze publications dedicated to the evaluation of postural balance in adolescents with cleft lip and palate combined with jaw relationship disorders and pathological bite formation.
 MATERIALS AND METHODS: The article includes an analysis and review of several studies that investigated the state of postural balance in adolescents with cleft lip and palate, particularly at the final stages of growth and formation of the musculoskeletal system. Scientific articles published in various medical journals, monographs, dissertations, and materials from scientific symposiums related to this topic were used in the literature review. PubMed, Medline, Scopus, Web of Science, and RSCI were searched without language restrictions. The search depth was 23 years, and 64 studies were selected.
 RESULTS: The article analyzes literature data related to theories of the mechanism of mutual influence between postural balance and the dentofacial apparatus (disorders and pathological bite formation). The state of postural balance is influenced by various factors, including the craniosacral system and anomalies of the cervical spine. Patients with cleft lip and palate, hemifacial microsomia, and other craniofacial dysostoses with growth disorders of jaw bones experience an imbalance in the entire “descending” chain, causing postural disturbances, increased plantar pressure, increased foot rigidity, and changes in photogrammetry indicators, which should be considered when developing an individual rehabilitation program for these patients. The treatment of these patients without considering postural balance disorders can lead to temporomandibular joint pathologies, unstable results of the conservative orthodontic treatment of bite pathologies, and bone-reconstructive operations on jaws.
 CONCLUSIONS: The study highlights the ways of adaptation of the musculoskeletal system in the presence of occlusal relationship disorders and emphasizes the need to evaluate this influence comprehensively for the treatment of these patients. The limitations of the presented studies should be emphasized: insufficient sample size, lack of control groups and prospective studies, limited types of examination, and lack of studies dedicated to more severe anomalies of craniofacial development.

Conduction slowing, conduction block and temporal dispersion in demyelinating, dysmyelinating and axonal neuropathies: Electrophysiology meets pathology.

Nerve conduction studies are usually the first diagnostic step in peripheral nerve disorders and their results are the basis for planning further investigations. However, there are some commonplaces in the interpretation of electrodiagnostic findings in peripheral neuropathies that, although useful in the everyday practice, may be misleading: (1) conduction block and abnormal temporal dispersion are distinctive features of acquired demyelinating disorders; (2) hereditary neuropathies are characterized by uniform slowing of conduction velocity; (3) axonal neuropathies are simply diagnosed by reduced amplitude of motor and sensory nerve action potentials with normal or slightly slow conduction velocity. In this review, we reappraise the occurrence of uniform and non-uniform conduction velocity slowing, conduction block and temporal dispersion in demyelinating, dysmyelinating and axonal neuropathies attempting, with a translational approach, a correlation between electrophysiological and pathological features as derived from sensory nerve biopsy in patients and animal models. Additionally, we provide some hints to navigate in this complex field.

Effect of chronic stress on the degree of acrylamide toxicity in rats

Introduction. Chronic stress plays an important role in the development of a wide range of mental, somatic and behavioural disorders, and therefore is a risk factor for the health in living organisms. A negative effect on the state of the nervous system is also observed when the body is poisoned with acrylamide, which is a substance of the second class of danger and is considered toxic and carcinogenic. Exposure of the body to mental and toxic stressors leads to autonomic and neuroendocrine activation, which, in turn, manifests itself as special behavioural patterns. 
 The purpose of the experiment was to assess the effect of chronic stress on the degree of acrylamide toxicity in rats.
 Materials and methods. The experiment was conducted on white outbred rats with an average weight of 200 g of both sexes (n=60), which were evenly distributed into five groups: negative control, chronic stress, acrylamide, acrylamide + treatment, acrylamide + chronic stress. Throughout the study, the animals were kept under standard conditions with 12 hours of artificial lighting during the day, a relatively constant level of humidity (30–70%) and an air temperature of 20–25 °C. Behavioural tests were conducted once a week for one calendar month using a 40×40 hole board, a multifunctional cage to assess general activity, and an elevated plus maze with an ANY-maze video tracking system. Biochemical parameters were assessed in accordance with the manufacturer’s instructions.
 Results. Analysis of behaviour on a board with holes did not reveal statistically significant results (H=8.987; p=0.061). When comparing vertical and horizontal motor activity between groups, statistically significant differences were found (p<0.05). AST levels were higher in the stress groups, while cholesterol levels in the same groups were lower (p<0.05).
 Limitations. Laboratory animals of only one biological species were used for the experiment. The toxicant was used only in one concentration.
 Conclusion. Chronic stress may influence on acrylamide toxicity in rats to a certain extent.

Integrative function of proprioceptive system in the acute effects of whole body vibration on the movement performance in young adults.

The proprioceptive system coordinates locomotion, but its role in short-term integration and recovery of motor activity in imbalance of motor patterns and body remains debated. The aim of this study is investigating the functional role of proprioceptive system in motor patterns and body balance in healthy young adults. 70 participants (aged 20.1 ± 0.3) were divided into experimental groups EG1 (n = 30), EG2 (n = 30), control group (CG, n = 10). EG1 performed single WBV session on Power Plate (7 exercises adapted to Functional Movement Screen (FMS). EG2 performed single session of FMS Exercises (FMSE). CG didn't perform any physical activity. All participants performed pre- and post-session of FMS and stabilometric measurements. FMS total score in EG1 increased by 2.0 ± 0.2 (p0 < 0.001), this was significantly differed (p0 < 0.001) from EG2 and CG. Acute effects of WBV and FMSE on rate of change and standard deviation (SD) of pressure center (COP) were shown in all groups during Static Test (p0 < 0.01). SD increased (p0 < 0.01) in Given Setting Test in EG1 and EG2, and in Romberg Test (p0 < 0.001) in EG1. Length, width and area (p0 < 0.01) of confidence ellipse, containing 95% of the statokinesiogram points, decreased in Static Test in EG1; width and area (p0 < 0.01) decreased in EG2 group. Significant (p0 < 0.01) decrease in Given Setting Test was in EG1, and significant (p0 < 0.01) increase was in Romberg Test (open eyes) in CG. Maximum amplitude of COP oscillations: significantly (p0 < 0.01) decreasing along X and Y axes in EG1 and EG2, and along Y axis in CG during Static Test; along Y axis (p0 < 0.01) in all groups during Given Setting Test. Significant differences were identified (p0 < 0.01) in calculated energy consumption for COP moving during all stabilometric tests. However, inter-group differences in COP after acute WBV and FMSE sessions have not been identified. Acute WBV session eliminates the deficits in motor patterns which is not the case after acute FMSE session, which, according to our integrative movement tuning hypothesis, is due to high activation of integrative function of proprioceptive system. Efficacy of WBV and FMSE on COP performance indicates a high sensitivity of postural control to different levels of proprioceptive system activity.

Modified Effect of Peptide Preparations on Spontaneous Motor Activity in Male Rats under the Conditions of Light Desynchronosis

This study examined the effect of peptide extracts from the epiphysis-pituitary gland of Reindeer (Rangifer tarandus) and a delta sleep-inducing peptide, simulating a modified release of drugs, on the spontaneous motor activity of male rats under the conditions of light desynchronosis. The study revealed changes in spontaneous motor activity under the influence of extracts of a peptide nature and a delta sleep-inducing peptide under the following polar light regimes. Under the conditions of constant lighting and constant darkness, an increase and a decrease in activity was observed, respectively. Under normal lighting, peptide extracts showed increased efficacy. This method of pharmacological adjustment of the body’s circadian oscillators using modified-release peptides can be used to develop a scheme for correcting light desynchronosis.

An 8-month adapted motor activity program in a young CMT1A male patient.

It is unclear whether prolonged periods of training can be well tolerated. In Charcot-Marie Tooth disease (CMT). We report the effects of an 8-month, adapted motor activity (AMA) program in a 16-years-old CMT1A male patient. The program included strength, mobility, and balance training (two sessions per week, 1h per session). Walking ability and walking velocity (Six-Minute Walking Test-6MWT, Ten Meters Walking Test-10mWT), balance (Y-Balance Test-YBT, Berg Balance Scale-BBS), functional mobility (Short Physical Performance Battery-Short physical performance battery), fatigue (Checklist Individual strength questionnaire - CIS20R), health and quality of life (Short Form Health Survey 36 questionnaire-SF-36) were evaluated in three moments: before (T0), after 5 (T1) and 8 (T2) months of adapted motor activity. Dorsal and plantar foot flexion strength (Maximal Voluntary Contraction-maximum voluntary contraction) and neuromuscular functions (Electromyography-sEMG, interpolated twitch technique-ITT) were measured at T1 and T2. Relative to T0, an amelioration of walking ability (6MWT, +9,3%) and balance (with improvements on Y-balance composite normalized mean reach of the right and left limb of 15,3% and 8,5%, respectively) was appreciable. Relative to T1, an increase in foot strength in three out of four movements (right plantar flexion, +39,3%, left plantar flexion, +22,7%, left dorsal flexion, 11,5%) was observed. Concerning voluntary muscle activation, a greater recruitment in the left, unlike right, medial gastrocnemius was observed. Results suggest the safety of an 8-month AMA program in a young patient affected by CMT1A.

Decoding kinematic information from beta-band motor rhythms of speech motor cortex: a methodological/analytic approach using concurrent speech movement tracking and magnetoencephalography.

Articulography and functional neuroimaging are two major tools for studying the neurobiology of speech production. Until now, however, it has generally not been feasible to use both in the same experimental setup because of technical incompatibilities between the two methodologies. Here we describe results from a novel articulography system dubbed Magneto-articulography for the Assessment of Speech Kinematics (MASK), which is technically compatible with magnetoencephalography (MEG) brain scanning systems. In the present paper we describe our methodological and analytic approach for extracting brain motor activities related to key kinematic and coordination event parameters derived from time-registered MASK tracking measurements. Data were collected from 10 healthy adults with tracking coils on the tongue, lips, and jaw. Analyses targeted the gestural landmarks of reiterated utterances/ipa/ and /api/, produced at normal and faster rates. The results show that (1) Speech sensorimotor cortex can be reliably located in peri-rolandic regions of the left hemisphere; (2) mu (8-12 Hz) and beta band (13-30 Hz) neuromotor oscillations are present in the speech signals and contain information structures that are independent of those present in higher-frequency bands; and (3) hypotheses concerning the information content of speech motor rhythms can be systematically evaluated with multivariate pattern analytic techniques. These results show that MASK provides the capability, for deriving subject-specific articulatory parameters, based on well-established and robust motor control parameters, in the same experimental setup as the MEG brain recordings and in temporal and spatial co-register with the brain data. The analytic approach described here provides new capabilities for testing hypotheses concerning the types of kinematic information that are encoded and processed within specific components of the speech neuromotor system.

Perinatal exposure to atazanavir-based antiretroviral regimens in a mouse model leads to differential long-term motor and cognitive deficits dependent on the NRTI backbone.

Combination antiretroviral therapy (ART) use in pregnancy has been pivotal in improving maternal health and reducing perinatal HIV transmission. However, children born HIV-exposed uninfected fall behind their unexposed peers in several areas including neurodevelopment. The contribution of in utero ART exposure to these deficits is not clear. Here we present our findings of neurocognitive outcomes in adult mice exposed in utero to ART. Dams were treated with a combination of ritonavir-boosted atazanavir with either abacavir plus lamivudine (ABC/3TC + ATV/r) or tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC + ATV/r), or water as a control, administered daily from day of plug detection to birth. Offspring underwent a battery of behavioral tests that investigated motor performance and cognition starting at 6-weeks of age and ending at 8 months. Changes in brain structure were assessed using magnetic resonance imaging and immunohistochemistry. Expression of genes involved in neural circuitry and synaptic transmission were assessed in the hippocampus, a region strongly associated with memory formation, using qPCR. Pups exposed to TDF/FTC + ATV/r showed increased motor activity and exploratory drive, and deficits in hippocampal-dependent working memory and social interaction, while pups exposed to ABC/3TC + ATV/r showed increased grooming, and deficits in working memory and social interaction. Significant volumetric reductions in the brain were seen only in the ABC/3TC + ATV/r group and were associated with reduced neuronal counts in the hippocampus. Altered neurotransmitter receptor mRNA expression as well as changes in expression of the neurotrophic factor BDNF and its receptors were observed in both ART-exposed groups in a sex-dependent manner. In our model, in utero ART exposure had long-term effects on brain development and cognitive and motor outcomes in adulthood. Our data show that neurological outcomes can be influenced by the type of nucleoside reverse transcriptase inhibitor backbone of the regimen and not just the base drug, and display sex differences.

Temporal binding and sense of agency in major depression.

Alterations in the experience of controlling oneself and one's environment are of high relevance to understanding the psychopathology of depression. This study investigated the relationship between Temporal Binding for action-event sequences, sense of agency, self-efficacy and symptom severity in Major Depressive Disorder. We employed the Sense of Agency Scale (SoAS) and the General Self-Efficacy Scale (GSE) to assess explicit Sense of Agency and self-efficacy in a group of 42 persons diagnosed with Major Depressive Disorder (MDD) [20 identifying as female, 19 as male; mean age 37.8 years (± 13.3)] and 40 control persons without a psychiatric diagnosis (CG) [22 identifying as female, 20 as male; mean age 38.0 years ( ± 13.3)]. Depressive symptom severity was measured using the BDI-II. We additionally performed a temporal binding paradigm as a potential correlate to Sense of Agency. Participants partook in a time estimation task judging three intervals (250ms, 450ms, 650ms) while either observing or causing stimulus presentations. The underestimation of intervals following intentional actions causing stimulus presentations (compared to merely observing the stimulus presentation) is interpreted as temporal binding. SoAS scores demonstrated an inverse correlation with depressive symptoms (CG: p=.032, R2=.113; MDD: p<.001, R2=.260) and a positive correlation with GSE scores (CG: p<.001, R2=.379; MDD: p<.001, R2=.254). We found distinct differences in temporal binding between healthy participants and the Major Depressive Disorder group without significant correlation between temporal binding and the SoAS or GSE scores. The data suggest group differences in time estimation particular pertaining to time intervals involving intentional action and increasingly complex multisensory stimuli. We investigated parameters of subjective control, namely Sense of Agency and Self Efficacy. Here, we were able to reveal their inverse relationship with depressive symptoms in patients with major depressive disorder, highlighting a profound experience of loss of control with increasing symptom load. Deficits in experiencing control, particularly involving intentional motor actions (and more complex multisensory stimuli), appear to be more pronounced in Major Depressive Disorder, involving not only negative self-efficacy expectations but also an altered Sense of Agency and temporal binding. Temporal binding and SoAS scores did not correlate, adding to the growing evidence that the two measures may not be directly related. We propose that future research be directed at this contiguous relationship between Sense of Agency and Self Efficacy in Major Depressive Disorder.

Neuroelectric indices of pre-motor planning and adiposity are selectively related to balance in children

BackgroundMotor function and weight status are components of physical fitness that have been implicated in childhood motor and cognitive development. The lateralized readiness potential (LRP), an index of motor planning and action, can provide context surrounding relationships between fitness and brain activity underlying cognitive and motor functions. This study evaluated the relationship between the LRP and motor skills, as well as associations between weight status and neural and behavioral motor functions. MethodsChildren aged 7–13 (n = 35) participated in a cross-sectional study, using the Movement Assessment Battery for Children 2nd edition (MABC-2) to assess balance, manual dexterity, and aiming/catching. The stimulus- (LRP-S) and response-locked (LRP-R) LRPs were elicited from a modified flanker task. Stepwise regressions tested the association between LRPs and MABC-2 components. Linear regressions were conducted to examine BMI and %Fat in relation to LRPs and MABC-2 components. ResultsAnalyses revealed that LRP-S mean amplitude difference (β = 0.401, P = 0.042) and reaction time interference scores (β = 0.545, P = 0.004) were positively associated with balance, after adjusting for covariates. The LRP-S and interference scores did not predict other MABC-2 outcomes and LRP-R did not predict any MABC-2 components. Further, %Fat (β = −0.439, P = 0.044), not BMI (β = −0.364, P = 0.082), only predicted balance. ConclusionWe found that changes in the LRP-S amplitude were positively associated with balance, and %Fat was negatively related to balance. This evidence is that fitness components such as weight status and coordination are related to neural markers of motor function which may be useful in intervention designs aimed to improve brain function via improvements in physical fitness and health behaviors.

Aquarium fish and temperature neuropharmacology: Update

At the end of the 20th century in Russia, research on temperature dependence of specific pharmacological activity of antihypoxants and some neurotropic drugs under normo- and hypothermia of various biological objects in experimental and clinical conditions was started. At the beginning of the 21st century, an original biological model of acute hypoxia in aquarium fish was developed. This model made it possible to start the study of fish resistance to hypoxia, screen biologically active substances, and evaluate the activity of antihypoxants under normo- and hypothermia. The initial results of using this model allowed us to conclude that the dynamics of motor activity of fish under acute hypoxic conditions are similar to that of motor activity of fetuses inside the uterus under diagnostic intrauterine hypoxia created by voluntary apnea in a pregnant woman. The period of immobility of fish and fetuses under hypoxia was directly proportional to the value of their resistance to hypoxia. The reduction in conditions of acute hypoxic water temperature with floating fish in it at 10°C lengthens the duration of the immobile state of fish and preservation of their viability more than two times, and the preliminary introduction of hydrogen peroxide in the water in therapeutic dose along with hypothermia lengthens the corresponding periods by four times. Neurotropic drugs such as ethyl alcohol and local and general anesthetics will completely eliminate the pain syndrome that develops during local hypothermia in healthy patients. In addition, immersing the hands of people under alcohol intoxication and/or surgical anesthesia in water with melting ice for 2 min alleviates pain in the hands and accelerates the development of subsequent hyperemia in the skin of the hands by two times compared with the norm.

Post-Stroke Impairments of Manual Dexterity and Finger Proprioception: Their Contribution to Upper Limb Activity Capacity

Background Knowing how impaired manual dexterity and finger proprioception affect upper limb activity capacity is important for delineating targeted post-stroke interventions for upper limb recovery. Objectives To investigate whether impaired manual dexterity and finger proprioception explain variance in post-stroke activity capacity, and whether they explain more variance than conventional clinical assessments of upper limb sensorimotor impairments. Methods Activity capacity and hand sensorimotor impairments were assessed using clinical measures in N = 42 late subacute/chronic hemiparetic stroke patients. Dexterity was evaluated using the Dextrain Manipulandum to quantify accuracy of visuomotor finger force-tracking (N = 36), timing of rhythmic tapping (N = 36), and finger individuation (N = 24), as well as proprioception (N = 27). Stepwise multivariate and hierarchical linear regression models were used to identify impairments best explaining activity capacity. Results Dexterity and proprioceptive components significantly increased the variance explained in activity capacity: (i) Box and Block Test was best explained by baseline tonic force during force-tracking and tapping frequency (adjusted R2 = .51); (ii) Motor Activity Log was best explained by success rate in finger individuation (adjusted R2 = .46); (iii) Action Research Arm Test was best explained by release of finger force and proprioceptive measures (improved reaction time related to use of proprioception; adjusted R2 = .52); and (iv) Moberg Pick-Up test was best explained by proprioceptive function (adjusted R2 = .18). Models excluding dexterity and proprioception variables explained up to 19% less variance. Conclusions Manual dexterity and finger proprioception explain unique variance in activity capacity not captured by conventional impairment measures and should be assessed when considering the underlying causes of post-stroke activity capacity limitations. URL: https://www.clinicaltrials.gov. Unique identifier: NCT03934073.

Effects of fluorene-9-bisphenol exposure on anxiety-like and social behavior in mice and protective potential of exogenous melatonin.

Fluorene-9-bisphenol (BHPF) is widely used in the manufacture of plastic products and potentially disrupts several physiological processes, but its biological effects on social behavior remain unknown. In this study, we investigated the effects of BHPF exposure on anxiety-like and social behavior in female mice and the potential mechanisms, thereby proposing a potential therapy strategy. We exposed female Balb/c mice to BHPF by oral gavage at different doses (0.5, 50 mg/kg bw/2-day) for 28 days, which were found BHPF (50 mg/kg) exposure affected motor activity in the open field test (OFT) and elevated cross maze (EPM), resulting in anxiety-like behaviors, as well as abnormal social behavioral deficits in the Social Interaction Test (SIT). Analysis of histopathological staining results showed that BHPF exposure caused damage to hippocampal neurons in the CA1/CA3/DG region and decreased Nissl pyramidal neurons in the CA1/CA3 regions of the hippocampus, as well as a decrease in parvalbumin neuron expression. In addition, BHPF exposure upregulated the expression of excitatory and inhibitory (E/I) vesicle transporter genes (Vglut1, Vglut2, VGAT, GAD67, Gabra) and axon growth gene (Dcc) in the mouse hippocampus. Interestingly, behavioral disturbances and E/I balance could be alleviated by exogenous melatonin (15 mg/kg bw/2-day) therapy. Our findings suggest that exogenous melatonin may be a potential therapy with protective potential for ameliorating or preventing BHPF-induced hippocampal neuronal damage and behavioral disturbances. This study provided new insight into the neurotoxicological effects on organisms exposed to endocrine-disrupting chemicals and aroused our vigilance in current environmental safety about chemical use.

The emergence of identity, agency and consciousness from the temporal dynamics of neural elaboration.

Identity-differentiating self from external reality-and agency-being the author of one's acts-are generally considered intrinsic properties of awareness and looked at as mental constructs generated by consciousness. Here a different view is proposed. All physiological systems display complex time-dependent regulations to adapt or anticipate external changes. To interact with rapid changes, an animal needs a nervous system capable of modelling and predicting (not simply representing) it. Different algorithms must be employed to predict the momentary location of an object based on sensory information (received with a delay), or to design in advance and direct the trajectory of movement. Thus, the temporal dynamics of external events and action must be handled in differential ways, thereby generating the distinction between self and non-self ("identity") as an intrinsic computational construct in neuronal elaboration. Handling time is not what neurons are designed for. Neuronal circuits are based on parallel processing: each bit of information diverges on many neurons, each of which combines it with many other data. Spike firing reports the likelihood that the specific pattern the neuron is designed to respond to is present in the incoming data. This organization seems designed to process synchronous datasets. However, since neural networks can introduce delays in processing, time sequences can be transformed into simultaneous patterns and analysed as such. This way predictive algorithms can be implemented, and continually improved through neuronal plasticity. To successfully interact with the external reality, the nervous system must model and predict, but also differentially handle perceptual functions or motor activity, by putting in register information that becomes available at different time moments. Also, to learn through positive/negative reinforcement, modelling must establish a causal relation between motor control and its consequences: the contrast between phase lag in perception and phase lead (and control) in motor programming produces the emergence of identity (discerning self from surrounding) and agency (control on actions) as necessary computational constructs to model reality. This does not require any form of awareness. In a brain, capable of producing awareness, these constructs may evolve from mere computational requirements into mental (conscious) constructs.

Quantifying Apathy in Late-Life Depression: Unraveling Neurobehavioral Links Through Daily Activity Patterns and Brain Connectivity Analysis

BackgroundBetter understanding apathy in late-life depression would help improve prediction of poor prognosis of diseases such as dementia. Actimetry provides an objective and ecological measure of apathy from patients’ daily motor activity. We aimed to determine whether patterns of motor activity were associated with apathy and brain connectivity in networks that underlie goal-directed behaviors. MethodsResting-state functional magnetic resonance imaging and diffusion magnetic resonance imaging were collected from 38 nondemented participants with late-life depression. Apathy was evaluated using the diagnostic criteria for apathy, the Apathy Evaluation Scale, and the Apathy Motivation Index. Functional principal components (fPCs) of motor activity were derived from actimetry recordings taken for 72 hours. Associations between fPCs and apathy were estimated by linear regression. Subnetworks whose connectivity was significantly associated with fPCs were identified via threshold-free network-based statistics. The relationship between apathy and microstructure metrics was estimated along fibers by diffusion tensor imaging and a multicompartment model called neurite orientation dispersion and density imaging via tractometry. ResultsWe found 2 fPCs associated with apathy: mean diurnal activity, negatively associated with Apathy Evaluation Scale scores, and an early chronotype, negatively associated with Apathy Motivation Index scores. Mean diurnal activity was associated with increased connectivity in the default mode, cingulo-opercular, and frontoparietal networks, while chronotype was associated with a more heterogeneous connectivity pattern in the same networks. We did not find significant associations between microstructural metrics and fPCs. ConclusionsOur findings suggest that mean diurnal activity and chronotype could provide indirect ambulatory measures of apathy in late-life depression, associated with modified functional connectivity of brain networks that underlie goal-directed behaviors.

Brain activation and connection across resting and motor-task states in patients with generalized tonic-clonic seizures.

Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism. Resting-state and motor-task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole-brain network connectivity across resting and motor states was further calculated and compared between groups. All patients showed over-activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated-measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor-task state. Decreased across-state network connectivity was also found in all patients. Convergent findings suggested the over-response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease.

Role of Central and Peripheral Physiological Markers in Understanding and Monitoring the Clinical Illness in Dementia

Patients with Alzheimer's dementia are known to have electrophysiological abnormalities such as increased slow wave power of resting electroencephalography (EEG), cortical excitability as detected using EEG epileptiform and epileptic activity, and deficits in cortical plasticity detected using brain stimulation combined with EEG. Understanding these neurophysiological abnormalities is important to improve our understanding of the mechanisms leading to brain dysfunction thus leading to the development of novel treatment interventions. Further, EEG is a non-invasive, low-cost, and portable technique that is widely available and can become an important tool in monitoring illness and response to treatment. To further improve objective measures to detect and monitor clinical symptoms of dementia, recently, there has been an increased interest in the development of peripheral physiological markers such as motor activity, skin conductance and temperature, and heart rate variability. These markers can be recorded using wearable devices and have shown usefulness in monitoring neuropsychiatric symptoms of dementia. Further development of these markers can improve clinical care by improving objective assessment of clinical profiles of persons with dementia living in the community or those admitted to hospitals and can help individualize care. In this session, we will first review novel findings from studies using EEG to assess central neurophysiological markers, and then discuss the role of peripheral physiological markers in the detection and monitoring of clinical symptoms of dementia in community and dementia care units.These talks will be followed by a discussion about the relevance of the central and peripheral physiological markers (biometrics) in dementia.