Single Subject Research Articles

Opponent control of reinforcement by striatal dopamine and serotonin.

The neuromodulators dopamine (DA) and serotonin (5-hydroxytryptamine; 5HT) powerfully regulate associative learning1-8. Similarities in the activity and connectivity of these neuromodulatory systems have inspired competing models of how DA and 5HT interact to drive the formation of new associations9-14. However, these hypotheses have not been tested directly because it has not been possible to interrogate and manipulate multiple neuromodulatory systems in a single subject. Here, we establish a mouse model enabling simultaneous genetic access to the brain's DA and 5HT neurons. Anterograde tracing revealed the nucleus accumbens (NAc) to be a putative hotspot for the integration of convergent DA and 5HT signals. Simultaneous recording of DA and 5HT axon activity, together with genetically encoded DA and 5HT sensor recordings, revealed that rewards increase DA signaling and decrease 5HT signaling in the NAc. Optogenetically dampening DA or 5HT reward responses individually produced modest behavioral deficits in an appetitive conditioning task, while blunting both signals together profoundly disrupted learning and reinforcement. Optogenetically reproducing DA and 5HT reward responses together was sufficient to drive acquisition of new associations and supported reinforcement more potently than either manipulation alone. Together, these results demonstrate that striatal DA and 5HT signals shape learning by exerting opponent control of reinforcement.

Contrastive learning for neural fingerprinting from limited neuroimaging data.

Neural fingerprinting is a technique used to identify individuals based on their unique brain activity patterns. While deep learning techniques have been demonstrated to outperform traditional correlation-based methods, they often require retraining to accommodate new subjects. Furthermore, the limited availability of samples in neuroscience research can impede the quick adoption of deep learning methods, presenting a challenge for their broader application in neural fingerprinting. This study addresses these challenges by using contrastive learning to eliminate the need for retraining with new subjects and developing a data augmentation methodology to enhance model robustness in limited sample size conditions. We utilized the LEMON dataset, comprising 3 Tesla MRI and resting-state fMRI scans from 138 subjects, to compute functional connectivity as a baseline for fingerprinting performance based on correlation metrics. We adapted a recent deep learning model by incorporating data augmentation with short random temporal segments for training and reformulated the fingerprinting task as a contrastive problem, comparing the efficacy of contrastive triplet loss against conventional cross-entropy loss. The results of this study confirm that deep learning methods can significantly improve fingerprinting performance over correlation-based methods, achieving an accuracy of about 98% in identifying a single subject out of 138 subjects utilizing 39 different functional connectivity profiles. The contrastive method showed added value in the "leave subject out" scenario, demonstrating flexibility comparable to correlation-based methods and robustness across different data sizes. These findings suggest that contrastive learning and data augmentation offer a scalable solution for neural fingerprinting, even with limited sample sizes.

A case-by-case analysis of EPN and LPP components within a "one-picture-per-emotion-category" protocol.

Stimuli encountered in the environment are continuously evaluated according to their affective stimulus significance. Numerous event-related potential studies have shown that the early posterior negativity (EPN) and the late positive potential (LPP) are larger for high than low arousing emotional pictures. The group approach has been recently extended to the study of the individual case. Usually, many exemplars are used to represent an emotion category. Determining how many pictures are needed to reliably assess affective stimulus evaluation processes at the individual level is crucial when moving toward the goal of exploring idiosyncratic emotional stimuli. Accordingly, in the present study (N = 16), singular images displaying erotic, neutral, and mutilation content were shown 800 times while dense sensor EEG was recorded. At the group level, enhanced EPN and LPP amplitudes for high compared to low arousing stimuli emerged. At the single subject level, significantly larger amplitudes to the erotic than neutral image were observed in 15 out of 16 tests for the EPN and LPP components. Regarding the mutilation image, 15 participants showed a significant EPN effect, while the LPP effect was only found in 10 cases. Notably, emotional modulation of the EPN and LPP was stable over time. The present study contributes to the development of experimental designs tailored to the needs of the case-by-case approach. Since the process of affective stimulus evaluation is considered as a process common-to-all, the use of a singular stimulus exemplar may prove useful to investigate the idiosyncratic nature of emotion.

CTNI-76. A PHASE 1/2 DOSE ESCALATION AND EXPANSION STUDY OF SONODYNAMIC THERAPY WITH SONALA-001 IN COMBINATION WITH NON-ABLATIVE MR-GUIDED FOCUSED ULTRASOUND IN SUBJECTS WITH PROGRESSIVE OR RECURRENT GLIOBLASTOMA

Abstract Recurrent glioblastoma (rGBM) is a lethal brain tumor with no effective standard of care option and an extremely poor prognosis (median survival 6 to 8 months after first recurrence). Sonodynamic therapy (SDT) is a non-invasive combination therapy that utilizes a drug, aminolevulinic acid HCL (SONALA-001, ALA), and a device, the Exablate 4000 Type 2.0 to deliver MR-guided focused ultrasound (MRgFUS). Preclinical studies have shown that SDT activates protoporphyrin IX (PpIX) to generate reactive oxygen species that lead to tumor cell death and improved survival in animal glioma models. A first-in-human Phase 0 trial (NCT04559685) indicated that ALA SDT was well-tolerated and not associated with off-target cellular or radiographic effects and provided direct evidence of reactive oxygen species formation and targeted tumor cell death in recurrent high-grade glioma (rHGG). SDT-202 is a Phase 1/2 multicenter, open-label, dose escalation and expansion study (NCT05370508) of iv SONALA-001 (ALA) in combination with MRgFUS for SDT in patients with progressive or recurrent GBM. Dose escalation will include an initial drug and energy dose escalation of ALA SDT utilizing an accelerated titration design with single subject cohorts for dose level cohorts 1 and 2, followed by cohort 3 with 3 + 3 design for additional dose escalation. SONALA-001 is administered 6 to 9 hours prior to MRgFUS treatment. Once the RP2D is determined, Phase 2 dose expansion will enroll approximately 36 additional subjects to assess safety and efficacy of repeated cycles of ALA SDT at the optimized RP2D. Endpoints of this study are safety evaluation, maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and determination of pharmacokinetic (PK) parameters. The Phase 2 portion will further characterize safety of RP2D along with evaluation of efficacy with PFS6 (mRANO), ORR, CBR, DOR, DOCR, TTR, and OS. Preliminary PK and safety results will be presented.

Research on the Functions and Obstacles of Rural Social Organizations in Rural Governance from the Perspective of Structural Functionalism

Since the reform and opening up, with the transformation of the national governance model, my country's rural social structure has undergone earth-shaking changes. The multi-center governance subject structure has gradually replaced the traditional single governance subject structure and has become the main model for the management of rural social public affairs in my country. As an important subject in governance activities, rural social organizations play a key role in promoting farmers' collective actions and nurturing grassroots democracy. As an important part of the rural social structure, rural social organizations not only have their structure and functions rooted in the transformation of the social structure, but their changes and development also play an important role in the transformation of the social structure. From the perspective of structural functionalism, analyzing the role and function of rural social organizations in the rural social structure has positive theoretical value and practical significance for achieving the effective fit of the structure and function of rural social organizations and building a benign management order in rural society under the background of the rural revitalization strategy.

Effects of Preferred Music on Older Adults with Dementia: An Observational Study

Dementia is becoming more prevalent as the population of adults over the age of 65 increases. With an increase in this disease comes a need for interventions, as dementia is incurable, nonpharmacological interventions are es-sential to reduce associated behaviors associated with de-mentia. This single subject A-B experimental design took place in the upper midwestern United States with indi-viduals diagnosed with dementia who had documented moderate-to-severe cognitive impairment and demon-strated dementia-related behaviors. Demographic and personalized treatment data were collected through chart reviews and interviews with staff and participants before starting baseline observations. The lead investigator con-ducted A-phase baseline behavioral observations using time sampling for five consecutive days followed by B-phase experimental behavioral observations using time sampling for five consecutive days. The data suggested that preferred music can impact dementia-related behaviors and has the potential to improve quality of life. Implications for recreational therapy practice are included.

Contribution of the plantar fascia and long plantar ligaments to the stability of the longitudinal arch of the foot

The contribution of the Plantar Fascia (PF) and Long Plantar Ligament (LPL), two ligaments extending from the hindfoot to the forefoot, to arch stability has been studied in the past using in vivo, in vitro, and in silico methodologies. In silico studies were based on one single model obtained from one single subject and did not account for the known inter-subject morphological and biomechanical variations. In the present study, we developed computational dynamic models of nine different legs obtained from nine different individuals to evaluate the role of the LPL and PF in arch support, accounting for biological differences between subjects. These models were validated by comparing the simulation results against experimental results from the corresponding cadaver legs. After validation, we simulated body weight conditions for each model by applying a vertical load to the tibia, starting from zero and increasing linearly to 720 N. Kinematic and dynamic parameters, including the variation of the medial arch angle and of the navicular height, as well as the passive forces developed by the LPL and PF, were used to evaluate the contribution of these ligaments to arch support under body weight. The results indicate that a total collapse of the medial longitudinal arch occurred only when both the LPL and PF were absent, but a stable arch was maintained when either one of these two ligament structures were present. The results varied significantly among the specific models, highlighting the importance of using multiple models to account for inter-subject morphological differences.

Biomechanical Analysis of the “Cuban Motion”

Abstract Purpose “Cuban Motion” (CM) is a term often used to label a basic movement of many Latin-American dances, such as salsa and bachata. It is characterized by a cyclical and rhythmic flexion and rotation of the pelvis, accompanied by ample movements of the spine and lower limbs. Since Latin dances are considered both a recreational activity and a kind of healthy gymnastics for young and older subjects, a biomechanical analysis of the CM was performed to quantitatively assess the main features of this movement, from joint kinematics to muscle activations. Method The study combined experimental acquisitions with a Vicon Motion Capture system and musculoskeletal analyses in OpenSim. Only one subject was considered, an instructor of Latin dances, who was equipped with 55 retro-reflective markers, according to the Full Body CGM2.5 marker set. Data were processed in OpenSim, using the ThoracoLumbar model (111 DoFs and 620 musculo-tendon actuators). Results The cycle of the CM and its main events were defined. Results showed a wide RoM of many joints, with correlations between hip and knee flexion angles and among list, between hip adduction and shoulder flexion. The main role of the iliopsoas and the ileus costalis muscles was observed. Conclusions The current study quantified the CM as a physical exercise using a biomechanical approach similar to a gait analysis. The main kinematic and kinetic features were described, also providing an estimation of the muscle activations and joint reactions, derived from simulation activity in OpenSim. The main limitation of this study is the focus on a single subject, but this step was necessary to define a context and guidelines for future investigations, where we are going to compare èlite vs. novices and male vs. female dancers.

Multifractality in monitored single-particle dynamics

We study multifractal properties in time evolution of a single particle subject to repeated measurements. For quantum systems, we consider circuit models consisting of local unitary gates and local projective measurements. For classical systems, we consider models for estimating the trajectory of a particle evolved under local transition processes by partially measuring particle occupations. In both cases, multifractal behaviors appear in the ensemble of wave functions or probability distributions conditioned on measurement outcomes after a sufficiently long time. While the nature of particle transport (diffusive or ballistic) qualitatively affects the multifractal properties, they are even quantitatively robust to the measurement rate or specific protocols. On the other hand, multifractality is generically lost by generalized measurements allowing erroneous outcomes or by postselection of the outcomes with no particle detection. We demonstrate these properties by numerical simulations and also propose several simplified models, which allow us to analytically obtain multifractal properties in the monitored single-particle systems. Published by the American Physical Society 2024

Using Network Analysis to Examine the Brain Regions Connectivity of Functional Neurological Disorder Patient and Healthy Participant

Introduction: Functional neurological disorder (FND) is one of the most common causes of neuropathy, However, its cause continues to be mysterious. Understanding the underlying mechanisms of that is crucial for treatment strategies. The study was conducted on brain images resting state fMRI taken from two volunteers (functional neurological disorder patient and healthy subject)who had the same characteristics. Methods: We fitted Gaussian Graphical Models to a single subject data using a network approach. Results: Based on the results of the networks, the number of significant edges was more in the left hemisphere in the patient, but in the healthy person, the number of these non-zero edges was more in the right hemisphere. Both the networks related to the healthy person and the patient had high density. Therefore, it indicated that the regions considered by these 2 people were strongly related to each other. The results showed the existence of more links and positive relationships between the regions, most of which showed a strong relationship. Among these connections, there were also negative connections. The networks of the healthy participant with almost symmetrical structures and the patient with Functional neurological disorder showed different characteristics, including asymmetry between the hemispheres. Conclusion: this study is the first to demonstrate that the brain regions of both functional neurological disorder patient and healthy participant can be conceptualized as networks. The findings of this study add to a growing body of literature that functional neurological disorder patient brain regions can be analyzed using network approaches.

The Antecedents of the Experience of Light in Dreams

The experience of inner light and ecstasy is widely accepted as a universal mystical experience, regardless of cultural or religious context. While one can read first-hand accounts in the historical record, the direct experience of light remains elusive for most people. This study analyzes a series of dream-based experiences of light provided by a single subject. In our analysis of 19 dreams, we pursue a process-oriented, relational analysis based on co-creative dream theory, which views the dream as an interactive experience in real time rather than a fixed product of the unconscious mind. By analyzing dreams as relational events, in which the metaphoric content emerges alongside the dreamer’s responses, we see how the dream ego influences the outcome through feelings, choices, and reactions. Through this analysis, we identify an array of subjective antecedents to the experience of light and provide a potential avenue of access to the core mystical experience.

Longitudinal single-subject neuroimaging study reveals effects of daily environmental, physiological, and lifestyle factors on functional brain connectivity.

Our behavior and mental states are constantly shaped by our environment and experiences. However, little is known about the response of brain functional connectivity to environmental, physiological, and behavioral changes on different timescales, from days to months. This gives rise to an urgent need for longitudinal studies that collect high-frequency data. To this end, for a single subject, we collected 133 days of behavioral data with smartphones and wearables and performed 30 functional magnetic resonance imaging (fMRI) scans measuring attention, memory, resting state, and the effects of naturalistic stimuli. We find traces of past behavior and physiology in brain connectivity that extend up as far as 15 days. While sleep and physical activity relate to brain connectivity during cognitively demanding tasks, heart rate variability and respiration rate are more relevant for resting-state connectivity and movie-watching. This unique data set is openly accessible, offering an exceptional opportunity for further discoveries. Our results demonstrate that we should not study brain connectivity in isolation, but rather acknowledge its interdependence with the dynamics of the environment, changes in lifestyle, and short-term fluctuations such as transient illnesses or restless sleep. These results reflect a prolonged and sustained relationship between external factors and neural processes. Overall, precision mapping designs such as the one employed here can help to better understand intraindividual variability, which may explain some of the observed heterogeneity in fMRI findings. The integration of brain connectivity, physiology data and environmental cues will propel future environmental neuroscience research and support precision healthcare.

95 - ​Single subject fMRI mapping at 7T during stimulation of the female urogenital region: a pilot study

95 - ​Single subject fMRI mapping at 7T during stimulation of the female urogenital region: a pilot study

Aerobic exercise and cognitive function in chronic severe traumatic brain injury survivors: a within-subject A-B-A intervention study

BackgroundFollowing acute and sub-acute rehabilitation from severe traumatic brain injury (TBI), minimal to no efficacious interventions to treat ongoing cognitive deficits are available. Aerobic exercise is a non-invasive behavioral intervention with promise to treat cognitive deficits in TBI populations.MethodsSix individuals, aged 24–62 years, with chronic (> 8 months since injury) severe (Glasgow Coma Scale of 3–8) TBI were recruited from two outpatient rehabilitation centers. In an A-B-A study design, 20-weeks of supervised aerobic exercise interventions were delivered three times per week (phase B) in addition to participants typical rehabilitation schedules (phases A). The effect of phase B was tested on a trail making test part B (primary outcome measure of executive function) as well as objective daily physical activity (PA), using both group level (linear mixed effect models) and single subject statistics.ResultsFive of six participants increased trail-making test part B by more than 10% pre-to-post phase B, with three of six making a clinically meaningful improvement (+ 1SD in normative scores). A significant main effect of time was seen with significant improvement in trail-making test part B pre-to-post exercise (phase B). No significant effects in other planned comparisons were found. Statistically significant increases in daily moderate-to-vigorous PA were also seen during phase B compared to phase A with three of six individuals making a significant behaviour change.ConclusionsThe addition of supervised aerobic exercise to typical rehabilitation strategies in chronic survivors of severe TBI can improve executive set shifting abilities and increase voluntary daily PA levels.Trial registrationRetrospective trial registration on July 11 2024 with trial number: ISRCTN17487462.

Relocating the linguistic repertoire: from in us to among us

ABSTRACT This inquiry into the location of the linguistic repertoire was driven by a pedagogical encounter with mounting putty, the white adhesive used to attach materials to another surface. This encounter began at a community writing center during a writing workshop I was teaching on poesía bilingüe when children took up the putty, creating objects that became poetry. I wondered whose linguistic repertoire these words and things had come from and to whose they belonged. If the linguistic repertoire remains within a user, it is unified as an absolute cognitive container of language. It cannot account for the visible, audible, dynamic, and creative linguistic practices of multilinguals while accounting for inward cognitive firings within that same multilingual. The location of the linguistic repertoire implicates pedagogical practice because if the repertoire is singular, unified, and located within the bounds of a single cognitive subject, then the pedagogical responsibility of knowing and using words remains within that subject, and the educator is left to their ontological and epistemological assumptions as to what is in that linguistic repertoire, often leading to problematic pedagogies. However, if the linguistic repertoire is relocated among us, there is theoretical and pedagogical potential for learning, surprise, and ever-elusive change.

The Effect of Using Quizizz Paper Mode Learning Media on Student Learning Outcomes in Mathematics Subjects at SDN Setu 02 Jakarta

This study investigates the impact of using Quizizz Paper Mode as a learning medium on the mathematics learning outcomes of fifth-grade students at SDN Setu 02 Jakarta. Employing a quantitative research method with a Posttest-Only Control Design, the study involved two groups: an experimental group utilizing Quizizz Paper Mode and a control group relying on conventional teaching methods. The results demonstrate a significant improvement in the experimental group's post-test scores compared to the control group, indicating the effectiveness of Quizizz Paper Mode in enhancing students' mathematical understanding and engagement. The study's findings suggest that integrating technology like Quizizz Paper Mode in education can positively influence learning outcomes, though limitations such as sample size and focus on a single subject should be considered. The research underscores the need for further exploration and implementation of educational technologies in primary school curricula.

Detecting dynamic interaction of multiple subjects in policy information communication in China

PurposeAs an important part of national governance, the online communication of education policies usually attracts the attention of many subjects, including the public and the media. Existing research mainly focuses on analysing communication behaviour of a single subject. However, with the rapid development of social media, policy information communication is often accompanied by the participation of multiple subjects and forms diversified communication behaviours and interaction patterns. The comprehensive identification of multiple subjects and their interactions can accurately depict the communication process and effectively support the efficient communication of policies. Therefore, this paper aims to conduct fine-grained analysis on the multiple subjects in information communication of the education policy.Design/methodology/approachThis paper explored the communication and interaction process of the education policy via multidimensional analysis. Specifically, the authors firstly obtained multi-source communication data to identify key communication subjects. Secondly, the authors mined the communication contents generated by communication subjects to measure the diversified correlations between subjects. Finally, the authors depicted the interaction of subjects in policy information communication.FindingsThe experimental results reveal that there are multiple key subjects in the policy information communication, and the communication roles of the subjects change with the communication process, including dominance role, one-way or two-way effect role. This further indicates the need to allocate resources dynamically in the process of policy communication.Originality/valueAnalysing the process of policy communication and identifying the dynamic interaction between communication subjects can provide more a comprehensive and detailed decision-making basis for policy formulation and implementation. In addition, the research ideas and methods presented in this paper expand the perspective of information communication research.

Do Tau Deposition and Glucose Metabolism Dissociate in Alzheimer's Disease Trajectory?

Tau aggregation demonstrates close associations with hypometabolism in Alzheimer's disease (AD), although differing pathophysiological processes may underlie their development. To establish whether tau deposition and glucose metabolism have different trajectories in AD progression and evaluate the utility of global measures of these pathological hallmarks in predicting cognitive deficits. 279 participants with amyloid-β (Aβ) status, and T1-weighted MRI scans, were selected from the Alzheimer's Disease Neuroimaging Initiative (http://adni.loni.usc.edu). We created the standard uptake value ratio images using Statistical Parametric Mapping 12 for [18F]AV1451-PET (tau) and [18F]FDG-PET (glucose metabolism) scans. Voxel-wise group and single-subject level SPM analysis evaluated the relationship between global [18F]FDG-PET and [18F]AV1451-PET depending on the Aβ status. Linear models assessed whether tau deposition or glucose metabolism better predicted clinical progression. There was a dissociation between global cerebral glucose hypometabolism and global tau load in amyloid-positive AD and amyloid-negative mild cognitive impairment (MCI) (p > 0.05). Global hypometabolism was only associated with global cortical tau in amyloid-positive MCI. Voxel-level single subject tau load better predicted neuropsychological performance, Alzheimer's disease assessment scale-cognitive (ADAS-Cog) 13 score, and one-year change compared with regional and global hypometabolism. A dissociation between tau pathology and glucose metabolism at a global level in AD could imply that other pathological processes influence glucose metabolism. Furthermore, as tau is a better predictor of clinical progression, these processes may have independent trajectories and require independent consideration in the context of therapeutic interventions.

Interventional Analysis of Music Therapy on Emotional Behavior in Children with Autism

Music therapy, as an emerging field of rehabilitation, has been studied by many people. However, it only proves the effectiveness of music therapy in addressing emotional and behavioral issues in children with autism, and there are no specific strategies and methods applicable to special education schools for reference. This study attempts to address this issue. This study adopted a cross subject multi trial design in a single subject experimental method, with music therapy as the independent variable. Using the emotional behavior of these four autistic children who cried for no reason as the dependent variable, data was collected during the baseline, intervention, and maintenance periods to verify the intervention effect of music therapy on emotional behavior. The research results indicate that music therapy has immediate, sustained, and generalized effects on typical emotional and behavioral problems in children with autism. After music therapy intervention, the frequency of emotional and behavioral problems in each of the four autistic children decreased significantly, their self-control ability improved significantly, and language interaction was significantly prolonged. Based on the observation of student expressions and actions, participation statistics, and family interviews, it can be seen that students are interested in the environment of visual music, rhythm training, and situational music. The correct grasp of the core concepts of music therapy and timely feedback on intervention content play a crucial role in the treatment effect in this study.

Design and Validation of a Modular, Backdrivable Ankle Exoskeleton.

Partial-assist ankle exoskeletons have been limited by inherent trade-offs between favorable characteristics including high torque capacity, high control bandwidth, back-drivability, compliance, and low mass. Emerging quasi-direct drive actuators have a rigid transmission with a low gear ratio, enabling inherent backdrivability and compliance with accurate torque and position control. Our existing modular, backdrivable exoskeleton system (M-BLUE) uses quasi-direct drive actuators at the hip and/or knee to deliver high assistive torques alongside low dynamic backdrive torques, enabling natural interaction with users with remnant voluntary motion. This paper extends our modular system with the design and validation of a back-drivable ankle exoskeleton module to assist both plantarflexion and dorsiflexion. The bi-directional torque capabilities enable the study of control methods and gait outcomes for able-bodied users and users with gait impairments. Benchtop tests of the actuator performance and control bandwidth indicate that the position, voltage, and current control modes can provide assistance to the ankle joint across activities of daily living (ADLs). We also implement an optimal task-agnostic energy shaping controller for an experiment with a single human subject to validate the ability of the ankle exoskeleton to provide biomimetic torque assistance across a circuit of ADLs.