Simple Behavioral Analysis (SimBA) as a platform for explainable machine learning in behavioral neuroscience.

The study of complex behaviors is often challenging when using manual annotation due to the absence of quantifiable behavioral definitions and the subjective nature of behavioral annotation. Integration of supervised machine learning approaches mitigates some of these issues through the inclusion of accessible and explainable model interpretation. To decrease barriers to access, and with an emphasis on accessible model explainability, we developed the open-source Simple Behavioral Analysis (SimBA) platform for behavioral neuroscientists.

A behavioral roadmap for the development of agency in the rodent.

Behavioral interactions within the nuclear family play a pivotal role in the emergence of agency: the capacity to regulate physiological, psychological and social needs. While behaviors may develop over days or weeks in line with nervous system maturation, individual behaviors can occur on sub-second time scales making it challenging to track development in lab studies with brief observation periods, or in field studies with limited temporal precision and animal identification. Here we study development in families of gerbils, a highly social rodent, collecting tens of millions of behavior time points and implementing machine learning methods to track individual subjects.

Lateral line ablation by ototoxic compounds results in distinct rheotaxis profiles in larval zebrafish.

The zebrafish lateral line is an established model for hair cell organ damage, yet few studies link mechanistic disruptions to changes in biologically relevant behavior. We used larval zebrafish to determine how damage via ototoxic compounds impact rheotaxis. Larvae were treated with CuSO or neomycin to disrupt lateral line function then exposed to water flow stimuli.

Toward the explainability, transparency, and universality of machine learning for behavioral classification in neuroscience.

The use of rigorous ethological observation via machine learning techniques to understand brain function (computational neuroethology) is a rapidly growing approach that is poised to significantly change how behavioral neuroscience is commonly performed. With the development of open-source platforms for automated tracking and behavioral recognition, these approaches are now accessible to a wide array of neuroscientists despite variations in budget and computational experience. Importantly, this adoption has moved the field toward a common understanding of behavior and brain function through the removal of manual bias and the identification of previously unknown behavioral repertoires.

Automated procedure to assess pup retrieval in laboratory mice.

All mammalian mothers form some sort of caring bond with their infants that is crucial to the development of their offspring. The Pup Retrieval Test (PRT) is the leading procedure to assess pup-directed maternal care in laboratory rodents, used in a wide range of basic and preclinical research applications. Most PRT protocols require manual scoring, which is prone to bias and spatial and temporal inaccuracies.

Spleen contraction elevates hemoglobin concentration at high altitude during rest and exercise.

Purpose: Hypoxia and exercise are known to separately trigger spleen contraction, leading to release of stored erythrocytes. We studied spleen volume and hemoglobin concentration (Hb) during rest and exercise at three altitudes.

Methods: Eleven healthy lowlanders did a 5-min modified Harvard step test at 1370, 3700 and 4200 m altitude.

Rage Against the Machine: Advancing the study of aggression ethology via machine learning.

Rationale: Aggression, comorbid with neuropsychiatric disorders, exhibits with diverse clinical presentations and places a significant burden on patients, caregivers, and society. This diversity is observed because aggression is a complex behavior that can be ethologically demarcated as either appetitive (rewarding) or reactive (defensive), each with its own behavioral characteristics, functionality, and neural basis that may transition from adaptive to maladaptive depending on genetic and environmental factors. There has been a recent surge in the development of preclinical animal models for studying appetitive aggression-related behaviors and identifying the neural mechanisms guiding their progression and expression.

Dorsal and ventral striatal dopamine D1 and D2 receptors differentially modulate distinct phases of serial visual reversal learning.

Impaired cognitive flexibility in visual reversal-learning tasks has been observed in a wide range of neurological and neuropsychiatric disorders. Although both human and animal studies have implicated striatal D-like and D-like receptors (D2R; D1R) in this form of flexibility, less is known about the contribution they make within distinct sub-regions of the striatum and the different phases of visual reversal learning. The present study investigated the involvement of D2R and D1R during the early (perseverative) phase of reversal learning as well as in the intermediate and late stages (new learning) after microinfusions of D2R and D1R antagonists into the nucleus accumbens core and shell (NAcC; NAcS), the anterior and posterior dorsomedial striatum (DMS) and the dorsolateral striatum (DLS) on a touchscreen visual serial reversal-learning task.

Dopamine D2-like receptor stimulation blocks negative feedback in visual and spatial reversal learning in the rat: behavioural and computational evidence.

Rationale: Dopamine D2-like receptors (D2R) are important drug targets in schizophrenia and Parkinson's disease, but D2R ligands also cause cognitive inflexibility such as poor reversal learning. The specific role of D2R in reversal learning remains unclear.

Objectives: We tested the hypotheses that D2R agonism impairs reversal learning by blocking negative feedback and that antagonism of D1-like receptors (D1R) impairs learning from positive feedback.

Differential Activation of Biceps Brachii Muscle Compartments for Human-Machine Interfacing.

A central challenge for myoelectric limb prostheses resides in the fact that, as the level of amputation becomes more proximal, the number of functions to be replaced increases, while the number of muscles available to collect input signals for control decreases. Differential activation of compartments from a single muscle could provide additional control sites. However, such feat is not naturally under voluntary control.

Continuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine.

The 22q11.2 deletion syndrome (22q11.2DS) confers high risk of neurodevelopmental disorders such as schizophrenia and attention-deficit hyperactivity disorder.

Selective effects of 5-HT2C receptor modulation on performance of a novel valence-probe visual discrimination task and probabilistic reversal learning in mice.

Rationale: Dysregulation of the serotonin (5-HT) system is a pathophysiological component in major depressive disorder (MDD), a condition closely associated with abnormal emotional responsivity to positive and negative feedback. However, the precise mechanism through which 5-HT tone biases feedback responsivity remains unclear. 5-HT2C receptors (5-HT2CRs) are closely linked with aspects of depressive symptomatology, including abnormalities in reinforcement processes and response to stress.

Treating Procrastination Using Cognitive Behavior Therapy: A Pragmatic Randomized Controlled Trial Comparing Treatment Delivered via the Internet or in Groups.

Procrastination is a common problem among university students, with at least half of the population reporting great difficulties initiating or completing tasks and assignments. Procrastination can have a negative impact on course grades and the ability to achieve a university degree, but can also lead to psychological distress. Cognitive behavior therapy (CBT) is believed to reduce procrastination, but few studies have investigated its effectiveness in a regular clinical setting.

Effects of anterior cingulate cortex lesions on a continuous performance task for mice.

Important tools in the study of prefrontal cortical-dependent executive functions are cross-species behavioural tasks with translational validity. A widely used test of executive function and attention in humans is the continuous performance task (CPT). Optimal performance in variations of this task is associated with activity along the medial wall of the prefrontal cortex, including the anterior cingulate cortex (ACC), for its essential components such as response control, target detection and processing of false alarm errors.

MAM-E17 rat model impairments on a novel continuous performance task: effects of potential cognitive enhancing drugs.

Rationale: Impairments in attention and inhibitory control are endophenotypic markers of neuropsychiatric disorders such as schizophrenia and represent key targets for therapeutic management. Robust preclinical models and assays sensitive to clinically relevant treatments are crucial for improving cognitive enhancement strategies.

Objectives: We assessed a rodent model with neural and behavioral features relevant to schizophrenia (gestational day 17 methylazoxymethanol acetate treatment (MAM-E17)) on a novel test of attention and executive function, and examined the impact of putative nootropic drugs.

Assessing the Cognitive Translational Potential of a Mouse Model of the 22q11.2 Microdeletion Syndrome.

A chromosomal microdeletion at the 22q11.2 locus is associated with extensive cognitive impairments, schizophrenia and other psychopathology in humans. Previous reports indicate that mouse models of the 22q11.

Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 microdeletion syndrome: a study in male mice.

Background: The hemizygous 22q11.2 microdeletion is a common copy number variant in humans. The deletion confers high risk for neurodevelopmental disorders, including autism and schizophrenia.

A mouse model of the 15q13.3 microdeletion syndrome shows prefrontal neurophysiological dysfunctions and attentional impairment.

Rationale: A microdeletion at locus 15q13.3 is associated with high incidence rates of psychopathology, including schizophrenia. A mouse model of the 15q13.

The continuous performance test (rCPT) for mice: a novel operant touchscreen test of attentional function.

Rationale: Continuous performance tests (CPTs) are widely used to assess attentional processes in a variety of disorders including Alzheimer's disease and schizophrenia. Common human CPTs require discrimination of sequentially presented, visually patterned 'target' and 'non-target' stimuli at a single location.

Objectives: The aims of this study were to evaluate the performance of three popular mouse strains on a novel rodent touchscreen test (rCPT) designed to be analogous to common human CPT variants and to investigate the effects of donepezil, a cholinesterase inhibitor and putative cognitive enhancer.

The rat's not for turning: Dissociating the psychological components of cognitive inflexibility.

Executive function is commonly assessed by assays of cognitive flexibility such as reversal learning and attentional set-shifting. Disrupted performance in these assays, apparent in many neuropsychiatric disorders, is frequently interpreted as inability to overcome prior associations with reward. However, non-rewarded or irrelevant associations may be of considerable importance in both discrimination learning and cognitive flexibility.

Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task.

Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR) function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward.

The touchscreen operant platform for assessing executive function in rats and mice.

This protocol details a subset of assays developed within the touchscreen platform to measure various aspects of executive function in rodents. Three main procedures are included: extinction, measuring the rate and extent of curtailing a response that was previously, but is no longer, associated with reward; reversal learning, measuring the rate and extent of switching a response toward a visual stimulus that was previously not, but has become, associated with reward (and away from a visual stimulus that was previously, but is no longer, rewarded); and the 5-choice serial reaction time (5-CSRT) task, gauging the ability to selectively detect and appropriately respond to briefly presented, spatially unpredictable visual stimuli. These protocols were designed to assess both complementary and overlapping constructs including selective and divided visual attention, inhibitory control, flexibility, impulsivity and compulsivity.

The touchscreen operant platform for testing learning and memory in rats and mice.

An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive rather than aversive reinforcement), has high translational potential and lends itself to a high degree of standardization and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.