Human Behavioral Pattern Monitor Research Articles

A Pilot Assessment of the Effects of HIV and Methamphetamine Dependence on Socially Dysregulated Behavior in the Human Behavioral Pattern Monitor.

Deficits in social cognition are seen in both people living with HIV (PWH) and people with a history of methamphetamine (METH) dependence. Dually affected individuals may experience additive negative effects on social cognition due to these conditions. We evaluated social cognition in 4 diagnostic groups (HIV-/METH-, HIV-/METH+, HIV+/METH-, HIV+/METH+). First, we used traditional social-emotional functioning assessments, the Difficulties in Emotion Regulation Scale and the Faux Pas Task, to determine any significant effects of METH dependence and HIV on social cognition. Next, we quantified social cognition using the Human Behavioral Pattern Monitor by evaluating social behavior represented by interaction with novel objects. METH dependence significantly affected social-emotional functions and HIV significantly affected on object interactions, however no significant additive effects were observed using these methods. The nuanced relationship between HIV and METH dependence suggests that other factors (i.e., adaptive life skills) likely mediate social cognition-related behaviors.

The relationship between novelty-seeking traits and behavior: Establishing construct validity for the human Behavioral Pattern Monitor

Novelty seeking is a tendency to approach new situations, putatively driven by the brain's catecholaminergic system. It is traditionally measured via self-report, but a laboratory-based paradigm, the human Behavioral Pattern Monitor (hBPM), quantifies behavior in a novel environment and has utility in cross-species studies of neuropsychiatric disorders. Our primary aim assessed whether self-reported novelty-seeking traits were associated with novelty-seeking behavior in the hBPM. An existing sample of 106 volunteers were categorized as high vs. low novelty seekers using the Temperament and Character Inventory (TCI). Subjects had been randomized to one dose of amphetamine (10 or 20 mg) or modafinil (200 or 400 mg), allowing us to explore whether a pharmacological catecholamine challenge further enhanced novelty-seeking behavior. High TCI novelty-seekers had more hBPM motor activity and novel object interactions. The exploratory analyses, although limited by low power, suggested that amphetamine and modafinil did not markedly moderate novelty-seeking traits. The hBPM demonstrates construct validity as a lab-based measure of novelty seeking and thus useful in translational studies of neuropsychiatric conditions and treatment options. Further research may illuminate whether a biological predisposition towards higher catecholaminergic activity, combined with the novelty-seeking trait, may increase propensity for risky and addictive behaviors.

The COMT Val158Met Polymorphism and Exploratory Behavior in Bipolar Mania

Background: The catechol-O-methyltransferase (COMT) Val158Met gene influences cognition and behavior in psychiatric illnesses; its low-activity allele, methionine (Met), may be associated with behavior reflecting catecholamine overactivity. Heightened motor activity and increased positive valence are central features of bipolar disorder (BD) and have been quantified in the human Behavioral Pattern Monitor (hBPM), an exploration paradigm based upon the rodent open field. We examined whether hBPM behavior was related to the COMT gene in a small sample of manic BD patients. Methods: Twenty-six acutely hospitalized manic BD patients were genotyped for the COMT Val158Met polymorphism and tested in the hBPM, an unfamiliar room containing novel objects. Movements around the hBPM and object interactions were video-recorded for 15 min and rated. Results: Met homozygote BD patients demonstrated significantly more interactions with multiple objects and more time spent with objects in the hBPM. Valine (Val) homozygote patients exhibited the least object exploration, while heterozygote patients demonstrated intermediate levels. Conclusion: This preliminary study suggests that arousal and positive valence are influenced in a linear fashion by COMT, presumably due to increased catecholamine in frontal regions, but these findings require replication in a larger sample. The hBPM can enable cross-species and transdiagnostic studies to inform neurobiology of psychiatric disorders.

Diagnosis and characterization of mania: Quantifying increased energy and activity in the human behavioral pattern monitor

Increased energy or activity is now an essential feature of the mania of Bipolar Disorder (BD) according to DSM-5. This study examined whether objective measures of increased energy can differentiate manic BD individuals and provide greater diagnostic accuracy compared to rating scales, extending the work of previous studies with smaller samples. We also tested the relationship between objective measures of energy and rating scales. 50 hospitalized manic BD patients were compared to healthy subjects (HCS, n=39) in the human Behavioral Pattern Monitor (hBPM) which quantifies motor activity and goal-directed behavior in an environment containing novel stimuli. Archival hBPM data from 17 schizophrenia patients were used in sensitivity and specificity analyses.Manic BD patients exhibited higher motor activity than HCS and higher novel object interactions. hBPM activity measures were not correlated with observer-rated symptoms, and hBPM activity was more sensitive in accurately classifying hospitalized BD subjects than observer ratings. Although the findings can only be generalized to inpatient populations, they suggest that increased energy, particularly specific and goal-directed exploration, is a distinguishing feature of BD mania and is best quantified by objective measures of motor activity. A better understanding is needed of the biological underpinnings of this cardinal feature.

Dopamine depletion attenuates some behavioral abnormalities in a hyperdopaminergic mouse model of bipolar disorder

BackgroundPatients with BD suffer from multifaceted symptoms, including hyperactive and psychomotor agitated behaviors. Previously, we quantified hyperactivity, increased exploration, and straighter movements of patients with BD mania in the human Behavioral Pattern Monitor (BPM). A similar BPM profile is observed in mice that are hyperdopaminergic due to reduced dopamine transporter (DAT) functioning. We hypothesized that dopamine depletion through alpha-methyl-p-tyrosine (AMPT) administration would attenuate this mania-like profile. MethodsMale and female DAT wild-type (WT; n=26) and knockdown (KD; n=28) mice on a C57BL/6 background were repeatedly tested in the BPM to assess profile robustness and stability. The optimal AMPT dose was identified by treating male C57BL/6 mice (n=39) with vehicle or AMPT (10, 30, or 100mg/kg) at 24, 20, and 4h prior to testing in the BPM. Then, male and female DAT WT (n=40) and KD (n=37) mice were tested in the BPM after vehicle or AMPT (30mg/kg) treatment. ResultsCompared to WT littermates, KD mice exhibited increased activity, exploration, straighter movement, and disorganized behavior. AMPT-treatment reduced hyperactivity and increased path organization, but potentiated specific exploration in KD mice without affecting WT mice. LimitationsAMPT is not specific to dopamine and also depletes norepinephrine. ConclusionsKD mice exhibit abnormal exploration in the BPM similar to patients with BD mania. AMPT-induced dopamine depletion attenuated some, but potentiated other, aspects of this mania-like profile in mice. Future studies should extend these findings into other aspects of mania to determine the suitability of AMPT as a treatment for BD mania.

Inhibitory deficits in euthymic bipolar disorder patients assessed in the human behavioral pattern monitor

BackgroundBipolar disorder (BD) is associated with inhibitory deficits characterized by a reduced ability to control inappropriate actions or thoughts. While aspects of inhibition such as exaggerated novelty-seeking and perseveration are quantified in rodent exploration of novel environments, similar models are rarely applied in humans. The human Behavioral Pattern Monitor (hBPM), a cross-species exploratory paradigm, has identified a pattern of impaired inhibitory function in manic BD participants, but this phenotype has not been examined across different BD phases. The objective of this study was to determine if euthymic BD individuals demonstrate inhibitory deficits in the hBPM, supporting disinhibition as an endophenotype for the disorder. Methods25 euthymic BD outpatients and 51 healthy comparison subjects were assessed in the hBPM, where activity was recorded by a concealed videocamera and an ambulatory monitoring sensor. ResultsEuthymic BD individuals, similar to manic subjects, demonstrated increased motor activity, greater interaction with novel objects, and more frequent perseverative behavior relative to comparison participants. The quantity of locomotion was also reduced in BD individuals treated with mood stabilizers compared to other patients. LimitationsLow sample size for treatment subgroups limits the evaluation of specific medication regimens. ConclusionsOur results suggest that BD is distinguished by both trait- and state-dependent inhibitory deficits optimally assessed with sophisticated multivariate measures. These data support the use of the hBPM as a tool to elucidate the effects of BD across various illness states, facilitate the development of BD animal models, and advance our understanding of the neurobiology underlying the disorder.

Repeated Assessment of Exploration and Novelty Seeking in the Human Behavioral Pattern Monitor in Bipolar Disorder Patients and Healthy Individuals

BackgroundExploration and novelty seeking are cross-species adaptive behaviors that are dysregulated in bipolar disorder (BD) and are critical features of the illness. While these behaviors have been extensively quantified in animals, multivariate human paradigms of exploration are lacking. The human Behavioral Pattern Monitor (hBPM), a human version of the animal open field, identified a signature pattern of hyper-exploration in manic BD patients, but whether exploratory behavior changes with treatment is unknown. The objective of this study was to assess the sensitivity of the hBPM to changes in manic symptoms, a necessary step towards elucidating the neurobiology underlying BD.Methodology and Principal FindingsTwelve acutely hospitalized manic BD subjects and 21 healthy volunteers were tested in the hBPM over three sessions; all subjects were retested one week after their first session and two weeks after their second session. Motor activity, spatial and entropic (degree of unpredictability) patterns of exploration, and interactions with novel objects were quantified. Manic BD patients demonstrated greater motor activity, extensive and more unpredictable patterns of exploration, and more object interactions than healthy volunteers during all three sessions. Exploration and novelty-seeking slightly decreased in manic BD subjects over the three sessions as their symptoms responded to treatment, but never to the level of healthy volunteers. Among healthy volunteers, exploration did not significantly decrease over time, and hBPM measures were highly correlated between sessions.Conclusions/SignificanceManic BD patients showed a modest reduction in symptoms yet still demonstrated hyper-exploration and novelty seeking in the hBPM, suggesting that these illness features may be enduring characteristics of BD. Furthermore, behavior in the hBPM is not subject to marked habituation effects. The hBPM can be reliably used in a repeated-measures design to characterize exploration and novelty seeking and, in parallel with animal studies, can contribute to developing treatments that target neuropsychiatric disease.

Quantifying over-activity in bipolar and schizophrenia patients in a human open field paradigm

It has been suggested that a cardinal symptom of mania is over-activity and exaggerated goal-directed behavior. Nevertheless, few attempts have been made to quantify this behavior objectively in a laboratory environment. Having a methodology to assess over-activity reliably might be useful in distinguishing manic bipolar disorder (BD) from schizophrenia (SCZ) during highly activated states. In the current study, quantifiable measures of object interaction were assessed using a multivariate approach. Additionally, symptom correlates of over-activity were assessed. Patients admitted to an acute care psychiatric hospital for either BD with mania or SCZ (paranoid and non-paranoid subtypes) as well as non-patient comparison (NC) participants were assessed in an open field setting referred to as the human Behavioral Pattern Monitor (hBPM). Activity and interactions with novel and engaging objects were recorded for 15 min via a concealed video camera and rated for exploratory behavior. Both BD and SCZ patients spent more time near the objects and exhibited more overall walking compared to NC. In contrast, BD patients exhibited greater physical contact with objects (number of object interactions and time spent with objects) relative to SCZ patients or NC participants, as well as more perseverative and socially disinhibited behaviors, indicating a unique pattern of over-activity and goal-directed behavior. Further analyses revealed a distinction between SCZ patients according to their subtype. The current study extends our methodology for quantifying exploration and over-activity in a controlled laboratory setting and aids in assessing the overlap and distinguishing characteristics of BD and SCZ.

GBR 12909 administration as a mouse model of bipolar disorder mania: mimicking quantitative assessment of manic behavior

RationaleMania is a core feature of bipolar disorder (BD) that traditionally is assessed using rating scales. Studies using a new human behavioral pattern monitor (BPM) recently demonstrated that manic BD patients exhibit a specific profile of behavior that differs from schizophrenia and is characterized by increased motor activity, increased specific exploration, and perseverative locomotor patterns as assessed by spatial d.ObjectivesIt was hypothesized that disrupting dopaminergic homeostasis by inhibiting dopamine transporter (DAT) function would produce a BD mania-like phenotype in mice as assessed by the mouse BPM.MethodsWe compared the spontaneous locomotor and exploratory behavior of C57BL/6J mice treated with the catecholamine transporter inhibitor amphetamine or the selective DAT inhibitor GBR 12909 in the mouse BPM. We also assessed the duration of the effect of GBR 12909 by testing mice in the BPM for 3 h and its potential strain dependency by testing 129/SvJ mice.ResultsAmphetamine produced hyperactivity and increased perseverative patterns of locomotion as reflected in reduced spatial d values but reduced exploratory activity in contrast to the increased exploration observed in BD patients. GBR 12909 increased activity and reduced spatial d in combination with increased exploratory behavior, irrespective of inbred strain. These effects persisted for at least 3 h.ConclusionsThus, selectively inhibiting the DAT produced a long-lasting cross-strain behavioral profile in mice that was consistent with that observed in manic BD patients. These findings support the use of selective DAT inhibition in animal models of the impaired dopaminergic homeostasis putatively involved in the pathophysiology of BD mania.

A Reverse-Translational Study of Dysfunctional Exploration in Psychiatric Disorders

Bipolar mania and schizophrenia are recognized as separate disorders but share many commonalities, which raises the question of whether they are the same disorder on different ends of a continuum. The lack of distinct endophenotypes of bipolar mania and schizophrenia has complicated the development of animal models that are specific to these disorders. Exploration is fundamental to survival and is dysregulated in these 2 disorders. Although exploratory behavior in rodents has been widely studied, surprisingly little work has examined this critical function in humans. To quantify the exploratory behavior of individuals with bipolar mania and schizophrenia and to identify distinctive phenotypes of these illnesses. Static group comparison by the use of a novel human open field paradigm, the human Behavioral Pattern Monitor (BPM). Psychiatric hospital. Fifteen patients with bipolar mania and 16 patients with schizophrenia were compared with 26 healthy volunteers in the human BPM. The effects of amphetamine sulfate, the selective dopamine transporter inhibitor GBR12909, and the genetic knockdown of the dopamine transporter were compared with controls in the mouse BPM. The amount of motor activity, spatial patterns of activity, and exploration of novel stimuli were quantified in both the human and mouse BPMs. Patients with bipolar mania demonstrated a unique exploratory pattern, characterized by high motor activity and increased object exploration. Patients with schizophrenia did not show the expected habituation of motor activity. Selective genetic or pharmacologic inhibition of the dopamine transporter matched the mania phenotype better than the effects of amphetamine, which has been the criterion standard for animal models of mania. These findings validate the human open field paradigm and identify defining characteristics of bipolar mania that are distinct from those of schizophrenia. This cross-species study of exploration calls into question an accepted animal model of mania and should help to develop more accurate human and animal models, which are essential to the identification of the neurobiological underpinnings of neuropsychiatric disorders.

The quantitative assessment of motor activity in mania and schizophrenia

Background Increased motor activity is a cardinal feature of the mania of Bipolar Disorder (BD), and is thought to reflect dopaminergic dysregulation. Motor activity in BD has been studied almost exclusively with self-report and observer-rated scales, limiting the ability to objectively quantify this behavior. We used an ambulatory monitoring device to quantify motor activity in BD and schizophrenia (SCZ) patients in a novel exploratory paradigm, the human Behavioral Pattern Monitor (BPM). Method 28 patients in the manic phase of BD, 17 SCZ patients, and 21 nonpatient (NC) subjects were tested in the BPM, an unfamiliar room containing novel objects. Motor activity was measured with a wearable ambulatory monitoring device (LifeShirt). Results Manic BD patients exhibited higher levels of motor activity when exploring the novel environment than SCZ and NC groups. Motor activity showed some modest relationships with symptom ratings of mania and psychosis and was not related to smoking or body mass index. Limitations Although motor activity did not appear to be impacted significantly by antipsychotic or mood-stabilizing medications, this was a naturalistic study and medications were not controlled, thus limiting conclusions about potential medication effects on motor activity. Conclusion Manic BD patients exhibit a unique signature of motoric overactivity in a novel exploratory environment. The use of an objective method to quantify exploration and motor activity may help characterize the unique aspects of BD and, because it is amenable to translational research, may further the study of the biological and genetic bases of the disease.