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RDoC Snapshot: Version 2 (saved 10/20/2016)

This is a snapshot of the RDoC matrix, and as such the links contained within may not work as future changes to the matrix may include removing or changing various elements of the matrix. This snapshot is intended simply to show what had been listed in the matrix at a previous time, and does not to contain any new information.

  • Domain: Negative Valence Systems
    • Construct: Acute Threat ("Fear")

      Genes

      5HT/5HTRs Acetylcholine BDNF Cam kinase Cannabinoid system COMT CRF DAT Dopamine FKBP5 GABAARs Glutamate system MAP kinase NMDARs Norepinephrine Opioid system PI-3 kinase PKA Pkap PKC Strathmin TRBC5

      Molecules

      BDNF CCK Cortisol/Corticosterone CRF family Dopamine Endogenous cannabinoids FGF2 GABA Glutamate Neuropeptide S Neurosteroids NMDAR NPY Orexin Oxytocin Serotonin Vasopressin

      Cells

      GABAergic cells Glia Neurons Pyramidal cells

      Circuits

      autonomic nervous system BasAmyg Central Nucleus d-hippocampus (ant) dmPFC (pl) dorsal ACC dPAG Hypothalamus ICMs insular cortex LatAmyg latPFC/insula LC Medial Amyg OFC PAG Pons rostral/vent ACC RPVM v-hippocampus (post) vmPFC (il) vPAG

      Physiology

      BP Context Startle EMG Eye Tracking Facial EMG Fear Potentiated Startle Heart Rate pupillometry Respiration Response accuracy Skin Conductance

      Behavior

      Analgesia approach (early development) Avoidance Facial expressions Freezing Open field Response inhibition Response time Risk assessment Social approach

      Self-Report

      Albany Panic and Phobia BAI Eilam Ethogram Fear Questionnaire Fear survey schedule STAI Structured Diagnostic and Assessment scales SUDS Trait Fear Inventory

      Paradigms

      emotional imagery Fear conditioning viewing aversive pictures or films
    • Construct: Potential Threat ("Anxiety")

      Genes

      CRF

      Molecules

      Cortisol CRF family

      Cells

      Pituitary cells

      Circuits

      Bed nucleus of stria terminalis

      Physiology

      ACTH Average cortisol levels Potentiated startle

      Paradigms

      Contextual Threat darkness (in humans) light (in rodents)
    • Construct: Sustained Threat

      Molecules

      ACTH CRF HPA-axis hormones

      Cells

      Hippocampal Microglia prefrontal

      Circuits

      Attention network Dysregulation of amygdala reactivity Dysregulation of cingulate reactivity Habit systems (Striatum/caudate/accumbens) Hypothalamic nuclei PVT Vigilance network

      Physiology

      Dysregulated HPA axis Error-related negativity

      Behavior

      Anhedonia/decreased appetitive behavior Anxious Arousal Attentional bias to threat Avoidance Decreased libido Helplessness behavior Increased conflict detection Increased perseverative behavior Memory retrieval deficits Punishment sensitivity
    • Construct: Loss

      Genes

      5-HTTLPR 5HTRs COMT DAT1 MAOA

      Molecules

      Androgens CRH Estrogens Glucocorticoid receptors Inflammatory molecules Oxytocin Vasopressin

      Circuits

      Amygdala Default mode network DLPFC Habit systems (Striatum/caudate/accumbens) Hippocampus Insula Orbitofrontal cortex Parietal cortex Posterior cingulate PVN Reward circuitry vmPFC

      Physiology

      ANS HPA neuroimmune Prolonged psychophysiological reactivity

      Behavior

      Amotivation Anhedonia Attentional bias to negative valenced information Crying Executive function Guilt Increased self-focus Loss of drive Loss-relevant recall bias Morbid Thoughts Psychomotor retardation Rumination Sadness Shame Withdrawal Worry

      Self-Report

      Change in attributional style Hopelessness
    • Construct: Frustrative Nonreward

      Genes

      5-HTTLPR 5HTRs COMT DAT1 MAOA

      Molecules

      Dopamine GABA Glutamate Serotonin steroids Vasopressin

      Circuits

      Amygdala Hypothalamus LC OFC PAG parasympathetic system Septum striatum

      Behavior

      physical and relational aggression

      Self-Report

      Buss-Durkee and Buss Perry Proactive/ reactive aggression questionnaire

      Paradigms

      Physical and relational aggression paradigms PSAP resident/human intruder test social dominance test
  • Domain: Positive Valence Systems
    • Construct: Approach Motivation
      • Subconstruct: Reward Valuation

        Molecules

        Dopamine Serotonin

        Circuits

        Anterior medial OFC Cortico-limbic circuit Ventral limbic striatum (incl. ventral caudate) Ventral tegmental area/Substantia Nigra

        Self-Report

        BAS reward sensitivity subscale Sensitivity to Reward sub scale of the Sensitivity to Reward and Sensitivity to Punishment questionnaire

        Paradigms

        Armed bandit task Counterfactual learning Delay discounting Kahneman-Spinner paradigm Value-based decision making (e.g., preference test)

        Paradigms can be explicit or implicit.

      • Subconstruct: Effort Valuation / Willingness to Work

        Molecules

        Adenosine Dopamine GABA

        Circuits

        Basolateral amygdala dorsal ACC Ventral pallidum Ventral striatum (nACC) VTA

        Self-Report

        Drive subscale of the Behavioral Activation Scale

        Paradigms

        EEfRT task Effort-related choice behavior (effort discounting) Progressive ratio task Scheduleless key press to view or avoid pictures (e.g., “beautiful faces”)
      • Subconstruct: Expectancy / Reward Prediction Error

        Molecules

        Dopamine Serotonin

        Circuits

        Amygdala Basal ganglia dorsal ACC Lateral habenula Orbitofrontal cortex Rostral medial tegmentum Substantia nigra/VTA Ventral striatum

        Physiology

        Cortical slow waves Heart Rate Change Skin Conductance

        Behavior

        Goal tracking Pavlovian approach Reward-related speeding Sign tracking

        Self-Report

        Affective forecasting ASAM scale Eating Expectancy Inventory Generalized reward and punishment expectancy scale Self-report of craving TEPS anticipatory scale

        Paradigms

        Cue reactivity Monetary Incentive Delay Non-learning/passive gambling/guessing tasks
      • Subconstruct: Action Selection / Preference-Based Decision Making

        Circuits

        Amygdala

        Paradigms

        Card choice/gambling task Modified Iowa Gambling Task
    • Construct: Initial Responsiveness to Reward Attainment

      Genes

      DAT DRD2 TREK1

      Molecules

      CREB Endocannabinoids FosB Glutamate Mu and delta opioid Orexin

      Circuits

      Anterior insula dorsal ACC Lateral hypothalamus Medial OFC Nucleus accumbens Ventral pallidum Ventromedial PFC VTA

      Behavior

      Taste reactivity

      Self-Report

      Consummatory subscale of TEPS PANAS (state version)

      Paradigms

      Gambling/guessing tasks Monetary Incentive Delay Taste reactivity
    • Construct: Sustained/Longer-Term Responsiveness to Reward Attainment

      Molecules

      Dopamine Endocannabinoids Opioid Orexin Serotonin

      Circuits

      Arcuate nucleus BA9/medial Medial preoptic area OFC Paraventricular hypothalamus Ventromedial hypothalamus

      Physiology

      GLP1 Gonadal hormones Peripheral endocannabinoids PYY Vagus nerve stimulation (CCK)

      Behavior

      Cessation of consumption/meal termination Meal pattern analysis Nipple refusal Satiety sequence

      Self-Report

      Drug effects questionnaire Loss of control scale Reward responsiveness subscale of BIS/BAS Visual analog scales of satiety

      Paradigms

      Devaluation task Snaith Hamilton Pleasure Scale
    • Construct: Reward Learning

      Genes

      Adenyl cyclase COMT DARP32 Dopamine synthesis, clearance, and receptor signaling genes HDAC methyl transferases NMDA receptors on D1 neurons synapse related genes

      Molecules

      Acetylcholine Co-released neuromodular glutamate CREB dopamine and dopamine-related molecules FosB

      Cells

      Dopaminergic neurons medium spiny neurons

      Circuits

      Amygdala dorsal striatum Medial prefrontal OFC Ventral striatum VTA/SN

      Physiology

      Correct related negativity Error related negativity Feedback related negativity Midline theta

      Behavior

      Approach behaviors Consummatory behaviors toward any goal object

      Self-Report

      Ambulatory assessment and monitoring Ecological momentary assessment

      Paradigms

      deterministic reinforcement learning Instrumental conditioning and all its variants Pavlovian conditioning Prediction error tasks probabilistic reinforcement learning
    • Construct: Habit

      Genes

      Adenyl cyclase COMT DARP32 Dopamine synthesis, clearance, and receptor signaling genes HDAC methyl transferases NMDA receptors on D1 neurons synapse related genes

      Molecules

      Acetylcholine Co-released neuromodular glutamate CREB dopamine and dopamine-related molecules FosB

      Cells

      Dopaminergic neurons medium spiny neurons Substantia Nigra

      Circuits

      dorsal striatum Medial prefrontal SN/VTA Ventral striatum

      Behavior

      Compulsive behaviors Repetitive behaviors Stereotypic behaviors

      Self-Report

      Aberrant behaviors checklist Measures of repetitive behaviors

      Paradigms

      attention blindness devaluation dual task paradigm knot tying long-term probabilistic response learning maze learning Perseveration tasks response time acceleration serial response task
  • Domain: Cognitive Systems
    • Construct: Attention

      Genes

      D4 D5 DAT1 Serotonin receptor gene

      Molecules

      Implementation

      GABA Glutamate

      Control

      Acetylcholine Dopamine Glutamate Histamine Serotonin

      Cells

      Parvalbumin-positive interneurons

      Circuits

      Balance between task positive network (TPN) vs DMN

      Implementation

      local circuit interactions pulvinar TRN

      Control

      Amygdala ascending/descending information pathways

      Attentional Systems

      basal forebrain limbic system Dorsal attention network Ventral attention network

      Physiology

      fMRI

      Sensory areas from peripheral to central

      Auditory ERP

      N1 N2 Neural oscillations P1 P300 processing negativity

      Visual ERP

      N2pc negativity (SN) Neural oscillations P300 Selection modulations of sensory ERP components slow waves

      Peripheral Physiology

      Heart rate deceleration Pupil dilation

      Behavior

      ANT task distractibility Attentional lapses vs sustained attention Distractibility Object/feature attention Psychophysics Spatial attention

      Paradigms

      attentional blink and psychological refractory period paradigm blocked channel-selection tasks dichotic listening distraction paradigms (capture) dual task paradigms inter-modal selective attention spatial and non-spatial cuing paradigms, time-series of response times to extract variability and frequency domain analyses visual search

      Target detection tasks in the absence of competition are considered measues of sustained attention, and not selective or divided attention, which are subsumed under cog control

    • Construct: Perception
      • Subconstruct: Visual Perception

        Genes

        Dysbindin Neurexin Neuroligin NRG1

        Molecules

        ACH Catecholamines GABA Glutamate NMDA Peptides Serotonin

        Cells

        Magno (non-linear gain control) Parvalbumin-positive interneurons Parvo Pyramidal cells

        Circuits

        Subcortical

        Koniocellular Magnocellular Parvocellular

        Cortical

        Cortico-cortical connections into supra- and infra-granular layers Dorsal/ventral streams

        Non-retinogeniculate

        Superior colliculus Suprachiasmatic nucleus

        Local circuitry

        Lateral interactions Top-down interactions

        Implicated in contextual fields and association fields (responsible for the influence of spatial context on target processing)

        Physiology

        Adaptation/ habituation BOLD activation of cortical regions ERP components Ncl Oscillations (scalp EEG, LFP, and single/multi-unit) ssVEP tVEP

        Behavior

        Discrimination, identification and localization Perceptual learning Perceptual priming Reading Stimulus detection Visual acuity

        Self-Report

        Perceptual anomalies of schizophrenia and depression

        Paradigms

        Scheme 1: Stages of Vision

        Early Vision
        Local computations Retinotopic representations
        Intermediate Vision
        Nonlocal properties of images Transformations beyond retinotopic representations
        Late Vision
        Representations of external objects

        Scheme 2: Commonly Used Research Paradigms

        Backward masking Biological motion processing Bistability Coherent motion Contour integration/interpolation Contrast sensitivity Cross modality paradigms Emotion expression identification Face identification Figure ground Lateral facilitation Multistability Object perception Object recognition/perceptual closure/perceptual organization Parallel/serial search Reading Vernier discrimination Visual illusion susceptibility

        Other Schemes

        Action-Perception loops Re-entrant processing
      • Subconstruct: Auditory Perception

        Genes

        BDNF

        Molecules

        Acetylcholine GABA Glutamate NMDA Serotonin

        Cells

        Cochlear hair cells Cortical and limbic inhibitory interneurons Ribbon synapses

        Circuits

        Nodes in Circuits

        A1 Anterior insula Brainstem Cochlea Inferior colliculus MGN STG

        Circuits

        Corticofugal Dorsal/ventral streams

        Physiology

        Adaptation/ habituation Auditory steady-state response (ASSR) fMRI Intracortical EEG Metabolic changes Mismatch negativity (MMN) N1 Neural oscillations P3a P50 startle and PPI

        Behavior

        Perceptual identification Perceptual learning Perceptual priming Spatial localization Stimulus detection

        Self-Report

        Auditory hallucinations Hyperacusis

        Paradigms

        Action-Perception loops Auditory masking auditory scene perception (e.g., streaming) Bistability Categorization Cross-modal interactions Detection of speech in noise Deviance detection Gating inhibitory control Manipulation of ISI and/or intensity McGurk (multisensory) novelty/oddball detection Object perception Regularity and change detection same-different tasks self-monitoring tone detection (e.g., JND tasks) Tone matching
      • Subconstruct: Olfactory/Somatosensory/Multimodal/Perception

        Paradigms

        Manipulation of ISI and/or intensity smell identification
    • Construct: Declarative Memory

      Genes

      BDNF KIBRA

      Molecules

      Cholinergic Glutamatergic Noradrenergic Opioid

      Cells

      Glia Granule cells Inhibitory and excitatory interneurons Pyramidal cells

      Circuits

      Extrinsic hippocampal circuitry Intrinsic hippocampal circuitry PFC and PPC interactions with multiple association cortices

      Physiology

      AMPA-related synaptic plasticity conjunction codes frontal/temporal coordinated oscillations LTP/LTD NMDA-related synaptic plasticity place cell activity subsequent memory effect (fMRI, ERP) up/down states

      Behavior

      Discrimination Familiarity Learning Recall Recognition

      Self-Report

      Cognitive Assessment Interview

      Paradigms

      acquired equivalence delayed recall list and story learning Paired associate learning transitive inference
    • Construct: Language

      Genes

      FOXP2 models based on songbirds mouse knockout models

      Circuits

      Inferior frontal cortex Inferior parietal cortex Inferior temporal cortex Lateral superior and middle temporal cortices Overlap with memory, motor, sensory, and emotional circuits

      Physiology

      anterior negativities N400 P600/late positivities

      Behavior

      Coherent discourse Coherent sentences Production and comprehension of words

      Self-Report

      Cognitive Assessment Interview

      Paradigms

      Language Production

      Linguistic corpus-based analyses of language output Naming

      Language Comprehension

      Ability to answer questions about the content of sentences and discourse Ability to distinguish between coherent and incoherent sentences and discourse Detection and classification of semantic relationships between words Listening and reading times to critical words and regions in linguistic input Patterns of eye movements (in eye tracking paradigms) or motor movements (in mouse tracking paradigms) to critical words and regions in linguistic input Patterns of eye movements to non-verbal visual stimuli during spoken language comprehension (the visual world paradigm)

      Experimental Manipulations

      Manipulations of different types of coherence and cohesion between clauses in discourse Manipulations of different types of relationships between individual words in priming paradigms Manipulations of predictability and acceptability, at different levels of representation, in a linguistic input Manipulations of relationships between language and non-verbal behaviors
    • Construct: Cognitive Control
      • Subconstruct: Goal Selection; Updating, Representation, and Maintenance

        Goal Selection

        Circuits

        Frontopolar/Anterior LPFC (BA10) Inhibition of DMN

        Self-Report

        BRIEF (Gioa)

        Paradigms

        Badre tasks Koechlin paradigm Task switching

        Updating, Representation, and Maintenance

        Genes

        5-HTTLPR 5HT2A BDNF COMT DISC1 DRD2 DRD4

        Molecules

        ACH GABA Glutamate Norepinephrine

        Cells

        PV Pyramidal cells

        Circuits

        DLPFC PPC Thalamocortical

        Physiology

        Gamma synchrony Pupilometry

        Behavior

        Distractibility Off-task behaviors

        Self-Report

        BRIEF (Gioa) Cognitive Failures Questionnaire SANS/SAPS/PANSS

        Paradigms

        AX paradigms Cued stimulus-response reversal tasks Task switching Tower tasks
      • Subconstruct: Response Selection; Inhibition/Suppression

        Response Selection

        Genes

        BDNF CHRM4 COMT DRD4

        Molecules

        ACH GABA Glutamate Norepinephrine

        Cells

        PV Pyramidal cells

        Circuits

        DLPFC PPC VLPFC

        Physiology

        Gamma Theta

        Behavior

        Impulsive behaviors

        Self-Report

        BRIEF (Gioa) SANS/SAPS/PANSS

        Paradigms

        Flanker Simon Stroop

        Inhibition/Suppression

        Genes

        5-HTT DAT1 DRD4 MAOA

        Molecules

        Acetylcholine Dopamine GABA Glutamate Norepinephrine

        Cells

        Pyramidal cells

        Circuits

        BA6/8 (FEF) PPC Pre-SMA Ventrofronto-striatal

        Physiology

        Alpha Pupilometry Short interval cortical inhibition (TMS)

        Behavior

        Distractibility Impulsive behaviors Off-task behaviors

        Self-Report

        ADHD Rating Scale (Dupaul) ATQ/CBQ Effortful Control BRIEF (Gioa) Conners impulsivity scale

        Paradigms

        Antisaccade Conflicting and contralateral motor response task Countermanding Go/Nogo Motor persistence paradigms (e.g. NEPSY statue task) Stimulus-Resp Incompat Stop-Signal Reaction Time
      • Subconstruct: Performance Monitoring

        Genes

        5-HTTLPR

        Molecules

        5HT Dopamine

        Circuits

        ACC / pre-SMA Insula

        Physiology

        ERN N2 N450

        Behavior

        Post-error or post-conflict adjustments in performance

        Self-Report

        YBOCS total score

        Paradigms

        Flanker Simon Stroop
    • Construct: Working Memory
      • Subconstruct: Active Maintenance

        Genes

        BDNF COMT DAT1 DISC1 DRD2 DTNBP1 NGR1

        Molecules

        D1 Dopamine GABA Glutamate NMDA

        Cells

        Distinct types of inhibitory neurons Pyramidal cells

        Circuits

        Inferior Parietal PFC-parietal-cingulate-dorsal thalamus-dorsal striatum VLPFC

        Physiology

        Delta Gamma waves Theta waves

        Paradigms

        AX-CPT/DPX Change detection tasks Complex Span tasks delayed match to non sample delayed match to sample keep track task Letter memory/running memory Letter Number Sequencing N-back Self-Ordered Pointing sequence encoding and reproduction Simple Span Tasks Sternberg Item Recognition
      • Subconstruct: Flexible Updating

        Genes

        BDNF COMT DAT1 DISC1 DRD2 DTNBP1 NGR1

        Molecules

        D2 Dopamine GABA Glutamate

        Cells

        Medium Spiny Neurons (basal ganglia)

        Circuits

        DLPFC dorsal striatum MD PFC-parietal-cingulate-dorsal thalamus-dorsal striatum VA thalamus

        Physiology

        Delta Gamma waves Theta waves

        Paradigms

        AX-CPT/DPX Complex Span tasks keep track task Letter memory/running memory Letter Number Sequencing N-back Self-Ordered Pointing Sternberg Item Recognition
      • Subconstruct: Limited Capacity

        Genes

        BDNF COMT DAT1 DISC1 DRD2 DTNBP1 NGR1

        Molecules

        D1 D2 Dopamine GABA Glutamate

        Circuits

        DLPFC Dorsal Parietal Inferior Parietal MD PFC-parietal-cingulate-dorsal thalamus-dorsal striatum VA thalamus VLPFC

        Physiology

        Delta Gamma waves Theta waves

        Paradigms

        AX-CPT/DPX Change detection tasks Complex Span tasks delayed match to non sample delayed match to sample keep track task Letter memory/running memory Letter Number Sequencing N-back Self-Ordered Pointing sequence encoding and reproduction Simple Span Tasks Sternberg Item Recognition
      • Subconstruct: Interference Control

        Genes

        BDNF COMT DAT1 DISC1 DRD2 DTNBP1 NGR1

        Molecules

        D1 D2 Dopamine GABA Glutamate

        Cells

        Calbindin Calretinin Distinct types of inhibitory neurons Parvalbumin

        Circuits

        DLPFC PFC-parietal-cingulate-dorsal thalamus-dorsal striatum

        Physiology

        Delta Gamma waves Theta waves

        Paradigms

        Complex Span tasks delayed match to non sample delayed match to sample keep track task Letter memory/running memory Letter Number Sequencing N-back Self-Ordered Pointing Simple Span Tasks Sternberg Item Recognition
  • Domain: Social Processes
    • Construct: Affiliation and Attachment

      Genes

      3CRF 3OXT AVPR1A CRFR2 DRD1 DRD2 KOR MOR OXTR Tyrosine Hydroxylase

      Molecules

      3CRF CRFR2 D1 Dopamine KOR Mu opioid receptor Oxytocin oxytocin receptor Vasopressin vasopressin 1a receptor

      Cells

      Magnocellular OT

      Circuits

      Amygdala BNST FF gyrus NAcc OFC PVN VMPFC VTA- NAcc- VP-amygdala

      Physiology

      activation of sympathetic activity HPA axis activation HPA down-regulation Immune markers immune responses (“sickness”) Sex steroid changes Vagal tone vagal withdrawal

      Behavior

      Attachment Formation

      Maintaining proximity Preference for individual

      Attachment Maintenance

      Distress upon separation

      Self-Report

      Adult Attachment Interview Attachment Questionnaire for Children Scale Attachment Style interview Bartholomew and Shaver Bereavement scales Experience in Close Relationships Scale Inventory of Parent and Peer Attachment Scale Parental Bonding Instrument QSORT Parent Attachment interview Social Anhedonia scale Social subscales of depression

      Paradigms

      Separation Social Buffering of Stress Strange Situation
    • Construct: Social Communication
      • Subconstruct: Reception of Facial Communication

        Genes

        5-HTT Autism risk genes BDNF CNTNAP2 COMT FMR1 OXTR

        Molecules

        Dopamine FMRP GABA Oxytocin Serotonin Testosterone Vasopressin

        Cells

        Face selective neurons Mirror neurons

        Circuits

        amygdala-brainstem IFG-INS-amygdala/VS OFC-ACC-amygdala-striatum Resting state networks V1-FFA-STS-amygdala V1-FFA-STS-VS

        Physiology

        ECoG frontal brain asymmetry Facial EMG ../respiration Local cerebral blood flow changes N170 N250 Network dynamics Pupil dilation SCR Startle reflex

        Behavior

        Behavioral observation/coding systems Eye gaze detection Identification of emotion Implicit mimicry Scanning patterns

        Self-Report

        Arousal ratings Face dimensional rating scales

        Paradigms

        Chimeric tasks Conditioning paradigms Distress paradigms Dynamic Social stimulus tasks Emotional face expression tests Emotional Stroop/emotional go/no-go Face feature manipulation Face priming tasks Implicit social perception tasks Joint attention tasks Masking paradigms Other attention paradigms Social Flanker Social Reward paradigms Still Face paradigm
      • Subconstruct: Production of Facial Communication

        Genes

        Autism risk genes CNTNAP2 FOXP2 NRX1 OXTR SHANK3

        Molecules

        AP Contactin

        Circuits

        Eye Movements

        PPC-SC-SNc-SEF-FEF-CB

        Facial Expression

        Regions including PAG, AC

        Physiology

        Facial EMG HR variability NIRS Photoplethysmography (skin color measure of capillary dilation; temperature) Pupil dilation SC Tear production

        Behavior

        Behavioral observation/coding systems Eye gaze aversion/contact Facial affect production Head turning Imitation of facial gestures Joint attention Reciprocal emotional expression Reciprocal eye contact

        Self-Report

        Berkeley Expressivity Questionnaire

        Paradigms

        Directed facial action tasks expression: FACS and FACES coding system Distress paradigms Human-Computer interaction Imitation of affect other automated facial analysis Provocative tasks/settings to elicit expressions Relived Memories paradigm Social games e.g. cyberball Still Face paradigm “Thin slices” of non-verbal behavior test
      • Subconstruct: Reception of Non-Facial Communication

        Genes

        CNTNAP2 FOXP2 NGF OXTR

        Molecules

        Oxytocin Vasopressin

        Circuits

        A1-RSTG MPFC STS VLPFC

        Physiology

        EEG features e.g., evoked gamma Local cerebral blood flow changes Network dynamics

        Behavior

        Comprehension of emotional prosody Comprehension of non-verbal gestures Humor comprehension Irony/sarcasm comprehension Metaphor comprehension

        Self-Report

        Social Responsiveness Scale

        Paradigms

        Biological Motion discrimination (with and without emotion), CELF Prosody Language vs. non-language discrimination Olfactory hedonics measures Profile of non-verbal sensitivity Sentence Prosody tests Still Face paradigm “Thin slices” of non-verbal behavior test
      • Subconstruct: Production of Non-Facial Communication

        Genes

        FOXP2 NGF OXTR

        Circuits

        R-IFG-RSTG Songbird circuits

        Behavior

        Crying/laughing Gestural/postural expressions Interactive play Response to distress/separation distress Speech (affective) prosody Vocalizations

        Paradigms

        computational linguistics Computer interface tasks Still Face paradigm Vocal production coding systems e.g., spectral analysis
    • Construct: Perception and Understanding of Self
      • Subconstruct: Agency

        Circuits

        Right insula-right inferior frontal Right parietal SMA-somatosensory-premotor

        Physiology

        Scalp Motor Potentials

        Behavior

        Delusions of control Evidence that one understands ownership of one’s own body parts or action (thoughts/behaviors) Hallucinations

        Self-Report

        Perceptual Aberration Scale

        Paradigms

        Ford Corollary Discharge Paradigm Identification of one’s own biological motion illusions of will Joy Stick manipulation (decoupling motor and sensory feedback) Reality Monitoring
      • Subconstruct: Self-Knowledge

        Cells

        Von Economo neurons

        Circuits

        left inferior frontal cortex MPFC posterior cingulate/precuneus ventral anterior cingulate (valence specific)

        Physiology

        P300s to self-relevant stimuli

        Behavior

        Developmentally appropriate perception of one’s competences, skills, abilities beliefs, intentions, desires, and/or emotional states

        Self-Report

        Levels of Emotional Awareness Private Self-Consciousness Self Components of Attributional Styles Questionnaire Self-monitoring scale Toronto Alexithymia scale

        Paradigms

        Discrepancies in self and peer ratings [i.e., peer nomination] Meta-cognition Tasks Self Judgments Self reference effect
    • Construct: Perception and Understanding of Others
      • Subconstruct: Animacy Perception

        Circuits

        extrastriate body area fusiform face area occipital face area STS

        Physiology

        MU Suppression

        Behavior

        Ability to appropriately attribute animacy to other agents

        Paradigms

        Attributions of contingent behavior Point-light displays
      • Subconstruct: Action Perception

        Cells

        Mirror neurons

        Circuits

        Inferior Parietal STS ventral/dorsal premotor

        Physiology

        cortico-spinal facilitation (TMS) MU Suppression

        Behavior

        Ability to identify what actions an agent is executing Gaze following Imitation Mimicry

        Self-Report

        Balanced Emotional Empathy Scale Empathy Quotient Perspective Taking and Empathic Concern subscales of the Interpersonal Reactivity Index

        Paradigms

        Action observation Empathic Accuracy Tasks How component of Why/How Task Imitation Non verbal decoding tasks Profile of non-verbal sensitivity Self-Other Morphs
      • Subconstruct: Understanding Mental States

        Genes

        Genes that influence Vasopressin or oxytocin

        Molecules

        Oxytocin Vasopressin

        Circuits

        MPFC precuneus STS temporal pole TPJ

        Behavior

        Developmentally appropriate interpretations of other intentions, goals and beliefs

        Self-Report

        Balanced Emotional Empathy Scale Empathy Quotient Other components of Attributional Styles Questionnaires Perspective Taking and Empathic Concern subscales of the Interpersonal Reactivity Index

        Paradigms

        Directors Task Dunbar’s Intentionality Questionnaire Empathic Accuracy Tasks Faux Pas Irony comprehension Other Trait or State Judgments Reading the Mind in the Eyes Strange Stores Theory of Mind Tasks in children Why component of Why/How Task
  • Domain: Arousal and Regulatory Systems
    • Construct: Arousal

      Genes

      16 nAChR genes 5-HTT 5HT1-7 A1-3 ACHE AMPA CHAT Cytokine receptors D1-5 DAT DBH Delta GABA-A GABA-B GABA-C Ghrelin receptors H1-4 HCRT2 Kainate Leptin M1-M5 mAChRs mGluRs NET NMDA OX1R OX2R/HCRT1 Tryptophan Hydroxylase VAChT α1 α2 β1-3

      Molecules

      Acetylcholine CRF Cytokines Dopamine GABA Ghrelin Glutamate Histamine Hypocretin/Orexin Leptin Neuropeptide Y Norepinephrine Opioid Oxytocin Serotonin Vasopressin

      Cells

      Basal Forebrain Nuclei Central Nucleus Amygdala Dorsal Raphe Lateral, perifornical, and dorsomedial hypothalamus LDT Locus Coeruleus PPT Tuberomammillary Nucleus Ventral Tegmental Area

      Circuits

      Basal forebrain nuclei to cortical circuits Brainstem monoaminergic and cholinergic projections to basal forebrain Central Amygdala to monoaminergic and basal forebrain cholinergic nuclei Cholinergic and monoaminergic nuclei projections to thalamic and cortical Circadian and Sleep-related circuits modulate arousal and are modulated by arousal Cortical circuits such as fronto-insular and dorsal anterior cingulate Hypothalamic to thalamic and cortical circuits Projections to midbrain and pontine monoaminergic and cholinergic nuclei Reciprocal hypothalamic Reciprocal NTS-Central N. Amygdala Reciprocoal cholinergic and monoaminergic projection

      Physiology

      EEG EMG ERP fMRI Neural activity Sex-Specific differences in arousal

      Autonomic

      Blood pressure Breathing Galvanic skin response Heart Rate Pupil size

      HPA axis

      ACTH CRF Glucocorticoids

      Behavior

      Affective states Agitation Cognition Emotional Reactivity Eye Blink Motivated Behavior Motor Activity Sensory Reactivity Startle Waking

      Self-Report

      ADACL POMS arousal subscale Self-assessment Mannequin

      Paradigms

      Actigraphy and other test of motor activity Auditory arousal threshold Cortisol awakening response EEG and EMG recording Eye-blink Eyelid closure fMRI/PET Indices of neural activity such as local field potentials and single neuron recordings Maintenance of wakefulness test Odd-ball tasks Psycho-motor vigilance and other continuous performance tasks Startle
    • Construct: Circadian Rhythms

      Genes

      Clock-controlled genes Epigenetic factors

      Canonical (Core) Clock Genes

      Bmal1 Bmal2 Clock Cry1,2 Npas2 Per1,2

      Clock-Associated Genes

      CK1 δ, ε CK2 α, β DEC2 Dio2 Dio3 FBXBL21 FBXL3 Gsk 3β Per3 Rev-Erbα, β Rorα, β

      Receptor Genes

      5HTr AMPAr GABAr MT1,2 NMDAr NPYr SPr VPAC1,2

      Transcription/Translation Factors

      cFos CREB Dbp JunB MAPK miRNA mTOR PGC1a

      Molecules

      Input

      5HT Dopamine GABA Glutamate Melanopsin NPY PACAP Substance P

      SCN Synchronizing and Modulating Agents

      AVP Calbindin cAMP cGMP NO Steroid hormones VIP

      Output

      AVP Cortisol GABA Melatonin VIP

      Cells

      Fibroblasts ipRGC medium spiny neurons Pars tuberalis cells Pineal cells rods and cones SCN “clock” cells

      Circuits

      Input

      Raphe to SCN projection Retinal cells Retino-hypothalamic tract Retinogeniculate tract

      Output

      Basolateral amygdala/ Hippocampus Central extended amygdala (central nucleus of the amygdala / Bed nucleus of the stria terminalis) HPA axis Hypothalamic neuroendocrine cell groups Hypothalamic orexin projections PVN, DMH, subparaventricular zone, PVT SCN/PVN/SCG/pineal Sympathetic / parasympathetic nervous system

      Intrinsic to SCN

      Suprachiasmatic nucleus (SCN) core/shell

      Seasonal

      SCN/PVN/SCG/pineal

      Physiology

      Gene expression Neural activity Neural transmitters

      Behavior

      Drive-regulated behaviors Locomotor activity Masking Neurobehavioral functions Sleep-rated and waking behaviors Sleep-wake

      Self-Report

      Diary-based measures of daily regularity/ rhythmicity (e.g., Social Rhythm Metric) Phase, diurnal preference, chronotype (e.g., Horne-Ostberg, CTQ) Sleepiness, alertness, well-being, mood

      Paradigms

      24 hour LD light/dark (LD) cycle (test for entrainment of rhythms) Actigraphy of human circadian rest-activity rhythms in the real world Acute melatonin suppression by light (relative index of the sensitivity of the circadian system to light, e.g. wavelength, intensity, duration curves) Bioluminscent/, fluorescent real-time gene expression imaging Dim Light Melatonin Onset (DLMO, phase estimate) Masking (e.g., sleep effect on cognitive behavioral therapy) Phase response curve (PRC, phase dependent effects of single light [or other stimulus] pulses delivered at different circadian phases) Pupillary light reflex (acute measure of rod, cone and melanopsin photosensitivity); Sensory threshold testing (ERG, ERP, etc.) Sleep measures (see Sleep-Wake paradigms) T cycles (non-24 hour LD cycles);

      Genetic Approaches – genome-wide association study, candidate gene, epigenomics, circadian genomics (temporal gene expression), mutagenesis, gene targeting, quantitative trait loci.

    • Construct: Sleep-Wakefulness

      Genes

      Genes with Sleep-Specific Effects

      Clock DEC2 Per3 Sur2

      Wakefulness

      Arousal and Circadian Rhythms genes also subserve wakefulness.

      Molecules

      Acetylcholine Adenosine CRF Cytokines Dopamine GABA Galanin Glutamate Histamine Hypocretin/Orexin Norepinephrine NPY Serotonin Vasopressin

      Cells

      Anterior hypothalamus and basal forebrain Brainstem (e.g., LC, Raphe, LDT/PPT, VTA) Lateral and perifornical hypothalamus Posterior hypothalamus (TMN) Thalamus (median thalamic nuclei, reticular nucleus)

      Circuits

      Sleep

      NREM (Forebrain)
      Basal forebrain and anterior hypothalamus projections to arousal promoting cell groups Thalamocortical
      REM (Brainstem)
      Mesopontine nuclei

      Wakefulness

      Arousal and Circadian Rhythms circuits also subserve wakefulness.

      Physiology

      Brain metabolic activity Capacity for wakefulness under low stimulation EEG sleep spindles EEG slow waves EEG theta rhythms EMG EOG NREM sleep and REM sleep Physiologic measures of sleepiness, homeostatic sleep drive during waking Sex-specific sleep physiology sleep hormones sleep latency Temporal and topographic organization of homeostatic sleep drive during sleep Temporal and topographic organization of sleep dynamics wakefulness

      Behavior

      Co-sleeping Intermediate/ admixed sleep-wake states Motor behaviors during sleep Rest-activity patterns Sensory arousal threshold Sex-specific sleep behaviors Sleep Sleep deprivation and satiation Sleep inertia Sleep timing and variability Sleep-dependent neurobehavioral functions Wakefulness

      Self-Report

      Alertness Dream reports Fatigue Sleep quality, restoration, quantity Sleep timing Sleep-modulated symptoms sleepiness Specific sleep symptoms

      Paradigms

      Arousal threshold testing Daily sleep diaries EEG Fear extinction fMRI Heart rate variability (HRV) Locomotor activity Maintenance of wakefulness testing Measurement of slow eye movements during wakefulness MEG Multiple sleep latency testing Neurobehavioral testing in relation to sleep Nocturnal polysomnography Non-24-hour sleep-wake schedules PET Self-report methods include retrospective symptom and sleep reports, daily sleep diaries Sleep-dependent memory consolidation, fear extinction TMS Total, partial, and stage-selective deprivation paradigms