Project Grant R01NS136739

CORTICOTHALAMIC NETWORK FUNCTION IN CHRONIC PAIN - PROJECT SUMMARY THIS STUDY FOCUSES ON UNDERSTANDING THE COMPLEX NATURE OF CHRONIC PAIN BY INVESTIGATING THE COMMUNICATION BETWEEN DISTINCT BRAIN CIRCUITS. WE AIM TO UNRAVEL THE MECHANISMS BY WHICH SOMATOSENSORY, COGNITIVE, AND AFFECTIVE INFORMATION IS INTEGRATED TO PRODUCE THE PERCEPT OF PAIN. BY STUDYING NETWORK DYNAMICS ACROSS KEY BRAIN REGIONS USING DIRECT INTRACRANIAL RECORDINGS AND GRAPH THEORY APPROACHES, WE WILL ELUCIDATE SPATIOTEMPORAL ACTIVITY PATTERNS THAT UNDERLIE THE AFFECTIVE AND COGNITIVE DIMENSIONS OF PAIN. PREVIOUS STUDIES HAVE IDENTIFIED SPECIFIC BRAIN REGIONS, SUCH AS THE ANTERIOR CINGULATE CORTEX (ACC), MEDIAL PREFRONTAL CORTEX (MPFC), INSULA, SENSORY AND MEDIAL THALAMUS, PERIVENTRICULAR GREY MATTER, AND PRIMARY SENSORIMOTOR CORTICES, AS CRUCIAL HUBS INVOLVED IN REGULATING CHRONIC PAIN TRAITS. HOWEVER, THE DYNAMIC FUNCTIONING OF THESE NETWORKS IN INFLUENCING THE FLUCTUATING NATURE OF CHRONIC PAIN, WHICH CAN VARY OVER MINUTES TO DAYS, REMAINS LESS UNDERSTOOD. TO BRIDGE THIS KNOWLEDGE GAP, THE STUDY PROPOSES THE USE OF DIRECT INTRACRANIAL RECORDINGS FROM PATIENTS WITH CHRONIC PAIN AND COMBINES THEM WITH GRAPH THEORY APPROACHES TO ANALYZE NETWORK DYNAMICS. WE AIM TO STUDY PAIN CIRCUITS IN THE LABORATORY AND NATURALISTIC ENVIRONMENTS BY INVESTIGATING THE IMPACT OF EXPECTATION AND MOOD ON DESCENDING CIRCUITS AND DETERMINING IF THEY INFLUENCE PAIN THROUGH SIMILAR MECHANISMS. THE HYPOTHESIS IS THAT BRAIN STIMULATION RELIEVING PAIN ENGAGES DESCENDING CONTROL MECHANISMS SIMILAR TO POSITIVE MOOD OR EXPECTATION, WHILE A BREAKDOWN IN CORTICOTHALAMIC FUNCTIONAL CONNECTIVITY IS ASSOCIATED WITH EPISODES OF ELEVATED PAIN. THE STUDY PROPOSES THREE SPECIFIC AIMS. AIM 1 INVOLVES ANALYZING INTRACRANIAL RECORDINGS FROM CHRONIC PAIN PATIENTS TO TRACK CHANGES IN FUNCTIONAL CONNECTIVITY WITHIN CORTICOTHALAMIC NETWORKS DURING SPONTANEOUS PAIN AND PAIN-RELIEVING BRAIN STIMULATION. AIM 2 FOCUSES ON EXAMINING THE INTERACTION BETWEEN ASCENDING AND DESCENDING CIRCUITS DURING A COGNITIVE PAIN-EXPECTATION TASK USING RECORDINGS FROM PATIENTS WITH DBS ELECTRODES. AIM 3 INVESTIGATES THE ROLE OF AFFECTIVE STATE ON PAIN PERCEPTION AND DESCENDING PAIN CIRCUITS DURING A MOOD MODULATING TASK. OUR GROUP AIMS TO IDENTIFY PATTERNS OF FUNCTIONAL CONNECTIVITY AND COHERENCE BETWEEN KEY BRAIN HUBS, SUCH AS THE ACC, MEDIAL PREFRONTAL CORTEX, INSULA, AND THALAMUS, AND UNDERSTAND THEIR RELATIONSHIP WITH PAIN PERCEPTION. BY CLARIFYING THE UNDERLYING MECHANISMS OF CHRONIC PAIN AND THE EFFECTS OF BRAIN STIMULATION, MOOD, AND EXPECTATION, THIS STUDY HAS THE POTENTIAL TO CONTRIBUTE TO THE DEVELOPMENT OF NOVEL DIAGNOSTIC TOOLS AND MORE EFFECTIVE TREATMENTS FOR CHRONIC PAIN DISORDERS.