Combined Functional MRI and Intracranial Recordings in Humans

Massachusetts General Hospital, Boston MA

Investigators

Abstract

With National Science Foundation support, Dr. Bush and colleagues will conduct a three-year project aimed at combining functional magnetic resonance imaging (fMRI) and intracranial recordings (ICR) with validated tasks to provide vital new data about (1) The neural mechanisms and interactions of cognition, emotion and vigilance, (2) the relationships between both increases and decreases in neuronal activity and the fMRI response, and (3) local and distant cortical responses to acute brain lesions. While the studies will involve patients having brain surgery for intractable illnesses (obsessive-compulsive disorder, depression, or seizures), the investigations are not focused on pathophysiology or treatment. Instead, we seek to take advantage of these rare opportunities to obtain both fMRI measures and neuronal recordings in essentially cognitively intact humans in order to address a number of unresolved neuroscientific and neuroimaging questions. Three groups of experiments are proposed. First, we will study the neural substrate of cognitive-emotional-vigilance interactions and fMRI signal decreases. Meta-analyses and pilot dataindicate that cognitive challenges decrease fMRI signal in brain regions that monitor/regulate the internal state (emotions, motivation) like perigenual anterior cingulate cortex (pACC)/ventromedial prefrontal cortex (vmPFC), and in those that monitor the external environment (vigilance) like amygdala, posterior cingulate cortex (PCC), and portions of posterior parietal cortex. Few studies have focused on fMRI signal decreases, and neuronal contributions to this effect are unknown. We will combine fMRI and ICR to demonstrate double dissociations. We predict: (1) cognitive challenge will activate task-specific cognitive brain areas (dorsal anterior cingulate cortex [dACC], dorsolateral prefrontal cortex [DLPFC]), emotional stimuli will activate pACC, and fearful faces will activate amygdala, (2) cognitive challenge will conversely decrease fMRI signal and neuronal activity in emotion-vigilance regions (pACC/vmPFC, amygdala, and PCC). The second group of experiments will combine fMRI and ICR to extend prior work on local cortical heterogeneity.a concept important for cognitive neuroscience and for understanding the neuron-fMRI relationship. Monkey single unit studies indicate many cortical areas are heterogeneous (i.e., contain different functional cell types, such as anticipation/timing, target detection, response selection, and feedback cells), and that the proportions of these cells vary regionally. Our study (Bush et al, 20021) showed regional cellular proportion data from monkeys could be used to predict parametric fMRI responses in human dACC, but direct quantification of cortical composition of humans is needed. We will combine fMRI and ICR to: (1) confirm local heterogeneity in human dACC, pACC, and DLPFC and parietal cortex, and (2) quantify and compare regional proportions of each cell type. The third group of experiments will use longitudinal fMRI and behavioral measures to assess local and distributed cortical plasticity and recovery processes that occur in response to a focal cerebral lesion (cingulotomy). This proposal is ideally suited for this funding mechanism, as it: (1) represents innovative research that will advance our understanding of the neural bases of cognition, emotion and vigilance, (2) will provide a more sophisticated understanding of how cognitive, emotional and vigilance processes interact and influence one another, (3) will provide important new data on the relationship between parametric increases and decreases in neuronal activity and the measured fMRI response, knowledge that is crucial to the proper interpretation of virtually all types of functional neuroimaging studies (fMRI, PET and SPECT), (4) will help delineate separate roles for pACC and amygdala, (5) uses a rarely available approach (combined fMRI and ICR), (6) leverages studies of clinical populations with adventitious lesions to elucidate normal brain mechanisms, (7) studies a new concept (local intracortical heterogeneity), (8) will establish and quantify local intracortical heterogeneity of different regions, a concept essential to the development of neurobiologically accurate computational models of cognitive, emotional and perceptual processes, (9) will help link comparative human and monkey studies, (10) will provide new data on cortical plasticity and recovery of function following focal cerebral lesions, and (11) can improve future studies of local and distributed (interregional) network interactions. This proposal outlines specific plans for education and training at multiple levels (from independent investigators and postdoctoral students down to middle school levels). In addition to disseminating findings through publications, scientific meetings, and invited lectures, we are already planning two separate workshops and a freely available database. It will broaden participation of underrepresented groups (the PI, being one of few minority fMRI researchers, actively supports diversity efforts). It will provide infrastructure support for future combined fMRI-ICR studies and strengthen nascent collaborative relationships. Finally, there are many potential benefits to society. (1) Improved understanding of cognitive, emotional and vigilance processes can help those with cognitive or mood disorders (ADHD, schizophrenia, Alzheimer's, depression, anxiety and bipolar disorder). (2) It can have a direct benefit for those who will be surgically treated for intractable OCD, depression, epilepsy, and pain. (3) Better understanding of cerebral recovery can help those with neurological insults like strokes or traumatic brain injuries. (4) Better understanding of reward circuitry and impulse inhibition may help those with impulse control and substance abuse disorders.