Investigation of memory related cortical thalamic circuitry in the human brain

This dissertation examined the role of medial prefrontal cortex (mPFC) and the hippocampus (HC) in episodic memory, and provides a novel approach to identify the midline thalamus mediating mPFC-HC interactions in humans. The mPFC and HC are critical to the temporal organization of episodic memory, and these interactions are disrupted in several mental health and neurological disorders. In the first study, I provide evidence that the mPFC is involved in ordinal retrieval, and the HC is active in temporal context retrieval in remembering the order of when events happen. In the second study, I focus on the anatomical basis of the mPFC-HC interactions which is reliant on the midline thalamus. I review in detail the anatomy of the midline thalamus both in location, and connectivity profile with the rest of the brain comparing the extensive anatomical evidence in rodents with the available evidence in monkeys and humans. This section also elaborates on the role of the midline thalamus in memory, stress regulation, wakefulness, and feeding behavior, and how pathological markers along the midline thalamus are a vanguard of several neurological disorders including Alzheimer’s Disease, schizophrenia, depression, and drug addiction. Lastly, I devised a new approach to identify the midline thalamus in humans in vivo using diffusion weighted imaging, capitalizing on known fiber connections gleaned from non-human animals, focusing on connections between the midline thalamus and the mPFC, medial temporal lobe and the nucleus accumbens. The success of this approach is promising for translational imaging. Overall, this dissertation provides new evidence on 1) complementary functional roles of the mPFC and HC in sequence memory, 2) a cross-species anatomical framework for understanding the midline thalamus in humans and neurological disorders, and 3) a new method for non-invasive identification of the midline thalamus in humans in vivo. Thus, this dissertation provides a new fundamental understanding of mPFC-midline thalamic-HC circuit in humans and tools for its non-invasive study in human disease.

Major Professor: Dr. Timothy Allen