Bipolar Disorder (BD) is a complex mood condition characterized by significant shifts in mood, energy, and activity levels. These fluctuations suggest a biological basis, leading researchers to use neuroimaging to investigate its underlying mechanisms. While brain scans are powerful tools for understanding the neurobiology of BD, they are not currently used to diagnose the condition. The current role of imaging is to identify patterns and differences that may lead to objective diagnostic markers in the future.
Brain Scans in Clinical Diagnosis Versus Research
The diagnosis of bipolar disorder remains a clinical process, relying on a detailed patient history and behavioral observations. Clinicians do not use a brain scan as a standalone test because no single, consistent finding exists across all individuals with the condition. The differences observed in the brains of people with BD are often subtle, varying with mood state, medication use, and illness duration.
If a doctor orders a brain scan, it is typically to rule out other medical conditions that could be mimicking psychiatric symptoms, such as a tumor or stroke. This is a safety measure to exclude neurological causes, not a diagnostic step for BD itself. Research, by contrast, focuses on finding patterns across large groups of people to identify a “biomarker” that could supplement the clinical interview.
The observed brain differences are not yet reliable or specific enough to serve as a routine diagnostic tool for an individual patient. A reliable clinical biomarker must consistently distinguish a person with BD from a healthy person and from someone with a different condition, such as major depressive disorder. Current imaging studies identify group-level differences, but they do not provide the definitive, individual-level answer needed for a clinical diagnosis today.
Imaging Technologies Used to Study Bipolar Disorder
Researchers use several types of advanced neuroimaging technologies to investigate the brain’s anatomy and function in bipolar disorder. Structural scans, such as Magnetic Resonance Imaging (MRI), capture high-resolution images of the physical brain structure. These scans measure the size, shape, and volume of different regions, as well as the thickness of the cortex.
To examine the brain’s wiring, Diffusion Tensor Imaging (DTI) maps the integrity and direction of white matter tracts, which are bundles of nerve fibers connecting different brain areas. Functional scans, like functional MRI (fMRI), measure brain activity by detecting changes in blood flow. Positron Emission Tomography (PET) scans also measure brain activity, sometimes using radioactive tracers to measure glucose metabolism or receptor density.
Magnetic Resonance Spectroscopy (MRS) is used to non-invasively measure the concentration of specific neurochemicals in the brain. This range of technologies allows scientists to investigate both the fixed architecture and the dynamic processes of the bipolar brain.
Observed Structural Differences in the Bipolar Brain
Structural neuroimaging studies consistently indicate subtle anatomical differences in the brains of individuals with bipolar disorder. A frequently reported finding is a reduction in gray matter volume and density in specific areas of the prefrontal cortex. This region is involved in executive functions like decision-making, emotional regulation, and impulse control.
Researchers have noted reduced volume in the medial prefrontal cortex and the anterior cingulate cortex, both central to regulating mood and attention. Subcortical structures also show alterations, with studies reporting volume changes in the amygdala and hippocampus. The amygdala is involved in emotional processing, and the hippocampus is linked to memory and stress response.
The brain’s white matter, which facilitates communication between regions, also appears to be affected in BD. Studies using DTI indicate changes in the integrity of these white matter pathways, suggesting altered connectivity between distant brain areas. Longitudinal research suggests that individuals experiencing more manic episodes may exhibit faster rates of frontal cortical thinning over time.
Observed Functional and Connectivity Differences
Functional imaging reveals that the bipolar brain processes information and emotions differently, particularly in how various regions communicate. A key finding is the dysregulation between the brain’s emotional processing centers (the limbic system) and its higher-level control centers in the prefrontal cortex. This imbalance is characterized by reduced functional connectivity between the ventrolateral prefrontal cortex and the amygdala, suggesting a weakened ability to modulate strong emotional responses.
Activity levels in the prefrontal cortex fluctuate depending on the current mood state, showing decreased metabolic activity during depressive phases. Individuals with BD may also show altered activity in the ventral prefrontal cortex when performing emotional tasks, pointing to a difference in how they process and regulate feelings. These activity shifts are linked to specific brain networks that work together to maintain normal functioning.
Research has focused on three major networks: the Default Mode Network (DMN), the Salience Network (SN), and the Central Executive Network (CEN). The DMN, active during internal reflection, and the SN, which identifies important stimuli, show altered functional connectivity in BD. For example, during a manic episode, individuals may show reduced connectivity within the DMN and increased connectivity within the SN, reflecting a shift toward external, attention-driven processes.