After years of trying, a group of researchers down at UCLA (led by Lori Altshuler) may have succeeded in identifying important changes in brain function that are associated with bipolar moods.
They have found two specific areas of the brain that show pretty consistent changes associated with bipolar. One area (the orbitofrontal cortex) is generally less activated in bipolar, no matter what the mood. Another part of the brain (the amygdala) is overactive in mania, underactive in depression and has about the same activity as seen in folks without bipolar, when the bipolar person is in a “normal” or euthymic mood.
Another great thing about this study is that it looked at folks with bipolar 2 (associated with less extreme manias than bipolar 1 and, although more common than type 1, studied a lot less). Other groups have seen the same thing in patients with bipolar 1.
What are these two areas?
The orbitofrontal cortex, sits essentially at the bottom of the frontal lobe, right above the nasal cavity.
It is the area of the frontal cortex (the planning part of the brain) that is specifically focused on anticipating emotional responses to decisions. So, if you are trying to decide whether spending much money on therapy or buying a new speed boat is going to make you happier, it is your orbitofrontal cortex that is doing the heavy lifting. Similarly, if you are trying to figure out if cheating on your wife is more likely to make you happy or sad, it is again the OFC that is working on the problem.
And in folks with bipolar it seems this area is less active no matter what the mood.
On the other hand, the amygdala is about motivating behavior. It is a relatively non-specific “knee jerk” reactor to 
good and bad events. As an example, it seems to be because of amygdala activity that folks with depression respond with fear when they see sad pictures, whereas folks who are not depressed don’t react that way. Think of it this way, the amygdala is the part of the brain that says, these are good times, or watch out…. It is not about making subtle decisions or planning behavior.
And in folks with bipolar, amygdala activity goes up and down depending on mood. In other words, this internal emotional processor is extra active, perhaps precisely because the thinking emotional things out part of the brain is less active.
In the bipolar brain, in mania, the amygdala activates behavior regardless of the specific situation (the risks, for instance, of starting a new relationship or buying an expensive car) and in depression it reduces the ability to act, whether or not the outside world is objectively safe.
Hence the solution in terms of therapies might focus on ways of activating the brain’s own emotional thinker – the orbitofrontal cortex.
For folks interested in the details,the picture at right shows brain activity in these two regions. in the bipolar amygdala (top graph) brain activity is determined by mood (this is not true in non-bipolar folks to anywhere near this degree). In the bipolar orbitofrontal cortex (bottom line) activity is uniformally lower than in non bipolar folks, no matter what the mood.
Ahmad R. Hariri; The Highs and Lows of Amygdala Reactivity in Bipolar Disorders. American Journal of Psychiatry. 2012 Aug;169(8):780-783.