Neuroscience Treatment of Bipolar Disorder

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I propose a new treatment for Bipolar Disorder (BD) based on electrical activation of the brain instead of drugs. The standard treatment of BD is not effective for many patients, lithium and other BD drugs can have onerous side effects, while the rate of suicide remains high. I suggest that manic and depressive phases in BD result from a failure of interhemispheric inhibition in the frontal lobes. Non-invasive electrical stimulation of the skull (TMS) may redress that failure.

Lesions to the right frontal lobe often lead to manic episodes and lesions to the left frontal lobe often lead to depression. Bipolar patients, however, do not have such lesions to the frontal lobes. What brain states could be the temporary equivalent of those lesions? They must be temporary, since in BD we have alternations between manic and depressive phases, with “neutral” periods called “euthymic.” In answering this question, I thought of an analogy to attention. In some mechanisms of attention the right and left hemispheres inhibit each other but tend to reach an equilibrium between them. Otherwise, if the left side, say, overwhelms the right, a person would be unable to consciously experience objects presented to his or her left visual field (which is handled by the right hemisphere) when similar objects are presented to the right visual field. This is the disturbing phenomenon called “extinction.” I then proposed the hypothesis that a similar failure of interhemispheric inhibition takes place in the frontal lobes of bipolar patients. To be specific, when the electrical activation of the left side overwhelms that of the right, the left frontal lobe dominates, thus leading to exaggerated states of elation (mania). Dominance in activation by the right side, in turn, leads to states of depression.

The neuroscience literature offers much support, e.g. large left-activation asymmetries in mania. We experimentally controlled left elation by right frontal lobe activation. Moreover, raising electrical activity in the left frontal lobe is now FDA-approved to treat monopolar depression. Using stem cell techniques, cultures of neurons developed from skin cells of bipolar patients exhibited electrical hyperactivity, likely because neurons coming from bipolar patients had more calcium ion channels. This unusual hyperactivity may explain why the frontal lobe inter-hemispheric inhibition mechanism gets stuck in a manic or a depressive phase, instead of returning to near equilibrium.

The idea is to determine such hyperactivity by using a new functional brain-imaging technology based on qEEG: standardized weighted low-resolution electromagnetic tomography (swLORETA). Its spatial resolution is good, while its temporal resolution is excellent, down to perhaps 2 milliseconds (a great advantage over fMRI, which has a temporal resolution of seconds). Another great advantage of swLORETA is the cost, in the thousands of dollars, as compared to the millions of dollars needed for an fMRI lab. It is also highly portable and flexible, key to treatment, which would consist in the restoration of interhemispheric inhibition balance using transcranial magnetic stimulation (TMS).

Success would lead to similar treatments for other brain disorders.


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  • Name:
    Gonzalo Munevar
  • Type of entry:
  • Profession:
  • Gonzalo is inspired by:
    Discovering how the brain works.
  • Software used for this entry:
    swLORETA (sLORETA for prototype)
  • Patent status: