Skip to Content (press ENTER)
2023-12-20in-the-newsNews<p>In patients diagnosed with bipolar I disorder, researchers at Spaulding Rehabilitation Hospital and Massachusetts General Hospital did not find significant differences in brain perfusion between manic and euthymic states. Still, they found the cognitive impairments accompanying mania persisted into euthymia.</p>

Cognitive Dysfunction During Mania in Bipolar I Disorder Persists Into Euthymia

December 20,  2023
  • This study of patients with bipolar I disorder investigated brain perfusion during a manic episode and again in the euthymic state six months later, exploring potential associations between altered brain perfusion and cognitive status
  • During mania, the 17 patients demonstrated impairment in immediate verbal learning, verbal fluency, and processing speed. In the eight patients who were followed up six months later, these deficits persisted in the euthymic state
  • No significant changes in brain perfusion were observed between the manic and euthymic states, but there was a trend toward reduced perfusion of the right parietal cortex during mania and evidence of left-right perfusion imbalance during mania
  • These findings suggest cognitive impairment may persist in bipolar I disorder, highlighting the need for therapeutic interventions targeting cognitive deficits

In patients diagnosed with bipolar I disorder (BD-I), some research has linked the switch between mood states to changes in the laterality of brain perfusion (cerebral blood flow). Mania has been associated with right-hemisphere hypoperfusion and left-hemisphere hyper perfusion compared with neuroimaging done while patients were in the euthymic state.

During a previous study of this "laterality hypothesis," published in Brain and Behavior, researchers also explored cognitive status. In 10 patients with BD-I who were experiencing a manic episode, they detected a positive association between cognitive impairments and perfusion in the right temporal pole, as measured with single-photon emission CT (SPECT), plus a negative association with perfusion in the right hemisphere.

A larger, longitudinal study by the research group, published in Frontiers in Psychiatry, has provided evidence that partly supports the laterality hypothesis but mainly underscores the need for therapeutic interventions that target cognitive defects in BD-I.

The authors are Maria Anayali Estudillo-Guerra, MD, a research scientist at Spaulding Rehabilitation Hospital, Clas Linnman, PhD, director of the Spaulding Neuroimaging Laboratory, Monica Flores Ramos, of Instituto Nacional de Psiquiatría in Mexico City, and colleagues.


Conducted between March 2015 and March 2019, the study involved 17 adults, mean age 41, diagnosed with BD-I within the past five years. While experiencing a moderate or severe manic episode and not receiving pharmacologic therapy, they underwent SPECT and completed tests of immediate verbal learning, verbal fluency, and processing speed.

Six months later, while in a euthymic state, eight of the same patients were re-imaged and completed the same cognitive tests.

Cognitive Function

During the manic episode, scores for immediate verbal learning, fluency, and processing speed were below normal. These aspects of cognitive impairment persisted during the euthymic state.

Brain Perfusion

Brain perfusion did not differ significantly between the manic state and follow-up. However, at a less stringent threshold, trends toward significance were observed:

  • Decreased perfusion in the left cerebellum and right superior parietal cortex during mania
  • Higher perfusion imbalance in the left superior and middle frontal gyrus during mania and in the right superior and middle frontal gyrus during euthymia

No correlations were detected between brain perfusion, mania severity symptom ratings, and cognitive performance.

The Need for New Therapeutics

In this cohort, the average time since diagnosis was 2.5 years (range, 0–4) and the average number of previous manic episodes was 1.29 (range, 1–3). These characteristics suggest cognitive impairment can start early during the disorder. Besides impairing daily functioning, recurrent manic episodes might increase cognitive deficits over time.

Thus, there's a vital need to develop treatments that improve and maintain cognitive function in BD-I and to identify neural therapeutic targets specific to the patient's clinical state.

Learn about the Spaulding Neuroimaging Laboratory >

Refer a patient to Spaulding Rehabilitation >