Neurologically, how different is a happy brain from a sad brain?

Happiness and sadness are emotions, which are states. Although there may be structural differences in a person who is depressed (more prone to be in a “sad state”) versus a brain who has a more balanced tendency to exist in a state (a euthymic person), only functional neuroimaging can be used to study differences in brains between a “happy” and a “sad state. This is challenging, as happiness and sadness are emotions that are subjective, and inducing emotions in the setting of an MRI or PET is also difficult. Furthermore fMRI and PET scans measure metabolic changes in brain regions, meaning that they only demonstrate changes in the time frame of seconds to minutes after a state is induced. Now to the neuroscience of emotion.

Attempts to localize happiness or sadness to activity in certain brain regions has been more or less futile. This is because emotions involve complex circuitry, and many overlapping regions are activated in emotional processing. Furthermore, the method of emotional induction can cause differing regional changes. For example, if the method of inducing happiness is having a person reminisce about a happy time, temporal or hippocampal regions may be more involved, while viewing emotionally charged stimuli may involve visual cortices to a larger extent.

One ALE meta-analysis observed increased activity in the superior temporal gyrus in happiness (versus neutral emotional stimuli) and increased medial frontal gyrus activity in sadness. Another meta-analysis observed no difference between happiness and sadness, and found them both to activate the ACC and areas of the prefrontal cortex. This is likely because they are both involved in emotional processing. Another Meta analysis reported increased activity of the subcallosal cingulate cortex in sadness, versus increased activity in the basal ganglia in happiness. Other studies have utilized different emotional models compared to the traditional classification of “happiness” and “sadness”, instead comparing things like general emotional valence, or approach emotions vs retreat emotions. Complex multiaxis models of emotions have been used, and classification of emotional systems have also been used, which puts into perspective the complexity of affective neuroscience.

From a pharmacological point, euphoria, which is in a sense pure happiness, can be induced by opioids or high doses of psychostimulants. Reward can also be mediated by physical stimulation of the NAcc. Following this logic, the euphoria of cocaine has been associated with decreased BOLD of the NAcc (possibly representing a metabolic change associated with opioid release, not inactivation). If we view sadness through the lens of depression, which would be a longer term more intense version of normal everyday sadness, then sadness involves increased activity of the anterior cingulate cortex, with decreased activity of the striatum and dorsolateral prefrontal cortex. However, these differences may just represent emotional biases that lead to depression, and therefore is not a great guide to what a non-pathologically sad brain looks like.

So in summary, it is difficult to determine or localize sadness or happiness, given current methodological limitations, as well as the possible poor classifications of “happiness” and “sadness”. However, from Phan et al, the knowledge of the association between the NAcc (a region of the striatum) and reward, and the studies of depression, it can be inferred that sadness involves increaed activity in the anterior cingulate, and happiness involves increased activity of the striatum. Chemically, the reward elicited by drugs correlates not with dopamine release, but with the opioid release in the NAcc elicited by said drug. So chemically, happiness would be represented by increased NAcc opioid release, and sadness by the opposite. So in short

·         Happiness=Striatum-increased activity, NAcc-increased endogenous opioid release

·         Sadness=Anterior Cingulate Cortex-increased activity, NAcc-decreased endogenous opioid release

Reference: Alexander Saytsev