Arif Najib’s scientific contributions

Separation from loved ones commonly leads to grief reactions. In some individuals, grief can evolve into a major depressive episode. The brain regions involved in grief have not been specifically studied. The authors studied brain activity in women actively grieving a recent romantic relationship breakup. It was hypothesized that while remembering their ex-partner, subjects would have altered brain activity in regions identified in sadness imaging studies: the cerebellum, anterior temporal cortex, insula, anterior cingulate, and prefrontal cortex. Nine right-handed women whose romantic relationship ended within the preceding 4 months were studied. Subjects were scanned using blood-oxygen-level-dependent functional magnetic resonance imaging while they alternated between recalling a sad, ruminative thought about their loved one (grief state) and a neutral thought about a different person they knew an equally long time. Acute grief (grief minus neutral state) was associated with increased group activity in posterior brain regions, including the cerebellum, posterior brainstem, and posterior temporoparietal and occipital brain regions. Decreased activity was more prominent anteriorly and on the left and included the anterior brainstem, thalamus, striatum, temporal cortex, insula, and dorsal and ventral anterior cingulate/prefrontal cortex. When a more lenient statistical threshold for regions of interest was used, additional increases were found in the lateral temporal cortex, supragenual anterior cingulate/medial prefrontal cortex, and right inferomedial dorsolateral prefrontal cortex, all of which were adjacent to spatially more prominent decreases. In nearly all brain regions showing brain activity decreases with acute grief, activity decreases were greater in women reporting higher grief levels over the past 2 weeks. During acute grief, subjects showed brain activity changes in the cerebellum, anterior temporal cortex, insula, anterior cingulate, and prefrontal cortex, consistent with the hypothesis. Subjects with greater baseline grief showed greater decreases in all these regions except for the cerebellum. Further imaging studies are needed to understand the relationship between normal sadness, grief, and depression.

Background: Separation from loved ones commonly leads to grief reactions, and in some individuals, grief can evolve into an episode of major depression. Here, we studied brain regions involved when women think sad thoughts about their recent romantic relationship breakup. We hypothesized that while ruminating about their loved one, these grieving women would have altered brain activity in regions identified in earlier sadness imaging studies (specifically, the dorsolateral prefrontal cortex, anterior temporal poles, orbitofrontal cortex, medial prefrontal cortex, anterior cingulate, insular cortex, and cerebellum). Methods: We recruited nine right-handed adult women who had a long-standing romantic relationship end within the past two months. These subjects were scanned using BOLD-fMRI while they alternated between recalling a sad, ruminative thought about their breakup from their loved one (RUM) and a neutral thought about a person they knew equally long (NEU). We compared group fMRI signal intensity differences between RUM and NEU using random effects analyses. Results: Ruminating about the loved one was associated with increased activity (RUM-NEU) in the right cerebellum, right pons, right parahippocampal gyrus, right posterior cingulate and bilateral occipital cortex and decreased activity (NEU-RUM) on the left side in the hypothalamus/anterior midbrain, basal ganglia (putamen, globus pallidus), medial temporal lobe (amygdala, uncus, hippocampus), lateral temporal lobe, orbitofrontal cortex, insula, dorsolateral prefrontal cortex, motor cortex and somatosensory cortex. Conclusions: The activity changes in insula and cerebellum are consistent with non-specific sadness induction in healthy volunteers. The dorsolateral prefrontal and orbitofrontal cortex activity changes are consistent with studies of depressed subjects. Further imaging studies are needed to understand the brain mechanisms by which some individuals spiral into an episode of depression.

In summary, rTMS is a safe, relatively noninvasive new technology that allows for the direct stimulation of cortical brain regions. It appears that rTMS at different frequencies has divergent effects on brain activity and can modulate mood in health and disease. The clinical role of rTMS in treating depression remains unclear. Many different groups are studying TMS effects on mood and the field is advancing rapidly. TMS is an exciting area with promise as a research and clinical tool.