Apathy might be more frequently associated with functional abilities and likely interact with the recovery process as compared with depression after stroke.

This study was designed to examine the correlation between damage to the basal ganglia or frontal lobe and depression status (both affective and apathetic dimensions) in 243 stroke patients. We assessed the affective dimension in post-stroke depression (PSD) using the Zung Self-rating Depression Scale (SDS) and the apathetic dimension in PSD using the apathy scale (AS). We classified basal ganglia or frontal lobe damage into four groups: no damage, damage to the left side only, damage to the right side only, and damage to both sides. Affective and/or apathetic PSD was found in 126 patients (51.9%). The severity of affective depression (SDS score) was associated with left frontal lobe (but not basal ganglia) damage, and that of apathetic depression (AS score) was related to damage to the bilateral basal ganglia (but not to the frontal lobe). The anatomical correlates of PSD differ depending on the PSD dimension (affective or apathetic) and may explain interstudy differences regarding the association between lesion location and type of PSD.

We studied the neural activation associated with the expectancy of emotional stimuli using whole brain fMRI. Fifteen healthy subjects underwent fMRI scanning during which they performed a warned reaction task using emotional pictures carrying pleasant, unpleasant, or neutral content. The task involved an expected or unexpected condition. Data were analyzed by comparing the images acquired under the different conditions. In the expected condition, compared with the unexpected condition, significant activation was observed in the medial, inferior and dorsolateral prefrontal cortex. Whereas the expectancy of pleasant stimuli produced activation in the left dorsolateral and left medial prefrontal cortex as well as in the right cerebellum, the expectancy of unpleasant stimuli produced activation in the right inferior and right medial prefrontal cortex, the right amygdala, the left anterior cingulate cortex, and bilaterally in the visual cortex. These results suggest that the expectancy of emotional stimuli is mediated by the prefrontal area including the medial, inferior, and dorsolateral prefrontal cortex. Furthermore, our data suggest that left frontal activation is associated with the expectancy of pleasant stimuli and that right frontal activation is associated with the expectancy of unpleasant stimuli. Finally, our findings suggest that the amygdala and anterior cingulate cortex may play an important role in the expectancy of unpleasant stimuli and that the input of this negative information is modulated by these specific brain areas.

Depression and apathy are often observed after stroke and are often confused with one another. In the present review, we argue that the current concept of 'post-stroke depression' (PSD) in fact consists of two core symptoms or syndromes: (i) affective (depressive) PSD; and (ii) apathetic PSD. We argue that these two core symptoms are each associated with a different underlying neuroanatomical mechanism, a pattern that influences functional recovery. Post-stroke disabilities can provoke several distinct emotional responses, some of which are associated with severe depression. We examined one of these emotional responses previously, namely 'insistence on recovery', which was believed to be a negative indicator of functional improvement in disabled stroke patients. However, an appropriate level of insistence on recovery may, in fact, be associated with reduced depression and apathy, resulting in enhanced recovery from stroke-related disabilities. Improvements in physical disabilities (trunk stability or activities of daily living, such as walking) also reduce depression and apathy. Therefore, the experience of PSD/apathy may be intertwined with various initial emotional responses and improvements in physical functioning. Effective treatment of PSD/apathy requires a multidisciplinary approach, such that neuroanatomical/neurobiological, emotional, and physical (rehabilitation) domains are all addressed.

Despite novel antidepressant development, 10–30% of patients with major depressive disorder (MDD) have antidepressant treatment-resistant depression (TRD). Although new therapies are needed, lack of knowledge regarding the neural mechanisms underlying TRD hinders development of new therapeutic options. We aimed to identify brain regions in which spontaneous neural activity is not only altered in TRD but also associated with early treatment resistance in MDD. Sixteen patients with TRD, 16 patients with early-phase non-TRD and 26 healthy control (HC) subjects underwent resting-state functional magnetic resonance imaging. To identify brain region differences in spontaneous neural activity between patients with and without TRD, we assessed fractional amplitude of low-frequency fluctuations (fALFF). We also calculated correlations between the percent change in the Hamilton Rating Scale for Depression (HRSD17) scores and fALFF values in brain regions with differing activity for patients with and without TRD. Patients with TRD had increased right-thalamic fALFF values compared with patients without TRD. The percent change in HRSD17 scores negatively correlated with fALFF values in patients with non-TRD. In addition, patients with TRD showed increased fALFF values in the right inferior frontal gyrus (IFG), inferior parietal lobule (IPL) and vermis, compared with patients with non-TRD and HC subjects. Our results show that spontaneous activity in the right thalamus correlates with antidepressant treatment response. We also demonstrate that spontaneous activity in the right IFG, IPL and vermis may be specifically implicated in the neural pathophysiology of TRD.