Similar to functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS) detects the changes of hemoglobin species inside the brain, but via differences in optical absorption. Within the near-infrared spectrum, light can penetrate biological tissues and be absorbed by chromophores, such as oxyhemoglobin and deoxyhemoglobin. What makes fNIRS more advantageous is its portability and potential for long-term monitoring. This paper reviews the basic mechanisms of fNIRS and its current clinical applications, the limitations toward more widespread clinical usage of fNIRS, and current efforts to improve the temporal and spatial resolution of fNIRS toward robust clinical usage within subjects. Oligochannel fNIRS is adequate for estimating global cerebral function and it has become an important tool in the critical care setting for evaluating cerebral oxygenation and autoregulation in patients with stroke and traumatic brain injury. When it comes to a more sophisticated utilization, spatial and temporal resolution becomes critical. Multichannel NIRS has improved the spatial resolution of fNIRS for brain mapping in certain task modalities, such as language mapping. However, averaging and group analysis are currently required, limiting its clinical use for monitoring and real-time event detection in individual subjects. Advances in signal processing have moved fNIRS toward individual clinical use for detecting certain types of seizures, assessing autonomic function and cortical spreading depression. However, its lack of accuracy and precision has been the major obstacle toward more sophisticated clinical use of fNIRS. The use of high-density whole head optode arrays, precise sensor locations relative to the head, anatomical co-registration, short-distance channels, and multi-dimensional signal processing can be combined to improve the sensitivity of fNIRS and increase its use as a widespread clinical tool for the robust assessment of brain function.

Background Recent neuroimaging studies have demonstrated resting-state functional connectivity (rsFC) abnormalities among intrinsic brain networks in Major Depressive Disorder (MDD); however, their role as predictors of treatment response has not yet been explored. Here, we investigate whether network-based rsFC predicts antidepressant and placebo effects in MDD. Methods We performed a randomized controlled trial of two weeklong, identical placebos (described as having either “active” fast-acting, antidepressant effects or as “inactive”) followed by a ten-week open-label antidepressant medication treatment. Twenty-nine participants underwent a rsFC fMRI scan at the completion of each placebo condition. Networks were isolated from resting-state blood-oxygen-level-dependent signal fluctuations using independent component analysis. Baseline and placebo-induced changes in rsFC within the default-mode, salience, and executive networks were examined for associations with placebo and antidepressant treatment response. Results Increased baseline rsFC in the rostral anterior cingulate (rACC) within the salience network, a region classically implicated in the formation of placebo analgesia and the prediction of treatment response in MDD, was associated with greater response to one week of active placebo and ten weeks of antidepressant treatment. Machine learning further demonstrated that increased salience network rsFC, mainly within the rACC, significantly predicts individual responses to placebo administration. Conclusions These data demonstrate that baseline rsFC within the salience network is linked to clinical placebo responses. This information could be employed to identify patients who would benefit from lower doses of antidepressant medication or non-pharmacological approaches, or to develop biomarkers of placebo effects in clinical trials.

Dopamine (DA) neurotransmission within the brain’s reward circuit has been implicated in the pathophysiology of depression and in both, cognitive and pharmacological mechanisms of treatment response. Still, a direct relationship between measures of DA neurotransmission and reward-related deficits in patients with depression has not been demonstrated. To gain insight into the symptom-specific alterations in the DA system in patients with depression, we used positron emission tomography (PET) and the D2/3 receptor-selective radiotracer [11C]raclopride in twenty-three non-smoking un-medicated Major Depressive Disorder (MDD) patients and sixteen healthy controls (HC). We investigated the relationship between D2/3 receptor availability and baseline measures of depression severity, anxiety, anhedonia, and cognitive and pharmacological mechanisms of treatment response. We found that, compared to controls, patients with depression showed greater D2/3 receptor availability in several striatal regions, including the bilateral ventral pallidum/nucleus accumbens (vPAL/NAc), and the right ventral caudate and putamen. In the depressed sample, D2/3 receptor availability in the caudal portion of the ventral striatum (NAc/vPAL) correlated with higher anxiety symptoms, whereas D2/3 receptor availability in the rostral area of the ventral striatum correlated negatively with the severity of motivational anhedonia. Finally, MDD non-remitters showed greater baseline anxiety, greater D2/3 availability in the NAc/vPAL, and greater placebo-induced DA release in the bilateral NAc. Our results demonstrate abnormally high D2/3 receptor availability in the ventral striatum of patients with MDD, which seem to be associated with comorbid anxiety symptoms and lack of response to antidepressants.

The hormone serotonin (5-hydroxytryptamine) has been implicated as the cause of the diarrhea seen in many patients with the carcinoid syndrome. To determine whether serotonin is an intestinal secretagogue, the effect of serotonin on intestinal water and electrolyte transport was evaluated in the rabbit. Two weeks of daily subcutaneous injection of serotonin suspended in oil resulted in a blood serotonin level elevated to twice that of controls. Intestinal transport was studied in vivo by a perfusion technique. Serotonin treatment resulted in ileal secretion and decreased mid-jejunal absorption of water and electrolytes but did not effect water absorption in the proximal jejunum or colon. Intestinal absorption of D-glucose and the amino acid L-tryptophan and glucose-dependent water and electrolyte absorption were normal in serotonin-treated animals. Serotonin-induced ileal secretion was reversed by methysergide, a peripheral antagonist of serotonin action. No alterations in intestinal histology or permeability occurred in serotonin-treated animals. Serotonin-induced intestinal secretion was not associated with alterations in the activities of intestinal mucosal adenylate cyclase, cyclic nucleotide phosphodiesterase, or Na-K-ATPase.

Brain-derived neurotrophic factor (BDNF) levels in dopaminergic (