Valence-specific effects of BDNF Val66Met polymorphism on dopaminergic stress and reward processing in humans.

Brain-derived neurotrophic factor (BDNF) levels in dopaminergic (DA) cells within the ventral tegmental area (VTA)/nucleus accumbens (NAc) circuitry appear to be a candidate mechanism for the neuroadaptive changes that follow stress and reward responses in animal models. However, the role of the BDNF gene variants in responses to salient cues through DA neurotransmission in humans remains unexplored. Here, we studied the effect of the common functional BDNF Val(66)Met (rs6265) polymorphism on rewarding experiences in the striatum and DA-mediated responses to stress. Seventy-two healthy controls were genotyped for the BDNF Val(66)Met polymorphism and underwent the monetary incentive delay task during an functional magnetic resonance imaging (fMRI) session. Forty-nine of them also underwent a sustained pain challenge with and without placebo administration with potential analgesic properties during PET measures of DA D2/3-receptor-mediated neurotransmission. Neuroimaging results revealed a significant effect of BDNF (Met(66) carriers > Val/Val) on brain responses during the anticipation of monetary losses, baseline D2/3 receptor availability, and pain-stress-induced DA release in the NAc. Conversely, BDNF Met(66) carriers showed no activation in response to monetary gains and a blunted DA response to the analgesic placebo in the NAc. These results provide initial human evidence regarding the effect of the BDNF Val(66)Met polymorphism on DA-mediated responses to stress, its cognitive regulation by positive expectations, and the anticipatory responses to monetary gains and losses in the VTA-NAc pathway. Our results are of relevance to the neurobiology of stress and reward interactions and the pathophysiology of stress-related disorders.

Somatosensory activity modulation during observation of other's pain and touch.

We examined whether somatosensory activity could be modulated by the observation of bodily experiences. For this purpose, somatosensory-evoked potentials elicited by non-painful stimulation were recorded when subjects were viewing a hand penetrated by a needle, touched by a cotton swab or at resting without stimulation. Participants were instructed to adopt an egocentric perspective when viewing the videos and to rate pain intensity and unpleasantness supposedly experienced by the model, as well as the unpleasantness induced by the video clips. Results indicated that pain videos were rated as more unpleasant than touch videos, and that observation of both pain and touch video clips led to a significant enhancement of P50 amplitudes as compared to viewing a hand without stimulation. Moreover, enhanced P50 amplitudes during observation of both pain and touch in others were associated with increased unpleasant ratings induced by the video clips, as well as with high scores in a perspective taking scale (IRI). These findings provide support for the involvement of an attentional bottom-up mechanism which could be responsible to enhance sensory processing of somatic information when observing bodily experiences in others irrespective of whether they are painful or not.

Disrupted functional connectivity of the pain network in fibromyalgia.

OBJECTIVE: To investigate the impact of chronic pain on brain dynamics at rest. METHODS: Functional connectivity was examined in patients with fibromyalgia (FM) (n = 9) and healthy controls (n = 11) by calculating partial correlations between low-frequency blood oxygen level-dependent fluctuations extracted from 15 brain regions. RESULTS: Patients with FM had more positive and negative correlations within the pain network than healthy controls. Patients with FM displayed enhanced functional connectivity of the anterior cingulate cortex (ACC) with the insula (INS) and basal ganglia (p values between .01 and .05), the secondary somatosensory area with the caudate (CAU) (p = .012), the primary motor cortex with the supplementary motor area (p = .007), the globus pallidus with the amygdala and superior temporal sulcus (both p values < .05), and the medial prefrontal cortex with the posterior cingulate cortex (PCC) and CAU (both p values < .05). Functional connectivity of the ACC with the amygdala and periaqueductal gray (PAG) matter (p values between .001 and .05), the thalamus with the INS and PAG (both p values < .01), the INS with the putamen (p = .038), the PAG with the CAU (p = .038), the secondary somatosensory area with the motor cortex and PCC (both p values < .05), and the PCC with the superior temporal sulcus (p = .002) was also reduced in FM. In addition, significant negative correlations were observed between depression and PAG connectivity strength with the thalamus (r = -0.64, p = .003) and ACC (r = -0.60, p = .004). CONCLUSIONS: These findings demonstrate that patients with FM display a substantial imbalance of the connectivity within the pain network during rest, suggesting that chronic pain may also lead to changes in brain activity during internally generated thought processes such as occur at rest.

Temporal dissociation in the brain processing of pain and anger faces with different intensities of emotional expression.

Facial expression is one of the most relevant nonverbal behaviors in the communication of pain. However, little is known about brain processing of pain expressions in comparison with other affective facial expressions. The present experiment aimed to examine the effects of pain expression intensity on affective ratings and brain dynamics by recording electroencephalography (EEG) from 20 female healthy volunteers 18-24 years of age. Participants were asked to rate the affective characteristics of 144 stimuli depicting facial expressions of pain and anger with 3 level of intensities (high, mild, and low), as well as neutral faces. Results indicated that pain faces were judged as more unpleasant and arousing than anger and neutral faces for all intensity levels. EEG results further showed that facial expressions of pain elicited more enhanced amplitudes of the visual evoked potentials than anger and neutral faces in the latency between 350 and 550 milliseconds after stimulus onset; whereas anger faces elicited greater P200 amplitudes than pain and neutral faces. In addition, more increased theta activity in the latency of 200 to 400 milliseconds after stimulus onset was observed to high-intense as compared with low-intense facial expressions. These findings indicate that brain activity elicited by affective faces is modulated by the intensity of facial expressions and suggest the involvement of different brain mechanisms during the processing and recognition of facial expressions of pain and anger in healthy volunteers.