scholarly journals Human ventromedial prefrontal cortex lesions enhance expectation-related pain modulation

2021 ◽  
Author(s):  
JC Motzkin ◽  
J Hiser ◽  
I Carroll ◽  
R Wolf ◽  
MK Baskaya ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Brain Damage ◽  
Pain Sensitivity ◽  
Sensory Information ◽  
Ventromedial Prefrontal Cortex ◽  
Pain Processing ◽  
Expectancy Effects ◽  
Cognitive Representations ◽  
The Impact ◽  
Pain Unpleasantness

AbstractPain is strongly modulated by expectations and beliefs. Research across species indicates that subregions of the ventromedial prefrontal cortex (VMPFC) play a fundamental role in learning and generating predictions about valued outcomes. Consistent with this overarching framework, neuroimaging studies of experimental pain indicate that VMPFC activation tracks expectations of pain relief and statistically mediates expectation-related reductions in responses to painful stimuli across a distributed pain processing network. However, lesion studies in preclinical models and in humans with refractory chronic pain suggest that VMPFC may play a more general role in representing the affective and motivational qualities of pain that contribute to its strong aversive drive. To test whether VMPFC is necessary for pain processing in general, or instead plays a more specific role in the modulation of pain by expectations, we studied responses to experimental heat pain in five adults with bilateral surgical lesions of VMPFC and twenty healthy adults without brain damage.All participants underwent quantitative sensory testing (QST) to characterize pain sensitivity, followed by a pain expectancy task. Participants were instructed that auditory cues would be followed by heat calibrated to elicit low or high pain. Following a conditioning phase, each cue was intermittently paired with a single temperature calibrated to elicit moderate pain. We compared ratings of moderate heat stimuli and subjective expectancy ratings as a function of cue to evaluate whether VMPFC lesions impact cue-based expectancy and expectancy effects on pain intensity and unpleasantness. We also analyzed QST measures to evaluate whether VMPFC lesions were associated with overall shifts in pain sensitivity.Compared to adults without brain damage, individuals with VMPFC lesions reported larger differences in expectations as a function of pain-predictive cues, and stronger cue-based modulation of pain ratings, particularly for ratings of pain unpleasantness. There were no group differences in pain sensitivity, nor in the relationship between pain and autonomic arousal, indicating that the impact of VMPFC lesions is specific to expectancy-based modulation of pain unpleasantness.Our findings suggest that the VMPFC is not essential for basic subjective and physiological responses to painful stimuli. Rather, our findings of significantly enhanced cue- related expectancy effects may suggest that VMPFC plays an important role in updating expectations or integrating sensory information with expectations to guide subjective judgements about pain. Taken together, these results expand our understanding VMPFC’s contribution to pain and highlight the role of VMPFC in integrating cognitive representations with sensory information to yield affective responses.

Characterization of Empathy Deficits following Prefrontal Brain Damage: The Role of the Right Ventromedial Prefrontal Cortex

2003 ◽  
Vol 15 (3) ◽  
pp. 324-337 ◽  
Author(s):  
S. G. Shamay-Tsoory ◽  
R. Tomer ◽  
B. D. Berger ◽  
J. Aharon-Peretz
Keyword(s):  
Prefrontal Cortex ◽  
Brain Damage ◽  
Cognitive Flexibility ◽  
Right Hemisphere ◽  
Ventromedial Prefrontal Cortex ◽  
Fundamental Aspect ◽  
Affect Recognition ◽  
Healthy Controls ◽  
Empathic Response ◽  
The Right

Impaired empathic response has been described in patients following brain injury, suggesting that empathy may be a fundamental aspect of the social behavior disturbed by brain damage. However, the neuroanatomical basis of impaired empathy has not been studied in detail. The empathic response of patients with localized lesions in the prefrontal cortex (n = 25) was compared to responses of patients with posterior (n = 17) and healthy control subjects (n = 19). To examine the cognitive processes that underlie the empathic ability, the relationships between empathy scores and the performance on tasks that assess processes of cognitive flexibility, affect recognition, and theory of mind (TOM) were also examined. Patients with prefrontal lesions, particularly when their damage included the ventromedial prefrontal cortex, were significantly impaired in empathy as compared to patients with posterior lesions and healthy controls. However, among patients with posterior lesions, those with damage to the right hemisphere were impaired, whereas those with left posterior lesions displayed empathy levels similar to healthy controls. Seven of nine patients with the most profound empathy deficit had a right ventromedial lesion. A differential pattern regarding the relationships between empathy and cognitive performance was also found: Whereas among patients with dorsolateral prefrontal damage empathy was related to cognitive flexibility but not to TOM and affect recognition, empathy scores in patients with ventromedial lesions were related to TOM but not to cognitive flexibility. Our findings suggest that prefrontal structures play an important part in a network mediating the empathic response and specifically that the right ventromedial cortex has a unique role in integrating cognition and affect to produce the empathic response.

scholarly journals Insula’s functional connectivity with ventromedial prefrontal cortex mediates the impact of trait alexithymia on state tobacco craving

2013 ◽  
Vol 228 (1) ◽  
pp. 143-155 ◽  
Author(s):  
Matthew T. Sutherland ◽  
Allison J. Carroll ◽  
Betty Jo Salmeron ◽  
Thomas J. Ross ◽  
Elliot A. Stein
Keyword(s):  
Prefrontal Cortex ◽  
Functional Connectivity ◽  
Ventromedial Prefrontal Cortex ◽  
The Impact

scholarly journals Locus coeruleus phasic discharge is essential for stimulus-induced gamma oscillations in the prefrontal cortex

2018 ◽  
Vol 119 (3) ◽  
pp. 904-920 ◽  
Author(s):  
Ricardo M. Neves ◽  
Silvia van Keulen ◽  
Mingyu Yang ◽  
Nikos K. Logothetis ◽  
Oxana Eschenko
Keyword(s):  
Prefrontal Cortex ◽  
Locus Coeruleus ◽  
Sensory Information ◽  
Gamma Oscillations ◽  
Phasic Response ◽  
Population Activity ◽  
Power Increase ◽  
Gamma Power ◽  
Sensory Responses ◽  
The Impact

The locus coeruleus (LC) noradrenergic (NE) neuromodulatory system is critically involved in regulation of neural excitability via its diffuse ascending projections. Tonic NE release in the forebrain is essential for maintenance of vigilant states and increases the signal-to-noise ratio of cortical sensory responses. The impact of phasic NE release on cortical activity and sensory processing is less explored. We previously reported that LC microstimulation caused a transient desynchronization of population activity in the medial prefrontal cortex (mPFC), similar to noxious somatosensory stimuli. The LC receives nociceptive information from the medulla and therefore may mediate sensory signaling to its forebrain targets. Here we performed extracellular recordings in LC and mPFC while presenting noxious stimuli in urethane-anesthetized rats. A brief train of foot shocks produced a robust phasic response in the LC and a transient change in the mPFC power spectrum, with the strongest modulation in the gamma (30–90 Hz) range. The LC phasic response preceded prefrontal gamma power increase, and cortical modulation was proportional to the LC excitation. We also quantitatively characterized distinct cortical states and showed that sensory responses in both LC and mPFC depend on the ongoing cortical state. Finally, cessation of the LC firing by bilateral local iontophoretic injection of clonidine, an α2-adrenoreceptor agonist, completely eliminated sensory responses in the mPFC without shifting cortex to a less excitable state. Together, our results suggest that the LC phasic response induces gamma power increase in the PFC and is essential for mediating sensory information along an ascending noxious pathway. NEW & NOTEWORTHY Our study shows linear relationships between locus coeruleus phasic excitation and the amplitude of gamma oscillations in the prefrontal cortex. Results suggest that the locus coeruleus phasic response is essential for mediating sensory information along an ascending noxious pathway.

Interactions between brain and spinal cord mediate value effects in nocebo hyperalgesia

Science ◽  
2017 ◽  
Vol 358 (6359) ◽  
pp. 105-108 ◽  
Author(s):  
A. Tinnermann ◽  
S. Geuter ◽  
C. Sprenger ◽  
J. Finsterbusch ◽  
C. Büchel
Keyword(s):  
Spinal Cord ◽  
Prefrontal Cortex ◽  
Treatment Outcomes ◽  
Therapeutic Effect ◽  
Active Substance ◽  
Pain Processing ◽  
Cognitive Representations ◽  
Neural Interactions ◽  
Flexible Mechanism ◽  
Brain And Spinal Cord

Value information about a drug, such as the price tag, can strongly affect its therapeutic effect. We discovered that value information influences adverse treatment outcomes in humans even in the absence of an active substance. Labeling an inert treatment as expensive medication led to stronger nocebo hyperalgesia than labeling it as cheap medication. This effect was mediated by neural interactions between cortex, brainstem, and spinal cord. In particular, activity in the prefrontal cortex mediated the effect of value on nocebo hyperalgesia. Value furthermore modulated coupling between prefrontal areas, brainstem, and spinal cord, which might represent a flexible mechanism through which higher-cognitive representations, such as value, can modulate early pain processing.

569-P: Prefrontal Cortex Brain Damage and Glycemic Control in Patients with Type 2 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 569-P
Author(s):  
SARAH E. CHOI ◽  
BHASWATI ROY ◽  
RAJESH KUMAR ◽  
MATTHEW FREEBY ◽  
RASHMI S. MULLUR ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Prefrontal Cortex ◽  
Glycemic Control ◽  
Brain Damage

Exogenous Neonatal Erythropoietin Mitigates Brain Damage After a Combination of Prenatal Hypoxic-Ischemia and Lipopolysaccharide Inflammation in Rats

2008 ◽  
Vol 1 (4) ◽  
pp. A353
Author(s):  
Shenandoah Robinson ◽  
Qing Li
Keyword(s):  
Brain Damage ◽  
Intracellular Signaling ◽  
System Development ◽  
Intrauterine Infection ◽  
Artery Occlusion ◽  
Nervous System Development ◽  
Human Infants ◽  
Hypoxic Ischemia ◽  
Show Evidence ◽  
The Impact

Introduction Many infants born very preterm who suffer brain damage most likely experienced a combined insult from intrauterine infection and placental insufficiency. Damage is thought to be synergistic rather than additive but the mechanisms of combined injury remain elusive. A combination of lipopolysaccharide-induced inflammation and hypoxia-ischemia has been used in rats to model the dual insult that occurs in human infants prenatally. Erythropoietin, a pleiotrophic cytokine that is essential for central nervous system development, ameliorates brain injury after isolated hypoxic-ischemic or inflammatory insults through different intracellular signaling pathways. We hypothesized that exogenous neonatal EPO administration would lessen the damage of a combined prenatal insult in rats. Methods On embryonic Day 18 fetal rats experienced 60 minutes of transient uterine artery occlusion with or without intracervical LPS administration with sham controls receiving surgery but no occlusion and saline for LPS. Survival was recorded and histological biochemical and functional assays were performed. Means were compared with ANOVA with Tukey HSD post hoc analysis. Results After a combined insult of HI and 0.15-mg/kg LPS on E18 the survival of pups by postnatal Day 1 (P1) decreased from 77% with HI alone to 22% for LPS plus HI. When exogenous systemic EPO was administered P1–P3 survival to P9 improved markedly from 40% (2 of 5) for saline-treated insult pups to 100% (6 of 6) for EPO-treated. Initial histological analyses show EPO decreases the number of brain activated caspase 3 and activated microglia by P9. Additional analyses will be presented. Conclusion As at least 60% of placentas from infants born pre-term show evidence of chorioamnionitis, assessment of the impact of exogenous EPO on a model of a combination injury is essential prior to proceeding with a clinical trial. Initial results indicate neonatal exogenous EPO mitigates damage from the combined insult.

Age differences in ventromedial prefrontal cortex functional connectivity during socioemotional content processing

2020 ◽  
Vol 48 (7) ◽  
pp. 1-19
Author(s):  
Ryan T. Daley ◽  
Holly J. Bowen ◽  
Eric C. Fields ◽  
Angela Gutchess ◽  
Elizabeth A. Kensinger
Keyword(s):  
Prefrontal Cortex ◽  
Functional Connectivity ◽  
Inferior Frontal Gyrus ◽  
Age Groups ◽  
Emotional Content ◽  
Ventromedial Prefrontal Cortex ◽  
Anterior Cingulate ◽  
Supramarginal Gyrus ◽  
Age Related ◽  
Content Processing

Self-relevance effects are often confounded by the presence of emotional content, rendering it difficult to determine how brain networks functionally connected to the ventromedial prefrontal cortex (vmPFC) are affected by the independent contributions of self-relevance and emotion. This difficulty is complicated by age-related changes in functional connectivity between the vmPFC and other default mode network regions, and regions typically associated with externally oriented networks. We asked groups of younger and older adults to imagine placing emotional and neutral objects in their home or a stranger's home. An age-invariant vmPFC cluster showed increased activation for self-relevant and emotional content processing. Functional connectivity analyses revealed age × self-relevance interactions in vmPFC connectivity with the anterior cingulate cortex. There were also age × emotion interactions in vmPFC functional connectivity with the anterior insula, orbitofrontal gyrus, inferior frontal gyrus, and supramarginal gyrus. Interactions occurred in regions with the greatest differences between the age groups, as revealed by conjunction analyses. Implications of the findings are discussed.

Sign in / Sign up

Export Citation Format

Share Document