Interhemispheric Dorsolateral Prefrontal Cortex Connectivity is Associated with Individual Differences in Pain Sensitivity in Healthy Controls

Sevel, Landrew S.; Letzen, Janelle E.; Staud, Roland; Robinson, Michael E.

doi:10.1089/brain.2015.0405

Cited by 47 publications

(35 citation statements)

References 42 publications

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“…In fact, other neuromodulation studies have also claimed that DLPFC is involved in modulating emotional-affective experience of pain, which represents individual's tolerance to pain (GraffGuerrero et al, 2005;Mylius et al, 2009). A recent fMRI study demonstrated that greater connectivity between bilateral DLPFCs was associated with higher heat pain thresholds (Sevel et al, 2016). These findings taken together highlight the role of DLPFC in pain modulation, particularly pain tolerance.…”

Section: Correlation Of Fc Changes To Individual Baseline Pain Threshmentioning

confidence: 86%

Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing

et al. 2017

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The pain matrix is comprised of an extensive network of brain structures involved in sensory and/or affective information processing. The thalamus is a key structure constituting the pain matrix. The thalamus serves as a relay center receiving information from multiple ascending pathways and relating information to and from multiple cortical areas. However, it is unknown how thalamocortical networks specific to sensory-affective information processing are functionally integrated. Here, in a proof-of-concept study in healthy humans, we aimed to understand this connectivity using transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC). We compared changes in functional connectivity (FC) with DLPFC tDCS to changes in FC with M1 tDCS. FC changes were also compared to further investigate its relation with individual's baseline experience of pain. We hypothesized that resting-state FC would change based on tDCS location and would represent known thalamocortical networks. Ten right-handed individuals received a single application of anodal tDCS (1 mA, 20 min) to right M1 and DLPFC in a single-blind, shamcontrolled crossover study. FC changes were studied between ventroposterolateral (VPL), the sensory nucleus of thalamus, and cortical areas involved in sensory information processing and between medial dorsal (MD), the affective nucleus, and cortical areas involved in affective information processing. Individual's perception of pain at baseline was assessed using cutaneous heat pain stimuli. We found that anodal M1 tDCS and anodal DLPFC tDCS both increased FC between VPL and sensorimotor cortices, although FC effects were greater with M1 tDCS. Similarly, anodal M1 tDCS and anodal DLPFC tDCS both increased FC between MD and motor cortices, but only DLPFC tDCS modulated FC between MD and affective cortices, like DLPFC. Our findings suggest that M1 stimulation primarily modulates FC of sensory networks, whereas DLPFC stimulation modulates FC of both sensory and affective networks. Our findings when replicated in a larger group of individuals could provide useful evidence that may inform future studies on pain to differentiate between effects of M1 and DLPFC stimulation. Notably, our finding that individuals with high baseline pain thresholds experience greater FC changes with DLPFC tDCS implies the role of DLPFC in pain modulation, particularly pain tolerance.

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Section: Correlation Of Fc Changes To Individual Baseline Pain Threshmentioning

confidence: 86%

Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing

et al. 2017

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“…In regard to the brain and pain, activation of the DLPFC is associated with cognitive decision making, including pain evaluations and response decisions, and is accomplished by modulation of the corticosubcortical and corticocortical pathways 36. Recent noninvasive brain stimulation studies have suggested that interhemispheric DLPFC connectivity influences pain tolerance and discomfort by altering interhemispheric inhibition,37 and these studies have also supported the preferential role of the right hemisphere in pain processing because of disrupted homotopic connectivity in the DLPFC 38. Microstructural abnormalities in the gray matter of the DLPFC provide a structural foundation for understanding the disruption in connectivity,5 as iFC is partially restored after pain treatment, which indicates that the DLPFC participates in cognitive task performance and also supports the concept that DLPFC connectivity participates in brain impairment during chronic pain 39.…”

Section: Discussionmentioning

confidence: 98%

Altered homotopic connectivity in postherpetic neuralgia: a resting state fMRI study

Jiang¹,

Bao

et al. 2016

JPR

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ObjectiveThe aim of this study was to explore interhemispheric intrinsic connectivity in patients with postherpetic neuralgia (PHN).MethodsWe obtained resting-state functional magnetic resonance imaging data from 18 right-handed PHN patients (11 males, 7 females; mean age, 59.67±8.41 years) and 18 well-matched healthy controls (11 males, 7 females; mean age, 38.50±7.51 years). Interhemispheric connectivity was examined using voxel-mirrored homotopic connectivity (VMHC), and seed-based functional connectivity analysis was performed.ResultsCompared with the healthy controls, the patients with PHN showed abnormally decreased homotopic connectivity in the dorsolateral prefrontal cortex and the precuneus and posterior cingulate cortex (PCUN/PCC). The decreased VMHC in the PCUN/PCC was positively correlated with the visual analog scale of PHN in the PHN patient group (ρ=0.651; P=0.006). Receiver operating characteristic (ROC) analysis revealed that the areas under the curves for the two brain regions were 0.898 for the prefrontal cortex and 0.923 for the PCUN/PCC, which indicated that the VMHC could be used to discriminate PHN patients from healthy controls. A subsequent seed-based functional connectivity analysis revealed widely disrupted intrinsic connectivity between the regions that showed local homotopic connectivity deficits and the areas subserving the default-mode network.ConclusionOur results indicated reduced interhemispheric functional connectivity in patients with PHN, which seems to be an important new avenue to investigate to better understand the nature of disconnection of the functional architecture in patients with PHN.

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“…In other words, the DLPFC suppressed insula and thalamus activity and reduced pain sensitization associated with uncontrollable pain. Finally, the connectivity between left and right DLPFC has been linked to individual pain sensitivity, such that stronger interhemispheric connectivity was associated with greater pain tolerance 93 .…”

Section: Dlpfc Functionmentioning

confidence: 99%

The Dorsolateral Prefrontal Cortex in Acute and Chronic Pain

Seminowicz

Moayedi

2017

The Journal of Pain

357

266

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The dorsolateral prefrontal cortex (DLPFC) is a functionally and structurally heterogeneous region and a key node of several brain networks, implicated in cognitive, affective, and sensory processing. As such, the DLPFC is commonly activated in experimental pain studies, and shows abnormally increased function in chronic pain populations. Furthermore, several studies have shown that some chronic pains are associated with decreased left DLPFC gray matter and that successful interventions can reverse this structural abnormality. In addition, studies have indicated that non-invasive stimulation of the left DLPFC effectively treats some chronic pains. Here, we review the neuroimaging literature regarding the role of the DLPFC and its potential as a therapeutic target for chronic pain conditions, including: studies showing the involvement of the DLPFC in encoding and modulating acute pain; studies demonstrating the reversal of DLPFC functional and structural abnormalities following successful interventions for chronic pain. We also review studies of non-invasive brain stimulation of the DLPFC showing acute pain modulation and some effectiveness as a treatment for certain chronic pain conditions. We further discuss the network architecture of the DLPFC, and postulate mechanisms by which DLPFC stimulation alleviates chronic pain. Future work testing these mechanisms will allow for more effective therapies.

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Interhemispheric Dorsolateral Prefrontal Cortex Connectivity is Associated with Individual Differences in Pain Sensitivity in Healthy Controls

Cited by 47 publications

References 42 publications

Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing

Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing

Altered homotopic connectivity in postherpetic neuralgia: a resting state fMRI study

The Dorsolateral Prefrontal Cortex in Acute and Chronic Pain

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