Two decades of functional imaging studies have demonstrated pain-related activations of primary somatic sensory cortex (S1), parasylvian cortical structures (PS) and medial frontal cortical structures (MF), which are often described as modules in a 'pain network'. The participation of thalamic modules in this network is very likely based upon the connectivity of thalamo-cortical assemblies. However, the directionality and temporal dynamics of dynamic interactions between and within the cortical modules is uncertain, and the role of the thalamic modules in this network is poorly understood. The proposed cortical studies would be carried out in the Johns Hopkins Epilepsy Monitoring Unit over the one week period between the implantation and removal of intracranial electrodes during the surgical treatment of epilepsy. Studies of thalamic neurons, local field potentials (LFPs) and EEG would be carried out during the awake microelectrode mapping which precedes the implantation of deep brain stimulating (DBS) electrodes for the treatment of essential tremor. We also propose to use attention and distraction as behavioral probes to study the psychophysics and neuroscience of the 'pain network'. These recordings during standard clinical recording procedures have unprecedented clarity and resolution, and will be examined by state-of-the-art techniques for neurobiological signal analysis to establish the dynamic directional functional interactions between modules (Granger Causality - GRC). Our recent studies have demonstrated changes in dynamic functional connectivity both between cortical modules, and between cortical and thalamic modules as a function of attention to versus distraction from a painful cutaneous laser stimulus. Therefore, this proposal has the potential to describe dynamic 'pain networks'in humans based upon task-specific, dynamic functional interactions within and between cortical and thalamic modules. These results in humans may be uniquely useful to design and optimize anatomically-based pain therapies, such as stimulation of the brain through transcutaneous magnetic fields or implanted electrodes.

Public Health Relevance

Two decades of imaging studies have demonstrated pain-related activations of widespread cortical structures, which are described as a 'pain network', although the nature and dynamics of connectivity in this network are uncertain. We now propose to study non-directional and directional functional interactions during attention to a painful cutaneous laser stimulus for evidence of both local and distributed components to the 'pain network'. These studies will examine dynamic functional connectivity recorded directly from brain structures in the 'pain network', and so may have a substantial effect on the concepts that drive this field.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Oshinsky, Michael L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Schools of Medicine
United States
Zip Code
Liu, C C; Chien, J H; Kim, J H et al. (2015) Cross-frequency coupling in deep brain structures upon processing the painful sensory inputs. Neuroscience 303:412-21
Zhao, L; Verhagen-Metman, L; Kim, J H et al. (2015) EMG activity and neuronal activity in the internal globus pallidus (GPi) and their interaction are different between hemiballismus and apomorphine induced dyskinesias of Parkinson's disease (AID). Brain Res 1603:50-64
Wang, Liping; Li, Xianchun; Hsiao, Steven S et al. (2015) Differential roles of delay-period neural activity in the monkey dorsolateral prefrontal cortex in visual-haptic crossmodal working memory. Proc Natl Acad Sci U S A 112:E214-9
Liu, C C; Chien, J H; Chang, Y W et al. (2015) Functional role of induced gamma oscillatory responses in processing noxious and innocuous sensory events in humans. Neuroscience 310:389-400
Klein, Max M; Treister, Roi; Raij, Tommi et al. (2015) Transcranial magnetic stimulation of the brain: guidelines for pain treatment research. Pain 156:1601-14
Kim, J H; Chien, J H; Liu, C C et al. (2015) Painful cutaneous laser stimuli induce event-related gamma-band activity in the lateral thalamus of humans. J Neurophysiol 113:1564-73
Eliades, Steven J; Crone, Nathan E; Anderson, William S et al. (2014) Adaptation of high-gamma responses in human auditory association cortex. J Neurophysiol 112:2147-63
Madhavan, Radhika; Millman, Daniel; Tang, Hanlin et al. (2014) Decrease in gamma-band activity tracks sequence learning. Front Syst Neurosci 8:222
Chien, J H; Liu, C C; Kim, J H et al. (2014) Painful cutaneous laser stimuli induce event-related oscillatory EEG activities that are different from those induced by nonpainful electrical stimuli. J Neurophysiol 112:824-33
Kobayashi, K; Liu, C C; Jensen, A L et al. (2013) Thalamic post-inhibitory bursting occurs in patients with organic dystonia more often than controls. Brain Res 1541:81-91

Showing the most recent 10 out of 65 publications