Phosphene and motor transcranial magnetic stimulation thresholds are correlated: A meta-analytic investigation.

Transcranial magnetic stimulation (TMS) is commonly delivered at an intensity defined by the resting motor threshold (rMT), which is thought to represent cortical excitability, even if the TMS target area falls outside of the motor cortex. This approach rests on the assumption that cortical excitability, as measured through the motor cortex, represents a 'global' measure of excitability. Another common approach to measure cortical excitability relies on the phosphene threshold (PT), measured through the visual cortex of the brain. However, it remains unclear whether either estimate can serve as a singular measure to infer cortical excitability across different brain regions. If PT and rMT can indeed be used to infer cortical excitability across brain regions, they should be correlated. To test this, we systematically identified previous studies that measured PT and rMT to calculate an overall correlation between the two estimates. Our results, based on 16 effect sizes from eight studies, indicated that PT and rMT are correlated (ρ = 0.4), and thus one measure could potentially serve as a measure to infer cortical excitability across brain regions. Three exploratory meta-analyses revealed that the strength of the correlation is affected by different methodologies, and that PT intensities are higher than rMT. Evidence for a PT-rMT correlation remained robust across all analyses. Further research is necessary for an in-depth understanding of how cortical excitability is reflected through TMS.

Intramuscular injection of nerve growth factor as a model of temporomandibular disorder: nature, time-course, and sex differences characterising the pain experience.

Background: Temporomandibular disorder (TMD) is a common condition that frequently transitions to chronic symptoms. Experimental pain models that mimic the symptoms of clinical TMD may be useful in understanding the mechanisms, and sex differences, present in this disorder. Here we aimed to comprehensively characterise the nature and time-course of pain, functional impairment and hyperalgesia induced by repeated intramuscular injection of nerve growth factor (NGF) into the masseter muscle, and to investigate sex differences in the NGF-induced pain experience. Methods: 94 healthy individuals participated in a longitudinal study with 30-day follow-up. NGF was injected into the right masseter muscle on Day 0 and Day 2. Participants attended laboratory sessions to assess pain (Numerical Rating Scale; NRS), functional limitation (mouth opening distance, Jaw Functional Limitation Scale; JFLS) and mechanical sensitization (pressure pain thresholds; PPTs) on Days 0, 2 and 5 and completed twice daily electronic pain dairies from Day 0 to day 30. Results: Peak pain averaged 2.0/10 (95 % CI: 1.6-2.4) at rest and 4.3/10 (95 % CI: 3.9-4.8) on chewing. Pain-free mouth opening distance reduced from 5.0 cm (95 % CI: 4.8-5.1 cm) on Day 0 to 3.7 cm (95 % CI: 3.5-3.9 cm) on Day 5. The greatest reduction in PPTs was observed over the masseter muscle. Females experienced higher pain, greater functional impairment, and greater sensitivity to mechanical stimuli than males. Conclusion: Intramuscular injection of NGF is a useful model with which to explore the mechanisms, and sex differences, present in clinical TMD.

Cognitive modulation of pain-related brain responses depends on behavioral strategy.

Interactions of pain and cognition have been studied in humans and animals previously, but the relationship between such behavioral interactions and brain activity is unknown. We aimed to show using functional MRI (fMRI) how a cognitively demanding task (Stroop) modulates pain-related brain activations and conversely, how pain modulates attention-related activity. Reaction time data indicated two types of pain responders: subjects in the A group had a faster Stroop reaction time when pain was concomitant to the attention task, while those in the P group had a slower Stroop performance during painful stimulation. fMRI data obtained during Stroop performance with and without noxious stimulation were subjected to region of interest analyses. We first tested whether brain activity during painful median nerve stimulation was modulated by cognitive load. We next tested whether brain activity during the high conflict cognitive task was modulated by pain. Pain-related activity in three regions, primary (S1), and secondary (S2) somatosensory cortices, and anterior insula, was attenuated by cognitive engagement, but this effect was specific to the A group. Pain-related activations in the caudal and rostral anterior cingulate cortex (ACC) and ventroposterior thalamus were not modulated by cognitive load. None of the areas showing attention-related responses, including bilateral dorsolateral prefrontal and posterior parietal cortices, were modulated by pain. These findings suggest that cortical regions associated with pain can be modulated by cognitive strategies. Furthermore, the distinction of behavioral subgroups may relate to cognitive coping strategies taken by patients with chronic pain.

Limbic-frontal circuitry in major depression: a path modeling metanalysis.

This paper reports the results of an across lab metanalysis of effective connectivity in major depression (MDD). Using FDG PET data and Structural Equation Modeling, a formal depression model was created to explicitly test current theories of limbic-cortical dysfunction in MDD and to characterize at the path level potential sources of baseline variability reported in this patient population. A 7-region model consisting of lateral prefrontal cortex (latF9), anterior thalamus (aTh), anterior cingulate (Cg24), subgenual cingulate (Cg25), orbital frontal cortex (OF11), hippocampus (Hc), and medial frontal cortex (mF10) was tested in scans of 119 depressed patients and 42 healthy control subjects acquired during three separate studies at two different institutions. A single model, based on previous theory and supported by anatomical connectivity literature, was stable for the three groups of depressed patients. Within the context of this model, path differences among groups as a function of treatment response characteristics were also identified. First, limbic-cortical connections (latF9-Cg25-OF11-Hc) differentiated drug treatment responders from nonresponders. Second, nonresponders showed additional abnormalities in limbic-subcortical pathways (aTh-Cg24-Cg25-OF11-Hc). Lastly, more limited limbic-cortical (Hc-latF9) and cortical-cortical (OF11-mF10) path differences differentiated responders to cognitive behavioral therapy (CBT) from responders to pharmacotherapy. We conclude that the creation of such models is a first step toward full characterization of the depression phenotype at the neural systems level, with implications for the future development of brain-based algorithms to determine optimal treatment selection for individual patients.