Regional hypothalamic, amygdala, and midbrain periaqueductal gray matter recruitment during acute pain in awake humans: A 7-Tesla functional magnetic resonance imaging study.

Over the past two decades, magnetic resonance imaging (MRI) studies have explored brain activation patterns during acute noxious stimuli. Whilst these human investigations have detailed changes in primarily cortical regions, they have generally not explored discrete changes within small brain areas that are critical in driving behavioural, autonomic, and endocrine responses to pain, such as within subregions of the hypothalamus, amygdala, and midbrain periaqueductal gray matter (PAG). Ultra-high field (7-Tesla) MRI provides enough signal-to-noise at high spatial resolutions to investigate activation patterns within these small brain regions during acute noxious stimulation in awake humans. In this study we used 7T functional MRI to concentrate on hypothalamic, amygdala, and PAG signal changes during acute noxious orofacial stimuli. Noxious heat stimuli were applied in three separate fMRI scans to three adjacent sites on the face in 16 healthy control participants (7 females). Images were processed using SPM12 and custom software, and blood oxygen level dependent signal changes within the hypothalamus, amygdala, and PAG assessed. We identified altered activity within eight unique subregions of the hypothalamus, four unique subregions of the amygdala, and a single region in the lateral PAG. Specifically, within the hypothalamus and amygdala, signal intensity largely decreased during noxious stimulation, and increased in the lateral PAG. Furthermore, we found sex-related differences in discrete regions of the hypothalamus and amygdala. This study reveals that the activity of discrete nuclei during acute noxious thermal stimulation in awake humans.

Mindfulness effects on lifestyle behavior and blood pressure: A randomized controlled trial.

BACKGROUND AND AIMS: HTN affects nearly 50% of U.S. adults and is the leading modifiable cardiovascular risk factor. A healthy diet and exercise can improve BP control, but adherence to these interventions is low. We tested whether a multimodal mind-body program, Mindful Awareness Practices (MAP) could improve BP and lifestyle behaviors associated with HTN when compared to a Health Promotion Program (HPP). METHODS: Adults with BP >120/80 were randomized to MAP or HPP. Outcome measurements of BP, self-reported diet, and exercise were analyzed with intent-to-treat group comparisons using repeated measures linear mixed models. RESULTS: There was an MAP-HPP between-group difference in interactions of time-by-systolic BP (P = 0.005) and time-by-diastolic BP (P = .003). The mean drops in SBP from baseline to week 13 for the MAP group was 19 mm Hg (138 ± 15 mm Hg-119 ± 6 mm Hg) compared to 7 mm Hg (134 ± 18 mm Hg-127 ± 22 mm Hg) in the HPP group. Similarly, a greater reduction in DBP was observed in the MAP group compared to the HPP group, 12 mm Hg (89 mm Hg ± 11-77 ± 7 mm Hg) and 1 mm Hg (81 ± 16 mm Hg-80 ± 18 mm Hg), respectively. Mediational analysis of the MAP group showed the total effect of mindfulness practice minutes on SBP with indirect effect (ab) of -.057 was significant, resulting in a 40% lower SBP for total effect (c) compared to direct (c') effect alone. The mediational model suggests MAP has a modest positive influence on participants initiating lifestyle behavior change, which partially explains the greater reduction in BP by the MAP group. CONCLUSION: Our findings suggest a multimodal mind-body program involving mindfulness practice may improve BP control in adults with HTN.

Altered regional cerebral blood flow and hypothalamic connectivity immediately prior to a migraine headache.

BACKGROUND: There is evidence of altered resting hypothalamic activity patterns and connectivity prior to a migraine, however it remains unknown if these changes are driven by changes in overall hypothalamic activity levels. If they are, it would corroborate the idea that changes in hypothalamic function result in alteration in brainstem pain processing sensitivity, which either triggers a migraine headache itself or allows an external trigger to initiate a migraine headache. We hypothesise that hypothalamic activity increases immediately prior to a migraine headache and this is accompanied by altered functional connectivity to pain processing sites in the brainstem. METHODS: In 34 migraineurs and 26 healthy controls, we collected a series comprising 108 pseudo-continuous arterial spin labelling images and 180 gradient-echo echo planar resting-state functional magnetic resonance volumes to measure resting regional cerebral blood flow and functional connectivity respectively. Images were pre-processed and analysed using custom SPM12 and Matlab software. RESULTS: Our results reflect that immediately prior to a migraine headache, resting regional cerebral blood flow decreases in the lateral hypothalamus. In addition, resting functional connectivity strength decreased between the lateral hypothalamus and important regions of the pain processing pathway, such as the midbrain periaqueductal gray, dorsal pons, rostral ventromedial medulla and cingulate cortex, only during this critical period before a migraine headache. CONCLUSION: These data suggest altered hypothalamic function and connectivity in the period immediately prior to a migraine headache and supports the hypothesis that the hypothalamus is involved in migraine initiation.

The relationship between thalamic GABA content and resting cortical rhythm in neuropathic pain.

Recurrent thalamocortical connections are integral to the generation of brain rhythms and it is thought that the inhibitory action of the thalamic reticular nucleus is critical in setting these rhythms. Our work and others' has suggested that chronic pain that develops following nerve injury, that is, neuropathic pain, results from altered thalamocortical rhythm, although whether this dysrhythmia is associated with thalamic inhibitory function remains unknown. In this investigation, we used electroencephalography and magnetic resonance spectroscopy to investigate cortical power and thalamic GABAergic concentration in 20 patients with neuropathic pain and 20 pain-free controls. First, we found thalamocortical dysrhythmia in chronic orofacial neuropathic pain; patients displayed greater power than controls over the 4-25 Hz frequency range, most marked in the theta and low alpha bands. Furthermore, sensorimotor cortex displayed a strong positive correlation between cortical power and pain intensity. Interestingly, we found no difference in thalamic GABA concentration between pain subjects and control subjects. However, we demonstrated significant linear relationships between thalamic GABA concentration and enhanced cortical power in pain subjects but not controls. Whilst the difference in relationship between thalamic GABA concentration and resting brain rhythm between chronic pain and control subjects does not prove a cause and effect link, it is consistent with a role for thalamic inhibitory neurotransmitter release, possibly from the thalamic reticular nucleus, in altered brain rhythms in individuals with chronic neuropathic pain.

Accelerated Echo Planer J-resolved Spectroscopic Imaging of Putamen and Thalamus in Obstructive Sleep Apnea.

UNLABELLED: Obstructive sleep apnea syndrome (OSAS) leads to neurocognitive and autonomic deficits that are partially mediated by thalamic and putamen pathology. We examined the underlying neurochemistry of those structures using compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (JRESI), and quantified values with prior knowledge fitting. Bilaterally increased thalamic mI/Cr, putamen Glx/Cr, and Glu/Cr, and bilaterally decreased thalamic and putamen tCho/Cr and GABA/Cr occurred in OSAS vs healthy subjects (p < 0.05). Increased right thalamic Glx/Cr, Glu/Cr, Gln/Cr, Asc/Cr, and decreased GPC/Cr and decreased left thalamic tNAA/Cr, NAA/Cr were detected. The right putamen showed increased mI/Cr and decreased tCho/Cr, and the left, decreased PE/Cr ratio. ROC curve analyses demonstrated 60-100% sensitivity and specificity for the metabolite ratios in differentiating OSAS vs. CONTROLS: Positive correlations were found between: left thalamus mI/Cr and baseline oxygen saturation (SaO2); right putamen tCho/Cr and apnea hypopnea index; right putamen GABA/Cr and baseline SaO2; left putamen PE/Cr and baseline SaO2; and left putamen NAA/Cr and SaO2 nadir (all p < 0.05). Negative correlations were found between left putamen PE/Cr and SaO2 nadir. These findings suggest underlying inflammation or glial activation, with greater alterations accompanying lower oxygen saturation. These metabolite levels may provide biomarkers for future neurochemical interventions by pharmacologic or other means.

Functional magnetic resonance signal changes in neural structures to baroreceptor reflex activation.

The sequence of neural responses to exogenous arterial pressure manipulation remains unclear, especially for extramedullary sites. We used functional magnetic resonance imaging procedures to visualize neural responses during pressor (phenylephrine) and depressor (sodium nitroprusside) challenges in seven isoflurane-anesthetized adult cats. Depressor challenges produced signal-intensity declines in multiple cardiovascular-related sites in the medulla, including the nucleus tractus solitarius, and caudal and rostral ventrolateral medulla. Signal decreases also emerged in the cerebellar vermis, inferior olive, dorsolateral pons, and right insula. Rostral sites, such as the amygdala and hypothalamus, increased signal intensity as arterial pressure declined. In contrast, arterial pressure elevation elicited smaller signal increases in medullary regions, the dorsolateral pons, and the right insula and signal declines in regions of the hypothalamus, with no change in deep cerebellar areas. Responses to both pressor and depressor challenges were typically lateralized. In a subset of animals, barodenervation resulted in rises and falls of blood pressure that were comparable to these resulting from the pharmacological challenges but different regional neural responses, indicating that the regional signal intensity responses did not derive from global perfusion effects but from baroreceptor mediation of central mechanisms. The findings demonstrate widespread lateralized distribution of neural sites responsive to blood pressure manipulation. The distribution and time course of neural responses follow patterns associated with early and late compensatory reactions.