John G. McHaffie

Neural correlates of interindividual differences in the subjective experience of pain

Some individuals claim that they are very sensitive to pain, whereas others say that they tolerate pain well. Yet, it is difficult to determine whether such subjective reports reflect true interindividual experiential differences. Using psychophysical ratings to define pain sensitivity and functional magnetic resonance imaging to assess brain activity, we found that highly sensitive individuals exhibited more frequent and more robust pain-induced activation of the primary somatosensory cortex, anterior cingulate cortex, and prefrontal cortex than did insensitive individuals. By identifying objective neural correlates of subjective differences, these findings validate the utility of introspection and subjective reporting as a means of communicating a first-person experience.

Subcortical loops through the basal ganglia

Parallel, largely segregated, closed-loop projections are an important component of cortical-basal ganglia-cortical connectional architecture. Here, we present the hypothesis that such loops involving the neocortex are neither novel nor the first evolutionary example of closed-loop architecture involving the basal ganglia. Specifically, we propose that a phylogenetically older, closed-loop series of subcortical connections exists between the basal ganglia and brainstem sensorimotor structures, a good example of which is the midbrain superior colliculus. Insofar as this organization represents a general feature of brain architecture, cortical and subcortical inputs to the basal ganglia might act independently, co-operatively or competitively to influence the mechanisms of action selection.

Brain Mechanisms Supporting the Modulation of Pain by Mindfulness Meditation

The subjective experience of ones environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a nonevaluative representation of sensory events. To better understand how meditation influences the sensory experience, we used arterial spin labeling functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After 4 d of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain unpleasantness by 57% and pain intensity ratings by 40% when compared to rest. A two-factor repeated-measures ANOVA was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contralateral primary somatosensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent input and executive-order brain areas. Together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information.

Mindfulness meditation-related pain relief: evidence for unique brain mechanisms in the regulation of pain.

The cognitive modulation of pain is influenced by a number of factors ranging from attention, beliefs, conditioning, expectations, mood, and the regulation of emotional responses to noxious sensory events. Recently, mindfulness meditation has been found attenuate pain through some of these mechanisms including enhanced cognitive and emotional control, as well as altering the contextual evaluation of sensory events. This review discusses the brain mechanisms involved in mindfulness meditation-related pain relief across different meditative techniques, expertise and training levels, experimental procedures, and neuroimaging methodologies. Converging lines of neuroimaging evidence reveal that mindfulness meditation-related pain relief is associated with unique appraisal cognitive processes depending on expertise level and meditation tradition. Moreover, it is postulated that mindfulness meditation-related pain relief may share a common final pathway with other cognitive techniques in the modulation of pain.

Opposing basal ganglia processes shape midbrain visuomotor activity bilaterally

The manner in which the nervous system allocates limited motor resources when confronted with conflicting behavioural demands is a crucial issue in understanding how sensory information is transformed into adaptive motor responses. Understanding this selection process is of particular concern in current models of functions of the basal ganglia. Here we report that the basal ganglia use simultaneous enhancing and suppressing processes synergistically to modulate sensory activity in the superior colliculi, which are bilaterally paired midbrain structures involved in the control of visual orientation behaviours. These complementary processes presumably ensure accurate gaze shifts mediated by the superior colliculi despite the presence of potential distractors.

Brain Mechanisms Supporting Spatial Discrimination of Pain

Pain is a uniquely individual experience that is heavily shaped by evaluation and judgments about afferent sensory information. In visual, auditory, and tactile sensory modalities, evaluation of afferent information engages brain regions outside of the primary sensory cortices. In contrast, evaluation of sensory features of noxious information has long been thought to be accomplished by the primary somatosensory cortex and other structures associated with the lateral pain system. Using functional magnetic resonance imaging and a delayed match-to-sample task, we show that the prefrontal cortex, anterior cingulate cortex, posterior parietal cortex, thalamus, and caudate are engaged during evaluation of the spatial locations of noxious stimuli. Thus, brain mechanisms supporting discrimination of sensory features of pain extend far beyond the somatosensory cortices and involve frontal regions traditionally associated with affective processing and the medial pain system. These frontoparietal interactions are similar to those involved in the processing of innocuous information and may be critically involved in placing afferent sensory information into a personal historical context.

A direct projection from superior colliculus to substantia nigra pars compacta in the cat.

Dopaminergic neurons exhibit a short-latency, phasic response to unexpected, biologically salient stimuli. The midbrain superior colliculus also is sensitive to such stimuli, exhibits sensory responses with latencies reliably less than those of dopaminergic neurons, and, in rat, has been shown to send direct projections to regions of the substantia nigra and ventral tegmental area containing dopaminergic neurons (e.g. pars compacta). Recent electrophysiological and electrochemical evidence also suggests that tectonigral connections may be critical for relaying short-latency (<100 ms) visual information to midbrain dopaminergic neurons. By investigating the tectonigral projection in the cat, the present study sought to establish whether this pathway is a specialization of the rodent, or whether it may be a more general feature of mammalian neuroanatomy. Anterogradely and retrogradely transported anatomical tracers were injected into the superior colliculus and substantia nigra pars compacta, respectively, of adult cats. In the anterograde experiments, abundant fibers and terminals labeled with either biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin were seen in close association with tyrosine hydroxylase-positive (dopaminergic) somata and processes in substantia nigra pars compacta and the ventral tegmental area. In the retrograde experiments, injections of biotinylated dextran amine into substantia nigra produced significant retrograde labeling of tectonigral neurons of origin in the intermediate and deep layers of the ipsilateral superior colliculus. Approximately half of these biotinylated dextran amine-labeled neurons were, in each case, shown to be immunopositive for the calcium binding proteins, parvalbumin or calbindin. Significantly, virtually no retrogradely labeled neurons were found either in the superficial layers of the superior colliculus or among the large tecto-reticulospinal output neurons. Taken in conjunction with recent data in the rat, the results of this study suggest that the tectonigral projection may be a common feature of mammalian midbrain architecture. As such, it may represent an additional route by which short-latency sensory information can influence basal ganglia function.

Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia

Mindfulness meditation reduces pain in experimental and clinical settings. However, it remains unknown whether mindfulness meditation engages pain-relieving mechanisms other than those associated with the placebo effect (e.g., conditioning, psychosocial context, beliefs). To determine whether the analgesic mechanisms of mindfulness meditation are different from placebo, we randomly assigned 75 healthy, human volunteers to 4 d of the following: (1) mindfulness meditation, (2) placebo conditioning, (3) sham mindfulness meditation, or (4) book-listening control intervention. We assessed intervention efficacy using psychophysical evaluation of experimental pain and functional neuroimaging. Importantly, all cognitive manipulations (i.e., mindfulness meditation, placebo conditioning, sham mindfulness meditation) significantly attenuated pain intensity and unpleasantness ratings when compared to rest and the control condition (p < 0.05). Mindfulness meditation reduced pain intensity (p = 0.032) and pain unpleasantness (p < 0.001) ratings more than placebo analgesia. Mindfulness meditation also reduced pain intensity (p = 0.030) and pain unpleasantness (p = 0.043) ratings more than sham mindfulness meditation. Mindfulness-meditation-related pain relief was associated with greater activation in brain regions associated with the cognitive modulation of pain, including the orbitofrontal, subgenual anterior cingulate, and anterior insular cortex. In contrast, placebo analgesia was associated with activation of the dorsolateral prefrontal cortex and deactivation of sensory processing regions (secondary somatosensory cortex). Sham mindfulness meditation-induced analgesia was not correlated with significant neural activity, but rather by greater reductions in respiration rate. This study is the first to demonstrate that mindfulness-related pain relief is mechanistically distinct from placebo analgesia. The elucidation of this distinction confirms the existence of multiple, cognitively driven, supraspinal mechanisms for pain modulation. SIGNIFICANCE STATEMENT Recent findings have demonstrated that mindfulness meditation significantly reduces pain. Given that the “gold standard” for evaluating the efficacy of behavioral interventions is based on appropriate placebo comparisons, it is imperative that we establish whether there is an effect supporting meditation-related pain relief above and beyond the effects of placebo. Here, we provide novel evidence demonstrating that mindfulness meditation produces greater pain relief and employs distinct neural mechanisms than placebo cream and sham mindfulness meditation. Specifically, mindfulness meditation-induced pain relief activated higher-order brain regions, including the orbitofrontal and cingulate cortices. In contrast, placebo analgesia was associated with decreased pain-related brain activation. These findings demonstrate that mindfulness meditation reduces pain through unique mechanisms and may foster greater acceptance of meditation as an adjunct pain therapy.

Neural correlates of mindfulness meditation-related anxiety relief

Anxiety is the cognitive state related to the inability to control emotional responses to perceived threats. Anxiety is inversely related to brain activity associated with the cognitive regulation of emotions. Mindfulness meditation has been found to regulate anxiety. However, the brain mechanisms involved in meditation-related anxiety relief are largely unknown. We employed pulsed arterial spin labeling MRI to compare the effects of distraction in the form of attending to the breath (ATB; before meditation training) to mindfulness meditation (after meditation training) on state anxiety across the same subjects. Fifteen healthy subjects, with no prior meditation experience, participated in 4 d of mindfulness meditation training. ATB did not reduce state anxiety, but state anxiety was significantly reduced in every session that subjects meditated. Meditation-related anxiety relief was associated with activation of the anterior cingulate cortex, ventromedial prefrontal cortex and anterior insula. Meditation-related activation in these regions exhibited a strong relationship to anxiety relief when compared to ATB. During meditation, those who exhibited greater default-related activity (i.e. posterior cingulate cortex) reported greater anxiety, possibly reflecting an inability to control self-referential thoughts. These findings provide evidence that mindfulness meditation attenuates anxiety through mechanisms involved in the regulation of self-referential thought processes.

The contribution of the putamen to sensory aspects of pain: insights from structural connectivity and brain lesions

Cerebral cortical activity is heavily influenced by interactions with the basal ganglia. These interactions occur via cortico-basal ganglia-thalamo-cortical loops. The putamen is one of the major sites of cortical input into basal ganglia loops and is frequently activated during pain. This activity has been typically associated with the processing of pain-related motor responses. However, the potential contribution of putamen to the processing of sensory aspects of pain remains poorly characterized. In order to more directly determine if the putamen can contribute to sensory aspects of pain, nine individuals with lesions involving the putamen underwent both psychophysical and functional imaging assessment of perceived pain and pain-related brain activation. These individuals exhibited intact tactile thresholds, but reduced heat pain sensitivity and widespread reductions in pain-related cortical activity in comparison with 14 age-matched healthy subjects. Using magnetic resonance imaging to assess structural connectivity in healthy subjects, we show that portions of the putamen activated during pain are connected not only with cortical regions involved in sensory-motor processing, but also regions involved in attention, memory and affect. Such a framework may allow cognitive information to flow from these brain areas to the putamen where it may be used to influence how nociceptive information is processed. Taken together, these findings indicate that the putamen and the basal ganglia may contribute importantly to the shaping of an individual subjective sensory experience by utilizing internal cognitive information to influence activity of large areas of the cerebral cortex.