Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Variations in neural circuitry, inherited or acquired, may underlie important individual differences in thought, feeling, and action patterns. Here, we used task-free connectivity analyses to isolate and characterize two distinct networks typically coactivated during functional MRI tasks. We identified a "salience network," anchored by dorsal anterior cingulate (dACC) and orbital frontoinsular cortices with robust connectivity to subcortical and limbic structures, and an "executive-control network" that links dorsolateral frontal and parietal neocortices. These intrinsic connectivity networks showed dissociable correlations with functions measured outside the scanner. Prescan anxiety ratings correlated with intrinsic functional connectivity of the dACC node of the salience network, but with no region in the executive-control network, whereas executive task performance correlated with lateral parietal nodes of the executive-control network, but with no region in the salience network. Our findings suggest that task-free analysis of intrinsic connectivity networks may help elucidate the neural architectures that support fundamental aspects of human behavior.

https://www.jneurosci.org/content/jneuro/27/9/2349.full.pdf

Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control

In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.

/pdf/from-inflammation-to-sickness-and-depression-when-the-immune-maw2hn72o8.pdf

From inflammation to sickness and depression: when the immune system subjugates the brain

The anterior insular cortex (AIC) is implicated in a wide range of conditions and behaviours, from bowel distension and orgasm, to cigarette craving and maternal love, to decision making and sudden insight. Its function in the re-representation of interoception offers one possible basis for its involvement in all subjective feelings. New findings suggest a fundamental role for the AIC (and the von Economo neurons it contains) in awareness, and thus it needs to be considered as a potential neural correlate of consciousness.

How do you feel--now? The anterior insula and human awareness.

As humans, we perceive feelings from our bodies that relate our state of well-being, our energy and stress levels, our mood and disposition. How do we have these feelings? What neural processes do they represent? Recent functional anatomical work has detailed an afferent neural system in primates and in humans that represents all aspects of the physiological condition of the physical body. This system constitutes a representation of 'the material me', and might provide a foundation for subjective feelings, emotion and self-awareness.

How do you feel? Interoception: the sense of the physiological condition of the body.

The distribution of terminal projections in the brainstem from lamina I neurons in the spinal dorsal horn was investigated with the anterograde tracer Phaseolus vulgaris–leucoagglutinin in the cat and the cynomolgus monkey. Iontophoretic injections made with physiological guidance were restricted to lamina I or to laminae I–III in the cervical (C6–8) or lumbar (L6–7) enlargement. The distribution of terminal labeling was essentially identical in the cat and the monkey, although consistently of greater intensity in the monkey. Terminations were observed in the solitary nucleus, the dorsomedial medullary reticular formation, the entire rostrocaudal extent of the ventrolateral medulla, the locus coeruleus, the subcoerulear region and the Kolliker–Fuse nucleus, the lateral and medial portions of the parabrachial nucleus, the cuneiform nucleus, the ventrolateral and lateral portions of the periaqueductal gray, and the intercollicular nucleus. Lamina I terminations were generally bilateral in the medulla but more dense contralaterally in the pons and mesencephalon. The density and laterality of labeling in the medulla varied between cases independently from that in the pons and mesencephalon, suggesting that the lamina I projections to these regions may originate from different subsets of neurons. A clear topographic organization was observed only in the lateral column of the periaqueductal gray, where lumbar lamina I terminations were found caudal to cervical terminations.



These observations indicate that spinal lamina I neurons project to a variety of brainstem sites involved in autonomic (cardiovascular, respiratory) and homeostatic processing and the control of behavioral state. These projections provide an afferent substrate for spino-bulbo-spinal somatoautonomic reflex arcs activated by nociceptive, thermoreceptive activity and for a spino-bulbo-hypothalamic relay of such activity by cells in the caudal ventrolateral medulla. These observations support the general concept that lamina I projections distribute modality-selective sensory information relevant to the physiological status and maintenance of the tissues and organs of the entire organism. © 1995 Wiley-Liss, Inc.

Distribution of brainstem projections from spinal lamina I neurons in the cat and the monkey.

Context: Chronic pain and depression are highly comorbid conditions, yet little is known about the neurobiological basis of pain processing in major depressive disorder (MDD). Objective: To examine the neural substrates underlying anticipation and processing of heat pain in a group of unmedicated young adults with current MDD. Design: Functional magnetic resonance neuroimaging data were collected during an event-related factorial experimental pain paradigm. Painful and nonpainful heat stimuli were applied to the left volar forearm while different color shapes explicitly signaled the intensity of the upcoming stimulus. Setting: University brain imaging center. Patients: Fifteen (12 female) young adults with current MDD and 15 (10 female) healthy subjects with no history of MDD were recruited and matched for age and level of education. The Structured Clinical Interview for DSM-IV was administered to all participants by a boardcertified psychiatrist. Main Outcome Measure: Between-group differences in blood oxygen level–dependent functional magnetic resonance neuroimaging signal change to anticipation and processing of painful vs nonpainful temperature stimuli. Results: Subjects with MDD compared with healthy controls showed (1) increased activation in the right anterior insular region, dorsal anterior cingulate, and right amygdala during anticipation of painful relative to nonpainful stimuli, (2) increased activation in the right amygdala and decreased activation in periaqueductal gray matter and the rostral anterior cingulate and prefrontal cortices during painful stimulation relative to nonpainful stimulation, and (3) greater activation in the right amygdala during anticipation of pain, which was associated with greater levels of perceived helplessness. Conclusions: These findings suggest that increased emotional reactivity during the anticipation of heat pain may lead to an impaired ability to modulate pain experience in MDD. Future studies should examine the degree to which altered functional brain response during anticipatory processing affects the ability to modulate negative affective states in MDD, which is a core characteristic of this disorder.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/482882/yoa80059_1275_1284.pdf

Association of major depressive disorder with altered functional brain response during anticipation and processing of heat pain.

Pain and temperature stimuli activate neurons of lamina I within the dorsal horn of the spinal cord, and although these neurons can be classified into three basic morphological types and three major physiological classes, earlier studies did not establish a structure/function correlation between their morphology and their physiological responses. We recorded and intracellularly labeled 38 cat lamina I neurons. All 12 fusiform cells were nociceptive-specific, responsive only to pinch and/or heat. All 11 pyramidal cells were thermoreceptive-specific, responsive only to innocuous cooling. Of ten multipolar cells, six were polymodal, responsive to heat, pinch and cold, and four were nociceptive-specific. Five unclassified cells had features consistent with this pattern. These results support the view that central pain and temperature pathways contain anatomically discrete sets of modality-selective neurons.

Nociceptive and thermoreceptive lamina I neurons are anatomically distinct.

How Do You Feel?: An Interoceptive Moment with Your Neurobiological Self

We briefly review the evidence for distinct neuroanatomical substrates that underlie interoception in humans, and we explain how they substantialize feelings from the body (in the insular cortex) that are conjoined with homeostatic motivations that guide adaptive behaviours (in the cingulate cortex). This hierarchical sensorimotor architecture coincides with the limbic cortical architecture that underlies emotions, and thus we regard interoceptive feelings and their conjoint motivations as homeostatic emotions . We describe how bivalent feelings, emotions and sympathovagal balance can be organized and regulated efficiently in the bicameral forebrain as asymmetric positive/negative, approach/avoidance and parasympathetic/sympathetic components. We provide original evidence supporting this organization from studies of cardiorespiratory vagal activity in monkeys and functional imaging studies in healthy humans showing activation modulated by paced breathing and passively viewed emotional images. The neuroanatomical architecture of interoception provides deep insight into the functional organization of all emotional feelings and behaviours in humans. This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.

https://royalsocietypublishing.org/doi/pdf/10.1098/rstb.2016.0010

A.D. (Bud) Craig

Papers

Distribution of brainstem projections from spinal lamina I neurons in the cat and the monkey.

Association of major depressive disorder with altered functional brain response during anticipation and processing of heat pain.

Nociceptive and thermoreceptive lamina I neurons are anatomically distinct.

How Do You Feel?: An Interoceptive Moment with Your Neurobiological Self

Interoception, homeostatic emotions and sympathovagal balance.