A. D. Craig

Forebrain emotional asymmetry : a neuroanatomical basis?

There is considerable psychophysiological evidence to indicate that the left and right halves of the human forebrain differentially associate with particular emotions and affective traits. A neurobiological model is needed. Here I propose that forebrain emotional asymmetry is anatomically based on an asymmetrical representation of homeostatic activity that originates from asymmetries in the peripheral autonomic nervous system. This proposal builds on recent evidence indicating that lateralized, higher-order re-representations of homeostatic sensory activity provide a foundation for subjective human feelings. It can subsume differing views of emotion and the forebrain because it suggests that emotions are organized according to the fundamental principle of autonomic opponency for the management of physical and mental energy.

Nociceptive and thermoreceptive lamina I neurons are anatomically distinct.

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.

Association of Major Depressive Disorder With Altered Functional Brain Response During Anticipation and Processing of Heat Pain

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 board-certified 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.

Distribution of trigeminothalamic and spinothalamic lamina I terminations in the macaque monkey

Thalamic terminations from trigeminal, cervical, and lumbosacral lamina I neurons were investigated with Phaseolus vulgaris leucoagglutinin (PHA‐L) and labeled dextrans. Iontophoretic injections guided by physiological recordings were restricted to lamina I or laminae I–II. PHA‐L‐labeled trigemino‐ and spinothalamic (TSTT) terminations were identified immunohistochemically. TRITC‐ and FITC‐labeled dextrans were injected at different levels to confirm topography. Terminations consistently occurred in two main locations: a distinguishable portion of posterolateral thalamus identified cytoarchitectonically as the posterior part of the ventral medial nucleus (VMpo) and a portion of posteromedial thalamus designated as the ventral caudal part of the medial dorsal nucleus (MDvc). In addition, isolated fibers bearing boutons of passage were observed in the ventral posterior medial and lateral (VPM and VPL) nuclei, and spinal terminations occurred in the ventral posterior inferior nucleus (VPI). Isolated terminations occasionally occurred in other sites (e.g., suprageniculate, zona incerta, hypothalamic paraventricular n.). Terminations in MDvc occurred in concise foci that were weakly organized topographically (posteroanterior = rostrocaudal). Terminations in VMpo consisted of dense clusters of ramified terminal arbors bearing multiple large boutons that were well organized topographically (anteroposterior = rostrocaudal). Terminations in VMpo colocalized with a field of calbindin‐immunoreactive terminal fibers; double‐labeled terminals were documented at high magnification. This propitious marker was especially useful at anterior levels, where VMpo can easily be misidentified as VPM. These findings demonstrate phylogenetically novel primate lamina I TSTT projections important for sensory and motivational aspects of pain, temperature, itch, muscle ache, sensual touch, and other interoceptive feelings from the body. J. Comp. Neurol. 477:119–148, 2004.

Morphological classes of spinothalamic lamina I neurons in the cat

We examined the morphology and distribution of retrogradely labeled spinothalamic tract (STT) neurons in lamina I (the marginal zone) of the spinal dorsal horn after large injections of cholera toxin subunit B (CTb) or Fast Blue (FB) into the contralateral thalamus of cats. Based on the shape and orientation of the somata and proximal dendrites in horizontal sections, three distinct cell types were identified: (1) fusiform cells with small, spindle‐shaped somata and bipolar, longitudinal dendritic arbors; (2) pyramidal cells with triangular somata and three main dendritic origins with primarily longitudinal arborizations; and (3) multipolar cells with larger, multiangular somata and four or more radiating dendritic arbors directed both longitudinally and mediolaterally. These three morphological types differed significantly in the number of primary dendrites and the size of the somata. Subclasses of multipolar cells were noted. Nearly all cells could be categorized into these three classes consistently in horizontal sections. A small number of cells with transitional shapes or with small, round somata were unclassified.

Effects of systemic morphine on lamina I spinothalamic tract neurons in the cat.

Lamina I spinothalamic tract (STT) neurons are an integral component of the central representation of pain and temperature and thus their sensitivity to various analgesics needs to be examined. In the present study, the effects of successive, cumulative doses (0.125-2.0 mg/kg) of intravenous morphine sulfate on the quantitative stimulus-response properties of nociceptive lamina I STT cells have been tested in the intact, barbiturate-anesthetized cat. Both nociceptive-specific (n = 7) and multireceptive (heat, pinch and cold sensitive; n = 7) lamina I STT cells were inhibited in a dose-dependent manner. Parallel dose-dependent effects on responses to noxious heat and pinch were generally observed that reduced ongoing discharge levels and the slopes of the stimulus-response functions. However, non-STT lamina I cells (n = 5) differed significantly; the responses of one multireceptive (heat, pinch and cold-sensitive) cell and the responses to pinch of 3 of 4 wide dynamic range cells were not inhibited. In addition, two-thirds of the nociceptive lamina I STT cells showed enhanced responses at the lowest dose of morphine (0.125 mg/kg). These results contrast with the varied effects of morphine reported for superficial dorsal horn cells with uncharacterized projections and they support the role of lamina I STT cells in pain. Furthermore, these observations are consistent with previous findings indicating that lamina I STT neurons are a distinct subpopulation of lamina I cells. These results support previous evidence that opiatergic modulation of sensory activity in lamina I is functionally organized.

The effects of slow breathing on affective responses to pain stimuli: an experimental study.

&NA; This study examined whether breathing rate affected self‐reported pain and emotion following thermal pain stimuli in women with fibromyalgia syndrome (FM: n = 27) or age‐matched healthy control women (HC: n = 25). FM and HC were exposed to low and moderate thermal pain pulses during paced breathing at their normal rate and one‐half their normal rate. Thermal pain pulses were presented in four blocks of four trials. Each block included exposure to both mild and moderate pain trials, and periods of both normal and slow paced breathing. Pain intensity and unpleasantness were recorded immediately following each pain trial, and positive and negative affect were assessed at the end of each block of trials. Compared to normal breathing, slow breathing reduced ratings of pain intensity and unpleasantness, particularly for moderately versus mildly painful thermal stimuli. The effects of slow breathing on pain ratings were less reliable for FM patients than for HCs. Slow versus normal breathing decreased negative affect ratings following thermal pain pulses for both groups, and increased positive affect reports, but only for healthy controls with high trait negative affect. Participants who reported higher levels of trait positive affect prior to the experiment showed greater decreases in negative affect as a result of slow versus normal breathing. These experimental findings provide support for prior reports on the benefits of yogic breathing and mindful Zen meditation for pain and depressed affect. However, chronic pain patients may require more guidance to obtain therapeutic benefit from reduced breathing rates.

Distinctive Neurons of the Anterior Cingulate and Frontoinsular Cortex: A Historical Perspective

Human anterior cingulate and frontoinsular cortices participate in healthy social-emotional processing. These regions feature 2 related layer 5 neuronal morphotypes, the von Economo neurons and fork cells. In this paper, we review the historical accounts of these neurons and provide a German-to-English translation of von Economos seminal paper describing the neurons which have come to bear his name. We close with a brief discussion regarding the functional and clinical relevance of these neurons and their home regions.

Increased Affective Bias Revealed Using Experimental Graded Heat Stimuli in Young Depressed Adults: Evidence of “Emotional Allodynia”

Objective: To examine the hypothesis that young adults with major depressive disorder (MDD) would show increased affective bias to painful and nonpainful experimental heat stimuli, as evidenced by an increased responsiveness to warm and hot temperatures. Pain and depression often occur together. Pain is both a sensation and an affective experience. Similarly, depression is associated frequently with somatic symptoms as well as emotional dysphoria. Existing evidence indicates that MDD may be associated with altered pain processing. However, the extent to which alterations in experimentally controlled heat pain sensations are related to increased affective bias in MDD is unknown. Method: Graded nonnoxious and noxious heat stimuli were delivered randomly with a thermode applied to the volar surface of the left arm of 15 unmedicated subjects with current MDD and 15 age- and gender-matched healthy comparison subjects. MDD and non-MDD subjects rated the intensity and unpleasantness of all stimuli. Results: Two main results were observed. First, MDD relative to non-MDD subjects showed decreased heat pain thresholds. Second, a significantly increased affective bias (unpleasantness/intensity) was observed in subjects with MDD, particularly over the range of nonnoxious heat stimuli. This bias was independent of the change in sensory pain thresholds. Conclusion: These findings represent corroborative evidence of abnormal affective heat pain processing in young adults with MDD, and suggest that MDD is associated with “emotional allodynia,” a qualitatively altered negative emotional response to normally nonaversive thermal stimuli. MDD = major depressive disorder.

Evidence for glutamate as neurotransmitter in trigemino-and spinothalamic tract terminals in the nucleus submedius of cats.

The nucleus submedius in the medial thalamus of cats is an important termination site for lamina I trigemino‐ and spinothalamic tract (TSTT) neurons, many of which are nociceptive‐specific, and the nucleus submedius has been proposed to be a dedicated nociceptive substrate involved in the affective aspect of pain. In the present study, the distribution of glutamate was examined by immunocytochemical methods in order to evaluate the possible role of this amino acid as a neurotransmitter in TSTT terminals in the nucleus submedius. TSTT terminals were identified by anterograde transport of horseradish peroxidase and wheatgerm agglutinin‐horseradish peroxidase conjugate from the spinal cord or the medullary dorsal horn. Quantitative analysis of immunogold labelling revealed that TSTT terminals contain about twice the tissue average of glutamate‐like immunoreactivity. A strong positive correlation was found between the density of synaptic vesicles and the density of gold particles in these terminals, whereas no relationship was seen between these variables in GABAergic presynaptic dendrites. Enrichment of glutamate‐like immunoreactivity (∼250% of the tissue average) was also observed in terminals of presumed cortical origin. Presynaptic dendrites and neuron cell bodies in the nucleus submedius were found to contain relatively low levels of glutamate‐like immunoreactivity, at or below the tissue average. These observations provide evidence that glutamate is a neurotransmitter in lamina I TSTT terminals in the nucleus submedius. The findings also suggest glutamatergic neurotransmission between cortical afferents and nucleus submedius neurons. Glutamate is therefore likely to be an important mediator of nociceptive processing in the medial thalamus.