General Introductory Comments & Issues

General Introductory Comments & Issues

Before wading into the details of cingulate organization and disruption by child abuse, let us look to a few issues that are of general interest and provide perspectives on cingulate cortex function.

Cingulate Cortex Is Involved In Pain Processing

The anterior midcingulate cortex (aMCC) is a site that is most often engaged during acute (short) noxious/painful stimulation of the skin (cutaneous stimulation), while the anterior cingulate cortex (ACC) is more frequently engaged by noxious stimulation of the viscera (colorectal tissues, stomach and esophagus). This is discussed in reference #7 in the Neuroscience Library. A picture is shown here of activity evoked in a positron emission tomography (PET) study showing blood flow increases (yellow areas in the figure). Subjects were asked to either evaluate in unpleasantness of a noxious stimulus (A.) or to localize a stimulus on the dorsal forearm (B.). While much of the unpleasantness response was in pregenual ACC, it also extended into aMCC as shown with the yellow arrows. Localization of the stimuli increased blood flow in a very different place in the posterior MCC (bil, bilateral; Left and Right hemispheres). Thus, these findings both emphasize the role of cingulate cortex in pain and the functional differences between the two parts of MCC.

Pain Relief

Most everyone at one time or another has taken ibuprofen for pain relief. Recognizing this drug has peripheral as well as central brain effects that support its role as a non-steroidal anti-inflammatory drug, we look at the medial surface of an arterial spin labeling study (another way to assess blood flow) by Hodkinson et al. (2015; Pain 156(7):1301-1310) before and after 3rd molar extraction. Reduced blood flow is represented in this figure with shades of blue with the lightest blue showing the region of greatest reduction in blood flow associated with pain relief. Of course, this is aMCC that plays a major role in pain perception. Interestingly, there was no reduction in pMCC; however, this study shows an increase in activity there (not shown) and raises many other interesting issues that are beyond the present consideration.

PTSD & Child Maltreatment

​Here we present a few other studies to begin our exploration into cingulate involvement in various diseases. The review by Shin et al. (#48 in the Neuro-science Library) shows that the primary effects of trauma provocation studies in patients with posttraumatic stress disorder (PTSD) implicate mainly ACC. As you will see in “Effects of Child Abuse,” a functional MRI study by Ringel et al. (2008) show a reduction in activity in patients with a history of child abuse, while there is an increase in activity in MCC.Emotional maltreatment of children results in shrinkage of MCC (van Harmelen et al, 2010 Biol Psychiatry 68:832-838) suggesting that structural and functional changes do not necessarily overlap or that chronic maltreatment evoking increased MCC activity is responsible for atrophy in MCC (hyper-excitation can kill neurons).

These are among the many issues that need to be resolved when considering the mechanisms of brain damage following child maltreatment.We find the study by Thomaes et al. (2010; J Clin Psychiatry 71:1636-1644) to be one of the most important in the context of child abuse because child abuse-related PTSD is the most severe form of PTSD. These patients have the most profound emotional disruptions and atrophy in MCC is prominent. Atrophy refers to shrinkage of the cortex and can result from pruning of neuron dendrites, shrinkage of neurons or their death and possibly changes in glial densities. None of these latter changes can be determined from human imaging studies where the brain is not available for analysis proximal to the childhood abuse. These are the reasons an animal model of harsh physical child abuse is a necessary part of our work and we expect that knowing such information will eventually lead to a treatment for patients with a recent history of harsh child abuse.

Another issue that arises but is often overlooked is the role of child abuse in prison populations. It is difficult to empathize with incarcerated psychopaths as they do everything they can to engender fear including extensive tattooing and aggressive behaviors. The bimonthly mass shootings in the US (36,000 people killed with guns each year) are often said to be the result of mental illness and used to shield the NRA and its anti-gun control lobbying. After each instance, the presidents of both parties rise to the occasion with useless statements about the perpetrator’s mental stability and nothing further changes.Once again, cingulate damage has a major role in the psychiatric underpinnings of this disease. While it is true that psychopathy is associated with “poor choices,” these “choices” are due to brain damage that in many instances could be averted with timely treatment.

This figure is from Kiehl et al. (2001; Limbic abnormalities in affective processing as revealed by functional MRI. Biol Psychiatry 50:677-684) who reported brain changes during an affective memory task. It shows cingulate areas that are not appropriately activated (empty red ovals) and those that are incorrectly inhibited (blue). Cingulate cortex is extremely damaged in these individuals.It is interesting that reduced activity occurs in the ventral posterior cingulate cortex (vPCC) where objects and events of a personal relevance are stored as well as a connected area in pregenual anterior cingulate cortex (pACC) that is inactivated where emotional responses are often evoked in normal human brains.Note also the lack of a response in the dorsal aMCC that is engaged in feedback-mediated decision making (Bush, 2009; Library #39). For further details on this subject and figure read the Library #53 article section titled “Cingulate Subregional Inactivations in Psychopathy.”