Differentiating among prefrontal substrates in psychopathy: neuropsychological test findings

Frontal lobe and consequent executive dysfunction have long been related to psychopathy. More recently, there have been suggestions that specific regions of frontal cortex, rather than all of frontal cortex, may be implicated in psychopathy. To examine this issue, the authors presented 25 individuals with psychopathy and 30 comparison individuals with measures preferentially indexing the orbitofrontal cortex (OFC; object alternation task), dorsolateral prefrontal cortex (DLPFC; spatial alternation task), and anterior cingulate cortex (ACC; number-Stroop reading and counting tasks). The individuals with psychopathy showed significant impairment on the measure preferentially sensitive to OFC functioning. In contrast, the 2 groups did not show impairment on the measures preferentially sensitive to the functioning of the DLPFC or ACC. These results are interpreted with reference to executive dysfunction accounts of the disorder.     

Altered calcium/calmodulin kinase II activity changes calcium homeostasis that underlies epileptiform activity in hippocampal neurons in culture

Epilepsy is characterized by the occurrence of spontaneous recurrent epileptiform discharges (SREDs) in neurons. A decrease in calcium/calmodulin-dependent protein kinase II (CaMK-II) activity has been shown to occur with the development of SREDs in a hippocampal neuronal culture model of acquired epilepsy, and altered calcium (Ca(2+)) homeostasis has been implicated in the development of SREDs. Using antisense oligonucleotides, this study was conducted to determine whether selective suppression of CaMK-II activity, with subsequent induction of SREDs, was associated with altered Ca(2+) homeostasis in hippocampal neurons in culture. Antisense knockdown resulted in the development of SREDs and a decrease in both immunocytochemical staining and enzyme activity of CaMK-II. Evaluation of [Ca(2+)](i) using Fura indicators revealed that antisense-treated neurons manifested increased basal [Ca(2+)](i), whereas missense-treated neurons showed no change in basal [Ca(2+)](i). Antisense suppression of CaMK-II was also associated with an inability of neurons to restore a Ca(2+) load. Upon removal of oligonucleotide treatment, CaMK-II suppression and Ca(2+) homeostasis recovered to control levels and SREDs were abolished. To our knowledge, the results demonstrate the first evidence that selective suppression of CaMK-II activity results in alterations in Ca(2+) homeostasis and the development of SREDs in hippocampal neurons and suggest that CaMK-II suppression may be causing epileptogenesis by altering Ca(2+) homeostatic mechanisms.     

Mild folate deficiency induces a proatherosclerotic phenotype in endothelial cells

Low folate/high homocysteine (Hcy) is an established risk marker for cardiovascular disease (CVD). Some in vivo studies suggest low folate may independently contribute to CVD. To study the effects of mild folate deficiency on endothelial function, we adapted the EA.hy 926 endothelial cell line to growth in medium containing 23 nM folic acid (LO cells) or 9 microM folic acid (HI cells). Folate derivatives were substantially depleted in LO cells relative to HI cells. No differences were seen in intracellular homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), the SAM:SAH ratio, or global DNA methylation, and there was no consistent difference in secreted homocysteine. A greater percentage of LO than HI cells were in S phase of the cell cycle; supplementation of LO cells with thymidine/hypoxanthine prevented this. LO cells were more elongated than HI cells and did not form tight monolayers. Stress fibers were very prominent in LO but not HI cells. Treatment of LO cells with rho kinase inhibitors abolished stress fibers and partially normalized cell shape. LO cell monolayers were more permeable than HI cell monolayers at confluence, and MCP-1 mRNA and protein expression was higher in LO than HI cells. Our results suggest that mild folate deficiency is proatherosclerotic.     

The role of the amygdala and rostral anterior cingulate in encoding expected outcomes during learning

Successful passive avoidance learning is thought to require the use of learned stimulus-reinforcement associations to guide decision making [Baxter, M.G., Murray, E.A., 2002. The amygdala and reward. Nature Reviews. Neuroscience 3, 563-573]. The current experiment investigated the neural correlates of successful passive avoidance learning in 19 healthy adults. Behaviorally, subjects showed a distinct pattern of performance: early indiscriminate responding to stimuli (pre-criterion performance), followed by relatively rapid learning before a plateau of successful performance (post-criterion performance). Neural responses to post-criterion correct responses were compared with neural responses to both incorrect responses and pre-criterion correct responses. Post-criterion correct responding was associated with increased activation in regions including rostral anterior cingulate, insula, caudate, hippocampal regions, and the amygdala.     

Doing the right thing: a common neural circuit for appropriate violent or compassionate behavior

Humans have a considerable facility to adapt their behavior in a manner that is appropriate to social or societal context. A failure of this ability can lead to social exclusion and is a feature of disorders such as psychopathy and disruptive behavior disorder. We investigated the neural basis of this ability using a customized video game played by 12 healthy participants in an fMRI scanner. Two conditions involved extreme examples of context-appropriate action: shooting an aggressive humanoid assailant or healing a passive wounded person. Two control conditions involved carefully matched stimuli paired with inappropriate actions: shooting the person or healing the assailant. Surprisingly, the same circuit, including the amygdala and ventromedial prefrontal cortex, was activated when participants acted in a context-appropriate manner, whether being compassionate towards an injured conspecific or aggressive towards a violent assailant. The findings indicate a common system that guides behavioral expression appropriate to social or societal context irrespective of its aggressive or compassionate nature.     

Pilot study of a commercialized human papillomavirus (HPV) genotyping assay: comparison of HPV risk group to cytology and histology

We evaluated a commercialized PCR assay, Linear Array, that detects 37 human papillomavirus (HPV) genotypes, using a sample of liquid cytology specimens (n = 534). We found a strong association of an increasing level of HPV risk (HPV type 16 [HPV16] > HPV18 > other carcinogenic types > noncarcinogenic types > negative specimens) with increasing severities of cytologic interpretations (P(Trend) < 0.0005) and histologic diagnoses (P(Trend) < 0.0005).