Effects of family history of alcohol use disorders on spatial working memory BOLD response in adolescents

Background:  A positive family history (FH) of alcohol use disorders (AUD) has been linked to increased risk for the development of AUD, and neurocognitive factors have been postulated as important underlying mechanisms of familial alcoholism transmission.
Methods:  We used functional magnetic resonance imaging (fMRI) during a spatial working memory (SWM) and vigilance paradigm to investigate potential neurodevelopmental differences linked to familial density of AUD in 72 adolescents aged 12 to 14 years.
Results:  Youth with denser family histories of AUD showed less activation during a simple vigilance condition relative to SWM in cingulate and medial frontal gyri (β = 0.28, p  = 0.03), and a trend for more relative activity during rest (β = −0.25, p  = 0.07) in this cluster.
Conclusions:  Youth with greater familial densities of AUD may be less successful at modulating activity of the default network, potentially indicating a greater propensity for task-independent thought or reduced inhibition of task-irrelevant processing. Failure to moderate activation of the default network may have implications for cognitive efficiency and goal directed behavior in youth with dense FH. Further, aberrant activation in cingulate regions may be linked to genetic variation in GABA receptor units, suggesting a useful endophenotype for risk associated with alcohol dependence.     

Chemical shift magnetic resonance spectroscopy of cingulate grey matter in patients with minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is frequently diagnosed in patients with liver cirrhosis who do not show overt clinical cirrhosis-associated neurological deficits. This condition manifests primarily with visuo-motor and attention deficits. We studied the association between visuo-motor deficits and magnetic resonance spectroscopic parameters in cingulate grey matter and white matter of centrum semiovale in patients with liver cirrhosis. The data revealed an increase in the glutamate–glutamine/creatine ratio and a decrease in choline/creatine and inositol/creatine ratios in patients with liver cirrhosis. The analysis of the data showed that cirrhosis-associated deterioration of the visuo-motor function significantly correlates with a decrease in the choline/creatine ratio and an increase in N-acetylaspartate/choline in cingulate grey matter but not in the neighbouring white matter. Furthermore, the increase in the glutamate–glutamine/creatine ratio correlated significantly with the increase in the N-acetylaspartate/creatine ratio. These data suggest an association between altered choline, glutamate-glutamine and NAA metabolism in cingulate grey matter and symptoms of MHE, and underline the importance of differentiation between grey and white matter in magnetic resonance spectroscopic studies on patients with cirrhosis-associated brain dysfunction.     

Cingulate lesions and behavioral adaptation to amino acid imbalanced diets

The effect of anterior cingulate cortex lesions on dietary intake and adaptation of disproportionate amounts of amino acids was examined. Rats with bilateral electrolytic lesions in the anterior cingulate cortex and sham-operated rats were fed, in turn, amino acid basal, imbalanced or devoid diets involving threonine and isoleucine as the growth limiting amino acids, and then a low protein (6% casein) followed by a high protein (75% casein) diet. Lesions of the anterior cingulate cortex did not prevent the initial depression in food intake of the amino acid imbalanced diets, but shortened the duration of anorexia associated with dietary amino acid imbalances. Cingulate lesions did not influence the food intake of rats fed amino acid devoid diets. When switched from a low protein to a high protein diet, animals bearing lesions and sham-operated controls reduced markedly their initial food intake and adapted to the high protein diet in similar manner. It was concluded that the initial food intake depression associated with a dietary amino acid imbalance is a direct response to postingestive cues which influence food intake. Moreover, that the difference in adaptive intakes of the cingulate cortex lesioned animals who ingested a diet of imbalanced amino acids or of high protein, indicates that separate mechanisms act to control food intake of animals fed diets containing imbalanced amino acid mixtures or diets with excessive amounts of protein.     

Effects of fornix transection and cingulate cortical ablation on spatial memory in rhesus monkeys

Summary This study, together with a parallel study in rats (Markowska et al. 1988), attempted to relate the effects of hippocampal-system damage on similar tasks in both rats and monkeys. Not only were monkeys given a task (Experiment 1) which was of the sort usually used with rats, but in the companion study rats were given tasks (Experiment 2) like those usually used with monkeys. Experiment 1 examined the performance of rhesus monkeys with hippocampal-system damage on a spatial working memory task. Monkeys were trained preoperatively on delayed nonmatching-to-sample in a T-maze, placed into groups matched for their preoperative learning scores, and then received one of three treatments: 1) transection of the fornix; 2) ablation of the cingulate cortex; or 3) a sham operation. Monkeys with fornix transection were severely and significantly impaired, but monkeys with cingulate cortical ablations were not significantly impaired, relative to the controls. The results demonstrate that monkeys with fornix transection are severely impaired on a spatial working memory task requiring locomotion and, taken together with earlier work, suggest that the effect of fornix transection in both rodents and nonhuman primates is at least qualitatively similar (see Markowska et al. 1988). Experiment 2 assessed the role of the fornix and cingulate cortex in three conditional tasks in which the monkeys were provided with various spatial cues to indicate which one of two objects was rewarded. Both experimental groups were unimpaired, relative to the control group, on all three tasks, indicating that fornix transection does not produce a general impairment in place learning.     

Testing perceptual limits of functional units: Are there “automatic” tendencies to associate tools and objects?

Prior work has demonstrated a unique network involving the insula, temporal cortex, and precuneus in evaluating appropriate relationships between tool–object pairings under instruction [20]. However, are there automatic tendencies to evaluate appropriate tool–object pairings? Using electroencephalography (EEG), we emulated our prior work to identify neural mechanisms that, in the absence of task-related consciousness, differentiate functionally matching from mismatching tool–object pairs. This was compared to any activation consistent with this using environmental image pairs. In addition, based on the paradigm we were able to discern any naïve processes that distinguish tools from non-tool environmental images. Results show that without task-related consciousness, the left occipitotemporal gyrus is preferentially active for tools compared to environmental images. Tool–object match and mismatch each versus control images show differences relative to a control image over the left temporal cortex, extending into the insula, yet there was no difference between tool–object match and mismatch. This suggests that there is no clear neural mechanism for continual evaluation of tool matching from mismatching, though there is for broad picture classifications. Taken together with our previous results, this creates a discussion for the role of intention when determining such relationships.     

Error-related negativity abnormalities in generalized anxiety disorder and obsessive-compulsive disorder

Enhanced error-related negativity (ERN) has been associated with anxiety among both non-clinical and clinical populations. However, whether it is abnormal among adult patients with generalized anxiety disorder (GAD) is still unknown. The present study investigated it across GAD and obsessive-compulsive disorder (OCD). Event related brain potentials (ERPs) were recorded from a group of 27 GAD patients, 25 OCD patients and 27 healthy control participants during a modified Erikson Flankers task. ERP difference waveforms were obtained by subtracting ERP to correct response (CRN) from ERP to error response (ERN). The Ne component of ERPs at medial frontal electrodes were analyzed and reported. The Ne component of ERP difference waveform was enhanced only in OCD patients, but not in GAD patients, as compared to the healthy controls. An exploratory analysis also revealed higher Ne amplitude of error trial waveforms in both GAD and OCD patients than in healthy controls, and an insignificant group difference in Ne component of correct trial waveforms. The Ne amplitude of error trial waveforms also correlated with Hamilton Anxiety Rating Scale (HAMA) scores and with Hamilton Depression Rating Scale (HAMD) scores across the three subject groups. The main findings of the present study suggest that error processing is altered in OCD but not in GAD, and that ERN abnormalities in GAD are possibly associated with an overactive response checking process or excessive response monitoring.     

GABAA but not GABAB receptors in the rostral anterior cingulate cortex selectively modulate pain-induced escape/avoidance behavior

The rostral anterior cingulate cortex (rACC) is involved in supraspinal nociceptive processing. ACC lesions relieve persistent pain, but do not affect the patient's ability to localize a noxious stimulus. Since the rACC has a high density of GABA receptors, it is possible that pain processing is influenced by these receptors in the rACC. The present experiments examined the involvement of rat rACC GABA(A) and GABA(B) receptors in regard to sensitivity to mechanical stimulation and escape/avoidance behavior in response to a noxious stimulus following L5 spinal nerve ligation. Rats were or were not afflicted with a neuropathic pain condition by an L5 spinal nerve ligation. rACC microinjection of 10 microg/microl GABA, a GABA(A) agonist (0.001 microg/microl, 0.1 microg/microl, or 0.5 microg/microl muscimol), a GABA(B) agonist (0.1 microg/microl, 1 microg/microl, or 5 microg/microl baclofen), or saline, did not alter mechanical withdrawal thresholds. Importantly, following 10 microg/microl GABA, 0.1 microg/microl, or 0.5 microg/microl muscimol microinjected into the rACC, place escape/avoidance behavior to a noxious mechanical stimulus was attenuated in injured animals. The attenuation was specific to the rACC and was blocked by a preadministered microinjection of the appropriate antagonist(s) into the rACC. In conclusion, microinjection of GABA and higher doses of muscimol did not decrease mechanical hyperalgesia but did attenuate place escape/avoidance behavior that is associated with mechanical stimulation of the ligated paw. These results provide additional support for the role of the rACC in higher order supraspinal processing of noxious events and suggest that rACC GABA(A) receptors significantly contribute to this processing.     

Borderline personality features possibly related to cingulate and orbitofrontal cortices dysfunction due to schizencephaly

Prefrontal cortex dysfunction has been associated with a series of behavioral symptoms, such as impulsivity and affective instability, which are the defining features of several personality disorders, notably, borderline personality disorder. We report on a 27-year-old patient with schizencephaly in the right frontal lobe (cingulate cortex lesion and secondary orbitofrontal cortex dysfunction) presenting with prominent borderline features and compromise of executive functions, decision-making and attention. We hypothesize that the personality disorder of our patient could be related to cingulate cortex lesion and secondary orbitofrontal cortex dysfunction associated with schizencephaly.     

Cortico-thalamic activation in generalized status epilepticus, a PET study

In a patient with a refractory generalized convulsive status epilepticus, the ictal distribution of regional cerebral glucose was assessed with positron emission tomography (PET). Synchronized seizure activity in the EEG was associated with bilateral metabolic activation of medial sensorimotor regions, anterior cingulate cortex, striatum and thalamus. This pattern with focal cortical activation supports the concept that a cortical focus may drive epilepsy, while the thalamus mediates synchronization of neuronal activity as reflected in the EEG.