Anterior Cingulate Desynchronization and Functional Connectivity with the Amygdala During a Working Memory Task Predict Rapid Antidepressant Response to Ketamine

Pregenual anterior cingulate cortex (pgACC) hyperactivity differentiates treatment responders from non-responders to various pharmacological antidepressant interventions, including ketamine, an N-methyl--aspartate receptor antagonist. Evidence of pgACC hyperactivition during non-emotional working memory tasks in patients with major depressive disorder (MDD) highlights the importance of this region for processing both emotionally salient and cognitive stimuli. However, it is unclear whether pgACC activity might serve as a potential biomarker of antidepressant response during working memory tasks as well, in line with previous research with emotionally arousing tasks. This study tested the hypothesis that during the N-back task, a widely used working memory paradigm, low pretreatment pgACC activity, as well as coherence between the pgACC and the amygdala, would be correlated with the clinical improvement after ketamine. Magnetoencephalography (MEG) recordings were obtained from 15 drug-free patients with MDD during working memory performance 1 to 3 days before receiving a single ketamine infusion. Functional activation patterns were analyzed using advanced MEG source analysis. Source coherence analyses were conducted to quantify the degree of long-range functional connectivity between the pgACC and the amygdala. Patients who showed the least engagement of the pgACC in response to increased working memory load showed the greatest symptomatic improvement within 4 h of ketamine administration (r=0.82, p=0.0002, false discovery rate (FDR) <0.05). Pretreatment functional connectivity between the pgACC and the left amygdala was negatively correlated with antidepressant symptom change (r=−0.73, p=0.0021, FDR <0.05).These data implicate the pgACC and its putative interaction with the amygdala in predicting antidepressant response to ketamine in a working memory task context.     

Preferential responses in amygdala and insula during presentation of facial contempt and disgust

Some authors consider contempt to be a basic emotion while others consider it a variant of disgust. The neural correlates of contempt have not so far been specifically contrasted with disgust. Using functional magnetic resonance imaging (fMRI), we investigated the neural networks involved in the processing of facial contempt and disgust in 24 healthy subjects. Facial recognition of contempt was lower than that of disgust and of neutral faces. The imaging data indicated significant activity in the amygdala and in globus pallidus and putamen during processing of contemptuous faces. Bilateral insula and caudate nuclei and left as well as right inferior frontal gyrus were engaged during processing of disgusted faces. Moreover, direct comparisons of contempt vs. disgust yielded significantly different activations in the amygdala. On the other hand, disgusted faces elicited greater activation than contemptuous faces in the right insula and caudate. Our findings suggest preferential involvement of different neural substrates in the processing of facial emotional expressions of contempt and disgust.     

Selective updating of working memory content modulates meso-cortico-striatal activity

Accumulating evidence from non-human primates and computational modeling suggests that dopaminergic signals arising from the midbrain (substantia nigra/ventral tegmental area) mediate striatal gating of the prefrontal cortex during the selective updating of working memory. Using event-related functional magnetic resonance imaging, we explored the neural mechanisms underlying the selective updating of information stored in working memory. Participants were scanned during a novel working memory task that parses the neurophysiology underlying working memory maintenance, overwriting, and selective updating. Analyses revealed a functionally coupled network consisting of a midbrain region encompassing the substantia nigra/ventral tegmental area, caudate, and dorsolateral prefrontal cortex that was selectively engaged during working memory updating compared to the overwriting and maintenance of working memory content. Further analysis revealed differential midbrain-dorsolateral prefrontal interactions during selective updating between low-performing and high-performing individuals. These findings highlight the role of this meso-cortico-striatal circuitry during the selective updating of working memory in humans, which complements previous research in behavioral neuroscience and computational modeling.     

Plasmatic cytokine network in patients with laryngeal carcinoma after surgical treatment

Alterations in host immunity, inflammation, angiogenesis and metabolism are all prominent clinical features in patients with laryngeal squamous cell carcinoma (LSCC). Although the origin of the signals and mechanisms underlying these responses are not well understood, their local and systematic nature suggest that squamous cell carcinoma-produced cytokines with proinflammatory and immunoregulatory activity may contribute to the pathogenesis of LSCC. In order to gain a better insight into the roles and relationships of the cytokines, we investigated serum IL-6, IL-10 and IL-12 concentrations in LSCC patients under baseline conditions and after surgery. In comparison with controls, all the patients had higher plasma IL-10 concentrations before surgical treatment (T0), while plasma IL-6 and IL-12 concentrations were higher in 22 (84.6%) and 24 patients (92.3%). The differences in plasma IL-6, IL-10 and IL-12 concentrations at T0 and T1 were statistically significant (p<0.001, p<0.0046 and p<0.011). Our finding suggest that plasma cytokines are overexpressed in LSCC patients. There was an independent increase in plasma IL-6 levels before and after surgical treatment. Furthermore, the up- and down-regulation of plasma IL-10 and IL-12 suggest a regulatory relationship between them.     

Early predictive variables for upper canine impaction as derived from posteroanterior cephalograms

The aim of this study was to identify a model of cephalometric variables for early diagnosis of the displacement of upper permanent canine and early prognosis of upper canine impaction. Postero-anterior (PA) cephalograms of 43 subjects (22 males and 21 females) with different types of malocclusions in the mixed dentition were analyzed at the time of first observation (mean age 8 years and 5 +/- 9 months). All subjects were reevaluated at the mean age of 14.3 years. At this time the sample was divided into 2 groups according to the presence of canine impaction: nonimpacted canine group (31 subjects) and impacted canine group (12 subjects). Stepwise variable selection on the measurements at the time of first observation identified 2 predictive variables on PA cephalograms, ie, the distance between the center of the canine crown and the midsagittal plane (A3cc to Cg Vertical) and the distance between the jugal process and the midsagittal plane (J to Cg Vertical). The closer the canine crowns to the midsagittal plane and the larger the posterior portion of the hemimaxilla, the higher the probability of canine impaction. Discriminant analysis assigned a classification power of 95.3% to the predictive model. On the basis of the equation generated by the multivariate statistical method, impaction of the maxillary canine for each new case at the age of 8 years can be predicted. The importance of PA cephalograms in the diagnosis and prediction of canine eruption disturbances is emphasized.     

Postoperative pain in laparoscopic surgery

The occurrence of post-operative pain, although less severe and frequent than in open surgery, may affect length of hospital stay and early return to normal activity in some patients operated on with laparoscopic surgery. Although several pathogenetic factors have been indicated in the literature, the mechanism responsible for post-operative pain after laparoscopy; still remains unclear. In this study the Authors evaluated post-operative pain in 90 patients submitted to laparoscopic cholecystectomy and correlated it to the length of operation, endoabdominal CO2 pressure maintained during surgery, and use of local anesthesia instilled din the liver bed and in the sites of introduction of trocars. Measuring post-operative pain by means of a modified Scott-Huskisson Visual Analogue Scale, no difference in the severity of the pain was noted in the two subgroups of patients with a length of operation inferior or superior to 60 minutes, respectively. Conversely, a statistical significant difference (p = 0.04 and p = 0.049 according to Fisher exact test and Pearson test, respectively) was observed evaluating the use of local anesthesia and the level of CO2 endoabdominal pressure, with less pain in patients whose pressure was maintained under 10 mmHg and in patients treated with instillation of local anesthetic drugs in the liver bed and in the sites of introduction of trocars.     

Subjective and metabolic effects of clodronate in patients with advanced breast cancer and symptomatic bone metastases.

Twenty postmenopausal women (aged between 46 and 67 years old) with skeletal metastases from breast carcinoma were treated with clodronate 450 mg i.v. daily for 5 days and thereafter with 100 mg i.m. daily for 10 days. All patients received standard hormonal therapy (tamoxifen). Symptomatic pain (evaluated according to a linear analog scale), performance status (according to Karnofsky), serum alkaline phosphatase, serum creatinine and osteocalcin were measured before and after treatment on days 5, 15, 30 and 45. Scanning by radiology were performed pre- and post-therapy. Bone pain was significantly reduced in 15 out of 20 patients. After clodronate treatment the base line value of circulating osteocalcin (3.2 +/- 1.6 ng/ml) showed a significant increase on days 30 and 45 (p less than 0.001). Radiological assessment of bone lesions showed stable disease in 18 patients and progression in two patients. No adverse side effects were observed. These data show that clodronate provided pain relief in 75% of treated patients and the increase in circulating osteocalcin levels can be considered a marker of the stabilization of skeletal metastatic lesions.     

Comparative ultrasonographic, magnetic resonance sialographic, and videoendoscopic assessment of salivary duct disorders

OBJECTIVES: Salivary duct disorders are the second most common cause of obstruction after calculi. Magnetic resonance sialography has been recently proposed as a means of diagnosing a heterogeneous group of salivary disorders, and so we compared it with sialoendoscopy in evaluating stenoses and sialectasia in 24 patients with obstructive symptoms and ultrasonographic results negative for calculi or masses. METHODS: All of the patients (19 of whom had recurrent unilateral or bilateral swollen parotid glands and 5 of whom also had recurrent swollen submandibular glands) underwent dynamic color Doppler ultrasonography and dynamic magnetic resonance sialography with lemon juice stimulation of saliva; 18 patients also underwent diagnostic sialoendoscopy. RESULTS: Ultrasonography and color Doppler ultrasonography showed duct dilatation in all patients (bilateral in 5 with parotid stenosis). Magnetic resonance sialography confirmed duct dilatation and stenosis in all of the patients, and revealed the simultaneous presence of calculi in 4 cases. A parotid sialocele was found in 4 cases. The magnetic resonance sialographic findings were confirmed in the patients who underwent sialoendoscopy. No side effects were observed. CONCLUSIONS: Magnetic resonance sialography following prediagnostic ultrasonography allows an adequate diagnosis of salivary duct disorders such as stenosis and sialectasia, as confirmed by objective sialoendoscopic assessment. Magnetic resonance sialography also makes it possible to visualize the salivary duct system up to its tertiary branches and, in this regard, may be considered a valid, noninvasive method for the evaluation of salivary duct disorders.