Lack of effect of citalopram on magnetic resonance spectroscopy measures of glutamate and glutamine in frontal cortex of healthy volunteers

Magnetic resonance spectroscopy (MRS) is a non-invasive imaging technique that can provide localised measures of brain chemistry in vivo. We previously found that healthy volunteers receiving the selective serotonin reuptake inhibitor, citalopram, daily for 1 week showed higher levels of a combined measure of glutamate and glutamine (Glx) in occipital cortex than those receiving placebo. The aim of this study was to assess if a similar effect could be detected in the frontal brain region. Twenty-three healthy volunteers randomised to receive either citalopram 20 mg or a placebo capsule daily for 7–10 days were studied and scanned using a 3T Varian INOVA system before and at the end of treatment. Standard short-TE (echo time) PRESS (Point-resolved spectroscopy) (TE = 26 ms) and PRESS-J spectra were acquired from a single 8-cm3 voxel in a frontal region incorporating anterior cingulate cortex. Glutamate and total Glx levels were quantified both relative to creatine and as absolute levels. Relative to placebo, citalopram produced no change in Glx or glutamate alone at the end of the study. Similarly, no effect was seen on other MRS measures studied: myo-inositol, choline, N-acetylaspartate and creatine. These data suggest that the effects of serotonin reuptake to modify cortical glutamatergic MRS measures may be regionally specific. This supports the potential for MRS in assessing neuroanatomically specific serotonin-glutamate interactions in the human brain

Pre- and postsurgical cognitive trajectories and quantitative MRI changes in Rasmussen syndrome

OBJECTIVE: To quantify the longitudinal cognitive trajectory, before and after surgery, of Rasmussen syndrome (RS), a rare disease characterized by focal epilepsy and progressive atrophy of one cerebral hemisphere. METHOD: Thirty-two patients (mean age = 6.7 years; 17 male, 16 left hemispheres affected) were identified from hospital records. The changes in intelligence scores during 2 important phases in the patients' journey to treatment were investigated: (1) during the preoperative period (n = 28, mean follow-up 3.4 years) and (2) from before to after surgery (n = 21 patients, mean time to follow-up 1.5 years). A volumetric magnetic resonance imaging (MRI) analysis of longitudinal changes in gray matter volume was conducted in a subsample of 18 patients. RESULTS: (1) IQ during the preoperative period: At baseline assessment (on average 2.4 years after seizure onset), the left RS group had lower verbal than nonverbal intellectual abilities, whereas the right group exhibited more difficulties in nonverbal than verbal intellect. Verbal and nonverbal scores declined during the follow-up in both groups, irrespective of the affected side. Hemispheric gray matter volumes declined over time in both groups in affected as well as unaffected hemispheres. (2) Postoperative IQ change: The left surgery group declined further in verbal and nonverbal intellect. The right group's nonverbal intellect declined after surgery, whereas verbal abilities did not. Patients with higher abilities preoperatively experienced large declines, whereas those with poorer abilities showed little change. Postoperative seizures negatively impacted on cognitive abilities. SIGNIFICANCE: During the chronic phase of the disease, parallel decline of verbal and nonverbal abilities suggest progressive bilateral hemispheric involvement, supported by evidence from MRI morphometry. Postsurgical cognitive losses are predicted by greater presurgical ability and continuing seizures. A shorter duration from seizure onset to surgery could reduce the postoperative cognitive burden by minimizing the decline in functions supported by the unaffected hemisphere

Impulsive choice in hippocampal but not orbitofrontal cortex-lesioned rats on a nonspatial decision-making maze task

Orbitofrontal cortical (OFC) and hippocampal (HPC) lesions in primates and rodents have been associated with impulsive behaviour. We showed previously that OFC- or HPC-lesioned rats chose the immediate low-reward (LR) option in preference to the delayed high-reward (HR) option, where LR and HR were associated with different spatial responses in a uniform grey T-maze. We now report that on a novel nonspatial T-maze task in which the HR and LR options are associated with patterned goal arms (black-and-white stripes vs. gray), OFC-lesioned rats did not show impulsive behaviour, choosing the delayed HR option, and were indistinguishable from controls. In contrast, HPC-lesioned rats exhibited impulsive choice in the nonspatial decision-making task, although they chose the HR option on the majority of trials when there was a 10-s delay associated with both goal arms. The previously reported impairment in OFC-lesioned rats on the spatial version of the intertemporal choice task is unlikely to reflect a general problem with spatial learning, because OFC lesions were without effect on acquisition of the standard reference memory water-maze task and spatial working memory performance (nonmatching-to-place) on the T-maze. The differential effect of OFC lesions on the two versions of the intertemporal choice task may be explained instead in terms of the putative role of OFC in using associative information to represent expected outcomes and generate predictions. The impulsivity in HPC-lesioned rats may reflect impaired temporal information processing, and emphasizes a role for the hippocampus beyond the spatial domain

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions

The statistical neuroanatomy of frontal networks in the macaque

We were interested in gaining insight into the functional properties of frontal networks based upon their anatomical inputs. We took a neuroinformatics approach, carrying out maximum likelihood hierarchical cluster analysis on 25 frontal cortical areas based upon their anatomical connections, with 68 input areas representing exterosensory, chemosensory, motor, limbic, and other frontal inputs. The analysis revealed a set of statistically robust clusters. We used these clusters to divide the frontal areas into 5 groups, including ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups. Each of these groups was defined by a unique set of inputs. This organization provides insight into the differential roles of each group of areas and suggests a gradient by which orbital and ventral-medial areas may be responsible for decision-making processes based on emotion and primary reinforcers, and lateral frontal areas are more involved in integrating affective and rational information into a common framework

Physicians' messages in problematic sickness certification: a narrative analysis of case reports

<p>Abstract</p> <p>Background</p> <p>Many physicians find sickness certification tasks problematic. There is some knowledge about situations that are experienced as problematic, whereas less is understood about how physicians respond to the problems they face. One way to acquire such knowledge is to consider "reflection-in-action", aspects of which are expressed in the physician's interpretation of the patient's story. The aim of this study was to gain knowledge about the meaning content of case reports about problematic sickness certification. Specifically, we looked for possible messages to the colleagues intended to read the reports.</p> <p>Methods</p> <p>A narrative approach was used to analyse reports about problematic sickness certification cases that had been written by GPs and occupational health service physicians as part of a sickness insurance course. The analysis included elements from both thematic and structural analysis. Nineteen case reports were used in the actual analysis and 25 in the validation of the results. Main narrative qualities and structural features of the written case reports were explored.</p> <p>Results</p> <p>Five types of messages were identified in the case reports, here classified as "a call for help", "a call for understanding", "hidden worries", "in my opinion", and "appearing neutral". In the reports, the physicians tried to achieve neutrality in their writing, and the patients' stories tended to be interpreted within a traditional biomedical framework. In some cases there was an open request for help, in others it was not obvious that the physician had any problems. Overall, the messages were about having problems as such, rather than the specific features of the problems.</p> <p>Conclusions</p> <p>The case reports clearly demonstrated different ways of writing about problems that arise during sickness certification, from being neutral and not mentioning the problems to being emotionally involved and asking for help. The general character of the messages suggests that they are also relevant for case reports in problematic areas other than sickness certification. If pertinent relationships can be found between reflection-in-practice and the narrative writing about practice, they will provide an approach to further research concerning consultations perceived as problematic and also to medical education.</p

Satisfaction is not all – patients' perceptions of outcome of general practice consultations, a qualitative study

BACKGROUND: Evaluation of outcome in general practice can be seen from different viewpoints. In this study we focus on the concepts patients use to describe the outcome of a consultation with a GP. METHOD: Patients were interviewed within a week after a consultation with a GP. The interviews were made with 20 patients in 5 focus groups and 8 individually. They were analysed with a phenomenographic research approach. RESULTS: From the patient's perspective, the outcome of a consultation is about cure or symptom relief, understanding, confirmation, reassurance, change in self-perception and satisfaction. CONCLUSION: General practice consultations are often more important for patients than generally supposed. Understanding is the most basic concept

Comparing the Phenylalanine/Tyrosine Pathway and Related Factors between Keratopathy and No-Keratopathy Groups as Well as between Genders in Alkaptonuria during Nitisinone Treatment

Nitisinone (NIT) causes tyrosinaemia and corneal keratopathy (KP), especially in men. However, the adaptation within the phenylalanine (PHE)/tyrosine (TYR) catabolic pathway during KP is not understood. The objective of this study is to assess potential differences in the PHE/TYR pathway during KP and the influence of gender in NIT-induced tyrosinaemia in alkaptonuria (AKU). Samples of serum and 24 h urine collected from patients treated with NIT during a 4-year randomized study in NIT vs. no-treatment controls (SONIA 2; Suitability Of Nitisinone In Alkaptonuria 2; EudraCT no. 2013-001633-41) at months 3 (V2), 12 (V3), 24 (V4), 36 (V5) and 48 (V6) were included in these analyses. Homogentisic acid (HGA), TYR, PHE, hydroxyphenylpyruvate (HPPA), hydroxyphenyllactate (HPLA) and sNIT were analysed at all time-points in serum and urine in the NIT-group. All statistical analyses were post hoc. Keratopathy occurred in 10 out of 69 AKU patients, eight of them male. Thirty-five sampling points (serum and 24 h urine) were analysed in patients experiencing KP and 272 in those with no-KP (NKP) during NIT therapy. The KP group had a lower HPLA/TYR ratio and a higher TYR/PHE ratio compared with the NKP group (p &lt; 0.05 for both). There were 24, 45, 100 and 207 sampling points (serum and 24 h urine) in the NIT group which were pre-NIT female, pre-NIT male, NIT female and NIT male, respectively. The PHE/TYR ratio and the HPLA/TYR ratio were lower in males (p &lt; 0.001 and p &lt; 0.01, respectively). In the KP group and in the male group during NIT therapy, adaptive responses to minimise TYR formation were impaired compared to NKP group and females, respectively

Hydration level is an internal variable for computing motivation to obtain water rewards in monkeys

In the process of motivation to engage in a behavior, valuation of the expected outcome is comprised of not only external variables (i.e., incentives) but also internal variables (i.e., drive). However, the exact neural mechanism that integrates these variables for the computation of motivational value remains unclear. Besides, the signal of physiological needs, which serves as the primary internal variable for this computation, remains to be identified. Concerning fluid rewards, the osmolality level, one of the physiological indices for the level of thirst, may be an internal variable for valuation, since an increase in the osmolality level induces drinking behavior. Here, to examine the relationship between osmolality and the motivational value of a water reward, we repeatedly measured the blood osmolality level, while 2 monkeys continuously performed an instrumental task until they spontaneously stopped. We found that, as the total amount of water earned increased, the osmolality level progressively decreased (i.e., the hydration level increased) in an individual-dependent manner. There was a significant negative correlation between the error rate of the task (the proportion of trials with low motivation) and the osmolality level. We also found that the increase in the error rate with reward accumulation can be well explained by a formula describing the changes in the osmolality level. These results provide a biologically supported computational formula for the motivational value of a water reward that depends on the hydration level, enabling us to identify the neural mechanism that integrates internal and external variables