The (dis)unity of nursing science.

This paper looks at the implications of contemporary work in philosophy of science for nursing science. Early work on the nature of theories in nursing was strongly influenced by logical empiricism, and this influence remains even long after nurse scholars have come to reject logical empiricism as an adequate philosophy of science. Combined with the need to establish nursing as an autonomous profession, nursing theory's use of logical empiricism has led to serious conceptual problems. Philosophers of science have also rejected many of the central tenets of logical empiricism, including its focus on the logical justification of theories and the idea that science is, or should be, unified. Instead, there has been an increasing focus on the practice of science, which in turn has led to a pluralist understanding of science that emphasizes the construction of scientific models that are appropriate for certain purposes or in certain contexts. I suggest that this approach to philosophy of science may provide better resources for nursing science.

"I just have to stick with it and it'll work": experiences of adolescents and young adults with mental health concerns.

Mental health issues are common among adolescents and young adults but service utilization in this group is low. This study aimed to better understand the experiences of older adolescents and young adults who were experiencing symptoms of depression or anxiety, including the factors that affected their decision to seek treatment and their feelings about their experience of mental health issues. We conducted semi-structured interviews with 37 older adolescents and young adults. Participants tended to have a sophisticated understanding of the causes of mental disorders, but to have been unsure about whether their own experiences of depression or anxiety were the result of a mental disorder, or just "normal" experiences. They reported concerns about taking medication and about keeping information about their condition private. They also felt that it was important to them to be active participants in their own care.

Default network connectivity during a working memory task.

The default network exhibits correlated activity at rest and has shown decreased activation during performance of cognitive tasks. There has been little investigation of changes in connectivity of this network during task performance. In this study, we examined task-related modulation of connectivity between two seed regions from the default network posterior cingulated cortex (PCC) and medial prefrontal cortex (mPFC) and the rest of the brain in 12 healthy adults. The purpose was to determine (1) whether connectivity within the default network differs between a resting state and performance of a cognitive (working memory) task and (2) whether connectivity differs between these nodes of the default network and other brain regions, particularly those implicated in cognitive tasks. There was little change in connectivity with the other main areas of the default network for either seed region, but moderate task-related changes in connectivity occurred between seed regions and regions outside the default network. For example, connectivity of the mPFC with the right insula and the right superior frontal gyrus decreased during task performance. Increased connectivity during the working memory task occurred between the PCC and bilateral inferior frontal gyri, and between the mPFC and the left inferior frontal gyrus, cuneus, superior parietal lobule, middle temporal gyrus and cerebellum. Overall, the areas showing greater correlation with the default network seed regions during task than at rest have been previously implicated in working memory tasks. These changes may reflect a decrease in the negative correlations occurring between the default and task-positive networks at rest.

Switching between executive and default mode networks in posttraumatic stress disorder: alterations in functional connectivity.

UNLABELLED: Working memory processing and resting-state connectivity in the default mode network are altered in patients with posttraumatic stress disorder (PTSD). Because the ability to effortlessly switch between concentration on a task and an idling state during rest is implicated in both these alterations, we undertook a functional magnetic resonance imaging study with a block design to analyze task-induced modulations in connectivity. METHODS: We performed a working memory task and psychophysiologic interaction analyses with the posterior cingulate cortex and the medial prefrontal cortex as seed regions during fixation in 12 patients with severe, chronic PTSD and 12 healthy controls. RESULTS: During the working memory task, the control group showed significantly stronger connectivity with areas implicated in the salience and executive networks, including the right inferior frontal gyrus and the right inferior parietal lobule. The PTSD group showed stronger connectivity with areas implicated in the default mode network, namely enhanced connectivity between the posterior cingulate cortex and the right superior frontal gyrus and between the medial prefrontal cortex and the left parahippocampal gyrus. LIMITATIONS: Because we were studying alterations in patients with severe, chronic PTSD, we could not exclude patients taking medication. The small sample size may have limited the power of our analyses. To avoid multiple testing in a small sample, we only used 2 seed regions for our analyses. CONCLUSION: The different patterns of connectivity imply significant group differences with task-induced switches (i.e., engaging and disengaging the default mode network and the central-executive network).

Dr. Cézanne and the art of re(peat)search: competing interests and obligations in clinical research.

Clinician researchers have a number of roles, each of which carries specific obligations. There are times when these obligations may be in competition (up to and including conflict) with each other. Using a narrative case study that describes a group of colleagues discussing their clinical department's participation in an industry-sponsored research protocol, we illustrate a number of the obligations faced by clinician researchers, and discuss how competing interests and obligations can lead to ethical problems. The case study is followed by a discussion of the effect of university-industry relations on competing interests and obligations in both clinical research and the role of the university, and a suggested framework that could be used to determine when university involvement in commercial research is ethically acceptable.

Retrosplenial cortex connectivity in schizophrenia.

In this paper, we build on our previous analysis [Bluhm, R.L., Miller, J., Lanius, R.A., Osuch, E.A., Boksman, K., Neufeld, R.W.J., et al., 2007 Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network. Schizophrenia Bulletin 33, 1004-1012] of resting state connectivity in schizophrenia by examining alterations in connectivity of the retrosplenial cortex. We have previously demonstrated altered connectivity of the posterior cingulate/precuneus, particularly with other regions of the "default network" (which includes the medial prefrontal cortex and bilateral lateral parietal cortex). It was hypothesized that the retrosplenial cortex would show aberrant patterns of connectivity with regions of the default network and regions associated with memory. Patients with schizophrenia (N=17) and healthy controls (N=17) underwent a 5.5-min resting functional magnetic resonance imaging scan. Lower correlations were observed in patients with schizophrenia than in healthy controls between the retrosplenial cortex and both the temporal lobe and regions of the default network. In patients with schizophrenia, activity in the retrosplenial cortex correlated negatively with activity in bilateral anterior cingulate gyrus/medial prefrontal cortex (BA 32/10), despite the fact that these regions, as part of the default network, were expected to show positive correlations in activity. Connectivity of the retrosplenial cortex was greater in patients with more positive symptoms with areas previously associated with hallucinations, particularly the left superior temporal gyrus. These results suggest that spontaneous activity in the retrosplenial cortex during rest is altered in patients with schizophrenia. These alterations may help to explain alterations in self-oriented processing in this patient population.

Brain activation to favorite music in healthy controls and depressed patients.

Reward-processing neurocircuitry has been delineated using verbal or visual processing and/or decision-making tasks. We examined more basic processes of listening to enjoyable music in healthy and depressed patients. The paradigm was passive, individualized, and brief. Sixteen depressed and 15 control individuals provided favorite music and identified neutral music from selections provided. In the fMRI scanner, individuals heard their neutral and their favorite music for 3 min each. Favorite versus neutral music-listening contrasts showed greater activation in controls than depressed patients in medial orbital frontal cortex and nucleus accumbens/ventral striatum. Left medial prefrontal cortex activity was positively correlated with pleasure scores, whereas middle temporal cortex and globus pallidus were negatively correlated with pleasure. This paradigm activated neurocircuitry of reward processing and showed clinically meaningful alterations in depression.

Alterations in default network connectivity in posttraumatic stress disorder related to early-life trauma.

BACKGROUND: The "default network" consists of a number of brain regions that exhibit correlated low-frequency activity at rest and that have been suggested to be involved in the processing of self-relevant stimuli. Activity in many of these areas has also been shown to be altered in individuals with posttraumatic stress disorder (PTSD). We hypothesized that the posterior cingulate cortex (PCC)/precuneus, part of the default network, would exhibit altered connectivity at rest with other areas of the default network and regions associated with PTSD. METHODS: Seventeen medicated and unmedicated female patients with chronic posttraumatic stress disorder (PTSD) related to early-life trauma and 15 healthy female controls underwent a 5.5-minute functional magnetic resonance imaging scan with their eyes closed. We assessed areas of the brain whose activity positively and negatively correlated with that of the PCC/precuneus in both groups. RESULTS: At rest, spontaneous low-frequency activity in the PCC/precuneus was more strongly correlated with activity in other areas of the default network in healthy controls than in patients with PTSD. Direct comparison of the 2 groups showed that PCC/ precuneus connectivity was also greater in healthy controls than in patients with PTSD in a number of areas previously associated with PTSD, including the right amygdala and the hippocampus/parahippocampal gyrus. LIMITATIONS: Because our PTSD sample comprised only women with chronic early-life trauma exposure, our results may not be generalizeable to male patients, to a population with single trauma exposure or to those who were adults when the trauma occurred. In addition, our sample included patients taking medication and it is not yet clear how altered connectivity is affected by medication. CONCLUSION: Spontaneous activity in the default network during rest, as measured using PCC correlations, is altered in patients with PTSD. The potential effects of psychotropic medications on default network connectivity in the present sample remain unknown. In this patient population, the observed alterations may be associated with the disturbances in self-referential processing often observed in patients with chronic PTSD related to early-life trauma.

Default mode network connectivity: effects of age, sex, and analytic approach.

The 'default mode network' is a set of brain regions showing correlated, low-frequency activity during rest. It includes the posterior cingulate/precuneus, medial prefrontal cortex, and bilateral inferior parietal cortex. Earlier studies have characterized this network using either region of interest-based correlation analyses or data-driven techniques; however, there is some disagreement over which method is superior. We conducted both types of analysis on a large (N=40) data set and also investigated age and sex differences in the network. Both region of interest-based analyses and independent component analysis identified the default mode network. Age and sex differences were small and there was less agreement between analytic techniques regarding age and sex effects than regarding default mode network structure.

Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network.

Spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (MRI) signal have been shown to reflect neural synchrony between brain regions. A "default network" of spontaneous low-frequency fluctuations has been described in healthy volunteers during stimulus-independent thought. Negatively correlated with this network are regions activated during attention-demanding tasks. Both these networks involve brain regions and functions that have been linked with schizophrenia in previous research. The present study examined spontaneous slow fluctuations in the BOLD signal at rest, as measured by correlation with low-frequency oscillations in the posterior cingulate, in 17 schizophrenic patients, and 17 comparable healthy volunteers. Healthy volunteers demonstrated correlation between spontaneous low-frequency fluctuations of the BOLD signal in the posterior cingulate and fluctuations in the lateral parietal, medial prefrontal, and cerebellar regions, similar to previous reports. Schizophrenic patients had significantly less correlation between spontaneous slow activity in the posterior cingulate and that in the lateral parietal, medial prefrontal, and cerebellar regions. Connectivity of the posterior cingulate was found to vary with both positive and negative symptoms in schizophrenic patients. Because these data suggest significant abnormalities in resting-state neural networks in schizophrenia, further investigations of spontaneous slow fluctuations of the BOLD signal seem warranted in this population.

Functional connectivity of dissociative responses in posttraumatic stress disorder: a functional magnetic resonance imaging investigation.

BACKGROUND: The purpose of this study was to assess interregional brain activity covariations during traumatic script-driven imagery in subjects with posttraumatic stress disorder (PTSD). METHODS: Functional magnetic resonance imaging and functional connectivity analyses were used to assess interregional brain activity covariations during script-driven imagery in PTSD subjects with a dissociative response, PTSD subjects with a flashback response, and healthy control subjects. RESULTS: Significant between-group differences in functional connectivity were found. Comparing dissociated PTSD patients and control subjects' connectivity maps in the left ventrolateral thalamus (VLT) [-14, -16, 4] revealed that control subjects had higher covariations between activations in VLT and in the left superior frontal gyrus (Brodmann's area [BA] 10), right parahippocampal gyrus (BA 30), and right superior occipital gyrus (BA 19, 39), whereas greater covariation with VLT in dissociated PTSD subjects occurred in the right insula (BA 13, 34), left parietal lobe (BA 7), right middle frontal gyrus (BA 8), superior temporal gyrus (BA 38, 34), and right cuneus (BA 19). Comparing dissociated PTSD and flashback PTSD connectivity maps in the right cingulate gyrus [3, 16, 30] revealed that dissociated PTSD subjects had higher covariations between activations in this region and the left inferior frontal gyrus (BA 47). CONCLUSIONS: Greater activation of neural networks involved in representing bodily states was seen in dissociated PTSD subjects than in non-PTSD control subjects. These findings might illuminate the mechanisms underlying distorted body perceptions often observed clinically during dissociative episodes.