A novel resting-state functional magnetic resonance imaging signature of resilience to recurrent depression.

BACKGROUND: A high proportion of patients with remitted major depressive disorder (MDD) will experience recurring episodes, whilst some develop resilience and remain in recovery. The neural basis of resilience to recurrence is elusive. Abnormal resting-state connectivity of the subgenual cingulate cortex (sgACC) was previously found in cross-sectional studies of MDD, suggesting its potential pathophysiological importance. The current study aimed to investigate whether resting-state connectivity to a left sgACC seed region distinguishes resilient patients from those developing recurring episodes. METHOD: A total of 47 medication-free remitted MDD patients and 38 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) at baseline. Over 14 months, 30 patients remained resilient whilst 17 experienced a recurring episode. RESULTS: Attenuated interhemispheric left-to-right sgACC connectivity distinguished the resilient from the recurring-episode and control groups and was not correlated with residual depressive symptoms. CONCLUSIONS: The current study revealed a neural signature of resilience to recurrence in MDD and thereby elucidates the role of compensatory adaptation in sgACC networks.

Cognitive dysfunction and functional magnetic resonance imaging in systemic lupus erythematosus.

Cognitive dysfunction is a common aspect of systemic lupus erythematosus (SLE) and is increasingly reported as a problem by patients. In many cases the exact cause is unclear. Limited correlations between specific autoantibodies or structural brain abnormalities and cognitive dysfunction in SLE have been reported. It may be that the most appropriate biomarkers have yet to be found. Functional magnetic resonance imaging (fMRI) is a technique used in many other conditions and provides sensitive measures of brain functionality during cognitive tasks. It is now beginning to be employed in SLE studies. These studies have shown that patients with SLE often perform similarly to healthy controls in terms of behavioural measures on cognitive tasks. However, SLE patients appear to employ compensatory brain mechanisms, such as increased response in fronto-parietal regions, to maintain adequate cognitive performance. As there have been only a few studies using fMRI in SLE to investigate cognitive dysfunction, many questions remain unanswered. Further research could, however, help to identify biomarkers for cognitive dysfunction in SLE.

State-dependent changes in hippocampal grey matter in depression.

Reduced hippocampal volume has been reported in depression and may be involved in the aetiology of depressive symptoms and vulnerability to depressive relapse. Neuroplasticity following antidepressant drug treatment in the hippocampus has been demonstrated in animal models but adaptive changes after such treatment have not been shown in humans. In this study, we determined whether grey matter loss in the hippocampus in depression (1) is present in medication-free depressed (2) changes in response to antidepressant treatment and (3) is present as a stable trait in medication-free remitted patients. Sixty-four medication-free unipolar depressed patients: 39 currently depressed and 25 in remission, and 66 healthy controls (HC) underwent structural magnetic resonance imaging in a cross-sectional and longitudinal design. Thirty-two currently depressed participants were then treated with the antidepressant citalopram for 8 weeks. Adherence to treatment was evaluated by measuring plasma citalopram concentration. We measured regional variation in grey matter concentration by using voxel-based morphometry-Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra. Patients with current depression had bilaterally reduced grey matter in the hippocampus compared with HC and untreated patients in stable remission with the latter groups not differing. An increase in grey matter was observed in the hippocampus following treatment with citalopram in currently depressed patients. Grey matter reduction in the hippocampus appears specific to the depressed state and is a potential biomarker for a depressive episode.

Femoral acetabular impingement: the sex- and age-linked distribution of alpha angles in 146 patients of service age without pre-existing osteoarthritic or other hip pathology.

The use of the alpha angle to help the diagnosis of Femoral Acetabular Impingement (FAI) is common. However, there is currently no standard value available across an asymptomatic pre-arthritic population. We present the first large cohort of Computerised Tomography (CT) based alpha angles in patients with no history of hip pathology, including intra- and interobserver validation. We carried out a retrospective analysis of 73 consecutive individuals (146 hip joints) with ages ranging from 18 to 39 years. The age range 18-39 represents 82.4% of those currently serving in the UK Armed Forces. The cohort was drawn from those patients who had received a CT scan in the Lothian Region between 1 Jan 2011 and 31 Dec 2011 due to abdominal pathology. These patients had their electronic patient record checked to rule out any hip-related problems. The alpha angle of Nötzli was measured on the axial view bilaterally. The mean value for the 18-39 age range was found to be 51.89 degree for the left hip and 52.53 degree for the right. Femoral alpha angle is a reproducible measurement for assessing the femoral neck. However, there is wide variability in the alpha angle for patients, irrespective of the presence of symptoms. Our results would suggest that the alpha angle alone should not be used to diagnose FAI in service personnel, as even large angles may be normal.

A temporal analysis of the central neural processing of itch.

BACKGROUND: Pruritus, or itch, is the most prevalent symptom of allergic and inflammatory skin disease. Although it is known that itch induces activation of a neural network in the brain, the temporal dynamics of the network as well as the pathophysiology and neurobiology are not well understood. OBJECTIVES: The study aimed to elucidate (i) the temporal dynamics of the itch response identified in earlier studies and (ii) the relationship between central and subjective responses to itch. METHODS: Using a novel time-series analysis, we performed a double-blind, placebo-controlled, randomized, within-subject functional magnetic resonance imaging (fMRI) study of the cerebral processing of histamine-induced itch in healthy volunteers (n = 16) by tracking the 8-min period following a single skin prick. RESULTS: Histamine-induced itch compared with saline resulted in significant area under the curve blood oxygen level dependent (BOLD) signal changes in the middle/superior temporal gyrus and right inferior frontal gyrus/insula. We observed negative itch-induced BOLD signal changes compared with saline in (i) the pregenual anterior cingulate cortex (ACC)/medial frontal gyrus, (ii) subgenual ACC/ventral striatum, (iii) bilateral temporal pole/parahippocampal gyrus and (iv) several regions within the cerebellum. We noted a trend significance in the left precentral gyrus part of the motor cortex. The BOLD signal change in several of these regions correlated with perception of itch intensity. CONCLUSIONS: In contrast to other fMRI studies we observed a multifocal negative signal. An improved understanding of both activated and deactivated brain regions during the itch response may in the long term facilitate development of more effective management strategies.

Interaction between a history of depression and rumination on neural response to emotional faces.

BACKGROUND: Both past depressive episodes and the personality trait of depressive rumination are strong risk factors for future depression. Depression is associated with abnormal emotional processing, which may be a neurobiological marker for vulnerability to depression. A consistent picture has yet to emerge as to how a history of depression and the tendency to ruminate influence emotional processing. The aim of this study was to investigate the relationship between rumination, past depression and neural responses when processing face emotions. METHOD: The Ruminative Responses Scale (RRS) was completed by 30 remitted depressives and 37 controls who underwent functional magnetic resonance imaging (fMRI) scanning while viewing happy, sad, fearful and neutral faces. RESULTS: The remitted depressives showed overall reductions in neural responses to negative emotions relative to the controls. However, in the remitted depressives, but not the controls, RRS scores were correlated with increased neural responses to negative emotions and decreased responses to happiness in limbic regions. CONCLUSIONS: Automatic emotion processing biases and rumination seem to be correlated to aspects of vulnerability to depression. However, remission from depression may be maintained by a general suppression of limbic responsiveness to negative emotion.

Neural correlates of choice behavior related to impulsivity and venturesomeness.

Impulsivity has been associated with several psychiatric disorders including drug addiction and gambling. Impulsive subjects typically have a preference for short-term over long-term rewards and make risky choices. This study used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of self-rated impulsivity and venturesomeness during tasks involving delayed and risky choice. A broader sampling approach was taken by recruiting participants with behaviors that have been linked to impulsivity (gambling N=15, and recreational drug use N=10) and those without these behaviors (N=9). Selection between delayed or probabilistic rewards was associated with activation in fronto-parietal regions in line with previous research. When selecting between delayed rewards, activity within the pregenual anterior cingulate cortex and ventrolateral prefrontal cortex correlated positively with impulsivity scores while activity within the orbitofrontal cortex, subgenual anterior cingulate cortex and caudate correlated positively with venturesomeness scores. Selection between probabilistic rewards revealed no correlation between scores and regional activations. The results from this study provide targets for future research investigating the neural substrates of impulsivity. They also provide targets for the further investigation into the pathophysiology of addiction and impulse-control disorders.

Attenuated responses to emotional expressions in women with generalized anxiety disorder.

BACKGROUND: Generalized anxiety disorder (GAD) is under-researched despite its high prevalence and large impact on the healthcare system. There is a paucity of functional magnetic resonance imaging (fMRI) studies that explore the neural correlates of emotional processing in GAD. The present study investigated the blood oxygen level dependent (BOLD) response to processing positive and negative facial emotions in patients with GAD. METHOD: A total of 15 female GAD patients and 16 female controls undertook an implicit face emotion task during fMRI scanning. They also performed a face emotion recognition task outside the scanner. RESULTS: The only behavioural difference observed in GAD patients was less accurate detection of sad facial expressions compared with control participants. However, GAD patients showed an attenuated BOLD signal in the prefrontal cortex to fearful, sad, angry and happy facial expressions and an attenuated signal in the anterior cingulate cortex to happy and fearful facial expressions. No differences were found in amygdala response. CONCLUSIONS: In contrast with previous research, this study found BOLD signal attenuation in the ventrolateral and medial prefrontal cortex and the anterior cingulate cortex during face emotion processing, consistent with a hypothesis of hypo-responsivity to external emotional stimuli in GAD. These decreases were in areas that have been implicated in emotion and cognition and may reflect an altered balance between internally and externally directed attentional processes.

Electrocardiographic abnormalities in a patient with subarachnoid haemorrhage.

A 69-year-old woman presented after collapsing. She denied chest pain, breathlessness or headache. She was afebrile and vital signs were unremarkable. She was confused but the remaining physical examination was unremarkable. Routine blood tests were unremarkable. Cardiac enzymes were raised with a troponin I of 0.54. ECG showed Q waves in leads V1-V3 and widespread T wave inversion in leads II, III, aVF and V1-V6. Acute coronary syndrome (ACS) was suspected and antiplatelet treatment started. The following day her confusion worsened. Further review of the ECG found extensive changes unexplained by occlusion of a single artery suggesting extra-cardiac pathology. An urgent CT head was arranged and revealed subarachnoid haemorrhage. ACS treatment was stopped and she was transferred to neurosurgery where her right posterior communicating artery aneurysm was coiled. Fortunately her recovery was uneventful and she was discharged home with no neurological impairment.

Central cannabinoid signaling mediating food intake: a pharmacological-challenge magnetic resonance imaging and functional histology study in rat.

Endocannabinoids have a variety of effects by acting through cannabinoid 1 (CB1) receptors located throughout the brain. However, since CB1 receptors are located presynaptically, and because the strength of downstream coupling varies with brain region, expression studies alone do not provide a firm basis for interpreting sites of action. Likewise, to date most functional studies have used high doses of drugs, which can bias results toward non-relevant adverse effects, and which mask more behaviourally-relevant actions. Here we use a low, orexigenic dose of the full CB1 agonist, CP55940, to map responsive brain regions using the complementary techniques of pharmacological-challenge functional magnetic resonance imaging (phMRI) and immediate-early gene activity. Areas of interest demonstrate a drug interaction when the CB1 receptor inverse agonist, rimonabant, is co-administered. This analysis highlights the corticostriatal-hypothalamic pathway, which is central to the motivational drive to eat.

Assessing human 5-HT function in vivo with pharmacoMRI.

A number of novel ways of using magnetic resonance imaging (MRI) to visualise the action of drugs on animal and human brain (pharmacoMRI or phMRI) are becoming established tools in translational psychopharmacology. Using drugs with known pharmacology it is possible to investigate how neurotransmitter systems are involved in neural systems engaged by other processes, such as cognitive challenge (modulation phMRI) or to examine the acute effects of the drug itself in the brain (challenge phMRI). In this article we discuss the principles behind phMRI and review studies investigating the effect of serotonin (5-HT) manipulations. 5-HT modulation phMRI studies show the involvement of 5-HT in a broad range of neural processes ranging from motor function through 'cold' cognition, such as memory and response inhibition, to emotional processing. We highlight findings in brain areas that show some consistency or complementarity across studies, such as the ventrolateral orbitofrontal cortex where modulation by 5-HT is task-specific, and the amygdala in emotional processing where 5-HT is predominantly inhibitory. 5-HT challenge phMRI is promising but as yet few studies have been carried out. New ways of analysing phMRI data include connectivity analysis which holds the promise of going beyond identifying isolated areas of activation/modulation to understanding functional circuits and their neurochemistry. 5-HT phMRI now needs to be taken into patient populations and methods of investigating treatment effects need to be developed. If this is successful then phMRI will provide a genuinely exciting opportunity for the rapid development of better treatments for psychiatric conditions.

Neuronal effects of acute citalopram detected by pharmacoMRI.

RATIONALE: Serotonin (5-hydroxytryptamine, 5-HT) is implicated in the aetiology and treatment of a variety of psychiatric disorders. A limitation of research has been the necessity to use indirect measures of 5-HT function. METHOD: We describe a method of analysing pharmacoMRI data using SPM and apply it to the direct i.v. infusion of selective 5-HT reuptake inhibitor, citalopram, in 12 healthy volunteers. Scanning took place on a 1.5-T Philips MRI scanner. RESULTS: Areas implicated in depression and its treatment were observed to have increasing signal with respect to time. These areas included the caudate, the amygdala, the hippocampus, the striatum and the thalamus. CONCLUSION: Direct pMRI using i.v. citalopram opens new ways of investigating 5-HT mechanism in depression and its treatment.

Features of cardiac disease demonstrated on CT pulmonary angiography.

The heart and mediastinal structures can be overlooked at CT pulmonary angiogram (CTPA). This pictorial review will demonstrate the features of cardiac disease that may be evident on a CTPA. CTPA allows assessment of not only the pulmonary arteries for embolism, but also of the bronchi, lung parenchyma, mediastinum and heart. Co-existent underlying or incidental cardiac disease is often present. Potentially life-threatening alternative diagnoses in a patient with chest symptoms can be reliably identified. Pathologies of the myocardium including hypertrophic cardio myopathy, pericardial disease, valvular disease, coronary artery disease, and intracardiac abnormalities are demonstrated pictorially. CTPA is increasingly used for the detection of pulmonary embolism. Most patients investigated have pathology other than PE as a cause of their symptoms. Frequently information about the heart is produced that provides important clues to determine the cause for the presenting symptoms and signs or reveals co-existing pathology. It is important to have a clear understanding of the features of cardiac disease which may be seen on a CTPA.

Delayed sequential ruptures of the index and thumb flexor tendons due to an occult scaphoid nonunion.

A case of sequential spontaneous loss of flexion in the thumb and index finger over a 10 year period is reported. Previously unrecognized carpal collapse as a consequence of a longstanding scaphoid nonunion was identified as the cause. Fusion of the interphalangeal joint of the thumb and suture of the index profundus tendon to the middle profundus tendon resulted in a good outcome.