Abnormal brain oscillations persist after recovery from bipolar depression.

When directly perturbed in healthy subjects, premotor cortical areas generate electrical oscillations in the beta range (20-40Hz). In schizophrenia, major depressive disorder and bipolar disorder (BD), these oscillations are markedly reduced, in terms of amplitude and frequency. However, it still remains unclear whether these abnormalities can be modulated over time, or if they can be still observed after treatment. Here, we employed transcranial magnetic stimulation (TMS) combined with EEG to assess the frontal oscillatory activity in eighteen BD patients before/after antidepressant treatments (sleep deprivation and light therapy), relative to nine healthy controls. In order to detect dominant frequencies, event related spectral perturbations (ERSP) were computed for each TMS/EEG session in all participants, using wavelet decomposition. The natural frequency at which the cortical circuit oscillates was calculated as the frequency value with the largest power across 300ms post-stimulus time interval. Severity of depression markedly decreased after treatment with 12 patients achieving response and nine patients achieving remission. TMS/EEG resulted in a significant activation of the beta/gamma band response (21-50Hz) in healthy controls. In patients, the main frequencies of premotor EEG responses to TMS did not significantly change before/after treatment and were always significantly lower than those of controls (11-27Hz) and comparable in patients achieving remission and in those not responding to treatment. These results suggest that the reduction of natural frequencies is a trait marker of BD, independent from the clinical status of the patients. The present findings shed light on the neurobiological underpinning of severe psychiatric disorders and demonstrate that TMS/EEG represents a unique tool to develop biomarkers in psychiatry.

Novelties in COPD prognosis: evolution of survival indexes.

Despite several techniques, such as non-invasive ventilation (NIV), have improved the outcome of the acute exacerbation, COPD remains affected by poor prognosis in the medium and long term. Moreover, the task of predicting prognosis remains a major challenge for respiratory physicians. In order to overcome this limitation, several indexes have been proposed to assess the COPD patient in his/her complexity. The rationale is that, by using numerical indexes physicians may improve their clinical judgment to tailor and share therapeutical choices, i.e. referring the patient for surgery or lung transplantation. On this ground, Almagro et al. recently proposed the CODEX index, as the latest evolution of the BODE through the BODEx (which takes into account exacerbations), by adding the evaluation of comorbidity to the severity of dyspnoea, airway obstruction and history of exacerbations. As afore mentioned, treatment of COPD with respiratory acidosis has been revolutionized by the use of NIV, by reducing the need for intubation and in-hospital mortality of patients with severe COPD exacerbations. Nowadays, new promising techniques, such as minimally invasive extracorporeal devices, may hasten the clearance of carbon dioxide and reduce the work of breathing and the need for ventilation of COPD patients. These techniques still lack of randomized controlled studies; however, the approach of extracorporeal CO2 removal has the potential to further improve the prognosis of severe exacerbation of COPD patients. In this paper we discuss the prognostic evaluation of patients affected by COPD through the evolution of dedicated indexes, which mirror the focus of current research on the disease.

Abnormal cortico-limbic connectivity during emotional processing correlates with symptom severity in schizophrenia.

BACKGROUND: Impaired emotional processing is a core feature of schizophrenia (SZ). Consistent findings suggested that abnormal emotional processing in SZ could be paralleled by a disrupted functional and structural integrity within the fronto-limbic circuitry. The effective connectivity of emotional circuitry in SZ has never been explored in terms of causal relationship between brain regions. We used functional magnetic resonance imaging and Dynamic Causal Modeling (DCM) to characterize effective connectivity during implicit processing of affective stimuli in SZ. METHODS: We performed DCM to model connectivity between amygdala (Amy), dorsolateral prefrontal cortex (DLPFC), ventral prefrontal cortex (VPFC), fusiform gyrus (FG) and visual cortex (VC) in 25 patients with SZ and 29 HC. Bayesian Model Selection and average were performed to determine the optimal structural model and its parameters. RESULTS: Analyses revealed that patients with SZ are characterized by a significant reduced top-down endogenous connectivity from DLPFC to Amy, an increased connectivity from Amy to VPFC and a decreased driving input to Amy of affective stimuli compared to HC. Furthermore, DLPFC to Amy connection in patients significantly influenced the severity of psychopathology as rated on Positive and Negative Syndrome Scale. CONCLUSIONS: Results suggest a functional disconnection in brain network that contributes to the symptomatic outcome of the disorder. Our findings support the study of effective connectivity within cortico-limbic structures as a marker of severity and treatment efficacy in SZ.

Fronto-limbic disconnection in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a severe, disabling and life-threatening illness. Disturbances in emotion and affective processing are core features of the disorder with affective instability being paralleled by mood-congruent biases in information processing that influence evaluative processes and social judgment. Several lines of evidence, coming from neuropsychological and imaging studies, suggest that disrupted neural connectivity could play a role in the mechanistic explanation of these cognitive and emotional symptoms. The aim of the present study is to investigate the effective connectivity in a sample of bipolar patients. METHODS: Dynamic causal modeling (DCM) technique was used to study 52 inpatients affected by bipolar disorders consecutively admitted to San Raffaele hospital in Milano and forty healthy subjects. A face-matching task was used as activation paradigm. RESULTS: Patients with BD showed a significantly reduced endogenous connectivity in the DLPFC to Amy connection. There was no significant group effect upon the endogenous connection from Amy to ACC, from ACC to Amy and from DLPFC to ACC. CONCLUSIONS: Both DLPFC and ACC are part of a network implicated in emotion regulation and share strong reciprocal connections with the amygdale. The pattern of abnormal or reduced connectivity between DLPFC and amygdala may reflect abnormal modulation of mood and emotion typical of bipolar patients.

Are benzodiazepines and opioids really safe in patients with severe COPD?

Breathlessness is a key symptom in chronic obstructive pulmonary disease (COPD) with prognostic implications on health status and survival. Since most conditions underlying chronic refractory breathlessness in COPD are not modifiable, the use of opioids and benzodiazepines has been proposed to relieve it. However, respiratory depression is a known adverse event of these drugs, and concerns have been raised on their use in patients with chronic respiratory failure. Despite safety-related concerns, benzodiazepines are frequently prescribed for a variety of reasons, including treatment of insomnia, depression and anxiety, as well as to relieve refractory dyspnea in patients with COPD. The key role of opioids in the end-of-life and in the management of dyspnea that is unresponsive to best-possible disease management is recognized. Moreover, the use of low dose opioids to treat dyspnea, discomfort or refusal for patient undergoing non-invasive ventilation is still debated. In the current review, we aim at discussing and analyzing recently published findings on the use of benzodiazepines and opioids in patients with COPD and at reviewing the literature on this topic. Recent observations favor the use of lower doses of opioids (≤30 mg oral morphine equivalents/day) for reduction of symptoms in those patients with severe COPD receiving long-term oxygen therapy. Low dose opioids are not associated with an increased risk of hospital admission or death in cohorts of COPD patients on long term oxygen therapy. On the contrary, benzodiazepines and opioids at higher doses might increase mortality.

Potentially harmful effects of inspiratory synchronization during pressure preset ventilation.

PURPOSE: Pressure preset ventilation (PPV) modes with set inspiratory time can be classified according to their ability to synchronize pressure delivery with patient's inspiratory efforts (i-synchronization). Non-i-synchronized (like airway pressure release ventilation, APRV), partially i-synchronized (like biphasic airway pressure), and fully i-synchronized modes (like assist-pressure control) can be distinguished. Under identical ventilatory settings across PPV modes, the degree of i-synchronization may affect tidal volume (VT), transpulmonary pressure (PTP), and their variability. We performed bench and clinical studies. METHODS: In the bench study, all the PPV modes of five ventilators were tested with an active lung simulator. Spontaneous efforts of -10 cmH2O at rates of 20 and 30 breaths/min were simulated. Ventilator settings were high pressure 30 cmH2O, positive end-expiratory pressure (PEEP) 15 cmH2O, frequency 15 breaths/min, and inspiratory to expiratory ratios (I:E) 1:3 and 3:1. In the clinical studies, data from eight intubated patients suffering from acute respiratory distress syndrome (ARDS) and ventilated with APRV were compared to the bench tests. In four additional ARDS patients, each of the PPV modes was compared. RESULTS: As the degree of i-synchronization among the different PPV modes increased, mean VT and PTP swings markedly increased while breathing variability decreased. This was consistent with clinical comparison in four ARDS patients. Observational results in eight ARDS patients show low VT and a high variability with APRV. CONCLUSION: Despite identical ventilator settings, the different PPV modes lead to substantial differences in VT, PTP, and breathing variability in the presence spontaneous efforts. Clinicians should be aware of the possible harmful effects of i-synchronization especially when high VT is undesirable.

Recent advances in interfaces for non-invasive ventilation: from bench studies to practical issues.

The interface is the defining element of non-invasive ventilation (NIV). Nowadays different types of interfaces, which differ in terms of shape, mechanical properties and comfort, are available, and their choice and fitting is a key element of NIV success. In the last decade, larger masks covering the entire face and specifically designed helmets have been developed for delivering NIV, theoretically improving comfort and patient tolerance. Recent studies have shown that, despite marked heterogeneity in mask internal volume and compliance, the dynamic dead space and, above all, the clinical efficacy of different masks is on average very similar. Thus, with the exception of the nasal mask and the mouthpiece, a variety of interfaces for NIV can be used in the acute care setting. However, prevention and monitoring of interfaces related side-effects and evaluation of patient tolerance are crucial to avoid NIV failure. To optimize effectiveness and costs, an interface strategy for NIV in acute respiratory failure could be convenient in clinical practice.