Objective:To evaluate the possible role of the default mode network (DMN) in consciousness and assess the diagnostic or prognostic potential of DMN connectivity measures in the assessment of a patient group lacking cognitive awareness.Methods: DMN connectivity was established using independent component analysis of restingstate fMRI data in patients with reversible (n ϭ 2) and irreversible (n ϭ 11) coma following cardiac arrest and compared to healthy controls (n ϭ 12).Results: A present and intact DMN was observed in controls and those patients who subsequently regained consciousness, but was disrupted in all patients who failed to regain consciousness. Conclusions:The results suggest that the DMN is necessary but not sufficient to support consciousness. Clinically, DMN connectivity may serve as an indicator of the extent of cortical disruption and predict reversible impairments in consciousness. Neurology ® 2012;78:175-181 GLOSSARY BOLD ϭ blood oxygenation level-dependent; DMN ϭ default mode network; FOV ϭ field of view; GCS ϭ Glasgow Coma Scale; GOS ϭ Glasgow Outcome Scale; ICA ϭ independent component analysis; PCC ϭ posterior cingulate cortex; SSEP ϭ somatosensory evoked potential; TE ϭ echo time; TR ϭ repetition time; VS ϭ vegetative state.Coma represents a state of unarousable psychological unresponsiveness with a total absence of awareness of both self and environment. 1 Currently, there are few tools available to adequately assess the cerebral function in this patient population, making prediction of future outcome particularly challenging. However, a growing body of research has shown that fMRI can reveal important insights into brain function and connectivity and may be well suited for the prognostication of comatose patients in a clinical setting. [2][3][4] Recently, increasing attention has been directed at investigating the default mode network (DMN) which includes cortical regions that characterize the baseline state of the brain thought to relate to unconstrained, spontaneous cognition, or stimulus-independent thoughts. 5-7 The DMN is comprised of several cortical areas including the posterior cingulate cortex/precuneus, medial prefrontal cortex, and bilateral temporoparietal junctions. 8,9 The proposed role of the DMN in internal mental processes and cognition has made it an attractive candidate as the neural correlate of the stream of consciousness. 10 -12 As such, the DMN may provide important insights into the cerebral function of patients with impaired states of consciousness such as coma. Altered connectivity in the DMN has been reported in case studies and case series of impaired consciousness including vegetative state (VS), 13 coma, 14 and brain death. 15 From the Graduate Program in Neuroscience (L.

The evidence-based medicine (EBM) paradigm has been associated with many benefits, but there have also been 'some negative consequences'. In part, the consequences may be attributable to: (1) limitations in some of the tenets of EBM, and (2) flawed or unethical decisions in healthcare related organisations. We hypothesise that at the core of both is a cascade of predominantly unconscious cognitive processes we have syndromically termed 'cognitive biases plus', with conflicts of interest (CoIs) as crucial elements. CoIs (financial, and non-financial including intellectual) catalyse self-serving bias and a cascade of other 'cognitive biases plus' with several reinforcing loops. Authority bias, herd effect, scientific inbreeding, replication publication biases, and ethical violations (especially subtle statistical), are key contributors to the cascade; automation biases through uncritical use of statistical software and applications (apps) of preappraised sources of evidence at point of care, may be other increasingly important factors. The 'cognitive biases plus' cascade which involves several intricately connected healthcare-related organisations has the potential to facilitate, compound and entrench flaws in the paradigm, evidence and decisions that converge to inform person-centered healthcare. Our reasoning is based on observational data and opinion. However, the susceptibility of all humans to 'cognitive biases plus' makes our hypothesis plausible. Individual and collective fallibility may be minimised and the quality of healthcare decisions (including those related to improving EBM) enhanced by being conscious of our vulnerability and open-minded to the 'outside view'.Sir Francis Bacon (1620): "The human understanding when it has once adopted an opinion (either as being the received opinion or as being agreeable to itself ) draws all things else to support and agree with it…" (Novum Organum: XLVI)

Reform is urgently needed to minimize continuing risks to patients. If our hypothesis is correct, then in addition to the suggestions made in part I, deficiencies in the paradigm must be corrected. Meaningful solutions are only possible if the biases of scientific inbreeding and groupthink are minimized by collaboration between EBM leaders and those who have been sounding warning bells.