• Consciousness is often conceptualized as en-compassing two cardinal elements (Laureys 2005): – wakefulness: refer to the level of consciousness– Awareness: refer to its contents

Introduction

• disorders of consciousness (DOC)(Monti. 2012)– Coma: lack both awareness and wakefulness– Vegetative State(VS): basic vegetative nervous functions

are preserved, but in the absence of any sensation and thought

– Minimally Conscious State(MCS): not only to be wakeful (like vegetative-state patients) but also exhibit inconsistent but reproducible signs of awareness of themselves or their surroundings

– locked-in syndrome(LIS): both awake and aware but are either unable to produce any motor response

Introduction

• self-referential processing in DOC:– Di et al. (2007): five out of seven VS patients exhibited primary

auditory activity in response to their own name. In addition, in two VS patients (and all MCS patients),activations in higher-level posterior temporal cortices were also detected.

– Qin et al. (2010) reported significant activations for six out of seven VS patients in one or more of three medial prefrontal regions previously linked to processing self-related stimuli

• Resting state in DOC:– alterations in cortical midline structures, abnormally low

functional connectivity (Boly et al., 2009; Cauda et al., 2009; Vanhaudenhuyse et al., 2010) and effective connectivity (Rosanova et al., 2012).

Questions

• 1) In DOC, the temporal dynamics of resting state activity, such as the amplitude of low-frequency fluctuations (ALFF)(Kannurpatti and Biswal, 2008; Zang et al., 2007) and standard deviation of neural activity changes across time (Garrett et al., 2011), remain to be thoroughly investigated. Importantly, the functional implications of abnormalities in the resting state remain unclear

• 2) It is unclear how to relate self-referential processing, resting state activity and consciousness in DOC patients.

Hypothesis and Aim

• (1) the neural response to self-referential stimuli in the midline regions would be present though abnormally reduced in DOC patients; a particularly strong link between neural responses in midline brain regions and the level of consciousness,

• (2) abnormal brain responses while processing self-referential tasks may be related to impairments not only in the spatial domain but also with temporal abnormalities in neuronal measures of resting state activity, e.g. lower ALFF and standard deviation within the midline regions

Materials and Methods

• Participants and patients – 12 healthy control subjects– 11 patients (six VS and five MCS)

fMRI scan procedure

Resting6min

task8’8’’

task8’8’’

task8’8’’

task8’8’’ T1

Trial Trial8s,10s,12s

20 self-referential & 20 non-self-referential, delivered in a pseudo-random order.

Results

• Behavioral data: from longitudinal behavioral assessments (CRS-R) – VS5 and VS6 exhibited clinical improvement and

were classified as MCS two months after the fMRI study

– Patients MCS3 and MCS4 recovered 2 months after the fMRI, and were able to repeatedly follow a command to move and verbally answer to their names.

fMRI Results

• healthy group > DOC patient group

Conclusion

• DOC patients exhibit reduced cortical responses compared with healthy controls during active self-referential processing in anterior and posterior midline regions.

• The magnitude of cortical responses in the anterior midline regions (e.g. PACC) was significantly correlated with DOC patients’ degree of consciousness.

• PACC displayed major resting-state abnormalities as manifested by reduced ALFF, FC, and SD of signal changes.