Sham-controlled randomized multicentre trial of transcranial direct current stimulation for prolonged disorders of consciousness.

BACKGROUND AND PURPOSE: Transcranial direct current stimulation (tDCS) has been shown to improve signs of consciousness in a subset of patients with disorders of consciousness (DoC). However, no multicentre study confirmed its efficacy when applied during rehabilitation. In this randomized controlled double-blind study, the effects of tDCS whilst patients were in rehabilitation were tested at the group level and according to their diagnosis and aetiology to better target DoC patients who might repond to tDCS. METHODS: Patients received 2 mA tDCS or sham applied over the left prefrontal cortex for 4 weeks. Behavioural assessments were performed weekly and up to 3 months' follow-up. Analyses were conducted at the group and subgroup levels based on the diagnosis (minimally conscious state [MCS] and unresponsive wakefulness syndrome) and the aetiology (traumatic or non-traumatic). Interim analyses were planned to continue or stop the trial. RESULTS: The trial was stopped for futility when 62 patients from 10 centres were enrolled (44 ± 14 years, 37 ± 24.5 weeks post-injury, 18 women, 32 MCS, 39 non-traumatic). Whilst, at the group level, no treatment effect was found, the subgroup analyses at 3 months' follow-up revealed a significant improvement for patients in MCS and with traumatic aetiology. CONCLUSIONS: Transcranial direct current stimulation during rehabilitation does not seem to enhance patients' recovery. However, diagnosis and aetiology appear to be important factors leading to a response to the treatment. These findings bring novel insights into possible cortical plasticity changes in DoC patients given these differential results according to the subgroups of patients.

Episodic autobiographical memory in amnestic mild cognitive impairment: what are the neural correlates?

Autobiographical memory in amnestic Mild Cognitive Impairment (aMCI) is characterized by impaired retrieval of episodic memories, but relatively preserved personal semantic knowledge. This study aimed to identify (via FDG-PET) the neural substrates of impaired episodic specificity of autobiographical memories in 35 aMCI patients compared with 24 healthy elderly controls. Significant correlations between regional cerebral activity and the proportion of episodic details in autobiographical memories from two life periods were found in specific regions of an autobiographical brain network. In aMCI patients, more than in controls, specifically episodic memories from early adulthood were associated with metabolic activity in the cuneus and in parietal regions. We hypothesized that variable retrieval of episodic autobiographical memories in our aMCI patients would be related to their variable capacity to reactivate specific sensory-perceptual and contextual details of early adulthood events linked to reduced (occipito-parietal) visual imagery and less efficient (parietal) attentional processes. For recent memories (last year), a correlation emerged between the proportion of episodic details and activity in lateral temporal regions and the temporo-parietal junction. Accordingly, variable episodic memory for recent events may be related to the efficiency of controlled search through general events likely to provide cues for the retrieval of episodic details and to the ability to establish a self perspective favouring recollection.

Valuing one's self: medial prefrontal involvement in epistemic and emotive investments in self-views.

Recent neuroimaging research has revealed that the medial prefrontal cortex (MPFC) is consistently engaged when people form mental representations of themselves. However, the precise function of this region in self-representation is not yet fully understood. Here, we investigate whether the MPFC contributes to epistemic and emotive investments in self-views, which are essential components of the self-concept that stabilize self-views and shape how one feels about oneself. Using functional magnetic resonance imaging, we show that the level of activity in the MPFC when people think about their personal traits (by judging trait adjectives for self-descriptiveness) depends on their investments in the particular self-view under consideration, as assessed by postscan rating scales. Furthermore, different forms of investments are associated with partly distinct medial prefrontal areas: a region of the dorsal MPFC is uniquely related to the degree of certainty with which a particular self-view is held (one's epistemic investment), whereas a region of the ventral MPFC responds specifically to the importance attached to this self-view (one's emotive investment). These findings provide new insight into the role of the MPFC in self-representation and suggest that the ventral MPFC confers degrees of value upon the particular conception of the self that people construct at a given moment.

Dorsomedial prefrontal metabolism and unawareness of current characteristics of personality traits in Alzheimer's disease.

Anosognosia is a complex symptom corresponding to a lack of awareness of one's current clinical status. Anosognosia for cognitive deficits has frequently been described in Alzheimer's disease (AD), while unawareness of current characteristics of personality traits has rarely been considered. We used a well-established questionnaire-based method in a group of 37 AD patients and in healthy controls to probe self- and hetero-evaluation of patients' personality and we calculated differential scores between each participant's and his/her relative's judgments. A brain-behavior correlation was performed using 18-fluorodeoxyglucose positron emission tomography (FDG-PET) images. The behavioral data showed that AD patients presented with anosognosia for current characteristics of their personality and their anosognosia was primarily explained by impaired third perspective taking. The brain-behavior correlation analysis revealed a negative relationship between anosognosia for current characteristics of personality and dorsomedial prefrontal cortex (dMPFC) activity. Behavioral and neuroimaging data are consistent with the view that impairment of different functions subserved by the dMPFC (self-evaluation, inferences regarding complex enduring dispositions of self and others, confrontation of perspectives in interpersonal scripts) plays a role in anosognosia for current characteristics of personality in AD patients.