Reductions of Thalamic Volume and Regional Shape Changes in the Vegetative and the Minimally Conscious States Davinia Ferna´ ndez-Espejo, 1,2 Carme Junque, 1,2 Montserrat Bernabeu, 3 Teresa Roig-Rovira, 4 Pere Vendrell, 1,2 and Jose M. Mercader 5,6 Abstract The thalamus is known to play a key role in arousal regulation and support of human consciousness. Neuro- pathological studies have identified thalamic damage as one of the most common abnormalities present in the brains of patients who were in a vegetative state (VS) or a minimally-conscious state (MCS) state at the time of their deaths. Nonetheless, no in vivo studies of thalamic abnormalities in these patients have been conducted. Using high-resolution T1-weighted magnetic resonance images and a novel approach to shape analysis, we investigated thalamic global and regional changes in a sample of patients in a VS or an MCS. Group comparisons and correlations with clinical variables were performed for the total thalamic volume and for each surface vertex. Total thalamic volume was significantly lower in patients than in healthy volunteers. Shape analysis revealed significant bilateral regional atrophy in the dorso-medial body in patients compared to controls; this atrophy was more widespread in VS than in MCS patients. Lower thalamic volume was significantly correlated with worse Disability Rating Scale scores. Shape analysis suggested that the dorso-medial nucleus and the internal medullar lamina were the main regions responsible for this correlation. Our findings suggest that MCS and VS patients present different patterns of regional thalamic abnormalities, and that these differences partially explain their clinical profile. Key words: disorders of consciousness; magnetic resonance imaging; shape analysis; traumatic brain injury; thalamus Introduction T he thalamus is known to play a key role in arousal regulation and support of human consciousness (Schiff, 2008). Direct widespread thalamic injuries can themselves produce a generally transient coma state, but also more per- sistent disturbances of consciousness in terms of goal-directed behavior and communication skills (Schiff and Plum, 2000). The thalamus may also be critically involved in non-focal brain injuries such as diffuse axonal injury (DAI). Post- mortem neuropathological studies of traumatic brain in- jury (TBI) patients who were in a vegetative state (VS) at the time of their deaths demonstrated that the thalamus was se- verely injured in 80% of the sample, in most cases associated with grades II or III DAI (Adams et al., 1999, 2000). Patients in a VS show wakefulness without awareness ( Jennett and Plum, 1972), while patients in a minimally- conscious state (MCS) demonstrate inconsistent, but repro- ducible, evidence of awareness of self or environment (Giacino et al., 2002). MCS typically describes a spectrum of severity and is generally associated with a better prognosis (Katz et al., 2009); in exceptional cases late recovery is possible (Lammi et al., 2005; Voss et al., 2006). By comparing histopathological findings in a group of VS patients and a group of severely disabled patients, including some who were considered to fulfill the diagnostic criteria for MCS, Jennett and colleagues 1 Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain. 2 Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 3 Head Injury Unit, Institut Universitari de Neurorehabilitacio´ Guttmann, Badalona, Spain. 4 Department of Neuropsychology, Institut Universitari de Neurorehabilitacio´ Guttmann, Badalona, Spain. 5 Centre de Diagno` stic per la Imatge Clinic (CDIC), Hospital Clı ´nic de Barcelona, Spain. 6 Department of Obstetrics and Gynaecology, Pediatrics, Radiology and Anatomy, University of Barcelona, Barcelona, Spain. JOURNAL OF NEUROTRAUMA 27:1187–1193 (July 2010) ª Mary Ann Liebert, Inc. DOI: 10.1089/neu.2010.1297 1187