Brain Research Bulletin 63 (2004) 269–281 Impaired fear processing in right mesial temporal sclerosis: a fMRI study Francesca Benuzzi a , Stefano Meletti b , Giovanna Zamboni a , Giovanna Calandra-Buonaura a , Marco Serafini c , Fausta Lui d , Patrizia Baraldi d , Guido Rubboli b , Carlo Alberto Tassinari b , Paolo Nichelli a,∗ a Dipartimento di Neuroscienze TCR, Università di Modena e Reggio Emilia, Via Del Pozzo 71, Modena I-41100, Italy b Dipartimento di Scienze Neurologiche, Ospedale Bellaria-Università di Bologna, Bologna I-40139, Italy c A.S.L. Modena, Modena I-41100, Italy d Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Modena I-41100, Italy Received 5 November 2003; received in revised form 24 February 2004; accepted 1 March 2004 Available online 10 May 2004 Abstract Lesion and neuroimaging studies have demonstrated that the mesial temporal lobe is crucial for recognizing emotions from facial expressions. In humans, bilateral amygdala damage is followed by impaired recognition of facial expressions of fear. To evaluate the influence of unilateral mesial temporal lobe damage we examined recognition of facial expressions and functional magnetic resonance (fMRI) brain activation associated with incidental processing of fearful faces in thirteen mesial temporal lobe epilepsy (MTLE) patients (eight with right MTLE, five with left MTLE). We also examined the effect of early versus later damage, comparing subjects with hippocampal–amygdalar sclerosis (MTS) and seizures occurring before five years of age to epilepsy patients with late onset seizures. Fourteen healthy volunteers participated as controls. Neuropsychological testing demonstrated that the ability of right MTLE patients to recognize fearful facial expressions is impaired. Patients with early onset of seizures were the most severely impaired. This deficit was associated with defective activation of a neural network involved in the processing of fearful expressions, which in controls and left MTLE included the left inferior frontal cortex and several occipito-temporal structures of both hemispheres. © 2004 Elsevier Inc. All rights reserved. Keywords: Mesial temporal lobe epilepsy; Amygdala; Facial expression; Emotion; Functional magnetic resonance 1. Introduction The structures of the mesial temporal lobe are crucial for the processing of emotions. The amygdala, in particular, is important for the recognition of certain emotions from fa- cial expressions [2,3,13,37,42,60] and from auditory stimuli [51], as well as for the processing of emotionally salient ol- factory and gustatory stimuli [48,62,63]. In the studies cited above, activation of the amygdala was most frequently found in response to negative emotions, especially fear. Functional imaging studies of healthy subjects have shown an association between the processing of facial ex- ∗ Corresponding author. Tel.: +39-059-4224298; fax: +39-059-4224299. E-mail address: nichelli@unimo.it (P. Nichelli). pressions of emotion and either bilateral [9] or unilateral [36] amygdala activation. These studies have suggested that the right amygdala is preferentially activated in response to subliminal presentation of such expressions, whereas the left amygdala is activated when the stimuli are presented for longer [36,38,60]. Moreover, this subcortical structure has a neuromodulatory effect on several other brain cortical regions (namely the fusiform gyrus, the superior temporal sulcus, and the frontal cortex) during the sensory processing of emotionally salient stimuli [31,35,36]. In humans, bilateral selective damage to the amygdala impaired conditioning of autonomic responses [6], memory for emotional material [11], auditory recognition of fear and anger [51], recognition of facial expressions of emotion [3,13], and social and emotional behaviour [56]. Unilat- eral damage generally results in more subtle impairment. 0361-9230/$ – see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.brainresbull.2004.03.005