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The spatial coordinate system in which a stimulus representation is embedded is known as its reference frame. Every visual representation has a reference frame [1], and the visual system uses a variety of reference frames to efficiently code visual information [e.g., 1, 2, 3-5]. The representation of faces in early stages of visual processing depends on retino-centered reference frames, but little is known about the reference frames that code the high-level representations used to make judgements about faces. Here we focus on a rare and striking disorder of face perception -hemi-prosopometamorphopsia (hemi-PMO) -to investigate these reference frames. Following a left splenium lesion, Patient A.D. perceives features on the right side of faces as if they had melted. The same features were distorted when faces were presented in either visual field, at different in-depth rotations, and at different picture-plane orientations including upside-down. A.D.'s results indicate faces are aligned to a view-and orientation-independent face template encoded in a face-centered reference frame, that these face-centered representations are present in both the left and right hemisphere, and that the representations of the left and right halves of a face are dissociable. KeywordsFace processing; Hemi-Prosopometamorphopsia; View-independent face representation; Splenium; Highlights• After a left splenium lesion, A.D. sees features in right face halves as distorted • A.D.'s distortions affect the same features under all stimulus manipulations tested • Face processing involves a view-and orientation-independent face template • The face vertical midline is an important representational divide in face processing In BriefAfter a left splenium lesion, patient A.D. sees the right halves of faces as melting. Almeida et al.show that the distortion affects the same features regardless of position, rotation in-depth, or in-plane inversion, indicating that faces are encoded in a view-and orientation independent manner.

Advances in functional imaging allowed us to visualize brain glucose metabolism in vivo and noninvasively with [ 18 F] uoro-2-deoxyglucose (FDG) positron emission tomography (PET) imaging. In the past decades, FDG-PET has been instrumental in the understanding of brain function in health and disease. The source of the FDG-PET signal has been attributed to neuronal uptake, with hypometabolism being considered as a direct index of neuronal dysfunction or death. However, other brain cells are also metabolically active, including astrocytes. Based on the astrocyte-neuron lactate shuttle hypothesis, the activation of the glutamate transporter 1 (GLT-1) acts as a trigger for glucose uptake by astrocytes. With this in mind, we investigated glucose utilization changes after pharmacologically downregulating GLT-1 with clozapine (CLO), an antipsychotic drug. MethodsAdult male Wistar rats (control, n = 14; CLO, n = 12) received CLO (25/35mg kg−1) for six weeks. CLO effects were evaluated in vivo with FDG-PET and cortical tissue was used to evaluate glutamate uptake, GLT-1 and GLAST levels. CLO treatment effects were also assessed in cortical astrocyte cultures (glucose and glutamate uptake, GLT-1 and GLAST levels) and in cortical neuronal cultures (glucose uptake). ResultsCLO markedly reduced in vivo brain glucose metabolism in several brain areas, especially in the cortex. Ex vivo analyses demonstrated decreased cortical glutamate transport along with GLT-1 mRNA and protein downregulation. In astrocyte cultures, CLO decreased GLT-1 density as well as glutamate and glucose uptake. By contrast, in cortical neuronal cultures, CLO did not affect glucose uptake. ConclusionThis work provides in vivo demonstration that GLT-1 downregulation induces astrocyte-dependent cortical FDG-PET hypometabolism -mimicking the hypometabolic signature seen in people developing dementiaand adds further evidence that astrocytes are key contributors of the FDG-PET signal.Recent important theoretical articles are already acknowledging the role of astrocytes in the brain FDG-PET signal [31][32][33][34]. Still, whether a reduction of glutamate uptake by astrocytes would cause in vivo FDG-PET hypometabolism -recapitulating what is seen in neurodegenerative disorders -remains unexplored. On the basis of the evidence presented above, we hypothesized that astrocyte GLT-1 downregulation would cause FDG-PET hypometabolism. To further test this hypothesis, we conducted in vivo and in vitro pharmacological challenges with CLO, a well-known anti-psychotic drug that reduces GLT-1 density [35] and glutamate transport [36], to assess its effects on cerebral FDG-PET signal in rats. Materials And Methods AnimalsAdult male Wistar rats, 90 days old, were maintained under a 12 h light-dark cycle (lights on at 7 A.M.), at a controlled room temperature (22 ± 1•C) and with free access to food and water. Animals' weight was