Background: The Supplementary Motor Area (SMA) plays a key role in motor programming and production, and is involved in internal-cued movements. SMA syndrome after lesion of the "SMA-proper" is characterized by transient impairment of voluntary movements and motor sequences. This syndrome is assumed to follow from interruption in the motor cortico-subcortical loop. A few case-reports indicate that such syndrome occurs after a lesion isolating SMA from subcortical structures.

Background: The supplementary motor area (SMA) plays a key role in motor programming and production and is involved in internally-cued movements. In neurological populations, SMA syndrome following a lesion to the "SMA proper" is characterized by transient impairment of voluntary movements and motor sequences. This syndrome is assumed to follow on from an interruption of the motor cortico-subcortical loop, and some case reports indicate that such a syndrome could occur after a brain lesion isolating the SMA from subcortical structures.Aim: To characterize the pattern of motor impairments in a patient whose stroke disconnects the SMA from the subcortical motor loop.Method: A patient developed a moderate transient left hemiparesis following a subcortical stroke in the right anterior cerebral artery area, which disconnected the SMA from basal ganglia. Eight days after the stroke, when the hemiparesis had regressed, the patient presented a specific SMA motor disorder of the left hand which manifested as an akinesia and was exacerbated when his visual attention was not directed towards his hand. We assessed finger tapping with left and right hands, eyes closed and open, in the left and right hemispace. We indexed movement speed as the number of taps filmed over 5-s periods.Results: Left motor weakness (grasping strength of right hand: 49 kg and left hand: 41 kg) was resolved in a week. Ideornotor and ideational gestures and motor sequences were preserved. On the tapping task, left-hand tapping was slower than right-hand tapping. Critically, visual feedback improved tapping speed for the left, but not for the right, hand. The hemispace of the task execution had no effect on tapping performance.Conclusion: Our results suggest that SMA-basal ganglia disconnection decreases contralateral movement initiation and maintenance and this effect is partly compensated by visual cues. (C) 2013 Elsevier Ltd. All rights reserved.

Fatigue associated with recovery from muscle damage has recently been linked to increases in brain and muscle proinflammatory cytokines. However, little is known regarding the origin of these cytokines. Since macrophage-like cells in the brain are a primary source of cytokines, we used a brain specific macrophage depletion technique involving liposome encapsulated clodronate (CLD) to examine the role of macrophages on brain IL-1beta and fatigue following eccentric exercise-induced muscle damage. Mice were assigned to six groups: Downhill saline (DWNSAL), downhill clodronate (DWNCLD), uphill saline (UPSAL), uphill clodronate (UPCLD), non-running saline (CONSAL) or non-running clodronate (CONCLD). Mice were given intracerebroventricular (ICV) (10 microL) injections of clodronate-filled liposomes (CLD) to deplete macrophages, or saline-filled liposomes (SAL) and run on a treadmill at 22m/min and -14% (DWN) or 14% (UP) grade for 150 min. A subset of uphill and downhill running mice (n=40) was then run to fatigue on a treadmill at 36m/min, 8% grade at 24h after the uphill and downhill runs. A second subset of uphill, downhill, and control mice (n=30) was sacrificed 24h after the run for analysis of brain IL-1beta concentration. Histological examination confirmed previous reports that CLD administration reduced perivascular and meningeal macrophage subsets in the brain. CLD reduced IL-1beta concentration in the cortex of DWN mice (P<0.05), which was associated with enhanced treadmill performance 24h after both uphill and downhill runs (P<0.05) although the magnitude was greater following the downhill run. These results suggest that brain macrophages can contribute to the increase in brain IL-1beta and fatigue that are associated with recovery from exercise-induced muscle damage.

Human eyes have a unique morphology and play a crucial role in social interactions and communication. The importance of the eyes for processing facial identity and expression has been clearly established with behavioural, image classification (e.g., Bubbles) and brain imaging studies. Humans are also highly sensitive where another person is looking, and functional Magnetic Resonance Imaging (fMRI) studies have consistently reported gaze related responses in the right Superior Temporal Sulcus (rSTS). Yet, whether information processed from the eyes during perception of facial identity, expression or gaze is coded by the same neural substrates is not yet understood. To address this question we tested PS, a pure case of acquired prosopagnosia with lesions sparing the neural substrates sensitive to eye gaze (rSTS) (Sorger et al., 2007), using a gaze adaptation paradigm and fMRI. We previously revealed with Bubbles (Gosselin & Schyns, 2001) that PS does not use the eyes but only the mouth to identify short-term familiar faces (Caldara et al., 2005) and to categorize facial expressions, even fear in which the eyes are highly diagnostic for normal observers (Caldara et al., 2006). Consequently, the PS case represents a unique opportunity to test whether the distributed neural face system relies on a unique set of substrates for coding information from the eyes. Adaptation to averted gaze eliminates perception of gaze in the adapted direction (Jenkins et al. 2006). Strikingly, PS showed sensitivity to gaze direction, but no gaze adaptation effect. Contrary to intuition however, PS showed larger activations in the rSTS for averted gaze than for direct gaze and eyes closed conditions. These data suggest separable functional routes for gaze information, with gaze adaptation requiring the integrity of the occipito-temporal face-sensitive network. Critically, sensitivity to gaze direction is independently coded in the rSTS.

Prosopagnosia is classically defined as a disorder of visual recognition specific to faces, following brain damage. However, according to a long-standing alternative view, these patients would rather be generally impaired in recognizing objects belonging to visually homogenous categories, including faces. We tested this alternative hypothesis stringently with a well-documented brain-damaged prosopagnosic patient (PS) in three delayed forced-choice recognition experiments in which visual similarity between a target and its distractor was manipulated parametrically: novel 3D geometric shapes, morphed pictures of common objects, and morphed photographs of a highly homogenous familiar category (cars). In all experiments, PS showed normal performance and speed, and there was no evidence of a steeper increase of error rates and RTs with increasing levels of visual similarity, compared to controls. These data rule out an account of acquired prosopagnosia in terms of a more general impairment in recognizing objects from visually homogenous categories. An additional experiment with morphed faces confirmed that PS was specifically impaired at individual face recognition. However, in stark contrast to the alternative view of prosopagnosia, PS was relatively more impaired at the easiest levels of discrimination, i.e. when individual faces differ clearly in global shape rather than when faces were highly similar and had to be discriminated based on fine-grained details. Overall, these observations as well as a review of previous evidence, lead us to conclude that this alternative view of prosopagnosia does not hold. Rather, it seems that brain damage in adulthood may lead to selective recognition impairment for faces, perhaps the only category of visual stimuli for which holistic/configural perception is not only potentially at play, but is strictly necessary to individualize members of the category efficiently.

The role of the occipito-temporal cortex in visual awareness remains an open question and with respect to faces in particular, it is unclear to what extent the fusiform face area (FFA) may be involved in conscious identification. An answer may be gleaned from prosopagnosia, a disorder in which familiar faces are no longer recognized. This impairment has sometimes been reported to be associated with implicit processing of facial identity, although the neural substrates responsible for unconscious processing remain unknown. In this study, we addressed these issues by investigating the functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) responses to familiar and unfamiliar faces in a well-known prosopagnosic patient (P.S.). Our fMRI results show that faces known prior to the onset of prosopagnosia produce an increase in activation in the lateral fusiform gyrus encompassing the FFA, as well as the right middle frontal gyrus, when compared to unknown faces. This effect is not observed with photographs of celebrities dating after the onset of prosopagnosia. Furthermore, electrophysiological responses show that previously familiar faces differ from unfamiliar ones at around 550 msec. Since covert processing of familiarity is associated with activation in FFA, this structure does not appear to be sufficient to produce awareness of identity. Furthermore, the results support the view that FFA participates in face individuation.

Symmetry pervades our visual world. Many biological organisms have acquired a particular sensitivity to subtle symmetry detection cues in their environment and conspecifics. The balanced distribution of duplicate body parts is a fundamental characteristic of living organisms, and for many biological species this structural property seems to be related to their phenotypic condition - an aspect that plays a key role in mate selection. Symmetrical human faces are perceived as sexually attractive, healthier and more intelligent - all representing crucial factors for social and biological interactions. Interestingly, symmetry detection is better for upright compared to inverted faces despite these visual stimuli are matched for their low-level properties (Rhodes, et al. 2005), suggesting that high-order mechanisms subtend to this human ability. Recently, the neural bases of facial symmetry perception have been investigated within the face-sensitive regions using functional Magnetic Resonance Imaging (fMRI). Chen et al. (2006) found sensitivity for symmetry uniquely in the right Occipital Face Area (rOFA), whereas Caldara and Seghier (2006) found such sensitivity only in the right Fusiform Face Area (rFFA). Consequently, the identification of the neural substrates involved in the processing of facial symmetry remains to be clarified. Here we tackled this discrepancy by testing facial symmetry perception in PS, a pure case of prosopagnosia, with a lesion encompassing the rOFA and sparing the rFFA (Sorger et al., 2007). We confronted PS and an age-matched control group of participants with a normal and a perfectly symmetrical version of the same face. The face-pairs were presented for 200ms and 500ms in separate blocs. PS identified symmetrical faces as accurately as the controls, showing that prosopagnosia does not necessarily involve a deficit in symmetry perception. Crucially, these observations provide unequivocal evidence that symmetry perception for faces does not rely on neural populations within the rOFA.

The understanding of the nature of prosopagnosia - classically defined as a disorder of visual recognition specific to faces following brain damage - can inform about how visual face recognition is performed in the normal human brain. However, according to a long-standing alternative view of prosopagnosia, the prosopagnosic impairment would rather reflect a general difficulty for fine-grained discrimination in visually homogenous object categories (Faust, 1955; Damasio et al., 1982; Gauthier et al., 1999). We tested this hypothesis stringently with a well-known brain-damaged prosopagnosic patient (PS, Rossion et al., 2003), in three delayed matching experiments in which the visual similarity between the target and distractor was manipulated parametrically. We used 3 kinds of stimuli: novel 3D geometric shapes manipulated on single or multiple dimensions, morphed common objects (Hahn et al., 2009), and morphed photographs of a highly homogenous familiar category (cars). In every experiment, there was no evidence of a steeper increase of error rates and RTs with increasing levels of visual similarity for the patient, relative to normal observers. These data categorically rule out an account of acquired prosopagnosia in terms of a general problem of fine-grained discrimination in a visually homogenous category. Finally, a fourth experiment with faces showed that, compared to normal observers, the patient's impairment with morphed faces was best revealed at the easiest levels of discrimination, i.e. when individual faces differ clearly in global shape rather than in fine-grained details. Overall, these observations indicate that the alternative view of prosopagnosia as a more general impairment for fine-grained discrimination in visually homogeneous object categories does not hold.

The human face transmits a wealth of nonverbal signals that readily provide crucial information for social interactions. The brain, as a decoder, flexibly filters the information arriving at the sensory inputs to rapidly achieve complex perceptual categorizations, such as people identification and expression. Response classification techniques have revealed that the face system uses differential effective information to achieve face identification (Bubbles - Gosselin & Schyns, 2001) and expression (Smith et al., 2005). Yet, a fundamental question remains unresolved (Calder and Young, 2005): does facial information used for face identity and expression tap into a unique facial representation system, or does this processing occur in dedicated systems? To address this question we tested PS, a pure case of acquired prosopagnosia with lesions sparing the neural substrates dedicated to expression (STS, amygdala). In marked contrast to normal observers, PS does not use the eyes to identify faces but the mouth (Caldara et al., 2005), highlighting defective representations for identity. However, PS' expression categorization is extremely effective compared to face identification. Consequently, the PS case represents an exceptional opportunity to test whether the face system relies on a unique representation system or can instead flexibly adapt to face expression categorization by using dedicated representations. Patient PS and normal observers categorized neutral, happy and fearful faces by expressions while using Bubbles. Strikingly, patient PS consistently used only the mouth to categorize these expressions, even for fear in which the eyes are highly diagnostic for normal observers. Importantly, eye movement patterns showed that PS spontaneously attempted to extract information from the eye region, indicating a general, selective deficit impinging on the representations for the eye region. Critically, these results clearly demonstrate that a unique representation system is used to code face features, and support a single, flexible (in normal observers) coding system for face representations.

Face processing can be modified by bottom-up and top-down influences, but it is unknown how these processes interact in patients with face-recognition impairments (prosopagnosia). We investigated a prosopagnosic with lesions in right occipital and left fusiform cortex but whose right fusiform gyrus is intact and still activated during face-processing tasks. P.S., a patient with a well-established and selective agnosia for faces, was instructed to detect the presence of either faces or houses in pictures with different amounts of noise. The right fusiform face area (FFA) showed reduced responses to face information when visual images were degraded with noise. However, her right FFA still activated to noise-only images when she was instructed to detect faces. These results reveal that fusiform activation is still selectively modulated by task demands related to the anticipation of a face, despite severe face-recognition deficits and the fact that no reliable stimulus-driven response is evoked by actual facial information. Healthy controls showed stimulus-driven responses to faces in fusiform, and in right but not left occipital cortex, suggesting that the latter area alone might provide insufficient facial information in P.S. These results provide a novel account for residual activation of the FFA and underscore the importance of controlling task demands during functional magnetic resonance imaging.

Although socio-emotional changes are very frequently encountered after traumatic brain injury (TBI), the psychological mechanisms underlying these disorders are still poorly understood. This study aimed to explore the relationships between dysexecutive syndrome (assessed with the Behavioural Assessment of the Dysexecutive Syndrome [BADS]) and socio-emotional changes assessed by the Iowa scales of personality change (ISPC) in patients with TBI. The BADS was thus administered to 25 patients with TBI and to 25 healthy controls. Simultaneously, a close relative of each patient was given the ISPC in order to assess socio-emotional changes. Results indicated that patients displayed significantly lower executive performances than controls and experimented significant socio-emotional changes. The Modified Six Elements Test was the only subtask of the BADS to be significantly related to behavioural changes, and more specifically to externalizing disorders. It is concluded that executive functions, and especially multitasking, encompass processes whereby one can consciously control one's emotional reactions and behaviours.

The present study investigated whether emotionally expressive faces guide attention and modulate fMRI activity in fusiform gyrus in acquired prosopagnosia. Patient PS, a pure case of acquired prosopagnosia with intact right middle fusiform gyrus, performed two behavioral experiments and a functional imaging experiment to address these questions. In a visual search task involving face stimuli, PS was faster to select the target face when it was expressing fear or happiness as compared to when it was emotionally neutral. In a change detection task, PS detected significantly more changes when the changed face was fearful as compared to when it was neutral. Finally, an fMRI experiment showed enhanced activation to emotionally expressive faces and bodies in right fusiform gyrus. In addition, PS showed normal body-selective activation in right fusiform gyrus, partially overlapping the fusiform face area. Together these behavioral and neuroimaging results show that attention was preferentially allocated to emotional faces in patient PS, as observed in healthy subjects. We conclude that systems involved in the emotional guidance of attention by facial expression can function normally in acquired prosopagnosia, and can thus be dissociated from systems involved in face identification.

The first part of this article covers the main discoveries that led to the concept of hemispheric specialisation, from Egyptian antiquity to present times, through the pivotal XIXth century period that saw the attribution of specific cognitive functions to the left and right hemispheres. Next, this dichotomous conception of cerebral function, attributing a given process to a hemisphere and hypothesising callosal transmission, is discussed in the light of recent studies on language comprehension. Present day knowledge suggesting an alternative to the structuralist view of hemispheric specialisation in the form of dynamic, complementary sharing of labour, and of cooperation through transcortical neural networks, is then considered. Finally, the role of the corpus callosum in interhemispheric communication is briefly covered. An emphasis is placed on the diversity of this structure that is at the origin of highly different functions (fibre size, homotopic vs heterotopic connections). Ultimately, we contrast the view of a corpus callosum serving as an information transmitting channel with that of a fibre tract co-activating the non-engaged hemisphere and preparing it for potential stimulation. In this manner, the corpus callosum minimises disparities in the distribution of attention between the two hemispheres.

Prosopagnosia is classically defined as an inability to recognize faces of people known to the patient on the basis of visual perception, despite the absence of low-level visual impairments, or cognitive alterations such as mental confusion or amnesia, with a preserved ability to recognize people through other cues: voice or other visual traits such as gait, size, clothes, or even facial features (moustache, scar, blemish) or accessories (ear-rings, eyeglasses). Prosopagnosics have also access to semantic knowledge concerning people. According to Grüsser and Landis (1991), this condition seems to have been first described by Wigan (1844), in a book in which he expressed his views on the interaction of the two cerebral hemispheres. Wigan stated (pp. 128 9):

In this study, we developed a digitizing tablet-based instrument for the clinical assessment of human voluntary movements targeting motor processes of planning, programming and execution. The tool was used to investigate an adaptation of Fitts' reciprocal tapping task [10], comprising four conditions, each of them modulated by three indices of difficulty related to the amplitude of movement required. Temporal, spatial and sequential constraints underlying the various conditions allowed the intricate motor processes to be dissociated. Data obtained from a group of elderly healthy subjects (N=50) were in agreement with the literature on motor control, in the temporal and spatial domains. Speed constraints generated gains in the temporal domain and costs in the spatial one, while spatial constraints generated gain in the spatial domain and costs in the temporal one; finally, sequential constraints revealed the integrative nature of the cognitive operations involved in motor production. This versatile instrument proved capable of providing quantitative, accurate and sensitive measures of the various processes sustaining voluntary movement in healthy subjects. Altogether, analyses performed in this study generated a theoretical framework and reference data which could be used in the future for the clinical assessment of patients with various movement disorders, in particular Parkinson's disease.

Cytokines in the brain, induced by various inflammatory challenges have been linked to sickness behaviors, including fatigue. However, the brain cytokine response to exercise is not well understood. Preliminary data show that exaggerated fatigue following downhill vs uphill running is associated with increased brain IL-1b concentration. PURPOSE: This study was designed to determine the role of brain macrophages in the increased IL-1b response to downhill running using a macrophage depletion technique involving ICV injection of clodronate-nlled liposomes (CLOD) that selectively targets perivascular and meningeal macrophages. METHODS: Male C57BL/6 mice (n=110) were assigned to 1 of 6 groups (UP-SAL, UP-CLOD, DWN-SAL, DWN-CLOD, CON-SAL & CON-CLOD). Initially mice were given lOuL ICV injections of either clodronate or saline-filled liposomes. Four days later, mice were run at 22 m/min and −14% or +14% grade, for 150-min. Con mice remained in their cages in the treadmill room. Fatigue was assessed 12–24hr later via voluntary wheel running (Exp. 1) or treadmill running to fatigue (Exp. 2). Brain IL-1b concentration was determined at 24-hr (Exp. 3). RESULTS: CLOD administration had no effect on any component (time, distance & peak speed) of wheel running (Exp 1), but did delay fatigue during treadmill running in both uphill (158 + 8 vs. 124 + 10 min) and downhill runners (126 + 15 vs. 65 + 8 min) compared to SAL (Exp 2). CLOD administration reduced IL-1b in the cortex of downhill runners (0.86 + 0.06 vs 1.05 + 0.1 pg/100ug total protein) and cerebellum of both uphill (3.5 + 0.2 vs. 4.1 + 0.18 pg/100ug total protein) and downhill runners (3.7 + 0.4 vs. 4.5 + 0.38 pg/100ug total protein) compared to SAL, but this effect didn't reach statistical significance (p=0.2). CONCLUSIONS: These results support a role of brain macrophages in some forms of fatigue, but the precise relationship between brain macrophages, IL-1b and central fatigue remain to be determined. This research was funded by a student research grant from the American College of Sports Medicine

The middle fusiform gyrus (MFG) and the inferior occipital gyrus (IOG) are activated by both detection and identification of faces. Paradoxically, patients with acquired prosopagnosia following lesions to either of these regions in the right hemisphere cannot identify faces, but can still detect faces. Here we acquired functional magnetic resonance imaging (fMRI) data during face processing in a patient presenting a specific deficit in individual face recognition, following lesions encompassing the right IOG. Using an adaptation paradigm we show that the fMRI signal in the rMFG of the patient, while being larger in response to faces as compared to objects, does not differ between conditions presenting identical and distinct faces, in contrast to the larger response to distinct faces observed in controls. These results suggest that individual discrimination of faces critically depends on the integrity of both the rMFG and the rIOG, which may interact through re-entrant cortical connections in the normal brain.

One of the most impressive disorders following brain damage to the ventral occipitotemporal cortex is prosopagnosia, or the inability to recognize faces. Although acquired prosopagnosia with preserved general visual and memory functions is rare, several cases have been described in the neuropsychological literature and studied at the functional and neural level over the last decades. Here we tested a brain-damaged patient (PS) presenting a deficit restricted to the category of faces to clarify the nature of the missing and preserved components of the face processing system when it is selectively damaged. Following learning to identify 10 neutral and happy faces through extensive training, we investigated patient PS's recognition of faces using Bubbles, a response classification technique that sampled facial information across the faces in different bandwidths of spatial frequencies [Gosselin, F., & Schyns, P. E., Bubbles: A technique to reveal the use of information in recognition tasks. Vision Research, 41, 2261-2271, 2001]. Although PS gradually used less information (i.e., the number of bubbles) to identify faces over testing, the total information required was much larger than for normal controls and decreased less steeply with practice. Most importantly, the facial information used to identify individual faces differed between PS and controls. Specifically, in marked contrast to controls, PS did not use the optimal eye information to identify familiar faces, but instead the lower part of the face, including the mouth and the external contours, as normal observers typically do when processing unfamiliar faces. Together, the findings reported here suggest that damage to the face processing system is characterized by an inability to use the information that is optimal to judge identity, focusing instead on suboptimal information.