Robot-assisted gait training improves walking and cerebral connectivity in children with unilateral cerebral palsy.

BACKGROUND: Robot-assisted gait training (RAGT) is promising to help walking rehabilitation in cerebral palsy, but training-induced neuroplastic effects have little been investigated. METHODS: Forty unilateral cerebral palsy children aged 4-18 years were randomly allocated in a monocentric study to ten 20-minute RAGT sessions with the G-EO system, five days a week (n = 20) or to a control group (who continued conventional care with six 30-minute physiotherapy sessions, three days a week) (n = 20), two weeks running, from September 2020 to December 2021. Clinical and MRI outcomes were compared before and one month after therapy. The primary outcome was gait speed. Secondary outcomes were a 6-minute walking test distance, Gross Motor Function Measure-88 (GMFM-88) dimensions D and E, Patient Global Impression of Improvement, resting-state functional connectivity within the sensorimotor network, and structural connectivity in the corticospinal tracts. RESULTS: Gait speed and the 6-minute walking test distance improved more after RAGT. Resting-state functional connectivity increased after RAGT but decreased in controls between superior and lateral healthy or lateral injured sensorimotor networks. GMFM-88 and structural connectivity in corticospinal tracts were unchanged. Impression of improvement in children was better after RAGT. CONCLUSION: Short-term benefit of repetitive RAGT on walking abilities and functional cerebral connectivity was found in unilateral cerebral palsy children. IMPACT STATEMENT: Short-term repetitive robot-assisted gait training improves gait speed and walking resistance and increases cerebral functional connectivity in unilateral cerebral palsy. GMFM dimensions D and E were unchanged after short-term repetitive robot-assisted gait training in unilateral cerebral palsy.

Deep brain stimulation of the subthalamic nucleus in severe Parkinson's disease: relationships between dual-contact topographic setting and 1-year worsening of speech and gait.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) alleviates severe motor fluctuations and dyskinesia in Parkinson's disease, but may result in speech and gait disorders. Among the suspected or demonstrated causes of these adverse effects, we focused on the topography of contact balance (CB; individual, right and left relative dual positions), a scantly studied topic, analyzing the relationships between symmetric or non-symmetric settings, and the worsening of these signs. METHOD: An observational monocentric study was conducted on a series of 92 patients after ethical approval. CB was specified by longitudinal and transversal positions and relation to the STN (CB sub-aspects) and totalized at the patient level (patient CB). CB was deemed symmetric when the two contacts were at the same locations relative to the STN. CB was deemed asymmetric when at least one sub-aspect differed in the patient CB. Baseline and 1-year characteristics were routinely collected: (i) general, namely, Unified Parkinson's Disease Rating Scores (UPDRS), II, III motor and IV, daily levodopa equivalent doses, and Parkinson's Disease Questionnaire of Quality of Life (PDQ39) scores; (ii) specific, namely scores for speech (II-5 and III-18) and axial signs (II-14, III-28, III-29, and III-30). Only significant correlations were considered (p < 0.05). RESULTS: Baseline characteristics were comparable (symmetric versus asymmetric). CB settings were related to deteriorations of speech and axial signs: communication PDQ39 and UPDRS speech and gait scores worsened exclusively with symmetric settings; the most influential CB sub-aspect was symmetric longitudinal position. CONCLUSION: Our findings suggest that avoiding symmetric CB settings, whether by electrode positioning or shaping of electric fields, could reduce worsening of speech and gait.

Increased links between language and motor areas: A proof-of-concept study on resting-state functional connectivity following Personalized Observation, Execution and Mental imagery therapy in chronic aphasia.

A tight coupling of language and motor processes has been established, which is consistent with embodied cognition theory. However, very few therapies have been designed to exploit the synergy between motor and language processes to help rehabilitate people with aphasia (PWA). Moreover, the underlying mechanisms supporting the efficacy of such approaches remain unknown. Previous work in our laboratory has demonstrated that personalized observation, execution, and mental imagery therapy (POEM)-a new therapy using three sensorimotor strategies to trigger action verb naming-leads to significant improvements in verb retrieval in PWA. Moreover, these improvements were supported by significant activations in language and sensorimotor processing areas, which further reinforce the role of both processes in language recovery (Durand et al., 2018). The present study investigates resting state functional connectivity (rsFC) changes following POEM in a pre-/post-POEM therapy design. A whole brain network functional connectivity approach was used to assess and describe changes in rsFC in a group of four PWA, who were matched and compared with four healthy controls (HC). Results showed increased rsFC in PWA within and between visuo-motor and language areas (right cuneal cortex-left supracalcarin (SCC) cortex/right precentral gyrus (PreCG)-left lingual gyrus (LG)) and between areas involved in action processing (right anterior parahippocampal gyrus (aPaHC)-left superior parietal lobule (SPL). In comparison to HC, the PWA group showed increased rsFC between the right inferior frontal gyrus (IFG) and left thalamus, which are areas involved in lexico-semantic processing. This proof-of-concept study suggests that the sensorimotor and language strategies used in POEM may induce modifications in large-scale networks, probably derived from the integration of visual and sensorimotor systems to sustain action naming, which is consistent with the embodied cognition theory.

Brain Diffusion Imaging and Tractography to Distinguish Clinical Severity of Human PLP1-Related Disorders.

AIMS: We performed quantitative diffusion tensor imaging and brain tractography to distinguish clinical severity in a series of 35 patients with hypomyelinating PLP1-related disorders classified using the Motor Developmental Score according to the best motor function acquired before the age of 5 years and the gross motor function measure (GMFM) at the time of magnetic resonance imaging acquisition. METHODS: We calculated fractional anisotropy and diffusivity values in 26 regions of interest and the numbers of fibers and volumes of hemisphere tractograms. Fiber bundles on tractograms were characterized according to 3 criteria: size, direction of main-stream fibers, and connectivity of bundles (extratelencephalic projections, commissural fibers, and intrahemispheric connections). RESULTS: Age-adjusted multivariate analysis in 3 severity groups revealed increased isotropic diffusion in the superior cerebellar peduncle and grey matter in the most severe group, and larger tractogram volumes and increased numbers of fibers in the least severely affected group. Tractogram patterns showed preserved extratelencephalic projections and a main anterior-posterior aspect of intrahemispheric fibers in most patients, whereas interhemispheric connectivity was variable. The most severely affected and intermediate patients had less intrahemispheric connectivity, with a frequent predominant anterior-posterior direction of main-stream fibers. INTERPRETATION: Diffusion tensor imaging and tractographic parameters can operate as biomarkers to distinguish clinical severity in PLP1-related disorders and could improve our understanding of hypomyelinating leukodystrophies.

Inter-individual variations and hemispheric asymmetries in structural connectivity patterns of the inferior fronto-occipital fascicle: a diffusion tensor imaging tractography study.

PURPOSE: Precise knowledge of the structural connectivity of white matter fascicles could yield new insights into function and is important for neurosurgical planning. Therefore, we aimed to provide a detailed map of the cortical terminations of the inferior fronto-occipital fascicle (IFOF), with special emphasis on putative inter-individual variations and hemispheric asymmetries. METHODS: Deterministic diffusion tensor imaging-based tractography was used to perform virtual dissection of the IFOF in 20 healthy subjects. The IFOF was probed from a single seed region of interest placed within the external/extreme capsule, i.e. the white matter region of "obligatory passage" along the known path of the IFOF. This enabled to reconstruct all the fibers belonging to the IFOF and to provide the complete map of their cortical terminations. RESULTS: We observed widespread projections over a total of 11 cortical territories within the occipital, parietal, temporal and frontal lobes. Importantly, compared to previous studies we consistently found some inter-individual variability with several distinct patterns connecting subsets of the 11 cortical territories, and tangible differences between the two hemispheres. IFOF terminations within the superior parietal lobule were rightward lateralized, whereas terminations within the inferior frontal gyrus were leftward lateralized. CONCLUSIONS: Our results provide a clinically relevant map of IFOF's cortical terminations, including intra- and inter-individual variations. Right-left differences in connectivity patterns might be related to known functional asymmetries in the human brain, and reinforce the general evidence that the IFOF likely supports distinct clinical features and functional roles according to the (affected) hemisphere, such as language and spatial attention.

Time-course of myelination and atrophy on cerebral imaging in 35 patients with PLP1-related disorders.

AIM: Brain magnetic resonance imaging (MRI) motor development score (MDS) correlations were used to analyze the natural time-course of hypomyelinating PLP1-related disorders (Pelizaeus-Merzbacher disease [PMD] and spastic paraplegia type 2). METHOD: Thirty-five male patients (ranging from 0.7-43.5y at the first MRI) with PLP1-related disorder were prospectively followed over 7 years. Patients were classified according to best motor function acquired before 5 years (MDS) into five categories (from PMD0 without motor acquisition to PMD4 with autonomous walking). We determined myelination and atrophy scores and measured corpus callosum area, volume of cerebellum, white matter and grey matter on 63 MRI. RESULTS: Age-adjusted multivariate analysis revealed that patients with PMD0-1 had higher-severity atrophy scores and smaller corpus callosum area than did patients with PMD2 and PMD3-4. Myelination score increased until 12 years. There was evidence that the mean myelination differed in frontal white matter, arcuate fibres, and internal capsules among the groups. Most patients showed worsening atrophy (brain, cerebellum, corpus callosum), whereas grey matter and white matter proportions did not change. INTERPRETATION: Brain atrophy and myelination of anterior cerebral regions appear to be pertinent biomarkers of motor development. The time-course of inter- and intra-individual cerebral white matter and grey matter atrophy suggests that both oligodendrocytes and neurons are involved in the physiopathology of PLP1-related disorders.

Intraoperative visualisation of language fascicles by diffusion tensor imaging-based tractography in glioma surgery.

BACKGROUND: For gliomas, the goal of surgery is to maximise the extent of resection (EOR) while minimising the postoperative morbidity. The purpose of this study was to evaluate the benefits of a protocol developed for the surgical management of gliomas located in language areas, where tractography-integrated navigation was used in conjunction with direct electrical stimulations (DES). METHODS AND MATERIALS: The authors included ten patients suffering of gliomas located in language areas. The preoperative planning for multimodal navigation was done by integrating anatomical magnetic resonance images and subcortical pathway volumes generated by diffusion tensor imaging. Six white matter fascicles implicated in language functions were reconstructed in each patient, including fibres for phonological processing (i.e. the arcuate fasciculus), fibres for lexical-semantic processing (i.e. the inferior frontooccipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus), and two premotor fasciculi involved in the preparation of speech movements (the subcallosal medialis fasciculus and cortical fibres originating from the medial and lateral premotor areas). During surgery, language fascicles were identified by direct visualisation on tractography-integrated navigation images and by observing transient language inhibition after subcortical DES. Language deficits were evaluated preoperatively and postoperatively, and compared with the EOR. RESULTS: Tractography was successfully performed in all patients, preoperatively demonstrating the relationships between the tumours to resect and the language fascicles to preserve from injury. With the use of the tractography-integrated navigation system and intraoperative DES, language functions were preserved in all patients. The mean volumetric resection was 93.0 ± 10.4 % of the preoperative tumour volume, with a gross total resection in 60 % of patients. CONCLUSION: The intraoperative combination of tractography and DES contributed to maximum safe resection of gliomas located in language areas.

Resting-State Functional Connectivity following Phonological Component Analysis: The Combined Action of Phonology and Visual Orthographic Cues.

Anomia is the most frequent and pervasive symptom for people with aphasia (PWA). Phonological component analysis (PCA) is a therapy incorporating phonological cues to treat anomia. Investigations of neural correlates supporting improvements following PCA remain scarce. Resting-state functional connectivity (rsFC) as a marker of therapy-induced neuroplasticity has been reported by our team. The present study explores the efficacy of PCA in French and associated therapy-induced neuroplasticity using whole-brain rsFC analysis. Ten PWA participated in a pre-/post-PCA fMRI study with cognitive linguistic assessments. PCA was delivered in French following the standard procedure. PCA led to significant improvement with trained and untrained items. PCA also led to changes in rsFC between distributed ROIs in the semantic network, visual network, and sub-cortical areas. Changes in rsFC can be interpreted within the frame of the visual and phonological nature of PCA. Behavioral and rsFC data changes associated with PCA in French highlight its efficacy and point to the importance of phonological and orthographic cues to consolidate the word-retrieval strategy, contributing to generalization to untrained words.

Disrupted Pallido-Thalamo-Cortical Functional Connectivity in Chronic Disorders of Consciousness.

Chronic disorders of consciousness (DOC) encompass unresponsive wakefulness syndrome and minimally conscious state. Their anatomo-functional correlates are not clearly defined yet, although impairments of functional cortical networks have been reported, as well as the implication of the thalamus and deep brain structures. However, the pallidal functional connectivity with the thalamus and the cortical networks has not been studied so far. Using resting-state functional MRI, we conducted a functional connectivity study between the pallidum, the thalamus and the cortical networks in 13 patients with chronic DOC and 19 healthy subjects. We observed in chronic DOC patients that the thalami were no longer connected to the cortical networks, nor to the pallidums. Concerning the functional connectivity of pallidums, we reported an abolition of the negative correlation with the default mode network, and of the positive correlation with the salience network. The disrupted functional connectivity observed in chronic DOC patients between subcortical structures and cortical networks could be related to the mesocircuit model. A better understanding of the DOC underlying physiopathology could provide food for thought for future therapeutic proposals.

Early Deformation of Deep Brain Stimulation Electrodes Following Surgical Implantation: Intracranial, Brain, and Electrode Mechanics.

INTRODUCTION: Although deep brain stimulation is nowadays performed worldwide, the biomechanical aspects of electrode implantation received little attention, mainly as physicians focused on the medical aspects, such as the optimal indication of the surgical procedure, the positive and adverse effects, and the long-term follow-up. We aimed to describe electrode deformations and brain shift immediately after implantation, as it may highlight our comprehension of intracranial and intracerebral mechanics. MATERIALS AND METHODS: Sixty electrodes of 30 patients suffering from severe symptoms of Parkinson's disease and essential tremor were studied. They consisted of 30 non-directional electrodes and 30 directional electrodes, implanted 42 times in the subthalamus and 18 times in the ventrolateral thalamus. We computed the x (transversal), y (anteroposterior), z (depth), torsion, and curvature deformations, along the electrodes from the entrance point in the braincase. The electrodes were modelized from the immediate postoperative CT scan using automatic voxel thresholding segmentation, manual subtraction of artifacts, and automatic skeletonization. The deformation parameters were computed from the curve of electrodes using a third-order polynomial regression. We studied these deformations according to the type of electrodes, the clinical parameters, the surgical-related accuracy, the brain shift, the hemisphere and three tissue layers, the gyration layer, the white matter stem layer, and the deep brain layer (type I error set at 5%). RESULTS: We found that the implanted first hemisphere coupled to the brain shift and the stiffness of the type of electrode impacted on the electrode deformations. The deformations were also different according to the tissue layers, to the electrode type, and to the first-hemisphere-brain-shift effect. CONCLUSION: Our findings provide information on the intracranial and brain biomechanics and should help further developments on intracerebral electrode design and surgical issues.

Risk-Taking Behaviors of Adult Bedridden Patients in Neurosurgery: What Could/Should We Do?

Risk-taking behaviors of adult bedridden patients in neurosurgery are frequent, however little analyzed. We aimed to estimate from the literature and our clinical experience the incidence of the different clinical pictures. Risk-taking behaviors seem to be more frequent than reported. They are often minor, but they can lead to death, irrespective of the prescription of physical or chemical constraints. We also aimed to contextualize the risks, and to describe the means reducing the consequences for the patients. Two main conditions were identified, the loss of awareness of risk-taking behaviors by the patient, and uncontrolled body motions. Besides, current experience feedback analyses and new non-exclusive technological solutions could limit the complications, while improving prevention with wearable systems, neighborhood sensors, or room monitoring and service robots. Further research is mandatory to develop efficient and reliable systems avoiding complications and saving lives. Ethical and legal issues must also be accounted for, notably concerning the privacy of patients and caregivers.

Deep brain stimulation in five patients with severe disorders of consciousness.

OBJECTIVE: The efficacy of deep brain stimulation in disorders of consciousness remains inconclusive. We investigated bilateral 30-Hz low-frequency stimulation designed to overdrive neuronal activity by dual pallido-thalamic targeting, using the Coma Recovery Scale Revised (CRS-R) to assess conscious behavior. METHODS: We conducted a prospective, single center, observational 11-month pilot study comprising four phases: baseline (2 months); surgery and titration (1 month); blind, random, crossover, 1.5-month ON and OFF periods; and unblinded, 5-month stimulation ON. Five adult patients were included: one unresponsive-wakefulness-syndrome male (traumatic brain injury); and four patients in a minimally conscious state, one male (traumatic brain injury) and three females (two hemorrhagic strokes and one traumatic brain injury). Primary outcome measures focused on CRS-R scores. Secondary outcome measures focused notably on baseline brain metabolism and variation in activity (stimulation ON - baseline) using normalized fluorodeoxyglucose positron emission tomography maps. Statistical analysis used random-effect models. RESULTS: The two male patients (one minimally conscious and one unresponsive wakefulness syndrome) showed improved mean CRS-R scores (stimulation ON vs. baseline), in auditory, visual and oromotor/verbal subscores, and visual subscores respectively. The metabolism of the medial cortices (low at baseline in all five patients) increased specifically in the two responders. INTERPRETATION: Our findings show there were robust but limited individual clinical benefits, mainly in visual and auditory processes. Overall modifications seem linked to the modulation of thalamo-cortico-basal and tegmental loops activating default mode network cortices. Specifically, in the two responders there was an increase in medial cortex activity related to internal awareness.

fMRI study of graduated emotional charge for detection of covert activity using passive listening to narratives.

Detection of awareness in patients with consciousness disorders is a challenge that can be facilitated by functional neuroimaging. We elaborated a functional magnetic resonance imaging (fMRI) protocol to detect covert activity in altered states of consciousness. We hypothesized that passive listening to narratives with graduated emotional charge triggers graduated cerebral activations. The fMRI protocol was designed in healthy subjects for further clinical applications. The emotional charge was graduated using voice familiarity and long-term declarative memory content: low emotional charge, unknown person telling general semantic memory; mean emotional charge, relative telling the same narratives; high emotional charge, same relative telling autobiographical memory. Autobiographical memory was subdivided into semantic autobiographical memory and episodic autobiographical memory. The protocol proved efficient at triggering graduated cerebral activations: low emotional charge, superior temporal gyri and sulci; mean emotional charge, same as low emotional charge plus bilateral premotor cortices and left inferior frontal gyrus; high emotional charge, cingulate, temporal, frontal, prefrontal and angular areas, thalamus and cerebellum. Semantic autobiographical memory revealed larger activations than episodic autobiographical memory. Independent ROI analysis confirmed the preponderant contribution of narratives with autobiographical memory content in triggering cerebral activation, not only in autobiographical memory-sensitive areas, but also in voice-sensitive, language-sensitive and semantic memory-sensitive areas.

Combined DTI Tractography and Functional MRI Study of the Language Connectome in Healthy Volunteers: Extensive Mapping of White Matter Fascicles and Cortical Activations.

Despite a better understanding of brain language organization into large-scale cortical networks, the underlying white matter (WM) connectivity is still not mastered. Here we combined diffusion tensor imaging (DTI) fiber tracking (FT) and language functional magnetic resonance imaging (fMRI) in twenty healthy subjects to gain new insights into the macroscopic structural connectivity of language. Eight putative WM fascicles for language were probed using a deterministic DTI-FT technique: the arcuate fascicle (AF), superior longitudinal fascicle (SLF), uncinate fascicle (UF), temporo-occipital fascicle, inferior fronto-occipital fascicle (IFOF), middle longitudinal fascicle (MdLF), frontal aslant fascicle and operculopremotor fascicle. Specific measurements (i.e. volume, length, fractional anisotropy) and precise cortical terminations were derived for each WM fascicle within both hemispheres. Connections between these WM fascicles and fMRI activations were studied to determine which WM fascicles are related to language. WM fascicle volumes showed asymmetries: leftward for the AF, temporoparietal segment of SLF and UF, and rightward for the frontoparietal segment of the SLF. The lateralization of the AF, IFOF and MdLF extended to differences in patterns of anatomical connections, which may relate to specific hemispheric abilities. The leftward asymmetry of the AF was correlated to the leftward asymmetry of fMRI activations, suggesting that the lateralization of the AF is a structural substrate of hemispheric language dominance. We found consistent connections between fMRI activations and terminations of the eight WM fascicles, providing a detailed description of the language connectome. WM fascicle terminations were also observed beyond fMRI-confirmed language areas and reached numerous cortical areas involved in different functional brain networks. These findings suggest that the reported WM fascicles are not exclusively involved in language and might be related to other cognitive functions such as visual recognition, spatial attention, executive functions, memory, and processing of emotional and behavioral aspects.

Maps of the adult human hypothalamus.

The human hypothalamus is a small deeply located region placed at the crossroad of neurovegetative, neuroendocrine, limbic, and optic systems. Although deep brain stimulation techniques have proven that it could be feasible to modulate these systems, targeting the hypothalamus and in particular specific nuclei and white bundles, is still challenging. Our goal was to make a synthesis of relevant topographical data of the human hypothalamus, under the form of magnetic resonance imaging maps useful for mastering its elaborated structure as well as its neighborhood. As from 1.5 Tesla, Inversion-Recovery sequence allows locating the hypothalamus and most of its components. Spotting hypothalamic compartments is possible according to specific landmarks: the anterior commissure, the mammillary bodies, the preoptic recess, the infundibular recess, the crest between the preoptic and the infundibular recesses, the optical tract, the fornix, and the mammillo-thalamic bundle. The identification of hypothalamus and most of its components could be useful to allow the quantification of local pathological processes and to target specific circuitry to alleviate severe symptoms, using physical or biological agents.

Preserved visual recognition memory in an amnesic patient with hippocampal lesions.

There is ongoing debate about whether performance on tests of recognition memory can remain preserved after hippocampal damage. In the present study, we report F.R.G., a patient who became severely amnesic following herpes simplex encephalitis. Although F.R.G. failed all tests involving recall and verbal recognition, she obtained normal performance on a wide number of tests evaluating visual recognition memory (14 of 18 different tests). Her performance was independent of various factors, such as test difficulty, duration of exposure to the stimuli, or delay separating encoding and recognition. F.R.G. also achieved normal performance on two tasks requiring that she associate pairs of visual stimuli. In addition, she demonstrated spared feeling of knowing, suggesting that her performance on recognition tests was explicit and likely to rely on familiarity. Brain imaging (MRI) revealed bilateral lesions of the hippocampus and lesions of the left parahippocampal gyrus, while the right parahippocampal gyrus remained relatively spared. The results of this study support the view that recognition memory can be preserved despite severe hippocampal damage and that familiarity is a distinct memory process that can be dissociated from recollection.

Entorhinal cortex involvement in human mesial temporal lobe epilepsy: an electrophysiologic and volumetric study.

PURPOSE: Several studies have demonstrated diminution in the volume of entorhinal cortex (EC) ipsilateral to the pathologic side in patients with temporal lobe epilepsy (TLE). The relation between the degree of EC atrophy and the epileptogenicity of this structure has never been directly studied. The purpose of the study was to determine whether atrophy of the EC evaluated by the quantitative magnetic resonance imaging (MRI) method is correlated with the epileptogenicity of this structure in TLE. METHODS: Intracerebral recordings (SEEG method) of seizures from 11 patients with mesial TLE were analyzed. Seizures were classified according to patterns of onset: pattern 1 was the emergence of a low-frequency, high-amplitude rhythmic spiking followed by a tonic discharge, and pattern 2 was the emergence of a tonic discharge in the mesial structures. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between hippocampus (Hip) and EC at seizure onset. MRI volumetric analysis was performed by using a T(1)-weighted three-dimensional gradient-echo sequence in TLE patients and 12 healthy subjects. RESULTS: Significant interactions between Hip and Ec were quantified at seizure onset. The EC was found to be the leader structure in most of the pattern 2 seizures. Volumetric measurements of EC demonstrated an atrophy in 63% of patients ipsilateral to the epileptic side. A significant correlation between the strength of EC-Hip coupling and the degree of atrophy was found. In addition, in those patients that had a normal EC volume, the EC was never the leader structure in Ec-Hip coupling. CONCLUSIONS: These results validate the potential role of volumetry to predict the epileptogenesis of the EC in patients with hippocampal sclerosis and MTLE.

Impaired configurational processing in a case of progressive prosopagnosia associated with predominant right temporal lobe atrophy.

F.G., a 71-year-old right-handed man, presented with a slowly progressive deterioration in his ability to recognize faces of familiar and famous persons, contrasting with the relative preservation of other cognitive domains. His primary face perception skills were intact. Along with his face-recognition deficit, F.G. also exhibited a mild visual agnosia. A more detailed analysis of his performance on visuoperceptual tests revealed a selective deficit in retrieving the configurational representation of complex visual entities and an over-reliance on analysing individual features. Quantitative volumetric measurements of his temporal lobe structures showed a prevalent atrophy of the right fusiform gyrus and parahippocampal cortex. The results of the present study suggest that a right temporal variant of frontotemporal lobar degeneration may be characterized over a period of several years by an impaired configurational processing of visually complex entities in the absence of any semantic deficit.