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Identification of the human medial temporal lobe regions on magnetic resonance images

The medial temporal lobe (MTL) plays a key role in learning, memory, spatial navigation, emotion, and social behavior. The improvement of noninvasive neuroimaging techniques, especially magnetic resonance imaging, has increased the knowledge about this region and its involvement in cognitive functions and behavior in healthy subjects and in patients with various neuropsychiatric and neurodegenerative disorders. However, cytoarchitectonic boundaries are not visible on magnetic resonance images (MRI), which makes it difficult to identify precisely the different parts of the MTL (hippocampus, amygdala, temporopolar, perirhinal, entorhinal, and posterior parahippocampal cortices) with imaging techniques, and thus to determine their involvement in normal and pathological functions. Our aim in this study was to define neuroanatomical landmarks visible on MRI, which can facilitate the examination of this region. We examined the boundaries of the MTL regions in 50 post‐mortem brains. In eight cases, we also obtained post‐mortem MRI on which the MTL boundaries were compared with histological examination before applying them to 26 in vivo MRI of healthy adults. We then defined the most relevant neuroanatomical landmarks that set the rostro‐caudal limits of the MTL structures, and we describe a protocol to identify each of these structures on coronal T1‐weighted MRI. This will help the structural and functional imaging investigations of the MTL in various neuropsychiatric and neurodegenerative disorders affecting this region. Hum Brain Mapp 35:248–256, 2014.

Dissociable neural effects of long-term stimulus-reward pairing in macaque visual cortex

It has been proposed that perceptual learning may occur through a reinforcement process, in which consistently pairing stimuli with reward is sufficient for learning. We tested whether stimulus–reward pairing is sufficient to increase the sensorial representation of a stimulus by recording local field potentials (LFPs) in macaque extrastriate area V4 with chronically implanted electrodes. Two oriented gratings were repeatedly presented; one was paired with a fluid reward, whereas no reward was given at any other time. During the course of conditioning the LFP increased for the rewarded compared to the unrewarded orientation. The time course of the effect of stimulus–reward pairing and its reversal differed between an early and late interval of the LFP response: a fast change in the later part of the neural response that was dissociated from a slower change in the early part of the response. The fast change of the late interval LFP suggests that this late LFP change is related to enhanced attention during the presentation of the rewarded stimulus. The slower time course of the early interval response suggests an effect of sensorial learning. Thus, simple stimulus–reward pairing is sufficient to strengthen stimulus representations in visual cortex and does this by means of two dissociable mechanisms.

Evaluating Alzheimer's disease progression using rate of regional hippocampal atrophy.

Alzheimer’s disease (AD) is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI) and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects.

The representation of Kanizsa illusory contours in the monkey inferior temporal cortex.

Stimulus reduction is an effective way to study visual performance. Cues such as surface characteristics, colour and inner lines can be removed from stimuli, revealing how the change affects recognition and neural processing. An extreme reduction is the removal of the very stimulus, defining it with illusory lines. Perceived boundaries without physical differences between shape and background are called illusory (or subjective) contours. Illusory and real contours activate early stages of the macaque visual pathway in similar ways. However, data relating to the processing of illusory contours in higher visual areas are scarce. We recently reported how illusory contours based on abutting‐line gratings affect neurones in the monkey inferotemporal cortex, an area essential for object and shape vision. We now present data on how inferotemporal cortical neurones of monkeys react to another type of shapes, the Kanizsa figures. A set of line drawings, silhouettes, their illusory contour‐based counterparts, and control shapes have been presented to awake, fixating rhesus monkeys while single‐cell activity was recorded in the anterior part of the inferotemporal cortex. Most of the recorded neurones were responsive and selective to shapes presented as illusory contours. Shape selectivity was proved to be different for line drawings and illusory contours, and also for silhouettes and illusory contours. Neuronal response latencies for Kanizsa figures were significantly longer than those for line drawings and silhouettes. These results reveal differences in processing for Kanizsa figures and shapes having real contours in the monkey inferotemporal cortex.

Neuroimaging of amblyopia and binocular vision: a review

Amblyopia is a cerebral visual impairment considered to derive from abnormal visual experience (e.g., strabismus, anisometropia). Amblyopia, first considered as a monocular disorder, is now often seen as a primarily binocular disorder resulting in more and more studies examining the binocular deficits in the patients. The neural mechanisms of amblyopia are not completely understood even though they have been investigated with electrophysiological recordings in animal models and more recently with neuroimaging techniques in humans. In this review, we summarize the current knowledge about the brain regions that underlie the visual deficits associated with amblyopia with a focus on binocular vision using functional magnetic resonance imaging. The first studies focused on abnormal responses in the primary and secondary visual areas whereas recent evidence shows that there are also deficits at higher levels of the visual pathways within the parieto-occipital and temporal cortices. These higher level areas are part of the cortical network involved in 3D vision from binocular cues. Therefore, reduced responses in these areas could be related to the impaired binocular vision in amblyopic patients. Promising new binocular treatments might at least partially correct the activation in these areas. Future neuroimaging experiments could help to characterize the brain response changes associated with these treatments and help devise them.

A new approach to corpus callosum anomalies in idiopathic scoliosis using diffusion tensor magnetic resonance imaging.

PurposeIdiopathic scoliosis (IS) is a frequent 3D structural deformity of the spine with a multi-factorial aetiology which remains largely unclear. In the last decade, human magnetic resonance imaging (MRI) morphometry studies (e.g. cortical thickness, 2D shape of the corpus callosum) have aimed to investigate the potential contribution of the central nervous system in the etiopathogenesis of IS. Recent developments in diffusion tensor imaging (DTI) allow us to extend the previous work to the study of white matter microstructure. Here, we hypothesized that part of the corpus callosum could show a difference in white matter microstructure in IS patients as compared to healthy controls.MethodsWe acquired DTI in 10 girls with IS and in 49 gender-matched controls to quantify the fractional anisotropy (FA) along the corpus callosum.ResultsDespite a very similar pattern of FA along the corpus callosum (maxima in the splenium and the genu and minimum in the isthmus), we found a significantly lower FA in the body in patients with IS as compared to control subjects. This region is known to connect the motor and premotor cortices of the two hemispheres.ConclusionThis first diffusion magnetic resonance imaging brain study in IS patients, suggests that differences in white matter development, such as synchronization of axonal myelination and pruning could be involved in the etiopathogenesis of IS.

Clinical Trial Simulations Based on Genetic Stratification and the Natural History of a Functional Outcome Measure in Creutzfeldt-Jakob Disease.

IMPORTANCE A major challenge for drug development in neurodegenerative diseases is that adequately powered efficacy studies with meaningful end points typically require several hundred participants and long durations. Prion diseases represent the archetype of brain diseases caused by protein misfolding, the most common subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. There is no well-established trial method in prion disease. OBJECTIVE To establish a more powerful and meaningful clinical trial method in sCJD. DESIGN, SETTING, AND PARTICIPANTS A stratified medicine and simulation approach based on a prospective interval-cohort study conducted from October 2008 to June 2014. This study involved 598 participants with probable or definite sCJD followed up over 470 patient-years at a specialist national referral service in the United Kingdom with domiciliary, care home, and hospital patient visits. We fitted linear mixed models to the outcome measurements, and simulated clinical trials involving 10 to 120 patients (no dropouts) with early to moderately advanced prion disease using model parameters to compare the power of various designs. MAIN OUTCOMES AND MEASURES A total of 2681 assessments were done using a functionally orientated composite end point (Medical Research Council Scale) and associated with clinical investigations (brain magnetic resonance imaging, electroencephalography, and cerebrospinal fluid analysis) and molecular data (prion protein [PrP] gene sequencing, PrPSc type). RESULTS Of the 598 participants, 273 were men. The PrP gene sequence was significantly associated with decline relative to any other demographic or investigation factors. Patients with sCJD and polymorphic codon 129 genotypes MM, VV, and MV lost 10% of their function in 5.3 (95% CI, 4.2-6.9), 13.2 (95% CI, 10.9-16.6), and 27.8 (95% CI, 21.9-37.8) days, respectively (P < .001). Simulations indicate that an adequately powered (80%; 2-sided α = .05) open-label randomized trial using 50% reduction in Medical Research Council Scale decline as the primary outcome could be conducted with only 120 participants assessed every 10 days and only 90 participants assessed daily, providing considerably more power than using survival as the primary outcome. Restricting to VV or MV codon 129 genotypes increased power even further. Alternatively, single-arm intervention studies (half the total sample size) could provide similar power in comparison to the natural history cohort. CONCLUSIONS AND RELEVANCE Functional end points in neurodegeneration need not require long and very large clinical studies to be adequately powered for efficacy. Patients with sCJD may be an efficient and cost-effective group for testing disease-modifying therapeutics. Stratified medicine and natural history cohort approaches may transform the feasibility of clinical trials in orphan diseases.

Reply to the letter to the editor of J. Domenech et al. concerning "A new approach to corpus callosum anomalies in idiopathic scoliosis using diffusion tensor magnetic resonance imaging" by O. Joly et al. (2014) Eur Spine J; 23:2643-9.

We appreciate the well-advised comments on our paper on a new approach to corpus callosum anomalies in idiopathic scoliosis (IS) using diffusion tensor imaging (DTI). These comments emphasise three important methodological issues that are legitimate, all of them discussed during the reviewing process. Unfortunately, it seems they do not appear clearly in the final version of our manuscript. The first issue refers to the differences in scanning protocols (including field strength) applied to the IS patients and controls (database), the second refers to the age and sample size of our patient population and the third concerns the diagnosis of our (youngest) IS patients. We would like to use this opportunity to clarify and address these issues.