Decoding of path-guided apparent motion from neural ensembles in posterior parietal cortex

We compared quantitatively the psychometric capacity of human subjects to detect path-guided apparent motion (PAM) and the accuracy of cell ensembles in area 7a to code the same type of stimuli. Nine human subjects performed a detection task of PAM. They were instructed to indicate with a key-press whether they perceived a circularly moving object when five stimuli were flashed successively at the vertices of a regular pentagon. The stimuli were presented along a low contrast circular path with one of 33 speeds (150-600°/s). The average psychometric curve revealed that the threshold for PAM detection was 314°/s. The minimum and maximum thresholds for individual subjects were 277° and 378°/s, respectively. In addition, the activity of cells in area 7a that were modulated by the stimulus position in real or apparent motion was used in a multivariate linear regression analysis to recover the stimulus position over time. Real stimulus motion was decoded successfully from neural ensemble activity at all speeds. In contrast, the decoding of PAM was poor at low stimulus speeds but improved markedly above 300°/s: in fact, this was very close to the threshold above for human subjects to perceive continuous stimulus motion in this condition. These results suggest that the posterior parietal cortex is part of a high-level system that is directly involved in the dynamic representation of complex motion. © Springer-Verlag 2004

Cortico-spinal modularity in the parieto-frontal system: a new perspective on action control

: Classical neurophysiology suggests that the motor cortex (MI) has a unique role in action control. In contrast, this review presents evidence for multiple parieto-frontal spinal command modules that can bypass MI. Five observations support this modular perspective: (i) the statistics of cortical connectivity demonstrate functionally-related clusters of cortical areas, defining functional modules in the premotor, cingulate, and parietal cortices; (ii) different corticospinal pathways originate from the above areas, each with a distinct range of conduction velocities; (iii) the activation time of each module varies depending on task, and different modules can be activated simultaneously; (iv) a modular architecture with direct motor output is faster and less metabolically expensive than an architecture that relies on MI, given the slow connections between MI and other cortical areas; (v) lesions of the areas composing parieto-frontal modules have different effects from lesions of MI. Here we provide examples of six cortico-spinal modules and functions they subserve: module 1) arm reaching, tool use and object construction; module 2) spatial navigation and locomotion; module 3) grasping and observation of hand and mouth actions; module 4) action initiation, motor sequences, time encoding; module 5) conditional motor association and learning, action plan switching and action inhibition; module 6) planning defensive actions. These modules can serve as a library of tools to be recombined when faced with novel tasks, and MI might serve as a recombinatory hub. In conclusion, the availability of locally-stored information and multiple outflow paths supports the physiological plausibility of the proposed modular perspective

A cortical mechanism linking saliency detection and motor reactivity in rhesus monkeys

: Sudden and surprising sensory events trigger neural processes that swiftly adjust behavior. To study the phylogenesis and the mechanism of this phenomenon, we trained two male rhesus monkeys to keep a cursor inside a visual target by exerting force on an isometric joystick. We examined the effect of surprising auditory stimuli on exerted force, scalp electroencephalographic (EEG) activity, and local field potentials (LFP) recorded from the dorso-lateral prefrontal cortex. Auditory stimuli elicited (1) a biphasic modulation of isometric force: a transient decrease followed by a corrective tonic increase, and (2) EEG and LFP deflections dominated by two large negative-positive waves (N70 and P130). The EEG potential was maximal at the scalp vertex, highly reminiscent of the human 'vertex potential'. Electrocortical potentials and force were tightly coupled: the P130 amplitude predicted the magnitude of the corrective force increase, particularly in the LFPs recorded from deep rather than superficial cortical layers. These results disclose a phylogenetically-preserved cortico-motor mechanism supporting adaptive behavior in response to salient sensory events.Significance Statement Survival in the natural world depends on an animal's capacity to adapt ongoing behavior to unexpected events. To study the neural mechanisms underlying this capacity, we trained monkeys to apply constant force on a joystick while we recorded their brain activity from the scalp and, invasively, from the prefrontal cortex contralateral to the hand holding the joystick. Unexpected auditory stimuli elicited a biphasic force modulation: a transient reduction followed by a corrective adjustment. The same stimuli also elicited EEG and LFP responses, dominated by a biphasic wave that predicted the magnitude of the behavioral adjustment. These results disclose a phylogenetically-preserved cortico-motor mechanism supporting adaptive behavior in response to unexpected events

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

A Brief History of the Encoding of Hand Position by the Cerebral Cortex: Implications for Motor Control and Cognition

Encoding hand position by the cerebral cortex is essential not only for the neural representation of the body image but also for different actions based on eye-hand coordination. These include reaching for visual objects as well as complex movement sequences, such as tea-making, tool use, and object construction, among many others. All these functions depend on a continuous refreshing of the hand position representation, relying on both predictive signaling and afferent information. The hand position influence on neural activity in the parietofrontal system, together with eye position signals, are the basic elements of an eye-hand matrix from which all the above functions can emerge and could be regarded as key features of a network with several entry points, command nodes and outflow pathways, as confirmed by the discovery of a direct parietospinal projection for the control of hand action. The integrity of this system is crucial for daily life, as testified by the consequences of cortical lesions, spanning from severe paralysis to complex forms of apraxia. In this review, I will sketch my personal understanding of the scientific and conceptual trajectory of a line of investigation with many unexpected influences on cortical function and disease, from motor behavior to cognition

Parieto-frontal networks for eye–hand coordination and movements

Eye-hand coordination lies at the core of our daily actions and interactions with objects and people around us, and is central to understanding how the brain creates internal models of the action space and generates movement within it. Eye-hand coordination remains a very complex and elusive problem, which is further complicated by its distributed representation in the brain. In fact, evolution did not confine such a crucial function to a single area, but rather assigned it to several distributed cortical and subcortical systems, where encoding mechanisms can satisfy multiple demands and the consequences of lesions are less disruptive. We will discuss evidence suggesting that eye-hand coordination is, indeed, an emerging function of internal parietal operations and of their interplay with frontal cortex, where the cortical eye and hand motor output domains reside. Therefore, coordination of eye and hand movements requires an appropriate spatiotemporal activation of the subcortical structures which control the eyes and hand. In this distributed network, information transfer between different cortical areas and with subcortical structures is based on temporally dispersed communication patterns

Optic ataxia as result of the breakdown of the global tuning fields of parietal neurons

Optic ataxia is characterized by an impaired visual control of the direction of arm reaching to a visual target, accompanied by defective hand orientation and grip formation. In humans, optic ataxia is associated with lesions of the superior parietal lobule (SPL), which also affect visually guided saccades and other forms of eye-hand coordination. In the last 10 years, anatomical and physiological studies of the SPL have shed new light on the role of parietal cortex in the control of combined eye-hand movements to visual targets, and on the underlying distributed network which links parietal to frontal cortex. A main emerging functional feature of SPL neurones seems to be their capacity to combine, in a spatially congruent fashion, different directional eye- and hand-related information, that any coding scheme so far proposed, considers essential for the composition of motor commands for reaching. This integration occurs within the global tuning field of parietal neurones, is context-dependent and involves eye and hand information that shares the same directional properties. Depending on task demands, this integration of signals can result in the representation of different reference frames for coordinated eye-hand movements. The dynamic operations occurring within the global tuning fields might depend, at least in part, on the reciprocal sets of association connections linking the SPL and the premotor areas of the frontal lobe. From this picture, the SPL emerges as both a main source of visual input to the frontal cortex and a key structure for visuomotor integration based on re-entrant signalling and, therefore, as a crucial node in the visual control of movement. It is hypothesized that in parietal patients, the directional errors that characterize reaching are a consequence of the breakdown of the combination of directional eye and hand information within the global tuning fields of parietal neurones. In these patients, the spatial match among information about target location, eye and hand position, and movement direction would be prevented, so as to impair the composition of visually guided eye-hand movements. This breakdown could be dependent, at least in part, on the failure of a re-entrant frontoparietal signalling, an obvious consequence of the degeneration of the cortico-cortical systems linking parietal and frontal cortex. Cortico-cortical connections are, in fact, essential for shaping the dynamic properties of cortical neurones

The parietal lobe evolution and the emergence of material culture in the human genus

Traditional and new disciplines converge in suggesting that the parietal lobe underwent a considerable expansion during human evolution. Through the study of endocasts and shape analysis, paleoneurology has shown an increased globularity of the braincase and bulging of the parietal region in modern humans, as compared to other human species, including Neandertals. Cortical complexity increased in both the superior and inferior parietal lobules. Emerging fields bridging archaeology and neuroscience supply further evidence of the involvement of the parietal cortex in human-specific behaviors related to visuospatial capacity, technological integration, self-awareness, numerosity, mathematical reasoning and language. Here, we complement these inferences on the parietal lobe evolution, with results from more classical neuroscience disciplines, such as behavioral neurophysiology, functional neuroimaging, and brain lesions; and apply these to define the neural substrates and the role of the parietal lobes in the emergence of functions at the core of material culture, such as tool-making, tool use and constructional abilities