Past events

Hierarchy provides a major conceptual framework for understanding structure-function relationships of the cortex (Felleman and Van Essen, Cerb Cortex 1991). Feedforward (rostral directed) projections link areas in an ascending series and have a driving influence; feedback (caudal directed) projections link areas in a descending series and have a modulatory influence. This has led to the suggestion that feedforward projections are uniquely reciprocated by feedback projections i.e no strong loops (Crick and Koch, Nature 1998). We have re-examined this issue by making retrograde tracer injections in 22 areas spanning the occipital, parietal, temporal and frontal lobes. Injections were placed in areas V1, V2, V4 TEO, STPa, STPm, STPp, AudPba, AudPbp, 5, 7a, 7b, F1, 2, 8a, 45b, 9/46d, 9/46v, 46d, F5, ProM, 24c. High frequency sampling allows determination of indices of laminar distribution (SLN) and the relative strength (FLN) of connections (Vezoli et al., The Neuroscientist 2004). Analysis shows an inverse relationship between strength of connection and distance and revealed many (30%) hitherto unknown long-distance connections. Elsewhere we have shown that cortico-cortical projections form a smooth gradient: long-distance ascending connections are strongly feedforward (high SLN XX 100%) and on approaching the injection site have progressively lower SLN values (reaching 51%); likewise long-distance descending connections are strongly feedback (low SLN XX 0) and approaching the injection site reduce SLN 49% (Barone and Kennedy, J. Neurosci. 2000). The Felleman and Van Essen data is strictly hierarchical (no strong loops). A topological model of our data shows small world features (high cluster index and short average path distances) and five strong loops. Strong loops link frontal areas with occipital (areas 45-V4, 8A-V4), temporal (areas 45-TEO, 46-TEO) and parietal (areas 8A-7A, 46-7A) areas. The areas participating in strong loops exhibit high degrees of connectivity and constitute the hubs promoting small world attributes in the cortical architecture. The strong loops make it possible to go from V4 to all higher areas and back to V4 by uniqely feedforward pathways in an average of 3 and a maximum of 8 steps. One consequence of these anti-hierarchical connections is that the computations carried out in the supragranular layers of the cortex (Douglas and Martin, Annual Rev Neurosci. 2004) can be widely distributed in large-scale cortical networks mediating top-down control.

We are interested in how the nervous system controls movements based on sensory-cued spatial choices. To this end, we have been studying how rats use olfactory stimuli to select, initiate, execute, and evaluate directional movements. We reasoned that the superior colliculus (SC), a midbrain structure, could play a critical role in these processes, since it is known to be involved in several species in processing sensory input and producing orienting movements. We tested this idea by using tetrodes to record simultaneously from several single neurons in the SC of rats performing a sensory-guided spatial choice task. In this task, an odor cue delivered at a central port determines whether water will be delivered upon entry into the left or right reward port. After sampling the odor, a well-trained rat will, in one fluid movement, withdraw from the odor port, orient left or right, and enter the selected reward port. This task thus requires that a freely moving animal make a spatial choice, while also affording reliable timing of task events and a large number of trials. In this context, not only did a substantial majority of SC neurons encode choice direction during a goal-directed movement, but many also predicted the upcoming choice, maintained selectivity for it after movement completion, or represented the trial outcome. In order to determine whether the observed neural activity is causally related to the movement, we used the GABAA agonist muscimol to unilaterally inactivate the SC in rats performing the spatial choice task. If SC output were necessary for initiating contralateral movements, we would expect inactivation to bias the rat towards ipsilateral choices. Indeed, we found that muscimol, but not saline, biased the rat ipsilaterally, and this bias was dosage-dependent. Our results demonstrate that the SC provides a rich representation of information relevant for several aspects of the control of orienting movements. These representations are necessary for executing appropriate movements. Together, these findings suggest a general role for the SC in behavior requiring sensory-guided navigation.

Recently, a unique population of neurons in the monkey ventral pre-motor cortex and in the rostral inferior parietal lobe, have been shown to respond during both execution of a goal-directed action and the perception of a goal-directed action performed by someone else. Since the activity of these motor neurons ‘reflects’ the perceived actions, these neurons have been termed mirror neurons. Due to their unique response properties, these neurons have been implicated in various behaviors such as imitation and empathy. Moreover, a dysfunction of this neural system has been implicated in various disorders such as autism. In humans, there is accumulating evidence from various techniques, supporting the existence of a parallel mirror neuron system however direct evidence is still lacking. We recorded extra-cellular activity of single neurons in medial pre-frontal and medial temporal regions of 23 epileptic patients while performing and observing hand movements and facial gestures. We found that 13.5% of the recorded neurons in both frontal and temporal lobes exhibited visuo-motor mirror properties. A subset of these mirror neurons responded with excitation action-observation and inhibition to action-execution suggesting a possible mechanism for inhibition of unwanted imitation. Our data supports a revision of the current definition of mirror neurons to include not only motor neurons that respond also to the perception of actions performed by others but also perceptual neurons in temporal lobe, responding to actions performed by oneself.

This is a review of measurements made mostly at the MIT Biomag Lab during the period of 1969 to 1983, partly in collaboration with Prof. Yoram Palti. These measurements are usually unique, in that their current sources are difficult to be seen with electric potentials. They are timely today because the new multi-channel SQUID systems are now being made capable of measuring DC fields from the head (and other organs). Our measurements were essentially a mapping over the whole body. DC fields were found almost everywhere, from many internal sources. They were larger over the limbs and head than over the torso proper, except over the abdomen, where it was largest. Over the head, there were puzzling signals from vicinity of healthy hair follicles, suggesting that so-called neural sources of the dcMEG could be overshadowed by more superficial sources. One major mechanism for generating these fields generally appeared to be a change in the K+ concentration in the vicinity of long excitable fibers. Overall, we concluded that DC fields are a rich and complex phenomena, including the dcMEG.

It is well established that faces are processed by specialized mechanisms. I will first review evidence for the existence of face-specific processing mechanisms from cognitive studies, functional MRI and electrophysiology (Event-related potentials). These methods provide complementary information about the way information is processed in the brain. It is therefore important to determine whether they all reflect the same mechanism. Our data show that face-selective fMRI markers are strongly associated with cognitive markers of face-selective mechanisms. Furthermore, a simultaneous fMRI-ERP study reveals strong associations between face-selective fMRI regions and event-related potentials. Based on these findings, I will propose an integrated theory on how, where and when faces are represented at early stages of visual processing.

In honeybees (Apis mellifera) natural plasticity in circadian rhythms is associated with the division of labor that organizes their colonies. "Nurse" bees (typically < 2 weeks old) care for brood around-the-clock whereas bees older than 3 weeks of age typically forage for flowers with strong circadian rhythms. We found that nurses care for brood around-the-clock even under a light/dark illumination regime. Brain oscillations in the abundance of the putative clock genes Period and Cryptochrom-m were attenuated or totally suppressed in nurses as compared to foragers, irrespective of the illumination regime. However, nurses showed circadian rhythms in locomotor activity and molecular oscillations in brain clock gene expression shortly after transfer from the hive to constant laboratory conditions. The onset of their activity occurred at the subjective morning, suggesting that some clock components were entrained even while in the hive and active around-the-clock. These results suggest that the hive environment induces reorganization of the molecular clockwork. To test this hypothesis, we studied activity and brain clock gene expression in young bees that were confined to a broodless area on the honeycomb in a light/ dark illuminated observation hive. These bees experienced the hive environment and could interact with other bees, but not with the brood. By contrast to same-age nurses from these colonies, the confined bees showed molecular oscillations in clock gene expression and were more active during the day. These findings are consistent with the hypothesis that interactions with the brood modulate plasticity in the molecular clockwork of the honeybee. These findings together with our previous research, suggest the evolution of sociality shaped the bee clock in a way that facilitate integration of individuals into a complex society.

Medication discovery and development for the treatment of addictive diseases has focused for many decades on so-called 'substitution' therapies such as methadone for opiate addiction and the nicotine patch or nicotine chewing gum for nicotine addiction. Recent developments in understanding the underlying neurobiology of addiction, craving, and relapse now augur to revolutionize such medication discovery and development. It has long been understood that the meso-accumbens dopamine circuitry of the ventral mesolimbic midbrain and forebrain plays a crucial role in the acutely euphoric 'high' or 'rush' or 'blast' produced by addictive drugs. More recently, it has come to be understood that this brain circuitry is also critically involved in mediating drug craving and relapse to drug-seeking behavior. The dopamine D3 receptor is a remarkable neurotransmitter receptor in the brain. It exists virtually only in those dopaminergic circuits known to mediate drug-induced reward, drug craving, and relapse to drug-seeking behavior. Moreover, blockade of the D3 receptor enhances dopaminergic tone in those circuits. If drug addiction is - to some degree &#8211; a 'reward deficiency' disease, as postulated by many workers in addiction medicine, enhancing dopaminergic tone in these circuits could be therapeutic. This lecture will focus on a lengthy series of experiments- using animal models of addiction - that suggest that highly-selective dopamine D3 receptor antagonists show remarkable therapeutic potential as anti-addiction, anti-craving, and anti-relapse medications."