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- The alleged existence of partially oxidized Mg[Pt(CN)4]Cl0.28.7H2O and the attempted preparation of the analogous beryllium(2+) and barium(2+) derivatives. A caveatKoch, Timothy R.; Gebert, E.; Williams, Jack M. (American Chemical Society, 1976-06)
- X-ray diffuse scattering of one-dimensional tetracyanoplatinate saltsSchultz, A. J.; Stucky, G. D.; Williams, Jack M.; Koch, Timothy R.; Maffly, R. L. (Elsevier, 1977-01)
- Structural studies of precursor and partially oxidized conducting complexes. II. A neutron diffraction study of disodium dibromotetracyanoplatinate dihydrateMaffly, Robert L.; Johnson, Paul L.; Koch, Timothy R.; Williams, Jack M. (International Union of Crystallography, 1977-02-01)
- Structural studies of precursor and partially oxidized conducting complexes. VI. A neutron diffraction study of dicesium tetracyanoplatinate(II) monohydrateJohnson, Paul L.; Koch, Timothy R.; Williams, Jack M. (International Union of Crystallography, 1977-04-15)
- Structural studies of precursor and partially oxidized conducting complexes. VII. A neutron diffraction study of disodium tetracyanoplatinate(II) trihydrateJohnson, Paul L.; Koch, Timothy R.; Williams, Jack M. (International Union of Crystallography, 1977-06-01)
- Structural studies of precursor and partially oxidized conducting complexes. XI. A neutron diffraction study of barium dibromotetracyanoplatinate(IV) hydrateKoch, Timothy R.; Johnson, Paul L.; Washecheck, Donald M.; Cornish, Thomas L.; Williams, Jack M. (International Union of Crystallography, 1977-10-01)
- Dendritic Spikes and Their Influence on Extracellular Calcium SignalingWiest, Michael C.; Eagleman, David M.; King, Richard D.; Montague, P. Read (American Physiological Society, 2000)Extracellular calcium is critical for many neural functions, including neurotransmission, cell adhesion, and neural plasticity. Experiments have shown that normal neural activity is associated with changes in extracellular calcium, which has motivated recent computational work that employs such fluctuations in an information-bearing role. This possibility suggests that a new style of computing is taking place in the mammalian brain in addition to current ‘circuit’ models that use only neurons and connections. Previous computational models of rapid external calcium changes used only rough approximations of calcium channel dynamics to compute the expected calcium decrements in the extracellular space. Using realistic calcium channel models, experimentally measured back-propagating action potentials, and a model of the extracellular space, we computed the fluctuations in external calcium that accrue during neural activity. In this realistic setting, we showed that rapid, significant changes in local external calcium can occur when dendrites are invaded by back-propagating spikes, even in the presence of an extracellular calcium buffer. We further showed how different geometric arrangements of calcium channels or dendrites prolong or amplify these fluctuations. Finally, we computed the influence of experimentally measured synaptic input on peridendritic calcium fluctuations. Remarkably, appropriately timed synaptic input can amplify significantly the decrement in external calcium. The model shows that the extracellular space and the calcium channels that access it provide a medium that naturally integrates coincident spike activity from different dendrites that intersect the same tissue volume.
- LTD Induction in Adult Visual Cortex: Role of Stimulus Timing and InhibitionPerrett, Stephen P.; Dudek, Serena M.; Eagleman, David M.; Montague, P. Read; Friedlander, Michael J. (Society for Neuroscience, 2001-04-01)One Hertz stimulation of afferents for 15 min with constant interstimulus intervals (regular stimulation) can induce longterm depression (LTD) of synaptic strength in the neocortex. However, it is unknown whether natural patterns of lowfrequency afferent spike activity induce LTD. Although neurons in the neocortex can fire at overall rates as low as 1 Hz, the intervals between spikes are irregular. This irregular spike activity (and thus, presumably, irregular activation of the synapses of that neuron onto postsynaptic targets) can be approximated by stimulation with Poisson-distributed interstimulus intervals (Poisson stimulation). Therefore, if low-frequency presynaptic spike activity in the intact neocortex is sufficient to induce a generalized LTD of synaptic transmission, then Poisson stimulation, which mimics this spike activity, should induce LTD in slices. We tested this hypothesis by comparing changes in the strength of synapses onto layer 2/3 pyramidal cells induced by regular and Poisson stimulation in slices from adult visual cortex. We find that regular stimulation induces LTD of excitatory synaptic transmission as assessed by field potentials and intracellular postsynaptic potentials (PSPs) with inhibition absent. However, Poisson stimulation does not induce a net LTD of excitatory synaptic transmission. When the PSP contained an inhibitory component, neither Poisson nor regular stimulation induced LTD. We propose that the short bursts of synaptic activity that occur during a Poisson train have potentiating effects that offset the induction of LTD that is favored with regular stimulation. Thus, natural (i.e., irregular) low-frequency activity in the adult neocortex in vivo should not consistently induce LTD.
- Predictability Modulates Human Brain Response to RewardBerns, Gregory S.; McClure, Samuel M.; Pagnoni, Giuseppe; Montague, P. Read (Society for Neuroscience, 2001-04-15)Certain classes of stimuli, such as food and drugs, are highly effective in activating reward regions. We show in humans that activity in these regions can be modulated by the predictability of the sequenced delivery of two mildly pleasurable stimuli, orally delivered fruit juice and water. Using functional magnetic resonance imaging, the activity for rewarding stimuli in both the nucleus accumbens and medial orbitofrontal cortex was greatest when the stimuli were unpredictable. Moreover, the subjects’ stated preference for either juice or water was not directly correlated with activity in reward regions but instead was correlated with activity in sensorimotor cortex. For pleasurable stimuli, these findings suggest that predictability modulates the response of human reward regions, and subjective preference can be dissociated from this response.
- When Things Are Better or Worse than Expected: The Medial Frontal Cortex and the Allocation of Processing ResourcesPotts, Geoffrey F.; Martin, Laura E.; Burton, Philip; Montague, P. Read (MIT, 2006)Access to limited-capacity neural systems of cognitive control must be restricted to the most relevant information. How the brain identifies and selects items for preferential processing is not fully understood. Anatomical models often place the selection mechanism in the medial frontal cortex (MFC), and one computational model proposes that the mesotelencephalic dopamine (DA) system, via its reward prediction properties, provides a ‘‘gate’’ through which information gains access to limited-capacity systems. There is a medial frontal eventrelated potential (ERP) index of attention selection, the anterior positivity (P2a), associated with DA reward system input to the MFC for the identification of task-relevant perceptual representations. The P2a has a similar spatio-temporal distribution as the medial frontal negativity (MFN), elicited to error responses or choices resulting in monetary loss. The MFN has also been linked to DA projections to the MFC but for action monitoring rather than attention selection. This study proposes that the P2a and the MFN reflect the same MFC evaluation function and use a passive reward prediction design containing neither instructed attention nor response to demonstrate that the ERP over medial frontal leads at the P2a/MFN latency is consistent with activity of midbrain DA neurons, positive to unpredicted rewards and negative when a predicted reward is withheld. This result suggests that MFC activity is regulated by DA reward system input and may function to identify items or actions that exceed or fail to meet motivational prediction.
- Policy Adjustment in a Dynamic Economic GameLi, Jian; McClure, Samuel M.; Casas, Brooks; Montague, P. Read (PLOS, 2006-12)Making sequential decisions to harvest rewards is a notoriously difficult problem. One difficulty is that the real world is not stationary and the reward expected from a contemplated action may depend in complex ways on the history of an animal’s choices. Previous functional neuroimaging work combined with principled models has detected brain responses that correlate with computations thought to guide simple learning and action choice. Those works generally employed instrumental conditioning tasks with fixed action-reward contingencies. For real-world learning problems, the history of reward-harvesting choices can change the likelihood of rewards collected by the same choices in the near-term future. We used functional MRI to probe brain and behavioral responses in a continuous decision-making task where reward contingency is a function of both a subject’s immediate choice and his choice history. In these more complex tasks, we demonstrated that a simple actor-critic model can account for both the subjects’ behavioral and brain responses, and identified a reward prediction error signal in ventral striatal structures active during these non-stationary decision tasks. However, a sudden introduction of new reward structures engages more complex control circuitry in the prefrontal cortex (inferior frontal gyrus and anterior insula) and is not captured by a simple actor-critic model. Taken together, these results extend our knowledge of reward-learning signals into more complex, history-dependent choice tasks. They also highlight the important interplay between striatum and prefrontal cortex as decision-makers respond to the strategic demands imposed by non-stationary reward environments more reminiscent of real-world tasks.
- Neural signature of fictive learning signals in a sequential investment taskLohrenz, Terry; McCabe, Kevin; Camerer, Colin F.; Montague, P. Read (NAS, 2007-04-13)Reinforcement learning models now provide principled guides for a wide range of reward learning experiments in animals and humans. One key learning (error) signal in these models is experiential and reports ongoing temporal differences between expected and experienced reward. However, these same abstract learning models also accommodate the existence of another class of learning signal that takes the form of a fictive error encoding ongoing differences between experienced returns and returns that ‘‘could-have-been-experienced’’ if decisions had been different. These observations suggest the hypothesis that, for all real-world learning tasks, one should expect the presence of both experiential and fictive learning signals. Motivated by this possibility, we used a sequential investment game and fMRI to probe ongoing brain responses to both experiential and fictive learning signals generated throughout the game. Using a large cohort of subjects (n 54), we report that fictive learning signals strongly predict changes in subjects’ investment behavior and correlate with fMRI signals measured in dopaminoceptive structures known to be involved in valuation and choice.
- Molecular mechanisms of experience-dependent plasticity in visual cortexVan Wart, Audra; Tropea, Daniela; Sur, Mriganka (Royal Society, 2008)A remarkable amount of our current knowledge of mechanisms underlying experience-dependent plasticity during cortical development comes from study of the mammalian visual cortex. Recent advances in high-resolution cellular imaging, combined with genetic manipulations in mice, novel fluorescent recombinant probes, and large-scale screens of gene expression, have revealed multiple molecular mechanisms that underlie structural and functional plasticity in visual cortex. We situate these mechanisms in the context of a new conceptual framework of feed-forward and feedback regulation for understanding how neurons of the visual cortex reorganize their connections in response to changes in sensory inputs. Such conceptual advances have important implications for understanding not only normal development but also pathological conditions that afflict the central nervous system.
- Gene expression patterns in visual cortex during the critical period: Synaptic stabilization and reversal by visual deprivationVan Wart, Audra; Lyckman, Alvin W.; Horng, Sam; Leamey, Catherine A.; Tropea, Daniela; Watakabe, Akiya; McCurry, Cortina; Yamamori, Tetsuo; Sur, Mriganka (National Academy of Sciences, 2008-07)The mapping of eye-specific, geniculocortical inputs to primary visual cortex (V1) is highly sensitive to the balance of correlated activity between the two eyes during a restricted postnatal critical period for ocular dominance plasticity. This critical period is likely to have amplified expression of genes and proteins that mediate synaptic plasticity. DNA microarray analysis of transcription in mouse V1 before, during, and after the critical period identified 31 genes that were up-regulated and 22 that were down-regulated during the critical period. The highest-ranked up-regulated gene, cardiac troponin C, codes for a neuronal calcium-binding protein that regulates actin binding and whose expression is activity-dependent and relatively selective for layer-4 star pyramidal neurons. The highest-ranked down-regulated gene, synCAM, also has actin-based function. Actinbinding function, G protein signaling, transcription, and myelination are prominently represented in the critical period transcriptome. Monocular deprivation during the critical period reverses the expression of nearly all critical period genes. The profile of regulated genes suggests that synaptic stability is a principle driver of critical period gene expression and that alteration in visual activity drives homeostatic restoration of stability.
- Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junctionNishimune, Hiroshi; Valdez, Gregorio; Jarad, George; Moulson, Casey L.; Müller, Ulrich; Miner, Jeffrey H.; Sanes, Joshua R. (The Rockefeller University Press, 2008-09-15)A prominent feature of synaptic maturation at the neuromuscular junction (NMJ) is the topological transformation of the acetylcholine receptor (AChR)-rich postsynaptic membrane from an ovoid plaque into a complex array of branches. We show here that laminins play an autocrine role in promoting this transformation. Laminins containing the α4, α5, and β2 subunits are synthesized by muscle fibers and concentrated in the small portion of the basal lamina that passes through the synaptic cleft at the NMJ. Topological maturation of AChR clusters was delayed in targeted mutant mice lacking laminin 5 and arrested in mutants lacking both α4 and α5. Analysis of chimeric laminins in vivo and of mutant myotubes cultured aneurally demonstrated that the laminins act directly on muscle cells to promote postsynaptic maturation. Immunohistochemical studies in vivo and in vitro along with analysis of targeted mutants provide evidence that laminin-dependent aggregation of dystroglycan in the postsynaptic membrane is a key step in synaptic maturation. Another synaptically concentrated laminin receptor, Bcam, is dispensable. Together with previous studies implicating laminins as organizers of presynaptic differentiation, these results show that laminins coordinate post- with presynaptic maturation.
- Remote Excitation of Neuronal Circuits Using Low- Intensity, Low-Frequency UltrasoundTyler, William J.; Tufail, Yusuf; Finsterwald, Michael; Tauchmann, Monica L.; Olson, Emily J.; Majestic, Cassondra (PLOS, 2008-10-29)Possessing the ability to noninvasively elicit brain circuit activity yields immense experimental and therapeutic power. Most currently employed neurostimulation methods rely on the somewhat invasive use of stimulating electrodes or photonemitting devices. Due to its ability to noninvasively propagate through bone and other tissues in a focused manner, the implementation of ultrasound (US) represents a compelling alternative approach to current neuromodulation strategies. Here, we investigated the influence of low-intensity, low-frequency ultrasound (LILFU) on neuronal activity. By transmitting US waveforms through hippocampal slice cultures and ex vivo mouse brains, we determined LILFU is capable of remotely and noninvasively exciting neurons and network activity. Our results illustrate that LILFU can stimulate electrical activity in neurons by activating voltage-gated sodium channels, as well as voltage-gated calcium channels. The LILFU-induced changes in neuronal activity were sufficient to trigger SNARE-mediated exocytosis and synaptic transmission in hippocampal circuits. Because LILFU can stimulate electrical activity and calcium signaling in neurons as well as central synaptic transmission we conclude US provides a powerful tool for remotely modulating brain circuit activity.
- Alexithymic Trait and Voluntary Control in Healthy AdultsGu, Xiaosi; Liu, Xun; Guise, Kevin G.; Fossella, John; Wang, Kaiwen; Fan, Jin (PLOS, 2008-11-12)Background: Alexithymia is a personality trait characterized by deficiency in understanding, processing, or describing emotions. Recent studies have revealed that alexithymia is associated with less activation of the anterior cingulate cortex, a brain region shown to play a role in cognitive and emotional processing. However, few studies have directly investigated the cognitive domain in relation to alexithymia to examine whether alexithymic trait is related to less efficient voluntary control. Methodology/ Principal Findings: We examined the relationship between alexithymic trait and voluntary control in a group of healthy volunteers. We used the 20-item Toronto Alexithymia Scale (TAS-20) to measure alexithymic trait. Additionally, we examined state and trait voluntary control using the revised Attention Network Test (ANT-R) and the Adult Temperament Questionnaire (ATQ), respectively. Alexithymic trait was positively correlated with the overall reaction time of the ANT-R, and negatively correlated with the Effortful Control factor of the ATQ. Conclusions/Significance: Our results suggest that alexithymic trait is associated with less efficient voluntary control.
- Congruence of BOLD Response across Intertemporal Choice Conditions: Fictive and Real Money Gains and LossesBickel, Warren K.; Pitcock, Jeffery A.; Yi, Richard; Angtuaco, Edgardo J.C. (Society for Neuroscience, 2009-07-08)Intertemporal choice is predicated on the valuation of commodities with respect to delay until their receipt. Subjective value of a future outcome decreases, or is discounted, as a function of that delay (Bickel and Johnson, 2003). Although behavioral studies suggest no difference between the devaluation of real and fictive outcomes, no neuroimaging studies have investigated potential differences in the underlying deliberative process. Here, we compare behavioral and neural correlates of intertemporal valuation of real and hypothetical monetary gains as well as hypothetical losses, which have been posited to involve different mechanisms. Behavioral and neuroimaging sessions were conducted in which participants made intertemporal choice decisions in a gains condition using both real and hypothetical $100 money and in a loss condition using a fictive $100 money. Within-subject comparison of behavioral data revealed no significant difference between levels of discounting across the three conditions. Random-effects analysis of functional magnetic resonance imaging (fMRI) data of each of the three discounting conditions independently revealed significant signal change in limbic (anterior cingulate, striatum, posterior cingulate) and executive functioning areas (lateral prefrontal cortex), whereas a repeated-measures ANOVA failed to detect differences in signal change across the three discounting conditions after correcting for multiple comparisons. These data support a concordance between real and hypothetical conditions from delay-discounting studies and further suggest a congruence of the fMRI blood oxygen level-dependent signal across brain regions associated with the deliberative process of different forms of intertemporal choice.
- Ready…Go: Amplitude of the fMRI Signal Encodes Expectation of Cue Arrival TimeCui, Xu; Stetson, Chess; Montague, P. Read; Eagleman, David M. (PLOS, 2009-08-04)What happens when the brain awaits a signal of uncertain arrival time, as when a sprinter waits for the starting pistol? And what happens just after the starting pistol fires? Using functional magnetic resonance imaging (fMRI), we have discovered a novel correlate of temporal expectations in several brain regions, most prominently in the supplementary motor area (SMA). Contrary to expectations, we found little fMRI activity during the waiting period; however, a large signal appears after the ‘‘go’’ signal, the amplitude of which reflects learned expectations about the distribution of possible waiting times. Specifically, the amplitude of the fMRI signal appears to encode a cumulative conditional probability, also known as the cumulative hazard function. The fMRI signal loses its dependence on waiting time in a ‘‘countdown’’ condition in which the arrival time of the go cue is known in advance, suggesting that the signal encodes temporal probabilities rather than simply elapsed time. The dependence of the signal on temporal expectation is present in ‘‘no-go’’ conditions, demonstrating that the effect is not a consequence of motor output. Finally, the encoding is not dependent on modality, operating in the same manner with auditory or visual signals. This finding extends our understanding of the relationship between temporal expectancy and measurable neural signals.
- Neural responses to sanction threats in two-party economic exchangeLi, Jian; Xiao, Erte; Houser, Daniel; Montague, P. Read (NAS, 2009-08-11)Sanctions are used ubiquitously to enforce obedience to social norms. However, recent field studies and laboratory experiments have demonstrated that cooperation is sometimes reduced when incentives meant to promote prosocial decisions are added to the environment. Although various explanations for this effect have been suggested, the neural foundations of the effect have not been fully explored. Using a modified trust game, we found that trustees reciprocate relatively less when facing sanction threats, and that the presence of sanctions significantly reduces trustee’s brain activities involved in social reward valuation [in the ventromedial prefrontal cortex (VMPFC), lateral orbitofrontal cortex, and amygdala] while it simultaneously increases brain activities in the parietal cortex, which has been implicated in rational decision making. Moreover,wefound that neural activity in a trustee’s VMPFC area predicts her future level of cooperation under both sanction and no-sanction conditions, and that this predictive activity can be dynamically modulated by the presence of a sanction threat.