The prefrontal cortex is made up of neocortical areas thought to mediate aspects of the temporal and spatial organization of behavior. One of the prime output targets of the prefrontal cortex is the striatum, which is thought to operate in series with the prefrontal cortex in some neural computations. We have analyzed this prefronto- striatal projection in cynomolgus monkeys by combining anterograde neuronal tract tracing methods with neurochemical markers for the striosome and matrix compartments of the striatum. Our results single out two parts of the frontal cortex as projecting densely to the striosome compartment of the striatum: the posterior orbitofrontal/anterior insular cortex and the mediofrontal prelimbic/anterior cingulate cortex. These areas jointly innervated striosomes in the anterior and ventromedial striatum, mainly in the caudate nucleus. Striosomes in the dorsolateral striatum were never labeled. Thus, the anatomical subsystem defined by striosome affiliation includes three cortical and ...

Difficult decisions and optimism for the future.

“Self-construal” refers to how individuals view and make meaning of the self, and at least two subtypes have been identified. Interdependent self-construal is a view of the self that includes relationships with others, and independent self-construal is a view of the self that does not include relations with others. It has been suggested that priming these two types of self-construal affects the cognitive processing style that an individual adopts, especially with regard to context sensitivity. Specifically, an interdependent self-construal is thought to promote attention to others and social context to a greater degree than an independent self-construal. To investigate this assertion, we elicited motor-evoked potentials with transcranial magnetic stimulation during an action observation task in which human participants were presented with either interdependent or independent self-construal prime words. Priming interdependent self-construal increased motor cortical output whereas priming independent self-co...

Hippocampal networks are capable of maintaining synchronized bursting activity for prolonged periods. Yet, in vitro synaptic terminals undergo a rapid depletion of their readily releasable pool (RRP) of vesicles in response to short trains of stimuli. The rate at which neurons can re-prime vesicles provides an upper limit for the rate of sustained synaptic signaling. Here, we estimate this replenishment rate at individual synapses by measuring postsynaptic Ca2+ transients mediated by NMDA receptors during high frequency stimulation. We reasoned that at the onset of train stimulation, the Ca2+ indicator would saturate in response the release of the RRP. After this initial phase, Ca2+ levels would fall back to baseline and subsequent postsynaptic Ca2+ transients would only arise from release of newly primed vesicles, which would then be used to estimate the rates of recovery. To monitor activity at single CA1 neuron synapses in acute slices, we measure postsynaptic Ca2+ influx (in response to continuous 20-5...

The acoustic click evokes no peristimulus firing in individual primary afferents. Hypothetically, then, click level must be encoded in the synchronous burst of voltage spikes evoked across the entire eighth nerve (E.A. Radionova, Sov. Phys.-Acoust. 8, 1963, 350-355). It is impossible to count those spikes, but they do produce a measurable epiphenomenon, the N1 component of the peripheral compound action potential (CAP). Each spike contributes equally, so that N1 can be assumed proportional to spike count. If spike count is assumed to have a Gaussian distribution whose variance does not change over a just-detectable-change in level, the intensity-difference limen is given by Signal Detection Theory as follows: d-prime times the standard deviation of N1, divided by the rate-of-change of N1 with level. The term “N1” can be replaced by “loudness” if loudness is assumed proportional to spike count, and if a just-detectable-change in loudness is the change in percept corresponding to a just-detectable-change in ...

Substance abusers show impaired performance on cognitive tests of decision making that engage the orbitofrontal cortex (OFC). This study evaluated the impact of chronic cocaine self-administration on OFC function in rhesus monkeys, using a stimulus reversal task. Two control animals trained to respond for food, and two animals that had chronically self-administered both cocaine and cocaethylene in progressive ratio comparisons of reinforcing efficacy over a period of two years were tested. Mean cumulative intakes were: cocaine 285 mg/kg and cocaethylene 68 mg/kg. A touch screen monitor was used to present stimuli and record responses, using E-prime software. Animals were chair restrained and rewarded with water. They were acquainted with the apparatus by initially being rewarded for touching a stimulus on the screen. Upon proficiency at that task, the reversal task was begun. Bitmap images were presented to the left and right of the screen. Touching one resulted in a larger water reward (3X) than the other...

We investigated the effects of repetitive presentations on neural processing of visually presented words. A string of mask pattern #, a character string (prime), and a word (target) were sequentially displayed; the mask pattern was replaced by primes which lasted for 70 ms, and then replaced by targets. The target words consisted of five Japanese katakana (syllabogram) characters, while the primes consisted of five hiragana (syllabogram) characters that had the same sounds and meanings as the following target words (repetition priming) or consisted of five pseudo-characters (control). Subjects were required to judge whether the target words belonged to the category informed before and to respond by pressing yes or no button. 320 magnetic responses were recorded with a whole-head 148-channel MEG system. In two cases of eight (four subjects times two sessions), reaction time for the affirmative (and correct) answers was significantly shorter by 66 ms and 76 ms for the repetition priming condition than for th...

The use of subliminal priming techniques together with MEG and beamformer analysis methods offer the potential to dissociate successive stages in the processing of words in the brain. MEG was used to measure cortical activity during subliminal priming of visual words. Four conditions between prime and targets were presented: direct repetition (e.g. HOUSE -> HOUSE), cross-case (e.g. house -> HOUSE), bigram (e.g. HUSE -> HOUSE) and unrelated (e.g. STAND -> HOUSE). Each of these conditions were presented with the letter strings in either the same or different absolute positions. Participants were instructed to maintain fixation and indicate by button press, whether the letter string they saw contained I or O. MEG data were collected from adult right-handed readers using a 151-channel CTF Omega system at Aston University. Data were sampled at 625 Hz with an antialiasing cut-off filter of 200 Hz. The MEG data were analyzed using Synthetic Aperture Magnetometry (SAM), which is an adaptive beamforming analysis te...

The dentate gyrus (DG) is among the few areas in the mammalian brain where production of new neurons continues in the adulthood. Although its functional significance is not completely understood, several lines of evidence suggest the role of DG neurogenesis in learning and memory. Considering that long-term potentiation (LTP) is a prime candidate for the process underlying hippocampal learning and memory, these studies raise the possibility that LTP and neurogenesis are linked together. Indeed, a previous study (Brain Res, 857:300-307, 2000) has shown that LTP induction in Mossy fiber projection to CA3, i.e., the efferent pathway of the DG, enhanced proliferation of progenitor cells in the DG. However, it is unknown whether LTP in the afferent pathway is associated with neurogenesis. We investigated this matter by inducing LTP in perforant path-DG synapses by theta burst stimulation in one hemisphere, and comparing newly generated progenitor (BrdU-positive) cells in the DG between two hemispheres. Compared...

The placebo effect is a phenomenon of importance in the clinical practice of medicine, and a prime example of cognitive-emotional influences on a number of physical processes. Dr. Benedetti will present work studying the placebo response in Parkinson patients at the single neuron level. Placebo administration induced a decrease of firing rate as well as the disappearance of bursting activity of subthalamic nucleus neurons. These neuronal changes were correlated with clinical assessments of decreased muscle rigidity. These data show that complex mental activities, like expectancies and beliefs, are capable of changing neuronal functioning which, in turn, induce clinical improvement. Dr. Mayberg will present data on the neural responses to placebo in clinical trials of antidepressants. In this study, placebo response was associated with a complex set of limbic and cortical metabolic changes that overlapped with those seen in responders treated with active fluoxetine. Dr. Wager will then present work on the n...