Organizing behavior in time is a fundamental process that is highly conserved across species. Here we study the neural basis of timing processes. First, we found that rodents had a burst of stimulus-triggered 4 Hz oscillations in the medial frontal cortex (MFC) during interval timing tasks. Second, rodents with focally disrupted MFC D 1 dopamine receptor (D1DR) signaling had impaired interval timing performance and weaker stimulus-triggered oscillations. Prior work has demonstrated that MFC neurons ramp during interval timing, suggesting that they underlie temporal integration. We found that MFC D1DR blockade strongly attenuated ramping activity of MFC neurons that correlated with behavior. These macro-and micro-level phenomena were linked, as we observed that MFC neurons with strong ramping activity tended to be coherent with stimulus-triggered 4 Hz oscillations, and this relationship was diminished with MFC D1DR blockade. These data provide evidence demonstrating how D1DR signaling controls the temporal organization of mammalian behavior.

Parker KL, Chen KH, Kingyon JR, Cavanagh JF, Narayanan NS. Medial frontal ϳ4-Hz activity in humans and rodents is attenuated in PD patients and in rodents with cortical dopamine depletion. J Neurophysiol 114: 1310 -1320, 2015. First published July 1, 2015; doi:10.1152/jn.00412.2015.-The temporal control of action is a highly conserved and critical mammalian behavior. Here, we investigate the neuronal basis of this process using an interval timing task. In rats and humans, instructional timing cues triggered spectral power across delta and theta bands (2-6 Hz) from the medial frontal cortex (MFC). Humans and rodents with dysfunctional dopamine have impaired interval timing, and we found that both humans with Parkinson's disease (PD) and rodents with local MFC dopamine depletion had attenuated delta and theta activity. In rodents, spectral activity in this range could functionally couple single MFC neurons involved in temporal processing. Without MFC dopamine, these neurons had less functional coupling with delta/theta activity and less temporal processing. Finally, in humans this 2-to 6-Hz activity was correlated with executive function in matched controls but not in PD patients. Collectively, these findings suggest that cue-evoked low-frequency rhythms could be a clinically important biomarker of PD that is translatable to rodent models, facilitating mechanistic inquiry and the development of neurophysiological biomarkers for human disease. medial frontal cortex; dopamine; Parkinson's disease; interval timing TEMPORAL CONTROL OF action, or guiding movements in time to achieve behavioral goals, is a crucial function of mammalian nervous systems. This process depends on the integrated activity of corticostriatal systems (Buhusi and Meck 2005;Jahanshahi et al. 2010;Matell et al. 2003) and requires intact dopaminergic signaling (Drew et al. 2003). Patients with Parkinson's disease (PD) with depleted dopamine have dramatically impaired temporal control (Malapani et al. 1998). Despite these data, the neural circuitry influenced by dopamine during temporal computations is not understood.Here we study this issue in PD patients and in animal models by investigating the neural basis of an elementary cognitive task: interval timing. In this task, participants estimate an interval of several seconds as instructed by a cue. In the range of seconds, interval timing requires executive resources, such as working memory and attention to time (Brown 2006;Parker et al. 2013), and is consistently impaired in patients with PD (Buhusi and Meck 2005;Malapani et al. 1998;Merchant et al. 2008). Because this task is highly conserved across mammalian species (Buhusi and Meck 2005;Merchant et al. 2013), it can be rapidly trained in rodent models, facilitating mechanistic hypothesis testing (Drew et al. 2003;Narayanan et al. 2012).Controlling the timing of action requires the integrated activity of corticostriatal circuits (Hinton and Meck 2004;Matell and Meck 2004) that are dysfunctional in PD patients (Jahanshahi et al. 2010). Recent work...

The subthalamic nucleus is a key site controlling motor function in humans. Deep brain stimulation of the subthalamic nucleus can improve movements in patients with Parkinson's disease; however, for unclear reasons, it can also have cognitive effects. Here, we show that the human subthalamic nucleus is monosynaptically connected with cognitive brain areas such as the prefrontal cortex. Single neurons and field potentials in the subthalamic nucleus are modulated during cognitive processing and are coherent with 4-Hz oscillations in medial prefrontal cortex. These data predict that low-frequency deep brain stimulation may alleviate cognitive deficits in Parkinson's disease patients. In line with this idea, we found that novel 4-Hz deep brain stimulation of the subthalamic nucleus improved cognitive performance. These data support a role for the human hyperdirect pathway in cognitive control, which could have relevance for brain-stimulation therapies aimed at cognitive symptoms of human brain disease.awx300media15660002226001.

The neural basis of human speech is unclear. Intracranial electrophysiological recordings have revealed that high-gamma band oscillations (70–150 Hz) are observed in frontal lobe during speech production and in the temporal lobe during speech perception. Here, we tested the hypothesis that the frontal and temporal brain regions had high-gamma coherence during speech. We recorded electrocorticography (ECoG) from the frontal and temporal cortices of five humans who underwent surgery for medically intractable epilepsy, and studied coherence between frontal and temporal cortex during vocalization and playback of vocalization. We report two novel results. First, we observed high-gamma band as well as theta (4–8 Hz) coherence between frontal and temporal lobes. Second, both high-gamma and theta coherence were stronger when subjects were actively vocalizing as compared to playback of the same vocalizations. These findings provide evidence that coupling between sensory-motor networks measured by high-gamma coherence plays a key role in feedback-based monitoring and control of vocal output for human vocalization.

The Hadronic Forward calorimeters of the CMS experiment are Cherenkov calorimeters that use quartz fibers and 1728 photomultiplier tubes (PMTs) for readout. The CMS detector upgrade project requires the current Hamamatsu R7525 PMTs to be replaced with 4-anode, high quantum efficiency R7600-M4 PMTs. The new PMTs will improve the detector resolution, as well as the capability of removing fake events due to signal created in the glass window of the PMT. Here, we report the dark current, anode gain, transit time, transit time spread, pulse width, rise time, and linearity measurements performed on 1800 Hamamatsu R7600-200-M4 PMTs.