@Article{ LogothetisEMASEBO2012,
title = {Hippocampal-cortical interaction during periods of subcortical silence},
journal = {Nature},
year = {2012},
month = {11},
volume = {491},
number = {7425},
pages = {547–553},
abstract = {Hippocampal ripples, episodic high-frequency field-potential oscillations primarily occurring during sleep and calmness, have been described in mice, rats, rabbits, monkeys and humans, and so far they have been associated with retention of previously acquired awake experience. Although hippocampal ripples have been studied in detail using neurophysiological methods, the global effects of ripples on the entire brain remain elusive, primarily owing to a lack of methodologies permitting concurrent hippocampal recordings and whole-brain activity mapping. By combining electrophysiological recordings in hippocampus with ripple-triggered functional magnetic resonance imaging, here we show that most of the cerebral cortex is selectively activated during the ripples, whereas most diencephalic, midbrain and brainstem regions are strongly and consistently inhibited. Analysis of regional temporal response patterns indicates that thalamic activity suppression precedes the hippocampal population burst, which itself is temporally bounded by massive activations of association and primary cortical areas. These findings suggest that during off-line memory consolidation, synergistic thalamocortical activity may be orchestrating a privileged interaction state between hippocampus and cortex by silencing the output of subcortical centres involved in sensory processing or potentially mediating procedural learning. Such a mechanism would cause minimal interference, enabling consolidation of hippocampus-dependent memory.},
web_url = {http://www.nature.com/nature/journal/v491/n7425/full/nature11618.html},
state = {published},
DOI = {10.1038/nature11618},
author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}, Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}, Murayama Y{yusuke}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes}, Steudel T{steudel}{Department Physiology of Cognitive Processes}, Evrard HC{evrard}{Department Physiology of Cognitive Processes}, Besserve M{besserve}{Department Physiology of Cognitive Processes} and Oeltermann A{axel}}
}

@Article{ 6272,
title = {Relationship between neural and hemodynamic signals during spontaneous activity studied with temporal kernel CCA},
journal = {Magnetic Resonance Imaging},
year = {2010},
month = {10},
volume = {28},
number = {8},
pages = {1095-1103},
abstract = {Functional magnetic resonance imaging (fMRI) based on the so-called blood oxygen level-dependent (BOLD) contrast is a powerful tool for studying brain function not only locally but also on the large scale. Most studies assume a simple relationship between neural and BOLD activity, in spite of the fact that it is important to elucidate how the “when” and “what” components of neural activity are correlated to the “where” of fMRI data. Here we conducted simultaneous recordings of neural and BOLD signal fluctuations in primary visual (V1) cortex of anesthetized monkeys. We explored the neurovascular relationship during periods of spontaneous activity by using temporal kernel canonical correlation analysis (tkCCA). tkCCA is a multivariate method that can take into account any features in the signals that univariate analysis cannot. The method detects filters in voxel space (for fMRI data) and in frequency–time space (for neural data) that maximize the neurovascular correlation without any assumption of a hemodynamic response function (HRF). Our results showed a positive neurovascular coupling with a lag of 4–5 s and a larger contribution from local field potentials (LFPs) in the γ range than from low-frequency LFPs or spiking activity. The method also detected a higher correlation around the recording site in the concurrent spatial map, even though the pattern covered most of the occipital part of V1. These results are consistent with those of previous studies and represent the first multivariate analysis of intracranial electrophysiology and high-resolution fMRI.},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T9D-4Y6T7WF-2-C&_cdi=5112&_user=29041&_pii=S0730725X09003087&_orig=search&_coverDate=01%2F21%2F2010&_sk=999999999&view=c&wchp},
state = {published},
DOI = {10.1016/j.mri.2009.12.016},
author = {Murayama Y{yusuke}{Department Physiology of Cognitive Processes}, Biessmann F{fbiessma}{Department Physiology of Cognitive Processes}, Meinecke FC, M\"uller K-R{klaus}, Augath M{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 6794,
title = {The effects of electrical microstimulation on cortical signal propagation},
journal = {Nature Neuroscience},
year = {2010},
month = {10},
volume = {13},
number = {10},
pages = {1283-1291},
abstract = {Electrical stimulation has been used in animals and humans to study potential causal links between neural activity and specific cognitive functions. Recently, it has found increasing use in electrotherapy and neural prostheses. However, the manner in which electrical stimulation–elicited signals propagate in brain tissues remains unclear. We used combined electrostimulation, neurophysiology, microinjection and functional magnetic resonance imaging (fMRI) to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We found that stimulation of a site in the lateral geniculate nucleus (LGN) increased the fMRI signal in the regions of primary visual cortex (V1) that received input from that site, but suppressed it in the retinotopically matched regions of extrastriate cortex. Consistent with previous observations, intracranial recordings indicated that a short excitatory response occurring immediately after a stimulation pulse was followed by a long-lasting inhibition. Following microinjections of GABA antagonists in V1, LGN stimulation induced positive fMRI signals in all of the cortical areas. Taken together, our findings suggest that electrical stimulation disrupts cortico-cortical signal propagation by silencing the output of any neocortical area whose afferents are electrically stimulated.},
web_url = {http://www.nature.com/neuro/journal/v13/n10/pdf/nn.2631.pdf},
state = {published},
DOI = {10.1038/nn.2631},
author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes}, Murayama Y{yusuke}{Department Physiology of Cognitive Processes}, Rauch A{arauch}{Department Physiology of Cognitive Processes}, Sultan F, Goense J{jozien}{Department Physiology of Cognitive Processes}, Oeltermann A{axel} and Merkle H{hellmut}}
}

@Article{ 5874,
title = {How not to study spontaneous activity},
journal = {NeuroImage},
year = {2009},
month = {5},
volume = {45},
number = {4},
pages = {1080-1089},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WNP-4VF56VB-1-7&_cdi=6968&_user=29041&_orig=search&_coverDate=05%2F01%2F2009&_sk=999549995&view=c&wchp=dGLbVlb-zSkWb&md5=89b06d7d2a46322519b4d916c334b3ba&ie=},
state = {published},
DOI = {10.1016/j.neuroimage.2009.01.010},
author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}, Murayama Y{yusuke}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes}, Steffen T{theodor}, Werner J{joachim}{Department Physiology of Cognitive Processes} and Oeltermann A{axel}}
}

@Article{ 4956,
title = {The Influence of Moderate Hypercapnia on Neural Activity in the Anesthetized Nonhuman Primate},
journal = {Cerebral Cortex},
year = {2008},
month = {11},
volume = {18},
number = {11},
pages = {2666-2673},
abstract = {Hypercapnia is often used as vasodilatory challenge in clinical applications and
basic research. In functional magnetic resonance imaging (fMRI), elevated CO2
is applied to derive stimulus-induced changes in the cerebral rate of oxygen
consumption (CMRO2) by measuring cerebral blood flow (CBF) and bloodoxygenation-
level-dependent (BOLD) signal. Such methods, however, assume
that hypercapnia has no direct effect on CMRO2. In this study, we used
combined intracortical recordings and fMRI in the visual cortex of anesthetized
macaque monkeys to show that spontaneous neuronal activity is in fact
significantly reduced by moderate hypercapnia. As expected, measurement of
cerebral blood volume using an exogenous contrast agent and of BOLD signal
showed that both are increased during hypercapnia. In contrast to this,
spontaneous fluctuations of local field potentials in the beta and gamma
frequency range as well as multi-unit activity are reduced by ~15% during
inhalation of 6% CO2 (pCO2 = 56 mmHg). A strong tendency toward a reduction
of neuronal activity was also found at CO2 inhalation of 3% (pCO2 = 45 mmHg).
This suggests that CMRO2 might be reduced during hypercapnia and caution
must be exercised when hypercapnia is applied to calibrate the BOLD signal.},
web_url = {http://cercor.oxfordjournals.org/cgi/reprint/bhn023v2},
state = {published},
DOI = {10.1093/cercor/bhn023},
author = {Zappe A-C{aczappe}{Department Physiology of Cognitive Processes}, Uludag K{kuludag}{Department High-Field Magnetic Resonance}, Oeltermann A{axel}, Ugurbil K and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 4951,
title = {Pharmacological MRI combined with electrophysiology in non-human primates: Effects of Lidocaine on primary visual cortex},
journal = {Neuroimage},
year = {2008},
month = {4},
volume = {40},
number = {2},
pages = {590-600},
abstract = {Pharmacological magnetic resonance imaging (phMRI) is a current direction in biomedical imaging, whose goal is the non-invasive monitoring of pharmacological manipulations on brain processes. We have developed techniques combining phMRI with simultaneous monitoring of electrophysiological activity during local injections of pharmacological agents into defined brain regions. We have studied effects of the local anesthetic Lidocaine on BOLD activity in primary visual cortex (V1) of non-human primates. Using independent component analysis (ICA), we describe and quantify the pharmacodynamics and spatial distribution of Lidocaine effects on visually evoked V1 BOLD signal in a dose-dependent manner. We relate these findings to effects of Lidocaine on neural activity as estimated by multi unit activity (MUA) and the local field potential (LFP). Our results open the way for specific fMRI-based investigations regarding the impact of pharmacological agents on the BOLD signal and its coupling to the underlying neuronal
activity.},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WNP-4RC6R7X-6-S&_cdi=6968&_user=29041&_orig=search&_coverDate=04%2F01%2F2008&_sk=999599997&view=c&wchp=dGLbVtb-zSkWb&md5=adf47eeb2d65fc8d3b28e4cb66bfd411&ie=/sdarticle.pdf},
state = {published},
DOI = {10.1016/j.neuroimage.2007.12.009},
author = {Rauch A{arauch}{Department Physiology of Cognitive Processes}, Rainer G{gregor}, Augath M{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 4626,
title = {In Vivo Measurement of Cortical Impedance Spectrum in Monkeys: Implications for Signal Propagation},
journal = {Neuron},
year = {2007},
month = {9},
volume = {55},
number = {5},
pages = {809-823},
abstract = {To combine insights obtained from electric field potentials (LFP) and neuronal spiking activity (MUA) we need a better understanding of the relative spatial summation of these indices of neuronal activity. Compared to MUA, the LFP has greater spatial coherence, resulting in lower spatial specificity and lower stimulus selectivity. A differential propagation of low- and high-frequency electric signals supposedly underlies this phenomenon, which could result from cortical tissue specifically attenuating higher frequencies, i.e. from a frequency-dependent impedance spectrum. Here we directly measure the cortical impedance spectrum in vivo in monkey primary visual cortex. Our results show that impedance is independent of frequency, is homogeneous, tangentially isotropic within gray matter and can be theoretically predicted assuming a pure-resistive conductor. We propose that the spatial summation of LFP and MUA is determined by the size of these signals’ generators and the nature of neural events underlying them
, rather than by biophysical properties of gray matter.},
file_url = {/fileadmin/user_upload/files/publications/Logothetis_Neuron_07_4626[0].pdf},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WSS-4PKGJV3-K-J&_cdi=7054&_user=29041&_orig=search&_coverDate=09%2F06%2F2007&_sk=999449994&view=c&wchp=dGLzVzz-zSkzV&md5=8fdcd6c3721b0e547ee76516d96c4634&ie=},
state = {published},
DOI = {10.1016/j.neuron.2007.07.027},
author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}, Kayser C{kayser}{Department Physiology of Cognitive Processes} and Oeltermann A{axel}}
}

@Article{ 4289,
title = {A novel functional magnetic resonance imaging compatible search-coil eye-tracking system},
journal = {Magnetic Resonance Imaging},
year = {2007},
month = {7},
volume = {25},
number = {6},
pages = {913-922},
abstract = {Measuring eye movements (EMs) using the search-coil eye-tracking technique is superior to video-based infrared methods [Collewijn H, van der Mark F, Jansen TC. Precise recording of human eye movements. Vision Res 1975;15(3):447-50], which suffer from the instability of pupil size, blinking behavior and lower temporal resolution. However, no conventional functional magnetic resonance imaging (fMRI)-compatible search-coil eye tracker exists. The main problems for such a technique are the interaction between the transmitter coils and the magnetic gradients used for imaging as well as the limited amount of space in a scanner. Here we present an approach to overcome these problems and we demonstrate a method to record EMs in an MRI scanner using a search coil. The system described has a spatial resolution of 0.07° (visual angle) and a high temporal resolution (22 kHz). The transmitter coils are integrated into the visual presentation system and the control/analysis unit is portable, which enables us to integrate the eye tracker with an MRI scanner. Our tests demonstrate low noise in the recorded eye traces and scanning with minimal artifact. Furthermore, the induced current in the search coil caused by the RF pulses does not lead to measurable heating. Altogether, this MR-compatible search-coil eye tracker can be used to precisely monitor EMs with high spatial and temporal resolution during fMRI. It can therefore be of great importance for studies requiring accurate fixation of a target, or measurement and study of the subject‘s oculomotor system.},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T9D-4NNPCF8-1-1&_cdi=5112&_user=29041&_orig=search&_coverDate=07%2F31%2F2007&_sk=999749993&view=c&wchp=dGLbVlb-zSkWz&md5=87f12a45a25b274ae1894c7e3f3ba632&ie=/sdarticle.pdf},
state = {published},
DOI = {10.1016/j.mri.2007.02.019},
author = {Oeltermann A{axel}, Ku S-P{shihpi}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 4433,
title = {Robust Controlled Functional MRI in Alert Monkeys at High Magnetic Field: Effects of Jaw and Body Movements},
journal = {NeuroImage},
year = {2007},
month = {7},
volume = {36},
number = {3},
pages = {550-570},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WNP-4NFXDGH-1-1G&_cdi=6968&_user=29041&_orig=browse&_coverDate=07%2F01%2F2007&_sk=999639996&view=c&wchp=dGLzVlz-zSkWb&md5=54c45acb296ee126362acb0f149797d8&ie},
state = {published},
DOI = {10.1016/j.neuroimage.2007.02.057},
author = {Keliris GA{george}{Department Physiology of Cognitive Processes}, Shmuel A{amirs}{Department Physiology of Cognitive Processes}, Ku S-P{shihpi}{Department Physiology of Cognitive Processes}, Pfeuffer J{josef}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Steudel T{steudel}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 4670,
title = {Simultaneous recording of neuronal signals and functional NMR imaging},
journal = {Magnetic Resonance Imaging},
year = {2007},
month = {7},
volume = {25},
number = {6},
pages = {760-774},
abstract = {We recently directly examined the relationship between blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals and neural activity by simultaneously acquiring electrophysiological and fMRI data from monkeys in a 4.7-T vertical scanner (Logothetis NK, Pauls J, Augath MA, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal. Nature 2001;412:150–157). Acquisition of electrical signals in the microvolt range required extensive development of new recording hardware, including electrodes, microdrives, signal conditioning and interference compensation devices. Here, we provide a detailed description of the interference compensation system that can be used to record field and action potentials intracortically within a high-field scanner.},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T9D-4NMV01F-1-1&_cdi=5112&_user=29041&_orig=browse&_coverDate=07%2F31%2F2007&_sk=999749993&view=c&wchp=dGLbVtb-zSkWz&md5=ac3178304240a357f9979f7e804047a4&ie=/sdarticle.pdf},
state = {published},
DOI = {10.1016/j.mri.2007.03.015},
author = {Oeltermann A{axel}, Augath MA{mark}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 3922,
title = {Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area V1},
journal = {Nature Neuroscience},
year = {2006},
month = {3},
volume = {9},
number = {4},
pages = {569-577},
abstract = {Most functional brain imaging studies use task-induced hemodynamic responses to infer underlying changes in neuronal activity. In addition to increases in cerebral blood flow and blood oxygenation level–dependent (BOLD) signals, sustained negative responses are pervasive in functional imaging. The origin of negative responses and their relationship to neural activity remain poorly understood. Through simultaneous functional magnetic resonance imaging and electrophysiological recording, we demonstrate a negative BOLD response (NBR) beyond the stimulated regions of visual cortex, associated with local decreases in neuronal activity below spontaneous activity, detected 7.15 +- 3.14 mm away from the closest positively responding region in V1. Trial-by-trial amplitude fluctuations revealed tight coupling between the NBR and neuronal activity decreases. The NBR was associated with comparable decreases in local field potentials and multiunit activity. Our findings indicate that a significant component of the NBR or
iginates in neuronal activity decreases.},
web_url = {http://www.nature.com/neuro/journal/v9/n4/pdf/nn1675.pdf},
state = {published},
DOI = {10.1038/nn1675},
author = {Shmuel A{amirs}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 3825,
title = {Simultaneous EEG and fMRI in the macaque monkey at 4.7 Tesla},
journal = {Magnetic Resonance Imaging},
year = {2006},
month = {3},
volume = {24},
number = {4},
pages = {335-342},
abstract = {Simultaneous electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) acquisition can identify the brain networks involved in generating specific EEG patterns. Yet, the combination of these methodologies is hampered by strong artifacts that arise due to electromagnetic interference during magnetic resonance (MR) image acquisition. Here, we report corrections of the gradient-induced artifact in phantom measurements and in experiments with an awake behaving macaque monkey during fMRI acquisition at a magnetic field strength of 4.7 T. Ninety-one percent of the amplitude of a 10 μV, 10 Hz phantom signal could successfully be recovered without phase distortions. Using this method, we were able to extract the monkey EEG from scalp recordings obtained during MR image acquisition. Visual evoked potentials could also be reliably identified. In conclusion, simultaneous EEG/fMRI acquisition is feasible in the macaque monkey preparation at 4.7 T and holds promise for investigating
the neural processes that give rise to particular EEG patterns.},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T9D-4JKJT32-1-C&_cdi=5112&_user=29041&_orig=browse&_coverDate=05%2F31%2F2006&_sk=999759995&view=c&wchp=dGLbVlz-zSkWW&md5=4823fcbe247a003382d5aee8e389b687&ie=},
state = {published},
DOI = {10.1016/j.mri.2005.12.024},
author = {Schmid MC{mschmid}, Oeltermann A{axel}, Juchem C{juchem}{Department Physiology of Cognitive Processes}, Smirnakis SM{stelios} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 4479,
title = {Mapping Cortical Activity Elicited with Electrical Microstimulation Using fMRI in the Macaque},
journal = {Neuron},
year = {2005},
month = {12},
volume = {48},
number = {6},
pages = {901-911},
abstract = {Over the last two centuries, electrical microstimulation has been used to demonstrate causal links between neural activity and specific behaviors and cognitive functions. However, to establish these links it is imperative to characterize the cortical activity patterns that are elicited by stimulation locally around the electrode and in other functionally connected areas. We have developed a technique to record brain activity using the blood oxygen level dependent (BOLD) signal while applying electrical microstimulation to the primate brain. We find that the spread of activity around the electrode tip in macaque area V1 was larger than expected from calculations based on passive spread of current and therefore may reflect functional spread by way of horizontal connections. Consistent with this functional transynaptic spread we also obtained activation in expected projection sites in extrastriate visual areas, demonstrating the utility of our technique in uncovering in vivo functional connectivity maps.},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WSS-4HVMT2J-7-2&_cdi=7054&_user=29041&_orig=browse&_coverDate=12%2F22%2F2005&_sk=999519993&view=c&wchp=dGLbVzb-zSkWz&md5=72ecd52a491258a743a50f885045465e&ie=/sdarticle.pdf},
state = {published},
DOI = {10.1016/j.neuron.2005.11.034},
author = {Tolias AS{atolias}{Department Physiology of Cognitive Processes}, Sultan F, Augath MA{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Tehovnik EJ, Schiller PH and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 883,
title = {Neurophysiological investigation of the basis of the fMRI signal},
journal = {Nature},
year = {2001},
month = {7},
volume = {412},
number = {6843},
pages = {150-157},
abstract = {Functional magnetic resonance imaging (fMRI) is widely used to study the operational organization of the human brain, but the exact relationship between the measured fMRI signal and the underlying neural activity is unclear. Here we present simultaneous intracortical recordings of neural signals and fMRI responses. We compared local field potentials (LFPs), single- and multi-unit spiking activity with highly spatio-temporally resolved blood-oxygen-level-dependent (BOLD) fMRI responses from the visual cortex of monkeys. The largest magnitude changes were observed in LFPs, which at recording sites characterized by transient responses were the only signal that significantly correlated with the haemodynamic response. Linear systems analysis on a trial-by-trial basis showed that the impulse response of the neurovascular system is both animal- and site-specific, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses. These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output.},
web_url = {http://www.nature.com/nature/journal/v412/n6843/pdf/412150a0.pdf},
state = {published},
DOI = {10.1038/news010712-13},
author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}, Pauls J{jpauls}{Department Physiology of Cognitive Processes}, Augath MA{mark}{Department Physiology of Cognitive Processes}, Trinath T{torsten}{Department Physiology of Cognitive Processes} and Oeltermann A{axel}}
}

@Poster{ EschenkoBOL2012,
title = {BOLD responses evoked by electrical stimulation of Locus Coeruleus in rats under anesthesia},
year = {2012},
month = {10},
volume = {42},
pages = {674.15},
abstract = {We performed a whole-brain fMRI imaging in the rat under urethane anesthesia and studied BOLD responses induced by electrical stimulation of the brain stem noradrenergic nucleus Locus Coeruleus (LC). The rat was implanted with a MRI-compatible custom-made iridium electrode into LC under electrophysiological guidance. A 7T (300 MHz) magnet with a 30-cm horizontal bore (Bruker BioSpec 70/30, Ettlingen, Germany) equipped with a 20cm inner diameter gradient (Bruker BGA-20S Ettlingen, Germany) was used for MRI scanning. The experimental paradigm consisted of 6s baseline sampling, followed by 4s of unilateral LC stimulation and 10s of post-stimulus sampling. Biphasic square pulses (0.05-0.4mA) were delivered to LC at 20-100Hz either continuously for 4s or grouped in 100-500ms trains. These stimulation parameters were efficient in eliciting LC burst firing bilaterally. We also collected BOLD responses induced by peripheral sensory stimulation in the same animal and using the same experimental design (6/4/10s). For visual stimulation we used a luminance flicker presented to both eyes at 16Hz and delivered via fiber optic cables. A mild electrical stimulation (1-5mA) of a forepaw was used as somatosensory stimulation. The fMRI images were collected with spatial resolution of 0.4x0.4x1.0mm and temporal resolution of 1s. BOLD maps were generated by using GLM with standard (HRF-convolved boxcar functions) or neural regressors. We observed a remarkable dichotomy between BOLD responses of cortical and subcortical structures. Specifically, LC stimulation produced positive BOLD responses in the majority of structures belonging to metencephalon, mesencephalon and diencephalon, while negative BOLD responses in the entire neocortex. The robust neuronal activation in thalamic projections of LC was further confirmed by electrophysiological recordings. The cortical inhibition as a result of LC stimulation and associated NE release in cortical targets of LC has been reported in earlier studies. The peripheral sensory stimulation evoked both sensory-specific and non-specific activation/deactivation pattern. Strikingly, the regions of non-specific BOLD responses were common for both sensory modalities and largely overlapped with brain regions that showed responses to LC stimulation. We hypothesize that sensory stimulation activates modality-specific sensory pathways along with LC-NE system; and the LC co-activation produces the observed non-specific BOLD responses.},
web_url = {http://www.sfn.org/am2012/},
event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)},
event_place = {New Orleans, LA, USA},
state = {published},
author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Oeltermann A{axel} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ ShmuelAOL2007,
title = {Spontaneous fluctuations in functional MRI signal reflect fluctuations in the underlying local neuronal activity},
journal = {NeuroImage},
year = {2007},
month = {6},
volume = {36},
number = {Supplement 1},
pages = {S58},
web_url = {http://www.sciencedirect.com/science/article/pii/S1053811907002789},
event_name = {13th Annual Meeting of the Organization for Human Brain Mapping (HBM 2007)},
event_place = {Chicago, IL, USA},
state = {published},
DOI = {10.1016/j.neuroimage.2007.03.045},
author = {Shmuel A{amirs}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ ShmuelSOL2006,
title = {Neuronal correlates of fMRI signal response in alert monkey V1},
year = {2006},
month = {10},
volume = {36},
number = {545.14},
abstract = {The majority of functional brain imaging studies rely on task induced hemodynamic responses to infer the underlying changes in neuronal activity. Characterizing the relationship between hemodynamic responses and locally measured neuronal activity is crucial for correct interpretation of functional MRI data. Most previous studies on this relationship have used anesthetized preparations with possible confounding effects of anesthesia. This study is aimed at characterizing the local neuronal correlates of Blood Oxygenation Level Dependent response to short presentation of visual stimuli in alert fixating monkey visual area V1.
Monkeys were trained to stay still throughout trials lasting 20 s, within which they fixated for 6 s and were presented with a stimulus for 4 s. Gradient Echo and Spin Echo functional MRI was performed using a 7 T vertical bore magnet and a surface RF coil positioned around a recording chamber (2 segments, TE 19 and 40 ms for Gradient Echo and Spin Echo respectively, resolution 1×1×2 mm, acquisition time 1 s / volume). Interleaved between functional MRI scans, electrophysiological signals were recorded using identical paradigms. The BOLD signal was sampled from a region of interest (6×6×2 mm) around the electrode in V1. Data will be shown on the coupling of different bands of the neuronal signal to the BOLD response, and on the relationship between the locally measured visual evoked response and BOLD response.},
web_url = {http://www.sfn.org/index.aspx?pagename=abstracts_ampublications},
event_name = {36th Annual Meeting of the Society for Neuroscience (Neuroscience 2006)},
event_place = {Atlanta, GA, USA},
state = {published},
author = {Shmuel A{amirs}{Department Physiology of Cognitive Processes}, Steudel T{steudel}{Department Physiology of Cognitive Processes}, Oeltermann A{axel} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ 3940,
title = {Decoupling of BOLD and neuronal activity in the gamma range during recovery from lidocaine inactivation},
year = {2006},
month = {7},
volume = {5},
number = {A179.20},
pages = {143},
abstract = {The underlying neurophysiological source of the BOLD signal is still not fully understood. The spike rate of single neurons is only poorly correlated with the time course of the BOLD signal. The BOLD signal seems rather to reflect the activity of the presynaptic network the neurons are embedded in. We therefore blocked the neuronal activity in a defined area with lidocaine, a reversible sodium channel blocker. In this way we could investigate, how the BOLD signal is coupled to the neuronal activity.
The effects were assessed by simultaneous intracortical recordings and fMRI. We examined BOLD responses in regions of interest defined by independent localizer scans, and assessed the spatial effect of the blocker at varying distances from the injection site.
Neuroimaging was performed in a 4.7 Tesla Scanner. We recorded multiunit activity (MUA) and local field potentials (LFPs). V1 was stimulated by rotating polar checkerboard stimulus. At a distance of 400 microns to the recording electrode we injected Lidocaine (2-6%). Applied quantities (5-25 microl) and flow rates (0.8-4 microl /min) were monitored by a flow meter.
Lidocaine injections were associated with reliable decreases in neuronal activity and local decreases in BOLD activity. Both neuronal and BOLD signals recovered at a timescale of several minutes. However, early in the recovery phase there was a clear transient increase in the gamma band LFP, while the MUA activity was still blocked. The BOLD signal showed a stimulus-modulated increase due to recovery, which however paralled neither the transient increase in LFP nor the still unmodulating MUA signal. The early period in the recovery from lidocaine inactivation thus represents a cortical state in which BOLD signal levels are largely decoupled from the neuronal ones. Our findings suggest that even general blockers (lidocaine) can generate interesting states of neurovascular decoupling that can be used for a better understanding of the BOLD signal.},
web_url = {http://fens2006.neurosciences.asso.fr/},
event_name = {5th Forum of European Neuroscience (FENS 2006)},
event_place = {Wien, Austria},
state = {published},
author = {Rauch A{arauch}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Rainer G{gregor} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ SchmidOJMSL2005,
title = {Simultaneous EEG and fMRI in the macaque monkey at 4.7 T},
year = {2005},
month = {11},
volume = {35},
number = {284.15},
abstract = {Introduction: Simultaneous EEG/fMRI acquisition can identify the brain networks involved in generating specific EEG patterns. Yet, the combination of these methodologies is hampered by strong susceptibility artifacts and electromagnetic interference. Specifically, (a) the susceptibility of EEG electrodes / gels distorts the MR image, and (b) depending on the loop area of the electrode-ground circuitry, and the rate/strength of gradient switching, MR image acquisition induces interference in the EEG signal (gradient artifact). Here we measure the strength of these artifacts and demonstrate the effectiveness of gradient artifact compensation (Allen, 2000).
Methods: We experimented with saline phantoms and with an alert macaque. MRI was performed in a 4.7 T magnet (Bruker), with a gradient field strength of 50 mT m-1. The EEG was recorded from the skull of the monkey using the BrainAmp system (5 kHz sampling rate, input range: +/- 6.4 mV, 250 Hz bandwidth).
Results: Common EEG electrodes / gels produced a susceptibility artifact of < 4 mm, which is in the range of the monkey's muscle thickness, and thus does not affect the MR images of the brain. The amplitude of the unfiltered gradient artifact in our setup was 50 mV (loop area: 166 cm2, slew rate: 333.33 T m-1 s-1) which would ordinarily swamp the EEG signal (~50 μV). After analog low-pass filtering at 250 Hz (30 dB) followed by gradient artifact compensation (Allen, 2000) however, we were able to recover 90 % of a 10 μV amplitude, 10 Hz control signal. The EEG can be recovered during image acquisition using this strategy.
Conclusion: Our results demonstrate the feasibility of simultaneous EEG and MRI experiments in the macaque monkey at high magnetic fields with strong gradients. Ongoing experiments examine the mechanism of generation of specific EEG patterns using event related fMRI in monkeys.},
web_url = {http://www.sfn.org/absarchive/},
event_name = {35th Annual Meeting of the Society for Neuroscience (Neuroscience 2005)},
event_place = {Washington, DC, USA},
state = {published},
author = {Schmid MC{mschmid}, Oeltermann A{axel}, Juchem C{juchem}{Department Physiology of Cognitive Processes}, Merkle H{hellmut}, Smirnakis SM and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ 3941,
title = {The effect of lidocaine on neural activity and BOLD activity in monkey primary visual cortex},
year = {2005},
month = {11},
volume = {35},
number = {742.15},
abstract = {The neurophysiological basis of BOLD contrast mechanism in fMRI is not fully understood. Therefore we started to investigate the role of different neuromodulators and channel blockers on the neural and hemodynamic responses. We first report the effects of local injection of Lidocaine, a reversible sodium channel blocker, in primary visual cortex (V1) of anesthetized monkeys. The effects were assessed by simultaneous intracortical recordings and fMRI. We examined BOLD responses in regions of interest defined by independent localizer scans, and assessed the spatial effect of the blocker at varying distances from the injection site.
Neuroimaging was performed in a 4.7 Tesla Scanner (Bruker, Germany). Recorded were spiking activity and local field potentials. V1 was stimulated by rotating polar checkerboard stimulus (blocks by 30 sec stimulus, 30 sec blank, 37 repetitions). 300 μm to the recording electrode we injected Lidocaine (2% solution) with a precision pump (M6 VICI, USA). Applied quantities (8-25 μl) and flow rates (0.8-4 μl /min) were monitored by a precision flow meter (Sensirion, Switzerland).
Consistent with previous reports, Lidocaine induced reliable decreases in neuronal activity at the injection site. In addition, we observed clear decreases in BOLD activity. The largest effect on both signals was observed closest to the injection site and decreased with increasing distance. The effect was reversible for both signals with a recovery time of 20-30 minutes. Injection of saline (0.9%), to rule out nonspecific effects, showed no change in neuronal or BOLD signals.
The findings suggest a close coupling between stimulus-evoked neuronal activity and the BOLD signal. This allows for a better quantification of the primarily interesting part of the BOLD signal involved in neuronal processing as we now can distinguish between the BOLD signal needed for information processing and the portion used for homeostasis of neurons and their embedding glial cells.},
web_url = {http://www.sfn.org/absarchive/},
event_name = {35th Annual Meeting of the Society for Neuroscience (Neuroscience 2005)},
event_place = {Washington, DC, USA},
state = {published},
author = {Rauch A{arauch}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Rainer G{gregor} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ 4502,
title = {Simultaneous electrical microstimulation and fMRI in the macaque},
year = {2003},
month = {11},
volume = {33},
number = {69.20},
abstract = {Electrical microstimulation has been used extensively to study both neuronal connectivity and the behavioral effects of focal neural excitation. Yet most behaviors involve concurrent activation of several structures that are directly or indirectly interconnected with the stimulated site. Microstimulation performed simultaneously with fMRI offers a unique opportunity to investigate the network of structures eliciting certain behaviors. Recently, simultaneous recording of neural activity and BOLD responses in the monkey has been developed to study the correlation between the fMRI signals and electrical activity in the brain (Logothetis et al., 2001). This work has also enabled us to carry out simultaneous electrical microstimulation and fMRI. The specific goal of the current study is to determine the electrical parameters which elicit activity in the brain similar to that generated by focal visual stimulation. We compared visual stimulation with constant-current charge-balanced biphasic electrical pulses delivered via monopolar microelectrodes placed in area V1. We find that under certain microstimulation parameters we obtain focal activity around the electrode tip in area V1 as well the corresponding retinotopic location in area V2, V3, and MT. Ongoing research examines the activity patterns elicited by stimulating at different cortical layers of V1. This study paves the way to incorporate the much needed anatomical information in the analysis of the electrical signals obtained in trained, awake animals.},
web_url = {http://www.sfn.org/index.aspx?pagename=annualmeeting_futureandpast},
event_name = {33rd Annual Meeting of the Society for Neuroscience (Neuroscience 2003)},
event_place = {New Orleans, LA, USA},
state = {published},
author = {Tolias AS{atolias}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes}, Pauls J{jpauls}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Tehovnik EJ, Schiller PH and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ FustPAOML2003,
title = {The influence of anaesthetic agents on spiking and subthreshold activity in visual cortex revealed by electrophysiology and high-resolution functional MRI},
year = {2003},
month = {11},
volume = {33},
number = {69.14},
abstract = {The state of unconsciousness during anaesthesia is not characterized by a global disruption of CNS activity. Instead consciousness is mediated by a specific subset of brain states or processes selectively affected by anaesthetics. Our aim is to study the action sites of different types of anaesthetics in the monkey brain (M. mulatta). Here we report on the neural effects of Ketamine, a dissociative anaesthetic acting primarily on the NMDA receptor, and Midazolam, a benzodiazepine affecting GABA(A)-receptors. Ketamine exhibits both inhibitory and excitatory effects at different brain sites. Midazolam, however, is known to increase the GABA(A)-receptor function, and therefore to inhibit cortical activity. To study the primary sites-of-action of these agents in the monkey brain, high-resolution functional magnetic resonance imaging (fMRI) was used to measure stimulus induced activity changes in the alert and anaesthetized monkey. The activity of neurons in visual cortex was recorded during scanning, as well as in separate experiments outside the scanner. Following the acquisition of base-line data, a bolus of the test-substance was applied intravenously via a computerized infusion pump. Brain activity was monitored continuously before, during and after the infusion. The data presented here focus on the effects of anaesthetics on subthreshold and spiking activity and the BOLD-signal. A comparison of the influences on these different neural signals allows studying the site and type of action of anaesthetics in more detail. In addition it has the potential to afford further insights into the neural processes underlying the BOLD-signal.},
web_url = {http://www.sfn.org/index.aspx?pagename=annualmeeting_futureandpast},
event_name = {33rd Annual Meeting of the Society for Neuroscience (Neuroscience 2003)},
event_place = {New Orleans, LA, USA},
state = {published},
author = {Fust A, Pauls J{jpauls}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Murayama Y{yusuke}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ 2406,
title = {The Negative BOLD Response in Monkey V1 is Associated with Decreases in Neuronal Activity},
year = {2003},
month = {11},
volume = {33},
number = {125.1},
abstract = {Negative BOLD responses (NBRs) are pervasive in human fMRI, but commonly ignored. A recent study (Shmuel et al., Neuron 2002) characterized a robust sustained NBR in the human occipital cortex associated with decreases in cerebral blood flow (CBF) and oxygen consumption, corroborating that the NBR could be triggered by decreases in neuronal activity (DsiNA).
Aims
1) Is the NBR associated with DsiNA?
2) Is the origin of the DsiNA vascular (e.g. from hypoxia due to blood steal) or neuronal?
Monkeys were visually stimulated with iso-eccentricity rings composed of rotating checkers. A blank gray stimulus was used to measure the baseline cortical signal.
Similar to the findings in humans, NBR was observed in monkeys: 1) in V1, V2, and V3, 2) in response to stimulation of part of the visual-field (VF), and 3) with a time course anti-correlated to that of the PBR.
To determine the neuronal correlates of the NBR, electrical recordings were obtained from the central VF representation in V1 simultaneously with fMRI. Central/peripheral VF stimulus elicited PBR/NBR in the vicinity of the electrode (Fig. 1). Note that: 1) the NBR was associated with DsiNA, 2) the onsets of the increases and DsiNA were approximately concurrent, and 3) the onset of the DsiNA preceded the corresponding onset of the NBR. The NBR was associated with comparable decreases in both the local-field potential and the multi-unit activity.
Conclusions
The NBR in monkey V1 is associated with DsiNA that could not be caused by blood steal. Most plausibly, the DsiNA trigger reductions in CBF that cause the NBR.},
web_url = {http://www.sfn.org/index.aspx?pagename=annualmeeting_futureandpast},
event_name = {33rd Annual Meeting of the Society for Neuroscience (Neuroscience 2003)},
event_place = {New Orleans, LA, USA},
state = {published},
author = {Shmuel A{amirs}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Pauls J{jpauls}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ 2404,
title = {The Negative BOLD Response in Monkey V1 Is Associated with Decreases in Neuronal Activity},
journal = {NeuroImage},
year = {2003},
month = {6},
volume = {19},
number = {2:Supplement},
pages = {e567-e568},
abstract = {Negative BOLD responses (NBRs; i.e. below baseline) are pervasive in human fMRI experiments, but commonly
ignored. A recent study characterized a robust sustained NBR in the human occipital cortex, triggered by
stimulating part of the visual-field (Shmuel et al., 2002). The NBR depends on the pattern of neuronal activity and
is coupled to the positive BOLD response (PBR). The NBR is correlated with reductions in cerebral blood flow
(CBF) and with decreases in oxygen consumption. The findings from this human study corroborate contributions
to the NBR by 1) a significant component of reduction in neuronal activity and possibly 2) a component of
hemodynamic changes independent of the local changes in neuronal activity.},
web_url = {http://www.sciencedirect.com/science/article/pii/S1053811905700033},
event_name = {Ninth Annual Meeting of the Organization for Human Brain Mapping (OHBM 2003)},
event_place = {New Orleans, LA, USA},
state = {published},
DOI = {http://www.sciencedirect.com/science/article/pii/S1053811905700033},
author = {Shmuel A{amirs}{Department Physiology of Cognitive Processes}, Augath MA{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Pauls J{jpauls}{Department Physiology of Cognitive Processes}, Murayama Y{yusuke}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ 1587,
title = {Combined neurophysiology and fMRI in the awake monkey},
year = {2002},
month = {11},
volume = {32},
number = {325.6},
abstract = {Simultaneous intracortical recordings of neural activity (NA) and BOLD responses in the anaesthetized monkey (Logothetis et al,2001)demonstrated various degrees of correlation between the fMRI data and LFP,MUA and SUA. The present work is a further step in the study of the relationship of BOLD to NA in the behaving monkey in a vertical-bore 7T/60cm scanner equipped with a 38-cm gradient insert (80mT/m,130us, Bruker Inc.). The upright positioning of the animal used in every alert monkey laboratory was also chosen for fMRI to minimize discomfort in the monkeys, expedite their training process, and ensure longer cooperation during psychophysical testing. Here, the monkeys were first trained to perform a fixation task (Wurtz, 1969) using juice as a reward. Stimuli were presented through a fiber-optic system (Silent Vision, FL), and eye movements were measured with the iView eye tracking system (SensorMotoric Inst.,GmbH). During data acquisition suction of juice and body movements were prevented by using a number of pressure and motion sensors and by training the animal to remain relaxed during the observation period. MR-compatible plastic chambers and electrodes made of platinum-iridium coated with glass were used for intracortical recordings. Gradient-induced interference was compensated with custom-made electronics (Patent 01116436.5). Brief pulse stimulation with full-field patterns and small stimuli placed within the receptive field of each recording site was used to elicit cortical responses followed by a BOLD response. The correlation of BOLD to different frequency bands with different spatio-temporal stimulation patterns will be discussed.},
web_url = {http://www.sfn.org/absarchive/},
event_name = {32nd Annual Meeting of the Society for Neuroscience (Neuroscience 2002)},
event_place = {Orlando, FL, USA},
state = {published},
author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes} and Oeltermann A{axel}}
}

@Poster{ 1586,
title = {Sustained negative BOLD response in the monkey brain},
year = {2002},
month = {11},
volume = {32},
number = {759.6},
abstract = {n a previous fMRI study (Shmuel et al., HBM 2001), a robust sustained negative BOLD response (NBR) and blood flow response was detected in the human occipital cortex. Here we report on a sustained (different from the initial dip) NBR in areas V1, V2, and V3 of the macaque.
Anesthetized monkeys were presented in 4 cycles with a rotating polar checker pattern (48 s) followed by a blank gray image (48 s). Fifteen axial slices were imaged (GE-EPI, 4.7 T, 0.750.752 mm, TR=.75 s, 6 s/volume).
In response to stimulation at 0-10 eccentricity, a positive BOLD response (PBR) and NBR were observed within the central and peripheral visual representation, respectively. The NBR was found preferentially in gray matter and was spatially reproducible across subjects. The time course of the NBR and PBR (mean amplitude ratio 0.5) were similar, suggesting similar mechanisms. Initial results from simultaneous fMRI and electrophysiology demonstrated NBR in 3 regions where no robust changes in electrical activity occurred. We are currently pursuing additional fMRI-electrophysiology experiments.
Discussion
1) Robust NBR exists in the monkey brain. 2) Since the activity in the periphery is not expected to increase, the NBR here is the result of a decrease in blood flow rather than increase in oxygen consumption.},
web_url = {http://www.sfn.org/absarchive/},
event_name = {32nd Annual Meeting of the Society for Neuroscience (Neuroscience 2002)},
event_place = {Orlando, FL, USA},
state = {published},
author = {Shmuel A{amirs}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ 1067,
title = {In vivo study of connectivity with electrical microstimulation and fMRI},
year = {2001},
month = {11},
volume = {31},
number = {783.5},
abstract = {We describe a new method that combines microstimulation with fMRI for the detailed study of neural connectivity in the alive animal. We used specially constructed microelectrodes to stimulate directly a selected subcortical or cortical area while simultaneously measuring changes in brain activity, indexed by the blood oxygen level dependent (BOLD) signal. The exact location of the stimulation site was achieved by means of anatomical scans as well as by the study of the physiological properties of neurons. Imaging was carried out in a Biospec 4.7T/40 cm vertical bore scanner (Bruker, Inc), using pulse sequences described elsewhere (Logothetis et. al. Nature Neuroscience 1999). Electrical stimulation was delivered using a biphasic pulse generator attached to a constant-current stimulus isolation unit. Constant-current charge-balanced biphasic pulses (300usec, 50 to 150 uA, at 50 to 500 Hz) were delivered to the brain for 12.5 sec preceded and followed by 12.5 and 39 sec respectively. The compensation circuit, designed to minimize interference generated by the switching gradients during recording, was always active alleviating all gradient-induced currents in the range of the stimulation current. Local microstimulation of striate cortex yielded both local BOLD signals and activation of areas V2, V3, and MT. Microstimulation of dLGN resulted in the activation of striate cortex, as well as areas V2, V3, and MT. Our findings show that microstimulation combined with fMRI can be exquisitely used to find and study target areas of regions of electrophysiological interest.},
web_url = {http://www.sfn.org/index.aspx?pagename=abstracts_ampublications},
event_name = {31st Annual Meeting of the Society for Neuroscience (Neuroscience 2001)},
event_place = {San Diego, CA, USA},
state = {published},
author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}, Pauls J{jpauls}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Augath M{mark}{Department Physiology of Cognitive Processes} and Trinath T{torsten}{Department Physiology of Cognitive Processes}}
}

@Poster{ 1050,
title = {The relationship of LFPs, MUA, and SUA to the bold fMRI signal},
year = {2000},
month = {11},
volume = {30},
number = {309.5},
abstract = {The contribution of fMRI to our understanding of the functional anatomy of the brain is directly related to the degree to which the relationship between the MRI signal and the underlying neural activity is understood. It is established that activity in the brain is characterized by time-varying spatial distributions of action potentials superimposed on relatively slow-varying field potentials. To study how such potentials relate to the BOLD signal we scanned the visual cortex of anesthetized monkeys in a 4.7T scanner while recording local field potentials (LFPs), single (SUA), and multi (MUA) unit activity, by means of a novel, recently-developed recording technique. The geometry of novel electrodes and the active compensation built into the recording system minimized magnetic and electrostatic coupling respectively, permitting the elimination of any interference in subsequent off-line analysis. In each session, active sites were selected by first imaging the entire brain with a multi-shot, multi-slice gradient-recalled EPI MRI sequence (TE=20ms, TR=750ms), with FOV=128x128mm^2,128^2 matrix, 2mm thickness. Single slices, with areas of interest, were subsequently imaged with quadrature, transmit/receive volume or implanted surface coils with a voxel size of 250x250x660um^3 using time-resolved MR imaging (TE=20ms, TR=250ms). Our results provide insights into (a) the relationship of slow waves, single unit activity, and coherence functions of simultaneously-recorded single-units to the BOLD signal; (b) the temporal response function of the signals, and (c) the effects of anesthesia depth and stimulus strength on the modulation of each signal-type.},
web_url = {http://www.sfn.org/absarchive/},
event_name = {30th Annual Meeting of the Society for Neuroscience (Neuroscience 2000)},
event_place = {New Orleans, LA, USA},
state = {published},
author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}, Pauls J{jpauls}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Augath M{mark}{Department Physiology of Cognitive Processes} and Trinath T{torsten}{Department Physiology of Cognitive Processes}}
}

@Conference{ 4997,
title = {Microstimulation-evoked BOLD responses of the macaque cerebellar cortex},
year = {2007},
month = {11},
volume = {37},
number = {339.3},
abstract = {Imaging brain activity evoked by intracortical electrical stimulation with fMRI is proving to be a useful tool to study functional characteristics of the brains connectivity in vivo. Here we stimulated the cerebellar cortex with microelectrodes in the anaesthetized rhesus monkey. BOLD responses in the cerebellar cortex were easily evoked with currents of 250 µA (pulse duration: 200µs; frequency: 100Hz). The spatial spread of the BOLD response after stimulation in the anterior lobe (intermediate zone of Lobule IV and V) was large and extended well to the contralateral cerebellar side. Based on the well known connectivity of the cerebellum the spread of such a bilateral activation can be explained through an antidromic excitation of mossy fibres, since these are the only excitatory fibres that can extend bilaterally in the cerebellum. Mossy fibres originating from the lateral reticular nucleus (LRN), for instance have a substantial bilateral contribution (Pijpers et al., 2006) and project heavily to the vermal and intermediate zone of the lobus anterior. So far our stimulation of the posterior lobe (Crus II) on the other hand yielded largely ipsilateral cerebellar activation. This cerebellar region receives its mossy fibres mainly from the pontine nuclei which have a strong contralateral and a weak ipsilateral contribution, indicating a lesser degree of bilaterality.
Cerebellar stimulation yielded a relatively larger spatial spread of BOLD responses than what we have previously observed after cerebral cortical extrastriate and striate stimulation. This is in contradiction to predictions based on the facts that cerebral cortex intraconnectivity is much more extended than the cerebellar short-range intracortical connections. Our observations indicate that this is either due to a larger bifurcation pattern of the cerebellar mossy fibres, or/and to lower thresholds for the activation of mossy fibres and for triggering metabolic changes. In summary, microstimulation-evoked BOLD responses of the cerebellar cortex reveals different patterns of connectivity within the cerebellum and points to some important functional characteristics of these connections.},
web_url = {http://www.sfn.org/am2007/},
event_name = {37th Annual Meeting of the Society for Neuroscience (Neuroscience 2007)},
event_place = {San Diego, CA, USA},
state = {published},
author = {Sultan FR, Augath M{mark}{Department Physiology of Cognitive Processes}, Hammodeh S, Oeltermann A{axel} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Conference{ LogothetisSMASO2006,
title = {Microstimulation and fMRI in anesthetized and alert monkeys: Conditions for transsynaptic BOLD activation},
year = {2006},
month = {10},
volume = {36},
number = {114.10},
abstract = {We have recently combined electrical stimulation and fMRI and demonstrated that the excitability properties of the directly stimulated elements in neocortex using this method are very similar to those obtained with either intracortical recordings or behavioral methods (Tolias et al., 2005). Microstimulation in cortical area V1 of the macaque activated mainly the pyramidal fibers, and the effective current spread, that was measured by means of the BOLD activation, was found to be greater than that obtained with the other two methods. Stimulation of V1 (and in later studies of MT), however, revealed mainly the monosynaptic targets of each stimulated region. Here we set out to elucidate the conditions for which transsynaptic effects can be obtained. Experiments were conducted in anesthetized and alert monkeys in a 4.7T/40cm and 7T/60 scanner, respectively. Electrical stimulation was delivered using a biphasic pulse generator attached to a constant-current stimulus isolation unit. Constant-current charge-balanced, band-limited pulses of different center frequency, pulse duration and current strength were delivered to the brain for periods of 4 sec preceded and followed by 4 sec and 12 sec blank periods, respectively. The compensation circuit, designed to minimize interference generated by the switching gradients during recording, was always active, alleviating all gradient-induced currents in the range of the stimulation current. Local microstimulation was applied in dLGN, pulvinar, striate and extrastriate cortex. The areas activated upon stimulation of each of these sites was found to depend primarily on the central frequency of the frequency band used. Transsynaptic activation also depended on stimulation condition. Differences between the anesthetized and alert monkey experiments will be discussed.},
web_url = {http://www.sfn.org/index.aspx?pagename=abstracts_ampublications},
event_name = {36th Annual Meeting of the Society for Neuroscience (Neuroscience 2006)},
event_place = {Atlanta, GA, USA},
state = {published},
author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}, Sultan F, Murayama Y{yusuke}{Department Physiology of Cognitive Processes}, Augath M{mark}{Department Physiology of Cognitive Processes}, Steudel T{steudel}{Department Physiology of Cognitive Processes} and Oeltermann A{axel}}
}

@Conference{ SultanAOTL2006,
title = {Microstimulation of the upper posterior bank of the STS},
year = {2006},
month = {10},
volume = {36},
number = {114.9},
abstract = {In the macaque the extrastriate area V5/MT is located within the dorsal half and on the posterior bank of the superior temporal sulcus. Neurons in V5/MT show directional tuning to moving stimuli. Furthermore, these neurons are organized in a retinotopic fashion with those responding to stimuli located at the center of gaze being more lateral and ventral within V5/MT (Gattass and Gross, 1981). We have now extended the technique of combined electrical microstimulation and fMRI from the striate cortex (Tolias et al., 2005) to this well-studied extrastriate region to further probe this technique as a tool to map the functional connectivity of the brain. We electrically stimulated V5/MT in the anaesthetized macaque in a 4.7T scanner with biphasic charge-balanced pulses (up to 1mA and 200us pulse width per phase) and evoked BOLD responses consistently in a number of brain areas known to be directly connected to V5/MT. BOLD responses were observed in ipsilateral V2, V3, V4, V4t, PO, MST, in the anterior and posterior banks of the IPS (corresponding to LIP) and in the superior colliculus. Two types of projection patterns could be discerned by stimulation of either the peripheral or the foveal retinal representation of area V5/MT. The latter showed activation of regions located on the lateral surface of the occipital cortex while the former showed activity in mesial occiptio-parietal cortex. BOLD responses were surprisingly rather difficult to evoke in V1 with our current stimulation paradigms. V1 responses were largely seen in peripheral V1 regions. This could indicate that the evoked BOLD responses are dominated by orthodromic vs antidromic pathway activation, however, electrical stimulation of the pulvinar in contrast to V5/MT evoked excellent BOLD responses in V1. Since the V1-pulvinar connectivity is mainly feedforeward, this then proves that antidromic pathway activation is well detected by our method. Hence the different activation patterns that we observe in V1 after MT/V5 and pulvinar stimulation are rather related to the different pathways characteristics, possibly related to differences in the type of synaptic connectivity. Thus microstimulation combined with fMRI may well prove to be a novel technique suited to reveal different characteristics of the brains functional connectivity.},
web_url = {http://www.sfn.org/index.aspx?pagename=abstracts_ampublications},
event_name = {36th Annual Meeting of the Society for Neuroscience (Neuroscience 2006)},
event_place = {Atlanta, GA, USA},
state = {published},
author = {Sultan FR, Augath M{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Tolias AS{atolias}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Conference{ ShmuelAOPL2004,
title = {Linking the negative BOLD response to decreases in neuronal activity in monkey V1},
year = {2004},
month = {10},
day = {23},
volume = {34},
number = {18.14},
abstract = {Previously we demonstrated that the negative BOLD response (NBR) in non-stimulated regions of V1 is associated with decreases in neuronal activity (DsiNA), and that the DsiNA cannot be caused by hypoxia due to the associated negative cerebral blood flow (CBF) response. DsiNA were observed 11 mm away from the stimulated region; thus they cannot be exclusively mediated by the horizontal connections.
Aims
1) Are the NBR and DsiNA independent or coupled phenomena?
2) Does the NBR reflect decreases in synaptic or in spiking activity?
Monkeys were stimulated visually with rotating checkers. Electrical recordings were obtained simultaneously with fMRI.
Peripheral visual-field (VF) stimuli elicited PosBR/NBR in peripheral/more central VF representations in V1. The amplitude of the NBR measured across single trials was correlated with the corresponding amplitude of the DsiNA within single sessions (p<0.0001). The NBR was correlated with the amplitudes of decreases in the comprehensive neuronal signal, LFP, MUA, and action potentials (APs) of single neurons. As expected, the variance of the time course of the PosBR could be better predicted by the variance of the LFP (r2=.69±.15, n=5 sessions) than by that of the MUA (r2=.57±.22) and the APs (r2=.52±.22). In contrast, the variance of the NBR could be comparably predicted using the decreases in LFP (r2=.59±.17), MUA (r2=.64±.10) or APs (r2=.60±.11). Similar DsiNA were observed outside of the scanner, ruling out the possibility of artifacts caused by electrical recordings simultaneously with fMRI.
Conclusions
1) Non-stimulated regions adjacent to active regions in V1 decrease their neuronal activity.
2) The comparable decreases in LFP, MUA and APs are consistent with decreases in the input to the NBR region and/or suppression within the NBR region.
3) The findings corroborate a model in which the DsiNA trigger reductions in CBF that contribute significantly to the NBR.},
web_url = {http://www.sfn.org/absarchive/},
event_name = {34th Annual Meeting of the Society for Neuroscience (Neuroscience 2004)},
event_place = {San Diego, CA, USA},
state = {published},
author = {Shmuel A{amir}, Augath M{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Pauls J{jpauls}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Conference{ 2407,
title = {The Negative BOLD Response in Monkey V1 is Associated with Decreases in Neuronal Activity},
year = {2003},
month = {7},
volume = {11},
number = {211},
pages = {51},
abstract = {This study aimed at revealing the neuronal correlates of the negative BOLD response (NBR). Electrical recordings were obtained from NBR regions in monkey V1 simultaneously with fMRI. The NBR was associated with a reduction in neuronal activity, both in the Multi-Unit-Activity and the Local-Field-Potential domains. The onset of the decrease in neuronal signal preceded the corresponding onset of the NBR, indicating that the origin of the NBR was a decrease in
neuronal activity that triggered a reduction in CBF, rather than decreased neuronal activity caused by reduced CBF.},
web_url = {http://www.ismrm.org/03/},
event_name = {11th Scientific Meeting of the International Society of Magnetic Resonance in Medicine (ISMRM 2003)},
event_place = {Toronto, Canada},
state = {published},
author = {Shmuel A{amirs}{Department Physiology of Cognitive Processes}, Augath MA{mark}{Department Physiology of Cognitive Processes}, Oeltermann A{axel}, Pauls J{jpauls}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}