Electrophysiology publications

A long debate in selective attention research is whether attention enhances sensory response or sharpens neural tuning by suppressing response to non-target input. In fact, both processes may occur as a function of load: an uncertain listener might use a broad attentional filter to enhance responses to all inputs (i.e., vigilance), yet employ sharpened tuning to focus on hard to discriminate targets. The present work used the greater signal gain, anatomical precision, and laterality separation of intracranial electrophysiological recordings (electrocorticograms) to investigate these competing effects. Data were recorded from acoustically-responsive cortex in the perisylvian region of a single hemisphere in five neurosurgery patients. Patients performed a dichotic listening task in which they alternately attended toward, away from, or completely ignored (silent reading) tones presented to designated ears at varying presentation rates. Comparisons between the grand-averaged event-related potential (ERP) waveforms show a striking change in the effect of selective auditory attention with attentional load. At slower presentation rates (low-load), ERPs were overall enhanced in response to both input channels and regardless of attended ear, including a significant enhancement of ipsilateral input. This result supports a broadly enhancing model of attention under low perceptual load conditions. At the fastest rate, however, only responses to attended inputs contralateral to grid location remained enhanced. This result supports an increasing suppression, or "sharpening," of neural responses to non-targets with increasing attentional load. These data provide support for an elastic model of attention in which attentional scope narrows with increasing load.

This study examines the feasibility of using electroencephalograms (EEGs) to rapidly detect the intent to open one's hand in individuals with complete hand paralysis following a subcortical ischemic stroke. If detectable, this motor-planning activity could be used in real time to trigger a motorized hand exoskeleton or an electrical stimulation device that opens/closes the hand. While EEG-triggered movement-assist devices could restore function, they may also promote recovery by reinforcing the use of remaining cortical circuits. EEGs were recorded while participants were cued to either relax or attempt to extend their fingers. Linear-discriminant analysis was used to detect onset of finger-extension from the EEGs in a leave-one-trial-out cross-validation process. In each testing trial, the classifier was applied in pseudo-real-time starting from an initial hand-relaxed phase, through movement planning, and into the initial attempted-finger-extension phase (finger-extension phase estimated from typical time-to-movement-onset measured in the unaffected hand). The classifiers detected attempted-finger-extension at a significantly higher rate during both motor-planning and early attempted execution compared to rest. To reduce inappropriate triggering of a movement-assist device during rest, the classification threshold could be adjusted to require more certainty about one's intent to move before triggering a device. Additionally, a device could be set to activate only after multiple time samples in a row were classified as finger-extension events. These options resulted in some sessions with no false triggers while the person was resting, but moderate-to-high true trigger rates during attempted-movements.

It is well established that auditory cortex is plastic on different time scales and that this plasticity is driven by the reinforcement that is used to motivate subjects to learn or to perform an auditory task. Motivated by these findings, we study in detail properties of neuronal firing in auditory cortex that is related to reward feedback. We recorded from the auditory cortex of two monkeys while they were performing an auditory categorization task. Monkeys listened to a sequence of tones and had to signal when the frequency of adjacent tones stepped in downward direction, irrespective of the tone frequency and step size. Correct identifications were rewarded with either a large or a small amount of water. The size of reward depended on the monkeys' performance in the previous trial: it was large after a correct trial and small after an incorrect trial. The rewards served to maintain task performance. During task performance we found three successive periods of neuronal firing in auditory cortex that reflected (1) the reward expectancy for each trial, (2) the reward-size received, and (3) the mismatch between the expected and delivered reward. These results, together with control experiments suggest that auditory cortex receives reward feedback that could be used to adapt auditory cortex to task requirements. Additionally, the results presented here extend previous observations of non-auditory roles of auditory cortex and shows that auditory cortex is even more cognitively influenced than lately recognized.

Many studies have demonstrated the ability of chronically implanted multielectrode arrays (MEAs) to extract information from the motor cortex of both humans and nonhuman primates. Similarly, many studies have shown the ability of intracortical microstimulation to impart information to the brain via a single or a few electrodes acutely implanted in sensory cortex of nonhuman primates, but relatively few microstimulation studies characterizing chronically implanted MEAs have been performed. Additionally, device and tissue damage have been reported at the levels of microstimulation used in these studies. Whether the damage resulting from microstimulation impairs the ability of MEAs to chronically produce physiological effects, however, has not been directly tested. In this study, we examined the functional consequences of multiple months of periodic microstimulation via chronically implanted MEAs at levels capable of evoking physiological responses, that is, electromyogram (EMG) activity. The functionality of the MEA and neural tissue was determined by measuring impedances, the ability of microstimulation to evoke EMG responses, and the recording of action potentials. We found that impedances and the number of recorded action potentials followed the previously reported trend of decreasing over time in both animals that received microstimulation and those which did not receive microstimulation. Despite these trends, the ability to evoke EMG responses and record action potentials was retained throughout the study. The results of this study suggest that intracortical microstimulation via MEAs did not cause functional failure, suggesting that MEA-based microstimulation is ready to transition into subchronic (< 30 days) human trials to determine whether complex spatiotemporal sensory percepts can be evoked by patterned microstimulation.

Peripheral sensory neurons respond to stimuli containing a wide range of spatio-temporal frequencies. We investigated electroreceptor neuron coding in the gymnotiform wave-type weakly electric fish Apteronotus leptorhynchus. Previous studies used low to mid temporal frequencies (<256 Hz) and showed that electroreceptor neuron responses to sensory stimuli could be almost exclusively accounted for by linear models, thereby implying a rate code. We instead used temporal frequencies up to 425 Hz, which is in the upper behaviorally relevant range for this species. We show that electroreceptors can: (A) respond up to the highest frequencies tested and (B) display strong nonlinearities in their responses to such stimuli. These nonlinearities were manifested by the fact that the responses to repeated presentations of the same stimulus were coherent at temporal frequencies outside of those contained in the stimulus waveform. Specifically, these consisted of low frequencies corresponding to the time varying contrast or envelope of the stimulus as well as higher harmonics of the frequencies contained in the stimulus. Heterogeneities in the afferent population influenced nonlinear coding as afferents with the lowest baseline firing rates tended to display the strongest nonlinear responses. To understand the link between afferent heterogeneity and nonlinear responsiveness, we used a phenomenological mathematical model of electrosensory afferents. Varying a single parameter in the model was sufficient to account for the variability seen in our experimental data and yielded a prediction: nonlinear responses to the envelope and at higher harmonics are both due to afferents with lower baseline firing rates displaying greater degrees of rectification in their responses. This prediction was verified experimentally as we found that the coherence between the half-wave rectified stimulus and the response resembled the coherence between the responses to repeated presentations of the stimulus in our dataset. This result shows that rectification cannot only give rise to responses to low frequency envelopes but also at frequencies that are higher than those contained in the stimulus. The latter result implies that information is contained in the fine temporal structure of electroreceptor afferent spike trains. Our results show that heterogeneities in peripheral neuronal populations can have dramatic consequences on the nature of the neural code.

It is widely assumed that intracranial recordings from the brain are only minimally affected by contamination due to ocular-muscle electromyogram (oEMG). Here we show that this is not always the case. In intracranial recordings from five surgical epilepsy patients we observed that eye movements caused a transient biphasic potential at the onset of a saccade, resembling the saccadic spike potential commonly seen in scalp EEG, accompanied by an increase in broadband power between 20 and 200 Hz. Using concurrently recorded eye movements and high-density intracranial EEG (iEEG) we developed a detailed overview of the spatial distribution and temporal characteristics of the saccade-related oculomotor signal within recordings from ventral, medial and lateral temporal cortex. The occurrence of the saccadic spike was not explained solely by reference contact location, and was observed near the temporal pole for small (<2 deg) amplitude saccades and over a broad area for larger saccades. We further examined the influence of saccade-related oEMG contamination on measurements of spectral power and interchannel coherence. Contamination manifested in both spectral power and coherence measurements, in particular, over the anterior half of the ventral and medial temporal lobe. Next, we compared methods for removing the contaminating signal and found that nearest-neighbor bipolar re-referencing and ICA filtering were effective for suppressing oEMG at locations far from the orbits, but tended to leave some residual contamination at the temporal pole. Finally, we show that genuine cortical broadband gamma responses observed in averaged data from ventral temporal cortex can bear a striking similarity in time course and band-width to oEMG contamination recorded at more anterior locations. We conclude that eye movement-related contamination should be ruled out when reporting high gamma responses in human intracranial recordings, especially those obtained near anterior and medial temporal lobe.

Many children with specific language impairment (SLI) have difficulty in perceiving stop consonant-vowel syllables (e.g., /ba/, /ga/, /da/) with rapid formant transitions, but perform normally when formant transitions are extended in time. This influential observation has helped lead to the development of the auditory temporal processing hypothesis, which posits that SLI is causally related to the processing of rapidly changing sounds in aberrantly expanded windows of temporal integration. We tested a potential physiological basis for this observation by examining whether syllables varying in their consonant place of articulation (POA) with prolonged formant transitions would evoke better differentiated patterns of activation along the tonotopic axis of A1 in awake monkeys when compared to syllables with short formant transitions, especially for more prolonged windows of temporal integration. Amplitudes of multi-unit activity evoked by /ba/, /ga/, and /da/ were ranked according to predictions based on responses to tones centered at the spectral maxima of frication at syllable onset. Population responses representing consonant POA were predicted by the tone responses. Predictions were stronger for syllables with prolonged formant transitions, especially for longer windows of temporal integration. Relevance of findings to normal perception and that occurring in SLI are discussed.

Adaptive behavior depends on an animal's ability to ignore uninformative stimuli, such as repeated presentations of the same stimulus, and, instead, detect informative, novel stimuli in its environment. The primate prefrontal cortex (PFC) is known to play a central role in this ability. However, the neural mechanisms underlying the ability to differentiate between repeated and novel stimuli are not clear. We hypothesized that the coupling between different frequency bands of the local field potential (LFP) underlies the PFC's role in differentiating between repeated and novel stimuli. Specifically, we hypothesized that whereas the presentation of a novel-stimulus induces strong cross-frequency coupling, repeated presentations of the same stimulus attenuates this coupling. To test this hypothesis, we recorded LFPs from the ventrolateral PFC (vPFC) of rhesus monkeys while they listened to a novel vocalization and repeated presentations of the same vocalization. We found that the cross-frequency coupling between the gamma-band amplitude and theta-band phase of the LFP was modulated by repeated presentations of a stimulus. During the first (novel) presentation of a stimulus, gamma-band activity was modulated by the theta-band phase. However, with repeated presentations of the same stimulus, this cross-frequency coupling was attenuated. These results suggest that cross-frequency coupling may play a role in the neural computations that underlie the differentiation between novel and repeated stimuli in the vPFC.

Reversible inactivation of the cortex by surface cooling is a powerful method for studying the function of a particular area. Implanted cooling cryoloops have been used to study the role of individual cortical areas in auditory processing of awake-behaving cats. Cryoloops have also been used in rodents for reversible inactivation of the cortex, but recently there has been a concern that the cryoloop may also cool non-cortical structures either directly or via the perfusion of blood, cooled as it passed close to the cooling loop. In this study we have confirmed that the loop can inactivate most of the auditory cortex without causing a significant reduction in temperature of the auditory thalamus or other subcortical structures. We placed a cryoloop on the surface of the guinea pig cortex, cooled it to 2°C and measured thermal gradients across the neocortical surface. We found that the temperature dropped to 20-24°C among cells within a radius of about 2.5 mm away from the loop. This temperature drop was sufficient to reduce activity of most cortical cells and led to the inactivation of almost the entire auditory region. When the temperature of thalamus, midbrain, and middle ear were measured directly during cortical cooling, there was a small drop in temperature (about 4°C) but this was not sufficient to directly reduce neural activity. In an effort to visualize the extent of neural inactivation we measured the uptake of thallium ions following an intravenous injection. This confirmed that there was a large reduction of activity across much of the ipsilateral cortex and only a small reduction in subcortical structures.

Objectives: Cisplatin, a widely used chemotherapeutic agent, has serious side effects, including nephrotoxicity and ototoxicity. Minocycline is a semisynthetic second-generation tetracycline that exerts anti-inflammatory and neuroprotective effects. The purpose of this study was to elucidate the protective effect of minocycline against cisplatin-induced ototoxicity in the auditory hair cell. Methods: The House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line and guinea pigs were used for in vitro and in vivo experiments. Cells were exposed to cisplatin with or without pre-treatment with minocycline. Cell survival was analyzed using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Whole-cell lysates were collected and immunoblotted with antibodies against Bcl-2, p-c-Jun, active caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), and apoptosis-inducing factor (AIF). The guinea pigs received intraperitoneal injections of cisplatin alone or following minocycline pretreatment. The auditory brainstem response was tested and the cochleae were harvested and evaluated using scanning electron microscopy. Results: Survival significantly increased in cells pretreated with minocycline compared with cells exposed to cisplatin alone. Cisplatin treatment increased the expression of active caspase 3, p-c Jun, PARP, and AIF, and pretreatment with minocycline attenuated this response. In animal study, the threshold shift by cisplatin injection in the auditory brainstem response was less pronounced in animals pretreated with minocycline. Scanning electron microscopy revealed more severe damage to the outer hair cells at the basal and middle turns than the apical turn. Conclusion: Minocycline partially protects against cisplatin-induced ototoxicity via both caspase-dependent and independent apoptosis pathways.

Electrocorticography (ECoG), multichannel brain-surface recording and stimulation with probe electrode arrays, has become a potent methodology not only for clinical neurosurgery but also for basic neuroscience using animal models. The highly evolved primate's brain has deep cerebral sulci, and both gyral and intrasulcal cortical regions have been implicated in important functional processes. However, direct experimental access is typically limited to gyral regions, since placing probes into sulci is difficult without damaging the surrounding tissues. Here we describe a novel methodology for intrasulcal ECoG in macaque monkeys. We designed and fabricated ultra-thin flexible probes for macaques with micro-electro-mechanical systems technology. We developed minimally invasive operative protocols to implant the probes by introducing cutting-edge devices for human neurosurgery. To evaluate the feasibility of intrasulcal ECoG, we conducted electrophysiological recording and stimulation experiments. First, we inserted parts of the Parylene-C-based probe into the superior temporal sulcus to compare visually evoked ECoG responses from the ventral bank of the sulcus with those from the surface of the inferior temporal cortex. Analyses of power spectral density and signal-to-noise ratio revealed that the quality of the ECoG signal was comparable inside and outside of the sulcus. Histological examination revealed no obvious physical damage in the implanted areas. Second, we placed a modified silicone ECoG probe into the central sulcus and also on the surface of the precentral gyrus for stimulation. Thresholds for muscle twitching were significantly lower during intrasulcal stimulation compared to gyral stimulation. These results demonstrate the feasibility of intrasulcal ECoG in macaques. The novel methodology proposed here opens up a new frontier in neuroscience research, enabling the direct measurement and manipulation of electrical activity in the whole brain.

Perinatal asphyxia, a naturally and commonly occurring risk factor in birthing, represents one of the major causes of neonatal encephalopathy with long term consequences for infants. Here, degraded spectral and temporal responses to sounds were recorded from neurons in the primary auditory cortex (A1) of adult rats exposed to asphyxia at birth. Response onset latencies and durations were increased. Response amplitudes were reduced. Tuning curves were broader. Degraded successive-stimulus masking inhibitory mechanisms were associated with a reduced capability of neurons to follow higher-rate repetitive stimuli. The architecture of peripheral inner ear sensory epithelium was preserved, suggesting that recorded abnormalities can be of central origin. Some implications of these findings for the genesis of language perception deficits or for impaired language expression recorded in developmental disorders, such as autism spectrum disorders, contributed to by perinatal asphyxia, are discussed.

Activity in the primary auditory cortex (A1) is essential for normal sound localization behavior, but previous studies of the spatial sensitivity of neurons in A1 have found broad spatial tuning. We tested the hypothesis that spatial tuning sharpens when an animal engages in an auditory task. Cats performed a task that required evaluation of the locations of sounds and one that required active listening, but in which sound location was irrelevant. Some 26-44% of the units recorded in A1 showed substantially sharpened spatial tuning during the behavioral tasks as compared with idle conditions, with the greatest sharpening occurring during the location-relevant task. Spatial sharpening occurred on a scale of tens of seconds and could be replicated multiple times in ∼1.5-h test sessions. Sharpening resulted primarily from increased suppression of responses to sounds at least-preferred locations. That and an observed increase in latencies suggest an important role of inhibitory mechanisms.

The significance of the mismatch negativity (MMN), an event-related potential measured in humans which indexes novelty in the auditory environment, has motivated a search for a cellular correlate of this process. A leading candidate is stimulus-specific adaptation (SSA) in auditory cortex units, which shares several characteristics with the MMN. Whether auditory cortex responses encode sensory novelty, a defining property of the MMN, however, has not been resolved. To evaluate this key issue, we used several variations of the auditory oddball paradigm from the human literature and examined psychophysical and pharmacological properties of multiunit activity in the auditory cortex of awake rodents. We found converging evidence dissociating SSA from sensory novelty and the MMN. First, during an oddball paradigm with frequency deviants, neuronal responses showed clear SSA but failed to encode novelty in a manner analogous to the human MMN. Second, oddball paradigms using intensity or duration deviants revealed a pattern of unit responses that showed sensory adaptation, but again without any measurable novelty correlates aligning to the human MMN. Finally NMDA antagonists, which are known to disrupt the MMN, suppressed the magnitude of multiunit responses in a nonspecific manner, leaving the process of SSA intact. Together, our results suggest that auditory novelty detection as indexed by the MMN is dissociable from SSA at the level of activity encoded by auditory cortex neurons. Further, the NMDA sensitivity reported for the MMN, which models the disruption of MMN observed in schizophrenia, may occur at a mechanistic locus outside of SSA.

The mouse is a promising model in the study of visual system function and development because of available genetic tools. However, a quantitative analysis of visual receptive field properties had not been performed in the mouse superior colliculus (SC) despite its importance in mouse vision and its usefulness in developmental studies. We have made single-unit extracellular recordings from superficial layers of the SC in urethane-anesthetized C57BL/6 mice. We first map receptive fields with flashing spot stimuli and show that most SC neurons have spatially overlapped ON and OFF subfields. With drifting sinusoidal gratings, we then determine the tuning properties of individual SC neurons, including selectivity for stimulus direction and orientation, spatial frequency tuning, temporal frequency tuning, response linearity, and size preference. A wide range of receptive field sizes and selectivity are observed across the population and in various subtypes of SC neurons identified morphologically. In particular, orientation-selective responses are discovered in the mouse SC, and they are not affected by cortical lesion or long-term visual deprivation. However, ON/OFF characteristics and spatial frequency tuning of SC neurons are influenced by cortical inputs and require visual experience during development. Together, our results provide essential information for future investigations on the functional development of the superior colliculus.

The human auditory cortex is engaged in monitoring the speech of interlocutors as well as self-generated speech. During vocalization, auditory cortex activity is reported to be suppressed, an effect often attributed to the influence of an efference copy from motor cortex. Single-unit studies in non-human primates have demonstrated a rich dynamic range of single-trial auditory responses to self-speech consisting of suppressed, nonsuppressed and excited auditory neurons. However, human research using noninvasive methods has only reported suppression of averaged auditory cortex responses to self-generated speech. We addressed this discrepancy by recording electrocorticographic activity from neurosurgical subjects performing auditory repetition tasks. We observed that the degree of suppression varied across different regions of auditory cortex, revealing a variety of suppressed and nonsuppressed responses during vocalization. Importantly, single-trial high-gamma power (γ High , 70–150 Hz) robustly tracked individual auditory events and exhibited stable responses across trials for suppressed and nonsuppressed regions.

The damped-oscillator pseudo-wavelet is presented as a method of time-frequency analysis along with a new spectral density measure, the data power. An instantaneous phase can be defined for this pseudo-wavelet, and it is easily inverted. The data power measure is tested on both computer generated data and in vivo intrahippocampal electrophysiological recordings from a rat. The data power spectral density is found to give better time and frequency resolution than the more conventional total energy measure, and additionally shows intricate time-frequency structure in the rat that is altered in association with the emergence of epilepsy. With epileptogenesis, the baseline theta oscillation is severely degraded and is absorbed into a broader gamma band. There are also broad 600 Hz and 2000 Hz bands which localize to hippocampal layers that are distinct from those of the theta and gamma bands. The 600 Hz band decreases in prominence with epileptogenesis while the 2000 Hz band increases in prominence. The origins of these high frequency bands await further study. In general, we find that the damped-oscillator pseudo-wavelet is easy to use and is particularly suitable for problems where a wide range of oscillator frequencies is expected.

The specific adaptation of neuronal responses to a repeated stimulus (Stimulus-specific adaptation, SSA), which does not fully generalize to other stimuli, provides a mechanism for emphasizing rare and potentially interesting sensory events. Previous studies have demonstrated that neurons in the auditory cortex and inferior colliculus show SSA. However, the contribution of the medial geniculate body (MGB) and its main subdivisions to SSA and detection of rare sounds remains poorly characterized. We recorded from single neurons in the MGB of anaesthetized rats while presenting a sequence composed of a rare tone presented in the context of a common tone (oddball sequences). We demonstrate that a significant percentage of neurons in MGB adapt in a stimulus-specific manner. Neurons in the medial and dorsal subdivisions showed the strongest SSA, linking this property to the non-lemniscal pathway. Some neurons in the non-lemniscal regions showed strong SSA even under extreme testing conditions (e.g., a frequency interval of 0.14 octaves combined with a stimulus onset asynchrony of 2000 ms). Some of these neurons were able to discriminate between two very close frequencies (frequency interval of 0.057 octaves), revealing evidence of hyperacuity in neurons at a subcortical level. Thus, SSA is expressed strongly in the rat auditory thalamus and contribute significantly to auditory change detection.

Background: Cortical neurons implement a high frequency-specific modulation of subcortical nuclei that includes the cochlear nucleus. Anatomical studies show that corticofugal fibers terminating in the auditory thalamus and midbrain are mostly ipsilateral. Differently, corticofugal fibers terminating in the cochlear nucleus are bilateral, which fits to the needs of binaural hearing that improves hearing quality. This leads to our hypothesis that corticofugal modulation of initial neural processing of sound information from the contralateral and ipsilateral ears could be equivalent or coordinated at the first sound processing level. Methodology/principal findings: With the focal electrical stimulation of the auditory cortex and single unit recording, this study examined corticofugal modulation of the ipsilateral cochlear nucleus. The same methods and procedures as described in our previous study of corticofugal modulation of contralateral cochlear nucleus were employed simply for comparison. We found that focal electrical stimulation of cortical neurons induced substantial changes in the response magnitude, response latency and receptive field of ipsilateral cochlear nucleus neurons. Cortical stimulation facilitated auditory response and shortened the response latency of physiologically matched neurons whereas it inhibited auditory response and lengthened the response latency of unmatched neurons. Finally, cortical stimulation shifted the best frequencies of cochlear neurons towards those of stimulated cortical neurons. Conclusion: Our data suggest that cortical neurons enable a high frequency-specific remodelling of sound information processing in the ipsilateral cochlear nucleus in the same manner as that in the contralateral cochlear nucleus.