Changes In Firing Rate Research Articles

Encoding of Race Categories by Single Neurons in the Human Brain

Previous research has suggested that race-specific features are automatically processed during face perception, often with out-group faces treated categorically. Functional imaging has illuminated the hemodynamic correlates of this process, with fewer studies examining single-neuron responses. In the present experiment, epilepsy patients undergoing microwire recordings in preparation for surgical treatment were shown realistic computer-generated human faces, which they classified according to the emotional expression shown. Racial categories of the stimulus faces varied independently of the emotion shown, being irrelevant to the patients’ primary task. Nevertheless, we observed race-driven changes in neural firing rates in the amygdala, anterior cingulate cortex, and hippocampus. These responses were broadly distributed, with the firing rates of 28% of recorded neurons in the amygdala and 45% in the anterior cingulate cortex predicting one or more racial categories. Nearly equal proportions of neurons responded to White and Black faces (24% vs. 22% in the amygdala and 26% vs. 28% in the anterior cingulate cortex). A smaller fraction (12%) of race-responsive neurons in the hippocampus predicted only White faces. Our results imply a distributed representation of race in brain areas involved in affective judgments, decision making, and memory. They also support the hypothesis that race-specific cues are perceptually coded even when those cues are task-irrelevant.

The Effects of Deep Brain Stimulation on Motor Unit Activities in Parkinson's Disease based on High-Density Surface EMG Analysis.

Tremor in Parkinson's disease (PD) is caused by synchronized activation bursts in limb muscles. Deep Brain Stimulation (DBS) is an effective clinical therapy for inhibiting tremor and improving movement disorders in PD patients. However, the neural mechanism of how tremor symptom is suppressed by DBS at motor unit (MU) level remains unclear. This paper developed a data acquisition platform for collecting physiological data in PD patients. Both high-density surface Electromyography (HD-sEMG) and kinematics data were collected concurrently before and after DBS surgery. The MU behaviors were obtained via HD-sEMG decomposition algorithm to reveal the effect of DBS on PD tremor. A data set of one tremor dominant PD patient acquired in pre-operation and post-operation (DBS-on) phases was analyzed. Preliminary results showed significant changes in MU firing rate and MU synchronization. The analysis approach introduced in this paper provides a novel perspective for studying the neural mechanism of DBS as revealed by MU activities. Clinical Relevance- This study presented an approach to investigate the effect of DBS therapy on improving tremor disorder of PD patients.

Influence of Rat Central Thalamic Neurons on Foraging Behavior in a Hazardous Environment.

Foraging entails a complex balance between approach and avoidance alongside sensorimotor and homeostatic processes under the control of multiple cortical and subcortical areas. Recently, it has become clear that several thalamic nuclei located near the midline regulate motivated behaviors. However, one midline thalamic nucleus that projects to key nodes in the foraging network, the central medial thalamic nucleus (CMT), has received little attention so far. Therefore, the present study examined CMT contributions to foraging behavior using inactivation and unit recording techniques in male rats. Inactivation of CMT or the basolateral amygdala (BLA) with muscimol abolished the normally cautious behavior of rats in the foraging task. Moreover, CMT neurons showed large but heterogeneous activity changes during the foraging task, with many neurons decreasing or increasing their discharge rates, with a modest bias for the latter. A generalized linear model revealed that the nature (inhibitory vs excitatory) and relative magnitude of the activity modulations seen in CMT neurons differed markedly from those of principal BLA cells but were very similar to those of fast-spiking BLA interneurons. Together, these findings suggest that CMT is an important regulator of foraging behavior. In the Discussion, we consider how CMT is integrated into the network of structures that regulate foraging.SIGNIFICANCE STATEMENT Foraging entails a complex balance between approach and avoidance alongside sensorimotor and homeostatic processes under the control of multiple cortical and subcortical areas. Although the central medial thalamic nucleus (CMT) is connected to many nodes in this network, its role in the regulation of foraging behavior has not been investigated so far. Here, we examined CMT contributions to foraging behavior using inactivation and unit recording techniques. We found that CMT inactivation abolishes the normally cautious foraging behavior of rats and that CMT neurons show large but heterogeneous changes in firing rates during the foraging task. Together, these results suggest that CMT is an important regulator of foraging behavior.

Patch-to-Seq and Transcriptomic Analyses Yield Molecular Markers of Functionally Distinct Brainstem Serotonin Neurons.

Acute regulation of CO2 and pH homeostasis requires sensory feedback from peripheral (carotid body) and central (central) CO2/pH sensitive cells – so called respiratory chemoreceptors. Subsets of brainstem serotonin (5-HT) neurons in the medullary raphe are CO2 sensitive or insensitive based on differences in embryonic origin, suggesting these functionally distinct subpopulations may have unique transcriptional profiles. Here, we used Patch-to-Seq to determine if the CO2 responses in brainstem 5-HT neurons could be correlated to unique transcriptional profiles and/or unique molecular markers and pathways. First, firing rate changes with hypercapnic acidosis were measured in fluorescently labeled 5-HT neurons in acute brainstem slices from transgenic, Dahl SS (SSMcwi) rats expressing T2/ePet-eGFP transgene in Pet-1 expressing (serotonin) neurons (SSePet1–eGFP rats). Subsequently, the transcriptomic and pathway profiles of CO2 sensitive and insensitive 5-HT neurons were determined and compared by single cell RNA (scRNAseq) and bioinformatic analyses. Low baseline firing rates were a distinguishing feature of CO2 sensitive 5-HT neurons. scRNAseq of these recorded neurons revealed 166 differentially expressed genes among CO2 sensitive and insensitive 5-HT neurons. Pathway analyses yielded novel predicted upstream regulators, including the transcription factor Egr2 and Leptin. Additional bioinformatic analyses identified 6 candidate gene markers of CO2 sensitive 5-HT neurons, and 2 selected candidate genes (CD46 and Iba57) were both expressed in 5-HT neurons determined via in situ mRNA hybridization. Together, these data provide novel insights into the transcriptional control of cellular chemoreception and provide unbiased candidate gene markers of CO2 sensitive 5-HT neurons. Methodologically, these data highlight the utility of the patch-to-seq technique in enabling the linkage of gene expression to specific functions, like CO2 chemoreception, in a single cell to identify potential mechanisms underlying functional differences in otherwise similar cell types.

Resistance exercise training and the motor unit.

Resistance exercise training (RET) is a key modality to enhance sports performance, injury prevention and rehabilitation, and improving overall health via increases in muscular strength. Yet, the contribution of neural mechanisms to increases in muscular strength are highly debated. This is particularly true for the involvement of the motor unit, which is the link between neural (activation) and mechanical (muscle fiber twitch forces) mechanisms. A plethora of literature that examines the effects of RET on skeletal muscle speculate the role of motor units, such as increases in firing rates partially explains muscular strength gains. Results, however, are mixed regarding changes in firing rates in studies that utilize single motor unit recordings. The lack of clarity could be related to vast or subtle differences in RET programs, methods to record motor units, muscles tested, types of contractions and intensities used to record motor units, etc. Yet to be discussed, mixed findings could be the result of non-uniform MU behavior that is not typically accounted for in RET research. The purpose of this narration is to discuss the effects of acute resistance exercise training studies on MU behavior and to provide guidance for future research.

Action-driven remapping of hippocampal neuronal populations in jumping rats

The current dominant view of the hippocampus is that it is a navigation "device" guided by environmental inputs. Yet, a critical aspect of navigation is a sequence of planned, coordinated actions. We examined the role of action in the neuronal organization of the hippocampus by training rats to jump a gap on a linear track. Recording local field potentials and ensembles of single units in the hippocampus, we found that jumping produced a stereotypic behavior associated with consistent electrophysiological patterns, including phase reset of theta oscillations, predictable global firing-rate changes, and population vector shifts of hippocampal neurons. A subset of neurons ("jump cells") were systematically affected by the gap but only in one direction of travel. Novel place fields emerged and others were either boosted or attenuated by jumping, yet the theta spike phase versus animal position relationship remained unaltered. Thus, jumping involves an action plan for the animal to traverse the same route as without jumping, which is faithfully tracked by hippocampal neuronal activity.

Short periods of bipolar anodal TDCS induce no instantaneous dose-dependent increase in cerebral blood flow in the targeted human motor cortex

Anodal transcranial direct current stimulation (aTDCS) of primary motor hand area (M1-HAND) can enhance corticomotor excitability, but it is still unknown which current intensity produces the strongest effect on intrinsic neural firing rates and synaptic activity. Magnetic resonance imaging (MRI) combined with pseudo-continuous Arterial Spin Labeling (pcASL MRI) can map regional cortical blood flow (rCBF). The measured rCBF signal is sensitive to regional changes in neuronal activity due to neurovascular coupling. Therefore, concurrent TDCS and pcASL MRI may reveal the relationship between current intensity and TDCS-induced changes in overall firing rates and synaptic activity in the cortical target. Here we employed pcASL MRI to map acute rCBF changes during short-duration aTDCS of left M1-HAND. Using the rCBF response as a proxy for regional neuronal activity, we investigated if short-duration aTDCS produces an instantaneous dose-dependent rCBF increase in the targeted M1-HAND that may be useful for individual dosing. Nine healthy right-handed participants received 30 s of aTDCS at 0.5, 1.0, 1.5, and 2.0 mA with the anode placed over left M1-HAND and cathode over the right supraorbital region. Concurrent pcASL MRI at 3 T probed TDCS-related rCBF changes in the targeted M1-HAND. Movement-induced rCBF changes were also assessed. Apart from a subtle increase in rCBF at 0.5 mA, short-duration aTDCS did not modulate rCBF in the M1-HAND relative to no-stimulation periods. None of the participants showed a dose-dependent increase in rCBF during aTDCS, even after accounting for individual differences in TDCS-induced electrical field strength. In contrast, finger movements led to robust activation of left M1-HAND before and after aTDCS. Short-duration bipolar aTDCS does not produce consistant instantaneous dose-dependent rCBF increases in the targeted M1-HAND at conventional intensity ranges. Therefore, the regional hemodynamic response profile to short-duration aTDCS may not be suited to inform individual dosing of TDCS intensity.

Effects of Intra‐arterial Fentanyl and Codeine on Medullary Respiratory Network Organization

The actions of mu‐opioid agonists to depress breathing are currently controversial, encompassing several proposed mechanisms that are focused on preferential effects in specific locations in the brainstem. We hypothesized that opioids have multiple actions at the respiratory network scale which include loss of synchrony and/or network dynamics. Experiments were conducted in 4 anesthetized, spontaneously breathing and 11 decerebrated, artificially ventilated, paralyzed and vagal intact cats. In spontaneously breathing animals, EMGs were recorded from diaphragm, parasternal, abdominal and upper airway muscles. In paralyzed animals, neurograms were recorded from phrenic and abdominal nerves. Fentanyl or codeine were administered via the vertebral artery (i.a.; fentanyl, 1‐10 ng/kg, codeine 1‐3000 μg/kg) while simultaneously recording from multiple medullary neurons. Analyses included assessment of autocorrelation histograms (ACH), significant features in cross correlation histograms (CCHs), and discharge identity (phenotype of firing frequency of a neuron during the breathing cycle). Qualitatively similar opioid‐induced changes in neuron firing rates, ACHs, CCHs, and discharge identity were observed during either fentanyl or codeine dose responses. Some neurons lost or gained excitability during the dose responses. ACHs of some neurons exhibited changes in spiking periodicity. Features in CCHs changed during administration of opioids including loss of some central or offset peaks. Detectability index (a metric of the magnitude of significant functional interactions) in some neuron pairs increased during opioid administration. Further, the discharge identity of many neurons changed during the dose responses with most of these changes occurring in neurons with tonic discharge during breathing. The extent of these changes strongly suggest that opioids induce significant changes in network organization including reduced synchrony and altered discharge identity of network members. These changes can occur at low doses of opioids that do not profoundly alter the breathing pattern.

Aged Rats Exhibit Altered Behavior-Induced Oscillatory Activity, Place Cell Firing Rates, and Spatial Information Content in the CA1 Region of the Hippocampus.

Hippocampal gamma and theta oscillations are associated with mnemonic and navigational processes and adapt to changes in the behavioral state of an animal to optimize spatial information processing. It has been shown that locomotor activity modulates gamma and theta frequencies in rats, although how age alters this modulation has not been well studied. Here, we examine gamma and theta local-field potential and place cell activity in the hippocampus CA1 region of young and old male rats as they performed a spatial eye-blink conditioning task across 31 d. Although mean gamma frequency was similar in both groups, gamma frequency increased with running speed at a slower rate in old animals. By contrast, theta frequencies scaled with speed similarly in both groups but were lower across speeds in old animals. Although these frequencies scaled equally well with deceleration and speed, acceleration was less correlated with gamma frequency in both age groups. Additionally, spike phase-locking to gamma, but not theta, was greater in older animals. Finally, aged rats had reduced within-field firing rates but greater spatial information per spike within the field. These data support a strong relationship between locomotor behavior and local-field potential activity and suggest that age significantly affects this relationship. Furthermore, observed changes in CA1 place cell firing rates and information content lend support to the hypothesis that age may result in more general and context-invariant hippocampal representations over more detailed information. These results may explain the observation that older adults tend to recall the gist of an experience rather than the details.SIGNIFICANCE STATEMENT Hippocampal oscillations and place cell activity are sensitive to sensorimotor input generated from active locomotion, yet studies of aged hippocampal function often do not account for this. By considering locomotion and spatial location, we identify novel age-associated differences in the scaling of oscillatory activity with speed, spike-field coherence, spatial information content, and within-field firing rates of CA1 place cells. These results indicate that age has an impact on the relationship between locomotion and hippocampal oscillatory activity, perhaps indicative of alterations to afferent input. These data also support the hypothesis that aged hippocampal place cells, compared with young, may more often represent more general spatial information. If true, these results may help explain why older humans tend to recall less specific and more gist-like information.

Physiological studies of timbre encoding in the auditory midbrain

Perceived timbre, especially brightness, is influenced by the spectral peaks of sounds. We hypothesize that spectral peaks are reliably encoded in the inferior colliculus (IC) due to capture and off-characteristic frequency (CF) inhibition. Capture occurs when a component near CF saturates the inner-hair-cell response, reducing the amplitude of neural fluctuations, the low-frequency changes in auditory-nerve firing rate that arise from the interaction of components within complex sounds. IC neurons are sensitive to amplitude modulation and respond to neural fluctuations with enhanced or suppressed rates. Extracellular single-unit recordings were made in the IC of awake rabbits in response to synthetic harmonic stimuli with triangular-shaped spectral magnitudes and zero-phase. Stimuli were presented at 40–80 dB SPL to test for robust encoding over a range of suprathreshold levels. Responses were compared to the output of an auditory-nerve model that exhibits capture followed by a modulation-tuned midbrain model. Results were generally consistent with model predictions, especially for cells suppressed by modulations. Dependent on the modulation transfer function type, responses show dips or peaks in average rate over many levels when the peak harmonic frequency matches CF. This work fills a gap in neural timbre research by investigating spectral peak encoding in the auditory midbrain.

Extensions of a neural-fluctuation perspective on simultaneous notched-noise masking

A previous paper [Maxwell et al., J. Acoust. Soc. Am. 3523, 3537 (2020)] suggested that listeners may identify the target interval in a simultaneous notched-noise task using neural fluctuations, which change with the addition of a tone to the masker. Neural fluctuations are changes in the instantaneous firing rate of auditory-nerve fibers, generally at a longer (slower) time scale than temporal fine structure, that are shaped by peripheral nonlinearities. Differences in neural-fluctuation amplitudes across the peripheral tonotopic axis are proposed to lead to differences in rates across the population of auditory midbrain neurons, due to the sensitivity of these neurons to amplitude modulation. Here, using similar methods to Maxwell et al. (2020) and stimuli matching those of Baker and Rosen (J.Ascoust. Soc. Am. 454, 462 (2006)], we extend previous work by demonstrating that neural fluctuations may account for additional features of simultaneous notched-noise masking results. These features include (1) increase in filter bandwidth at higher stimulus frequencies, (2) higher bandwidth with increasing masker level, and (3) filter asymmetry. These results, in conjunction with the previous conclusion that auditory-nerve excitation patterns cannot explain notched-noise thresholds in all cases, support the interpretation that psychophysical auditory filters may be based on the output of the subcortical auditory system. [Work supported by NIDCD-R01-010813.]

Comparing Vestibular Responses to Linear and Angular Whole-Body Accelerations in Real and Immersive Environments.

The vestibular end organs differ in terms of anatomical and physiological characteristics. Sensory modalities' stimuli including visual stimuli and vestibular sensation can influence these organs differently. This paper explores differences between vestibular responses to axial tilts in physical and virtual environments. Four passive whole-body movements (linear: up-down, and angular: yaw, pitch, and roll) were applied to twenty-seven healthy participants once using a hydraulic chair (physical) and once visually using a head-mounted display (virtual). Electrovestibulography (EVestG) was used as the outcome measure to investigate the magnitude of vestibular-response-change in both ears for physical and virtual stimuli. Three features including average action potential (AP) area, AP amplitude, and mean detected firing rate change were used as indices of response. The results show that for both physical and virtual stimuli (1) generally the pitch and roll tilts produce the largest EVestG changes compared to other tilts (2) roll and pitch tilt responses are not significantly different from each other and (3) right side and left side roll tilts' responses are not significantly different. The findings indicate although visually- and physically-induced vestibular responses are different in terms of afferent activity, visual stimuli can still result in distinct responses when exposed to different axial tilts.

Dopamine depletion can be predicted by the aperiodic component of subthalamic local field potentials

Electrophysiological biomarkers reflecting the pathological activities in the basal ganglia are essential to gain an etiological understanding of Parkinson's disease (PD) and develop a method of diagnosing and treating the disease. Previous studies that explored electrophysiological biomarkers in PD have focused mainly on oscillatory or periodic activities such as beta and gamma oscillations. Emerging evidence has suggested that the nonoscillatory, aperiodic component reflects the firing rate and synaptic current changes corresponding to cognitive and pathological states. Nevertheless, it has never been thoroughly examined whether the aperiodic component can be used as a biomarker that reflects pathological activities in the basal ganglia in PD. In this study, we examined the parameters of the aperiodic component in hemiparkinsonian rats and tested its practicality as an electrophysiological biomarker of pathological activity. We found that a set of aperiodic parameters, aperiodic offset and exponent, were significantly decreased by the nigrostriatal lesion. To further prove the usefulness of the parameters as biomarkers, acute levodopa treatment reverted the aperiodic offset. We then compared the aperiodic parameters with a previously established periodic biomarker of PD, beta frequency oscillation. We found a significantly low negative correlation with beta power. We showed that the performance of the machine learning-based prediction of pathological activities in the basal ganglia can be improved by using both beta power and the aperiodic component, which showed a low correlation with each other. We suggest that the aperiodic component will provide a more sensitive measurement to early diagnosis PD and have the potential to use as the feedback parameter for the adaptive deep brain stimulation.

Microsaccades as a marker not a cause for attention-related modulation.

Recent evidence suggests that microsaccades are causally linked to the attention-related modulation of neurons-specifically, that microsaccades toward the attended location are required for the subsequent changes in firing rate. These findings have raised questions about whether attention-related modulation is due to different states of attention as traditionally assumed or might instead be a secondary effect of microsaccades. Here, in two rhesus macaques, we tested the relationship between microsaccades and attention-related modulation in the superior colliculus (SC), a brain structure crucial for allocating attention. We found that attention-related modulation emerged even in the absence of microsaccades, was already present prior to microsaccades toward the cued stimulus, and persisted through the suppression of activity that accompanied all microsaccades. Nonetheless, consistent with previous findings, we also found significant attention-related modulation when microsaccades were directed toward, rather than away from, the cued location. Thus, despite the clear links between microsaccades and attention, microsaccades are not necessary for attention-related modulation, at least not in the SC. They do, however, provide an additional marker for the state of attention, especially at times when attention is shifting from one location to another.

Neural correlates of distinct levels of predatory threat in dorsal periaqueductal grey neurons.

The dorsal periaqueductal grey (PAG) is an important site for integrating predatory threats. However, it remains unclear whether predator-related activation in PAG primarily reflects threat itself and thus can distinguish between various degrees of threat, or rather reflects threat-oriented behaviours, with the PAG potentially orchestrating different types of defensive repertoire. To address this issue, we performed extracellular recording of dorsal PAG neurons in freely behaving rats and examined neuronal and behavioural responses to stimulus conditions with distinct levels of predatory threat. Animals were sequentially exposed to a nonthreatening stimulus familiar environment (exposure to habituated environment) and to a novel nonthreatening stimulus (i.e., a toy animal-plush) and to conditions with high (exposure to a live cat), intermediate (exposure to the environment just visited by the cat, with remnant predator scent), and low (exposure on the following day to the predatory context) levels of predatory threat. To test for contributions of both threat stimuli and behaviour to changes in firing rate, we applied a Poisson generalized linear model regression, using the different predator stimulus conditions and defensive repertoires as predictor variables. Analysis revealed that the different predator stimulus conditions were more predictive of changes in firing rate (primarily threat-induced increases) than the different defensive repertoires. Thus, the dorsal PAG may code for different levels of predatory threat, more than it directly orchestrates distinct threat-oriented behaviours. The present results open interesting perspectives to investigate the role of the dorsal PAG in mediating primal emotional and cognitive responses to fear-inducing stimuli.

Enhanced firing of locus coeruleus neurons and SK channel dysfunction are conserved in distinct models of prodromal Parkinson\u2019s disease

Parkinson’s disease (PD) is clinically defined by the presence of the cardinal motor symptoms, which are associated with a loss of dopaminergic nigrostriatal neurons in the substantia nigra pars compacta (SNpc). While SNpc neurons serve as the prototypical cell-type to study cellular vulnerability in PD, there is an unmet need to extent our efforts to other neurons at risk. The noradrenergic locus coeruleus (LC) represents one of the first brain structures affected in Parkinson’s disease (PD) and plays not only a crucial role for the evolving non-motor symptomatology, but it is also believed to contribute to disease progression by efferent noradrenergic deficiency. Therefore, we sought to characterize the electrophysiological properties of LC neurons in two distinct PD models: (1) in an in vivo mouse model of focal α-synuclein overexpression; and (2) in an in vitro rotenone-induced PD model. Despite the fundamental differences of these two PD models, α-synuclein overexpression as well as rotenone exposure led to an accelerated autonomous pacemaker frequency of LC neurons, accompanied by severe alterations of the afterhyperpolarization amplitude. On the mechanistic side, we suggest that Ca2+-activated K+ (SK) channels are mediators of the increased LC neuronal excitability, as pharmacological activation of these channels is sufficient to prevent increased LC pacemaking and subsequent neuronal loss in the LC following in vitro rotenone exposure. These findings suggest a role of SK channels in PD by linking α-synuclein- and rotenone-induced changes in LC firing rate to SK channel dysfunction.

Cortical and hippocampal dynamics under logical fragmentation of environmental space

Navigation is often constrained to pathways, and a recurring problem concerns whether to turn left or right when approaching an intersection. We examined this problem during T-maze performance in which the maze location in the recording environment varied over five-trial blocks and analyzed the associated positional firing patterns of hippocampal CA1 and posterior parietal cortex neurons. An arbitrary partitioning of the environmental space determined the left versus right turning rule for T-maze behavior. Under these conditions, rats learned the logical fragmentation of allocentric space into left turn and right turn sub-regions. Paradoxically, under these conditions, the spatial tuning of both posterior parietal cortex and hippocampal CA1 neurons followed the frame of reference given by the T-maze, as opposed to the location in the environment. Moreover, first trials within each block were associated with distinct firing rate changes for both posterior parietal cortex and hippocampal CA1 neurons. These data support a model where spatial tuning by hippocampus and cortex can interact to guide choice behavior in complex, path-based environments where a correct turn choice varies across environmental locations, and as a function of recent experience.

Estimating null and potent modes of feedforward communication in a computational model of cortical activity

Communication across anatomical areas of the brain is key to both sensory and motor processes. Dimensionality reduction approaches have shown that the covariation of activity across cortical areas follows well-delimited patterns. Some of these patterns fall within the "potent space" of neural interactions and generate downstream responses; other patterns fall within the "null space" and prevent the feedforward propagation of synaptic inputs. Despite growing evidence for the role of null space activity in visual processing as well as preparatory motor control, a mechanistic understanding of its neural origins is lacking. Here, we developed a mean-rate model that allowed for the systematic control of feedforward propagation by potent and null modes of interaction. In this model, altering the number of null modes led to no systematic changes in firing rates, pairwise correlations, or mean synaptic strengths across areas, making it difficult to characterize feedforward communication with common measures of functional connectivity. A novel measure termed the null ratio captured the proportion of null modes relayed from one area to another. Applied to simultaneous recordings of primate cortical areas V1 and V2 during image viewing, the null ratio revealed that feedforward interactions have a broad null space that may reflect properties of visual stimuli.

Dependence of Working Memory on Coordinated Activity Across Brain Areas.

Neural signatures of working memory (WM) have been reported in numerous brain areas, suggesting a distributed neural substrate for memory maintenance. In the current manuscript we provide an updated review of the literature focusing on intracranial neurophysiological recordings during WM in primates. Such signatures of WM include changes in firing rate or local oscillatory power within an area, along with measures of coordinated activity between areas based on synchronization between oscillations. In comparing the ability of various neural signatures in any brain area to predict behavioral performance, we observe that synchrony between areas is more frequently and robustly correlated with WM performance than any of the within-area neural signatures. We further review the evidence for alteration of inter-areal synchrony in brain disorders, consistent with an important role for such synchrony during behavior. Additionally, results of causal studies indicate that manipulating synchrony across areas is especially effective at influencing WM task performance. Each of these lines of research supports the critical role of inter-areal synchrony in WM. Finally, we propose a framework for interactions between prefrontal and sensory areas during WM, incorporating a range of experimental findings and offering an explanation for the observed link between intra-areal measures and WM performance.

Context-dependent relationships between locus coeruleus firing patterns and coordinated neural activity in the anterior cingulate cortex.

Ascending neuromodulatory projections from the locus coeruleus (LC) affect cortical neural networks via the release of norepinephrine (NE). However, the exact nature of these neuromodulatory effects on neural activity patterns in vivo is not well understood. Here, we show that in awake monkeys, LC activation is associated with changes in coordinated activity patterns in the anterior cingulate cortex (ACC). These relationships, which are largely independent of changes in firing rates of individual ACC neurons, depend on the type of LC activation: ACC pairwise correlations tend to be reduced when ongoing (baseline) LC activity increases but enhanced when external events evoke transient LC responses. Both relationships covary with pupil changes that reflect LC activation and arousal. These results suggest that modulations of information processing that reflect changes in coordinated activity patterns in cortical networks can result partly from ongoing, context-dependent, arousal-related changes in activation of the LC-NE system.