Prefrontal Lesions Disrupt Posterior Alpha-Gamma Coordination of Visual Working Memory Representations.

How does the human brain prioritize different visual representations in working memory (WM)? Here, we define the oscillatory mechanisms supporting selection of "where" and "when" features from visual WM storage and investigate the role of pFC in feature selection. Fourteen individuals with lateral pFC damage and 20 healthy controls performed a visuospatial WM task while EEG was recorded. On each trial, two shapes were presented sequentially in a top/bottom spatial orientation. A retro-cue presented mid-delay prompted which of the two shapes had been in either the top/bottom spatial position or first/second temporal position. We found that cross-frequency coupling between parieto-occipital alpha (α; 8-12 Hz) oscillations and topographically distributed gamma (γ; 30-50 Hz) activity tracked selection of the distinct cued feature in controls. This signature of feature selection was disrupted in patients with pFC lesions, despite intact α-γ coupling independent of feature selection. These findings reveal a pFC-dependent parieto-occipital α-γ mechanism for the rapid selection of visual WM representations.

A neural correlate of visual feature binding in primate lateral prefrontal cortex.

We effortlessly perceive visual objects as unified entities, despite the preferential encoding of their various visual features in separate cortical areas. A 'binding' process is assumed to be required for creating this unified percept, but the underlying neural mechanism and specific brain areas are poorly understood. We investigated 'feature-binding' across two feature dimensions, using a novel stimulus configuration, designed to disambiguate whether a given combination of color and motion direction is perceived as bound or unbound. In the "bound" condition, two behaviorally relevant features (color and motion) belong to the same object, while in the "unbound" condition they belong to different objects. We recorded local field potentials from the lateral prefrontal cortex (lPFC) in macaque monkeys that actively monitored the different stimulus configurations. Our data show a neural representation of visual feature binding especially in the 4-12 Hz frequency band and a transmission of binding information between different lPFC neural subpopulations. This information is linked to the animal's reaction time, suggesting a behavioral relevance of the binding information. Together, our results document the involvement of the prefrontal cortex, targeted by the dorsal and ventral visual streams, in binding visual features from different dimensions, in a process that includes a dynamic modulation of low frequency inter-regional communication.

Single-Trial Decoding from Local Field Potential Using Bag of Word Representation.

Neural decoding allows us to study the brain functions by investigating the relationship between a stimulus and the corresponding response. Recently, the local field potential (LFP) has been targeted as a hallmark of brain activity for neural decoding. Despite several decoding methods, there is still a lack of a comprehensive framework to decode cognitive functions in an integrated structure. Here, we addressed this issue by developing a dictionary-based method to represent the LFP signals via a bag-of-words (BOW) approach. First, we defined a general dictionary consisting of various Gabor wavelets as the words which enabled us to represent LFPs in word domain. For each trial, the LFP signal was convolved with the dictionary words. The integral of the absolute value and the mean phase of the complex output were considered as histogram weights. In the next step, using cross-validation leave-one-out method, the trials were split into the training and test sets. The weights of each individual word were swapped across trials within a certain category of the training set while the sequential order was maintained. Finally, the test trial was classified using label voting in the k-nearest training trials. We conducted the proposed method on two independent LFP data sets, recorded from the rat primary auditory cortex (A1) and monkey middle temporal area in order to evaluate its efficiency. In addition to the chance level, the proposed method was compared with a standard BOW approach that has been extended recently for biomedical signals classification. Results show a high efficiency (~ 15% improvement in decoding accuracy) of the proposed method. Together, the aforementioned method provides a comprehensive framework for single-trial decoding from short-length electrophysiological signals.

Quantification of 1 H-MRS signals based on sparse metabolite profiles in the time-frequency domain.

MRS is an analytical approach used for both quantitative and qualitative analysis of human body metabolites. The accurate and robust quantification capability of proton MRS (1 H-MRS) enables the accurate estimation of living tissue metabolite concentrations. However, such methods can be efficiently employed for quantification of metabolite concentrations only if the overlapping nature of metabolites, existing static field inhomogeneity and low signal-to-noise ratio (SNR) are taken into consideration. Representation of 1 H-MRS signals in the time-frequency domain enables us to handle the baseline and noise better. This is possible because the MRS signal of each metabolite is sparsely represented, with only a few peaks, in the frequency domain, but still along with specific time-domain features such as distinct decay constant associated with T2 relaxation rate. The baseline, however, has a smooth behavior in the frequency domain. In this study, we proposed a quantification method using continuous wavelet transformation of 1 H-MRS signals in combination with sparse representation of features in the time-frequency domain. Estimation of the sparse representations of MR spectra is performed according to the dictionaries constructed from metabolite profiles. Results on simulated and phantom data show that the proposed method is able to quantify the concentration of metabolites in 1 H-MRS signals with high accuracy and robustness. This is achieved for both low SNR (5 dB) and low signal-to-baseline ratio (-5 dB) regimes.

Enhanced Behavioral Performance through Interareal Gamma and Beta Synchronization.

Cognitive functioning requires coordination between brain areas. Between visual areas, feedforward gamma synchronization improves behavioral performance. Here, we investigate whether similar principles hold across brain regions and frequency bands, using simultaneous local field potential recordings from 15 areas during performance of a selective attention task. Short behavioral reaction times (RTs), an index of efficient interareal communication, occurred when occipital areas V1, V2, V4, DP showed gamma synchronization, and fronto-central areas S1, 5, F1, F2, F4 showed beta synchronization. For both area clusters and corresponding frequency bands, deviations from the typically observed phase relations increased RTs. Across clusters and frequency bands, good phase relations occurred in a correlated manner specifically when they processed the behaviorally relevant stimulus. Furthermore, the fronto-central cluster exerted a beta-band influence onto the occipital cluster whose strength predicted short RTs. These results suggest that local gamma and beta synchronization and their inter-regional coordination jointly improve behavioral performance.

Enhanced behavioral performance through interareal gamma and beta synchronization.

Cognitive functioning requires coordination between brain areas. Between visual areas, feedforward gamma synchronization improves behavioral performance. Here, we investigate whether similar principles hold across brain regions and frequency bands, using simultaneous electrocorticographic recordings from 15 areas of two macaque monkeys during performance of a selective attention task. Short behavioral reaction times (RTs), suggesting efficient interareal communication, occurred when occipital areas V1, V2, V4, and DP showed gamma synchronization, and fronto-central areas S1, 5, F1, F2, and F4 showed beta synchronization. For both area clusters and corresponding frequency bands, deviations from the typically observed phase relations increased RTs. Across clusters and frequency bands, good phase relations occurred in a correlated manner specifically when they processed the behaviorally relevant stimulus. Furthermore, the fronto-central cluster exerted a beta-band influence onto the occipital cluster whose strength predicted short RTs. These results suggest that local gamma and beta synchronization and their inter-regional coordination jointly improve behavioral performance.

In vivo magnetic recording of single-neuron action potentials.

Measuring fast neuronal signals is the domain of electrophysiology and magnetophysiology. While electrophysiology is much easier to perform, magnetophysiology avoids tissue-based distortions and measures a signal with directional information. At the macroscale, magnetoencephalography (MEG) is established, and at the mesoscale, visually evoked magnetic fields have been reported. At the microscale however, while benefits of recording magnetic counterparts of electric spikes would be numerous, they are also highly challenging in vivo. Here, we combine magnetic and electric recordings of neuronal action potentials in anesthetized rats using miniaturized giant magneto-resistance (GMR) sensors. We reveal the magnetic signature of action potentials of well isolated single units. The recorded magnetic signals showed a distinct waveform and considerable signal strength. This demonstration of in vivo magnetic action potentials opens a wide field of possibilities to profit from the combined power of magnetic and electric recordings and thus to significantly advance the understanding of neuronal circuits.

Task-specific modulation of PFC activity for matching-rule governed decision-making.

Storing information from incoming stimuli in working memory (WM) is essential for decision-making. The prefrontal cortex (PFC) plays a key role to support this process. Previous studies have characterized different neuronal populations in the PFC for working memory judgements based on whether an originally presented stimulus matches a subsequently presented one (matching-rule decision-making). However, much remains to be understood about this mechanism at the population level of PFC neurons. Here, we hypothesized differences in processing of feature vs. spatial WM within the PFC during a matching-rule decision-making task. To test this hypothesis, the modulation of neural activity within the PFC during two types of decision-making tasks (spatial WM and feature WM) in comparison to a passive fixation task was determined. We discovered that neural population-level activity within the PFC is different for the match vs. non-match condition exclusively in the case of the feature-specific decision-making task. For this task, the non-match condition exhibited a greater firing rate and lower trial-to-trial variability in spike count compared to the feature-match condition. Furthermore, the feature-match condition exhibited lower variability compared to the spatial-match condition. This was accompanied by a faster behavioral response time for the feature-match compared to the spatial-match WM task. We attribute this lower across-trial spiking variability and behavioral response time to a higher task-relevant attentional level in the feature WM compared to the spatial WM task. The findings support our hypothesis for task-specific differences in the processing of feature vs. spatial WM within the PFC. This also confirms the general conclusion that PFC neurons play an important role during the process of matching-rule governed decision-making.

Prefrontal lesions disrupt oscillatory signatures of spatiotemporal integration in working memory.

How does the human brain integrate spatial and temporal information into unified mnemonic representations? Building on classic theories of feature binding, we first define the oscillatory signatures of integrating 'where' and 'when' information in working memory (WM) and then investigate the role of prefrontal cortex (PFC) in spatiotemporal integration. Fourteen individuals with lateral PFC damage and 20 healthy controls completed a visuospatial WM task while electroencephalography (EEG) was recorded. On each trial, two shapes were presented sequentially in a top/bottom spatial orientation. We defined EEG signatures of spatiotemporal integration by comparing the maintenance of two possible where-when configurations: the first shape presented on top and the reverse. Frontal delta-theta (δθ; 2-7 Hz) activity, frontal-posterior δθ functional connectivity, lateral posterior event-related potentials, and mesial posterior alpha phase-to-gamma amplitude coupling dissociated the two configurations in controls. WM performance and frontal and mesial posterior signatures of spatiotemporal integration were diminished in PFC lesion patients, whereas lateral posterior signatures were intact. These findings reveal both PFC-dependent and independent substrates of spatiotemporal integration and link optimal performance to PFC.

Adaptation Modulates Spike-Phase Coupling Tuning Curve in the Rat Primary Auditory Cortex.

Adaptation is an important mechanism that causes a decrease in the neural response both in terms of local field potentials (LFP) and spiking activity. We previously showed this reduction effect in the tuning curve of the primary auditory cortex. Moreover, we revealed that a repeated stimulus reduces the neural response in terms of spike-phase coupling (SPC). In the current study, we examined the effect of adaptation on the SPC tuning curve. To this end, employing the phase-locking value (PLV) method, we estimated the spike-LFP coupling. The data was obtained by a simultaneous recording from four single-electrodes in the primary auditory cortex of 15 rats. We first investigated whether the neural system may use spike-LFP phase coupling in the primary auditory cortex to encode sensory information. Secondly, we investigated the effect of adaptation on this potential SPC tuning. Our data showed that the coupling between spikes' times and the LFP phase in beta oscillations represents sensory information (different stimulus frequencies), with an inverted bell-shaped tuning curve. Furthermore, we showed that adaptation to a specific frequency modulates SPC tuning curve of the adapter and its neighboring frequencies. These findings could be useful for interpretation of feature representation in terms of SPC and the underlying neural mechanism of adaptation.

Stimulus-Specific Adaptation Decreases the Coupling of Spikes to LFP Phase.

Stimulus repetition suppresses the neural activity in different sensory areas of the brain. This mechanism of so-called stimulus-specific adaptation (SSA) has been observed in both spiking activity and local field potential (LFP) responses. However, much remains to be known about the effect of SSA on the spike-LFP relation. In this study, we approached this issue by investigating the spike-phase coupling (SPC) in control and adapting paradigms. For the control paradigm, pure tones were presented in a random unbiased sequence. In the adapting paradigm, the same stimuli were presented in a random pattern but it was biased to an adapter stimulus. In fact, the adapter occupied 80% of the adapting sequence. During the tasks, LFP and multi-unit activity were recorded simultaneously from the primary auditory cortex of 15 anesthetized rats. To clarify the effect of adaptation on the relation between spike and LFP responses, the SPC of the adapter stimulus in these two paradigms was evaluated. Here, we employed phase locking value method for calculating the SPC. Our data show a strong coupling of spikes to LFP phase most prominently in beta band. This coupling was observed to decrease in the adapting condition compared to the control one. Importantly, we found that adaptation reduces spikes dominantly from the preferred phase of LFP in which spikes are more likely to be present there. As a result, the preferred phase of LFP may play a key role in coordinating neuronal spiking activity in neural adaptation mechanism. This finding is important for interpretation of the underlying neural mechanism of adaptation and also can be used in the context of the network and related connectivity models.

Neural Activity Predicts Reaction in Primates Long Before a Behavioral Response.

How neural activity is linked to behavior is a critical question in neural engineering and cognitive neurosciences. It is crucial to predict behavior as early as possible, to plan a machine response in real-time brain computer interactions. However, previous studies have studied the neural readout of behavior only within a short time before the action is performed. This leaves unclear, if the neural activity long before a decision could predict the upcoming behavior. By recording extracellular neural activities from the visual cortex of behaving rhesus monkeys, we show that: (1) both, local field potentials (LFPs) and the rate of neural spikes long before (>2 s) a monkey responds to a change, foretell its behavioral performance in a spatially selective manner; (2) LFPs, the more accessible component of extracellular activity, are a stronger predictor of behavior; and (3) LFP amplitude is positively correlated while spiking activity is negatively correlated with behavioral reaction time (RT). These results suggest that field potentials could be used to predict behavior way before it is performed, an observation that could potentially be useful for brain computer interface applications, and that they contribute to the sensory neural circuit's speed in information processing.

The effect of adaptation on the tuning curves of rat auditory cortex.

Repeated stimulus causes a specific suppression of neuronal responses, which is so-called as Stimulus-Specific Adaptation (SSA). This effect can be recovered when the stimulus changes. In the auditory system SSA is a well-known phenomenon that appears at different levels of the mammalian auditory pathway. In this study, we explored the effects of adaptation to a particular stimulus on the auditory tuning curves of anesthetized rats. We used two sequences and compared the responses of each tone combination in these two conditions. First sequence consists of different pure tone combinations that were presented randomly. In the second one, the same stimuli of the first sequence were presented in the context of an adapted stimulus (adapter) that occupied 80% of sequence probability. The population results demonstrated that the adaptation factor decreased the frequency response area and made a change in the tuning curve to shift it unevenly toward the higher thresholds of tones. The local field potentials and multi-unit activity responses have indicated that the neural activities strength of the adapted frequency has been suppressed as well as with lower suppression in neighboring frequencies. This aforementioned reduction changed the characteristic frequency of the tuning curve.