Based on prior findings of content-specific beta synchronization in working memory and decision making, we hypothesized that beta oscillations support the (re-)activation of cortical representations by mediating neural ensemble formation. We found that beta activity in monkey dorsolateral prefrontal cortex (dlPFC) and pre-supplementary motor area (preSMA) reflects the content of a stimulus in relation to the task context, regardless of its objective properties. In duration- and distance-categorization tasks, we changed the boundary between categories from one block of trials to the next. We found that two distinct beta-band frequencies were consistently associated with the two relative categories, with activity in these bands predicting the animals' responses. We characterized beta at these frequencies as transient bursts, and showed that dlPFC and preSMA are connected via these distinct frequency channels. These results support the role of beta in forming neural ensembles, and further show that such ensembles synchronize at different beta frequencies.

AbstractThe thalamus and cortex are interconnected both functionally and anatomically and share a common developmental trajectory. Interactions between the mediodorsal thalamus (MD) and different parts of the prefrontal cortex are essential in cognitive processes, such as learning and adaptive decision‐making. Cortico‐thalamocortical interactions involving other dorsal thalamic nuclei, including the anterior thalamus and pulvinar, also influence these cognitive processes. Our work, and that of others, indicates a crucial influence of these interdependent cortico‐thalamocortical neural networks that contributes actively to the processing of information within the cortex. Each of these thalamic nuclei also receives potent subcortical inputs that are likely to provide additional influences on their regulation of cortical activity. Here, we highlight our current neuroscientific research aimed at establishing when cortico‐MD thalamocortical neural network communication is vital within the context of a rapid learning and memory discrimination task. We are collecting evidence of MD–prefrontal cortex neural network communication in awake, behaving male rhesus macaques. Given the prevailing evidence, further studies are needed to identify both broad and specific mechanisms that govern how the MD, anterior thalamus and pulvinar cortico‐thalamocortical interactions support learning, memory and decision‐making. Current evidence shows that the MD (and the anterior thalamus) are crucial for frontotemporal communication, and the pulvinar is crucial for frontoparietal communication. Such work is crucial to advance our understanding of the neuroanatomical and physiological bases of these brain functions in humans. In turn, this might offer avenues to develop effective treatment strategies to improve the cognitive deficits often observed in many debilitating neurological disorders and diseases and in neurodegeneration.
image

AbstractPerceptual categorization depends on the assignment of different stimuli to specific groups based, in principle, on the notion of flexible categorical boundaries. To determine the neural basis of categorical boundaries, we record the activity of pre-SMA neurons of monkeys executing an interval categorization task in which the limit between short and long categories changes between blocks of trials within a session. A large population of cells encodes this boundary by reaching a constant peak of activity close to the corresponding subjective limit. Notably, the time at which this peak is reached changes according to the categorical boundary of the current block, predicting the monkeys’ categorical decision on a trial-by-trial basis. In addition, pre-SMA cells also represent the category selected by the monkeys and the outcome of the decision. These results suggest that the pre-SMA adaptively encodes subjective duration boundaries between short and long durations and contains crucial neural information to categorize intervals and evaluate the outcome of such perceptual decisions.

AbstractWe determined the response properties of neurons in the primate medial premotor cortex that were classified as sensory or motor during isochronous tapping to a visual or auditory metronome, using different target intervals and three sequential elements in the task. The cell classification was based on a warping transformation, which determined whether the cell activity was statistically aligned to sensory or motor events, finding a large proportion of cells classified as sensory or motor. Two distinctive clusters of sensory cells were observed, i.e. one cell population with short response‐onset latencies to the previous stimulus, and another that was probably predicting the occurrence of the next stimuli. These cells were called sensory‐driven and stimulus‐predicting neurons, respectively. Sensory‐driven neurons showed a clear bias towards the visual modality and were more responsive to the first stimulus, with a decrease in activity for the following sequential elements of the metronome. In contrast, stimulus‐predicting neurons were bimodal and showed similar response profiles across serial‐order elements. Motor cells showed a consecutive activity onset across discrete neural ensembles, generating a rapid succession of activation patterns between the two taps defining a produced interval. The cyclical configuration in activation profiles engaged more motor cells as the serial‐order elements progressed across the task, and the rate of cell recruitment over time decreased as a function of the target interval. Our findings support the idea that motor cells were responsible for the rhythmic progression of taps in the task, gaining more importance as the trial advanced, while, simultaneously, the sensory‐driven cells lost their functional impact.

This study describes the psychometric similarities and differences in motor timing performance between 20 human subjects and three rhesus monkeys during two timing production tasks. These tasks involved tapping on a push-button to produce the same set of intervals (range of 450 to 1,000 ms), but they differed in the number of intervals produced (single vs. multiple) and the modality of the stimuli (auditory vs. visual) used to define the time intervals. The data showed that for both primate species, variability increased as a function of the length of the produced target interval across tasks, a result in accordance with the scalar property. Interestingly, the temporal performance of rhesus monkeys was equivalent to that of human subjects during both the production of single intervals and the tapping synchronization to a metronome. Overall, however, human subjects were more accurate than monkeys and showed less timing variability. This was especially true during the self-pacing phase of the multiple interval production task, a behavior that may be related to complex temporal cognition, such as speech and music execution. In addition, the well-known human bias toward auditory as opposed to visual cues for the accurate execution of time intervals was not evident in rhesus monkeys. These findings validate the rhesus monkey as an appropriate model for the study of the neural basis of time production, but also suggest that the exquisite temporal abilities of humans, which peak in speech and music performance, are not all shared with macaques.

Allelic variants in the promoter region of the serotonin transporter (5-HTT) gene have been implicated in several psychiatric disorders and personality traits. In particular, two common alleles in a variable repeat sequence of the promoter region (SLC6A4) have been differentially associated with a display of abnormal levels of anxiety and affective illness in individuals carrying the "s" allele. The aim of this study was to compare the basal cerebral metabolic activity of non-psychiatric subjects in fronto-limbic structures to determine whether differences exist in basal metabolic activity within this functional polymorphism. PET scans with fluorine-18 fluorodeoxyglucose as radiotracer were performed in 71 non-psychiatric subjects previously screened for psychopathology and subsequently genotyped for SLC6A4; PET images were compared with SPM2 according to s/s (n = 27), s/l (n = 25), and l/l (n = 19) groups considering a significance threshold in a priori selected areas of P < 0.001 and an extent threshold > or =5 voxels. The analysis showed an effect of interest among the three genotype groups in right anterior cingulate gyrus (ACC), left middle frontal gyrus, and left posterior cingulate gyrus (PCC). Comparison between l/l vs. s/s showed increased metabolism for l/l in left middle frontal gyrus and an increase for s/s in right ACC and left PCC. Comparison between s/s vs. s/l showed an increase for s/s in left PCC and right ACC. Increased basal metabolism in fronto-limbic structures for the s/s group may be conceived as an "overactive metabolic state" of these structures, possibly related to an increased susceptibility for developing an anxiety-depression spectrum disorder.

Dorsolateral prefrontal cortex (DLPFCx) has been implicated in pain perception and in a pain modulation pathway. However, the precise participation of this region is not completely understood. The aim of this study was to evaluate whether 1 Hz rTMS of DLPFCx modifies threshold and tolerance in experimental pain. The effect of 1 Hz rTMS during 15 min at 100% motor threshold was tested in one hundred and eighty right-handed healthy volunteers, using a parallel-group stimulation design. The stimulation sites were right or left DLPFCx, right or left motor cortex, vertex or sham. rTMS was applied in two experimental contexts: (1) to evaluate its transitory effect (interference or facilitation) during cold pressor threshold (CPTh) and tolerance (CPTt) and (2) to evaluate its long-term effect by stimulating before CPTh, CPTt, pain heat thermal threshold, pain pressure threshold and tolerance. During rTMS of right DLPFCx, an increase in left hand CPTt (mean +/- SD; 17.63 s +/- 5.58 to 30.94 s +/- 14.84, P < 0.001) and in right hand CPTt (18.65 s +/- 6.47 to 26.74 s +/- 11.85, P < 0.001) were shown. No other stimulation site modified any of the pain measures during or after rTMS. These results show that 1 Hz rTMS of right DLPFCx has a selective effect by increasing pain tolerance and also sustains a right hemisphere preference in pain processing.