Reconfiguration of Behavioral Signals in the Anterior Cingulate Cortex Based on Emotional State.

Behaviors and their execution depend on the context and emotional state in which they are performed. The contextual modulation of behavior likely relies on regions such as the anterior cingulate cortex (ACC) that multiplex information about emotional/autonomic states and behaviors. The objective of the present study was to understand how the representations of behaviors by ACC neurons become modified when performed in different emotional states. A pipeline of machine learning techniques was developed to categorize and classify complex, spontaneous behaviors in male rats from the video. This pipeline, termed Hierarchical Unsupervised Behavioural Discovery Tool (HUB-DT), discovered a range of statistically separable behaviors during a task in which motivationally significant outcomes were delivered in blocks of trials that created three unique "emotional contexts." HUB-DT was capable of detecting behaviors specific to each emotional context and was able to identify and segregate the portions of a neural signal related to a behavior and to emotional context. Overall, ∼10× as many neurons responded to behaviors in a contextually dependent versus a fixed manner, highlighting the extreme impact of emotional state on representations of behaviors that were precisely defined based on detailed analyses of limb kinematics. This type of modulation may be a key mechanism that allows the ACC to modify the behavioral output based on emotional states and contextual demands.

Data-Driven Prediction of Fatigue in Parkinson's Disease Patients.

Introduction: Numerous non-motor symptoms are associated with Parkinson's disease (PD) including fatigue. The challenge in the clinic is to detect relevant non-motor symptoms while keeping patient-burden of questionnaires low and to take potential subgroups such as sex differences into account. The Fatigue Severity Scale (FSS) effectively detects clinically significant fatigue in PD patients. Machine learning techniques can determine which FSS items best predict clinically significant fatigue yet the choice of technique is crucial as it determines the stability of results. Methods: 182 records of PD patients were analyzed with two machine learning algorithms: random forest (RF) and Boruta. RF and Boruta calculated feature importance scores, which measured how much impact an FSS item had in predicting clinically significant fatigue. Items with the highest feature importance scores were the best predictors. Principal components analysis (PCA) grouped highly related FSS items together. Results: RF, Boruta and PCA demonstrated that items 8 ("Fatigue is among my three most disabling symptoms") and 9 ("Fatigue interferes with my work, family or social life") were the most important predictors. Item 5 ("Fatigue causes frequent problems for me") was an important predictor for females, and item 6 ("My fatigue prevents sustained physical functioning") was important for males. Feature importance scores' standard deviations were large for RF (14-66%) but small for Boruta (0-5%). Conclusion: The clinically most informative questions may be how disabling fatigue is compared to other symptoms and interference with work, family and friends. There may be some sex-related differences with frequency of fatigue-related complaints in females and endurance-related complaints in males yielding significant information. Boruta but not RF yielded stable results and might be a better tool to determine the most relevant components of abbreviated questionnaires. Further research in this area would be beneficial in order to replicate these findings with other machine learning algorithms, and using a more representative sample of PD patients.

How Much Does Movement and Location Encoding Impact Prefrontal Cortex Activity? An Algorithmic Decoding Approach in Freely Moving Rats.

Specialized brain structures encode spatial locations and movements, yet there is growing evidence that this information is also represented in the rodent medial prefrontal cortex (mPFC). Disambiguating such information from the encoding of other types of task-relevant information has proven challenging. To determine the extent to which movement and location information is relevant to mPFC neurons, tetrodes were used to record neuronal activity while limb positions, poses (i.e., recurring constellations of limb positions), velocity, and spatial locations were simultaneously recorded with two cameras every 200 ms as rats freely roamed in an experimental enclosure. Regression analyses using generalized linear models revealed that more than half of the individual mPFC neurons were significantly responsive to at least one of the factors, and many were responsive to more than one. On the other hand, each factor accounted for only a very small portion of the total spike count variance of any given neuron (<20% and typically <1%). Machine learning methods were used to analyze ensemble activity and revealed that ensembles were usually superior to the sum of the best neurons in encoding movements and spatial locations. Because movement and location encoding by individual neurons was so weak, it may not be such a concern for single-neuron analyses. Yet because these weak signals were so widely distributed across the population, this information was strongly represented at the ensemble level and should be considered in population analyses.

Differences in the emergent coding properties of cortical and striatal ensembles.

The function of a given brain region is often defined by the coding properties of its individual neurons, yet how this information is combined at the ensemble level is an equally important consideration. We recorded multiple neurons from the anterior cingulate cortex (ACC) and the dorsal striatum (DS) simultaneously as rats performed different sequences of the same three actions. Sequence and lever decoding was markedly similar on a per-neuron basis in the two regions. At the ensemble level, sequence-specific representations in the DS appeared synchronously, but transiently, along with the representation of lever location, whereas these two streams of information appeared independently and asynchronously in the ACC. As a result, the ACC achieved superior ensemble decoding accuracy overall. Thus, the manner in which information was combined across neurons in an ensemble determined the functional separation of the ACC and DS on this task.