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Bloem, B.

Publications and source records attributed to Bloem, B..

3 recordsLinked to original sources

Rapid dynamic naturalistic monitoring of bradykinesia in Parkinson's disease using a wrist-worn accelerometer

IntroductionMotor fluctuations in Parkinsons disease are characterized by unpredictability in the timing and duration of dopaminergic therapeutic benefit on symptoms including bradykinesia and rigidity. These fluctuations significantly impair the quality of life of many Parkinsons patients. However, current clinical evaluation tools are not designed for the continuous, naturalistic (real-world) symptom monitoring needed to optimize clinical therapy to treat fluctuations. Although commercially available wearable motor monitoring, used over multiple days, can augment neurological decision making, the feasibility of rapid and dynamic detection of motor fluctuations is unclear. So far, applied wearable monitoring algorithms are trained on group data. Here, we investigate the influence of individual model training on short timescale classification of naturalistic bradykinesia fluctuations in Parkinsons patients using a single wrist-accelerometer. MethodsAs part of the Parkinson@Home study protocol, 20 Parkinson patients were recorded with bilateral wrist-accelerometers for a one hour OFF medication session and a one hour ON medication session during unconstrained activities in their own homes. Kinematic metrics were extracted from the accelerometer data from the bodyside with the largest unilateral bradykinesia fluctuations across medication states. The kinematic accelerometer features were compared over the whole one-hour recordings, and medication-state classification analyses were performed on one-minute segments of data. The influence of individual versus group model training, data window length, and total amount of training patients included in group model training on classification was analyzed. ResultsStatistically significant areas under the curves (AUCs) for medication induced bradykinesia fluctuation classification were seen in 85% of the Parkinson patients at the single minute timescale using the group models. Individually trained models performed at the same level as the group trained models (mean AUC both 0.70, +/- respectively 0.18 and 0.10) despite the small individual training dataset. AUCs of the group models improved as the length of the feature windows was increased to 300 seconds, and with additional training patient datasets. ConclusionMedication induced fluctuations in bradykinesia can be classified using wrist worn accelerometery at the time scale of a single minute. Rapid, naturalistic Parkinson motor monitoring has important clinical potential to evaluate dynamic symptomatic and therapeutic fluctuations and help tailor treatments on a fast timescale.

neuroscience↗

Multiplexed action-outcome representation by striatal striosome-matrix compartments detected with a novel cost-benefit foraging task

Learning about positive and negative outcomes of actions is crucial for survival and underpinned by conserved circuits including the striatum. How associations between actions and outcomes are formed is not fully understood, particularly when the outcomes have mixed positive and negative features. We developed a novel foraging ( bandit) task requiring mice to maximize rewards while minimizing punishments. By 2-photon Ca++ imaging, we monitored activity of 5831 identified anterodorsal striatal striosomal and matrix neurons. Surprisingly, we found that action-outcome associations for reward and punishment were combinatorially encoded rather than being integrated as overall outcome value. Single neurons could, for one action, encode outcomes of opposing valence. Striosome compartments consistently exhibited stronger representations of reinforcement outcomes than matrix, especially for high reward or punishment prediction errors. These findings demonstrate a remarkable multiplexing of action-outcome contingencies by single identified striatal neurons and suggest that striosomal neurons are differentially important in action-outcome learning.

neuroscience↗

Two-Photon Imaging of Striatum Demonstrates Distinct Functions for Striosomes and Matrix in Reinforcement Learning

Despite the discovery of striosomes several decades ago, technical difficulties have hampered the study of their functions. Here we used 2-photon calcium imaging in neuronal birthdate-labeled Mash1-CreER mice to image simultaneously the activity of striosomal and matrix neurons in vivo. We report that with this method we can visually identify circumscribed zones of neuropil that correspond to striosomes as verified in immunostained sections. We find that striosomal neurons, relative to matrix neurons, preferentially encode reward-predicting cues, and that their activity contains more information about expected outcome. These characteristics emerge during training and further strengthen during overtraining. Both striatal compartments are active similarly after reward delivery, firing at neuron-specific times during or after consummatory licking. Finally, we find that immediate reward history strongly modulates neuronal activation in the next trial, especially in matrix neurons. These results suggest that striosomes and matrix have distinct functions in relation to reinforcement learning.

neuroscience↗