Probabilistic Decision-Making in Children With Dyslexia.

Background: Neurocognitive mechanisms underlying developmental dyslexia (dD) remain poorly characterized apart from phonological and/or visual processing deficits. Assuming such deficits, the process of learning complex tasks like reading requires the learner to make decisions (i.e., word pronunciation) based on uncertain information (e.g., aberrant phonological percepts)-a cognitive process known as probabilistic decision making, which has been linked to the striatum. We investigate (1) the relationship between dD and probabilistic decision-making and (2) the association between the volume of striatal structures and probabilistic decision-making in dD and typical readers. Methods: Twenty four children diagnosed with dD underwent a comprehensive evaluation and MRI scanning (3T). Children with dD were compared to age-matched typical readers (n = 11) on a probabilistic, risk/reward fishing task that utilized a Bayesian cognitive model with game parameters of risk propensity (γ+) and behavioral consistency (ß), as well as an overall adjusted score (average number of casts, excluding forced-fail trials). Volumes of striatal structures (caudate, putamen, and nucleus accumbens) were analyzed between groups and associated with game parameters. Results: dD was associated with greater risk propensity and decreased behavioral consistency estimates compared to typical readers. Cognitive model parameters associated with timed pseudoword reading across groups. Risk propensity related to caudate volumes, particularly in the dD group. Conclusion: Decision-making processes differentiate dD, associate with the caudate, and may impact learning mechanisms. This study suggests the need for further research into domain-general probabilistic decision-making in dD, neurocognitive mechanisms, and targeted interventions in dD.

Report of a patient undergoing chronic responsive deep brain stimulation for Tourette syndrome: proof of concept.

Deep brain stimulation (DBS) has emerged as a promising intervention for the treatment of select movement and neuropsychiatric disorders. Current DBS therapies deliver electrical stimulation continuously and are not designed to adapt to a patient's symptoms. Continuous DBS can lead to rapid battery depletion, which necessitates frequent surgery for battery replacement. Next-generation neurostimulation devices can monitor neural signals from implanted DBS leads, where stimulation can be delivered responsively, moving the field of neuromodulation away from continuous paradigms. To this end, the authors designed and chronically implemented a responsive stimulation paradigm in a patient with medically refractory Tourette syndrome. The patient underwent implantation of a responsive neurostimulator, which is capable of responsive DBS, with bilateral leads in the centromedian-parafascicular (Cm-Pf) region of the thalamus. A spectral feature in the 5- to 15-Hz band was identified as the control signal. Clinical data collected prior to and after 12 months of responsive therapy revealed improvements from baseline scores in both Modified Rush Tic Rating Scale and Yale Global Tic Severity Scale scores (64% and 48% improvement, respectively). The effectiveness of responsive stimulation (p = 0.16) was statistically identical to that of scheduled duty cycle stimulation (p = 0.33; 2-sided Wilcoxon unpaired rank-sum t-test). Overall, responsive stimulation resulted in a 63.3% improvement in the neurostimulator's projected mean battery life. Herein, to their knowledge, the authors present the first proof of concept for responsive stimulation in a patient with Tourette syndrome.

Measures of impulsivity in Parkinson's disease decrease after DBS in the setting of stable dopamine therapy.

INTRODUCTION: Recent evidence suggests deep brain stimulation can alter impulse control. Our objective was to prospectively evaluate the effects of subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation on impulse control disorders (ICDs) in the setting of a conservative dopamine reduction strategy. METHODS: Patients (n = 37) undergoing de novo, unilateral STN or GPi DBS lead implantation were evaluated pre-operatively and 6-12 months post-operatively for the presence of ICDs using the Questionnaire for Impulsivity in Parkinson's disease (QUIP) and by clinical interview. RESULTS: Of the patients enrolled, 23 underwent electrode implantation in the globus pallidus internus and 14 were implanted in the subthalamic nucleus. Mean time to long term follow-up was 9.7 ± 2.4 months. Post-operative LEDD was not significantly lower than pre-operative LEDD (pre-op: 1238.53 ± 128.47 vs. post-op: 1178.18 ± 126.43, p = 0.2972, paired t-test). Mean QUIP scores were significantly lower at follow up compared to pre-operative baseline (1.51 ± 0.45 vs. 2.51 ± 0.58, p = 0.0447, paired t-test). Patients with ICDs pre-operatively (n = 14, 37.8%) had significant improvement in QUIP scores at follow-up (6.00 ± 0.94 vs. 2.64 ± 0.98, p = 0.0014, paired t-test). Improvement was not uniform across the cohort: 1 patient with ICD at baseline developed worsening symptoms, and 4 patients with no ICD pre-operatively developed clinically significant ICDs post-operatively. CONCLUSION: When LEDD is relatively unchanged following STN or GPi DBS for PD, ICD symptoms tend toward improvement, although worsening and emergence of new ICDs can occur. In the setting of stable LEDD, these findings suggest that the intrinsic effects of DBS may play a significant role in altering impulsive behavior.

Thalamocortical network activity enables chronic tic detection in humans with Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. Deep brain stimulation (DBS) is an emerging therapy for severe cases of TS. We studied two patients with TS implanted with bilateral Medtronic Activa PC + S DBS devices, capable of chronic recordings, with depth leads in the thalamic centromedian-parafascicular complex (CM-PF) and subdural strips over the precentral gyrus. Low-frequency (1-10 Hz) CM-PF activity was observed during tics, as well as modulations in beta rhythms over the motor cortex. Tics were divided into three categories: long complex, complex, and simple. Long complex tics, tics involving multiple body regions and lasting longer than 5 s, were concurrent with a highly detectable thalamocortical signature (average recall [sensitivity] 88.6%, average precision 96.3%). Complex tics were detected with an average recall of 63.9% and precision of 36.6% and simple tics an average recall of 39.3% and precision of 37.9%. The detections were determined using data from both patients.

Scheduled, intermittent stimulation of the thalamus reduces tics in Tourette syndrome.

INTRODUCTION: Personalized, scheduled deep brain stimulation in Tourette syndrome (TS) may permit clinically meaningful tic reduction while reducing side effects and increasing battery life. Here, we evaluate scheduled DBS applied to TS at two-year follow-up. METHODS: Five patients underwent bilateral centromedian thalamic (CM) region DBS. A cranially contained constant-current device delivering stimulation on a scheduled duty cycle, as opposed to the standard continuous DBS paradigm was utilized. Baseline vs. 24-month outcomes were collected and analyzed, and a responder analysis was performed. A 40% improvement in the Modified Rush Tic Rating Scale (MRTRS) total score or Yale Global Tic Severity Scale (YGTSS) total score defined a full responder. RESULTS: Three of the 4 patients followed to 24 months reached full responder criteria and had a mean stimulation time of 1.85 h per day. One patient lost to follow-up evaluated at the last time point (month 18) was a non-responder. Patients exhibited improvements in MRTRS score beyond the improvements previously reported for the 6 month endpoint; on average, MRTRS total score was 15.6% better at 24 months than at 6 months and YGTSS total score was 14.8% better. Combining the patients into a single cohort revealed significant improvements in the MRTRS total score (-7.6 [5.64]; p = 0.02). CONCLUSION: Electrical stimulation of the centromedian thalamic region in a scheduled paradigm was effective in suppressing tics, particularly phonic tics. Full responders were able to achieve the positive DBS effect with a mean of 2.3 ± 0.9 (SEM) hours of DBS per day.

Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies.

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies.

The Subthalamic Nucleus, Limbic Function, and Impulse Control.

It has been well documented that deep brain stimulation (DBS) of the subthalamic nucleus (STN) to address some of the disabling motor symptoms of Parkinson's disease (PD) can evoke unintended effects, especially on non-motor behavior. This observation has catalyzed more than a decade of research concentrated on establishing trends and identifying potential mechanisms for these non-motor effects. While many issues remain unresolved, the collective result of many research studies and clinical observations has been a general recognition of the role of the STN in mediating limbic function. In particular, the STN has been implicated in impulse control and the related construct of valence processing. A better understanding of STN involvement in these phenomena could have important implications for treating impulse control disorders (ICDs). ICDs affect up to 40% of PD patients on dopamine agonist therapy and approximately 15% of PD patients overall. ICDs have been reported to be associated with STN DBS. In this paper we will focus on impulse control and review pre-clinical, clinical, behavioral, imaging, and electrophysiological studies pertaining to the limbic function of the STN.

Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline.

The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.