Between 30 and 50% of MS patients may prematurely discontinue disease modifying therapies. Little research has examined how to best talk with patients who have discontinued treatment against medical advice. The aim of this pilot study was to determine whether telephone counseling increases disease modifying therapy (DMT) re-initiation among nonadherent patients with multiple sclerosis (MS). Participants were eligible if they had relapsing-remitting disease, had stopped taking a DMT, and had no plan to re-initiate treatment despite a provider recommendation. Following a baseline assessment, 81 patients were randomly assigned to either five 20 min, weekly sessions of Motivational Interviewing/Cognitive Behavioral Therapy (MI-CBT) or Treatment as Usual (TAU) with brief education. At 10 weeks, patients initially assigned to TAU switched over to MI-CBT. Compared to patients in the TAU group, patients undergoing MI-CBT were significantly more likely to indicate they were re-initiating DMT (41.7 vs. 14.3%). These significant results were replicated among patients crossing over from TAU to MI-CBT. Treatment satisfaction was high, with 97% of participants reporting that they would recommend MI-CBT to other patients with MS. Results of this pilot study provide initial support for the use of MI-CBT among MS patients who have discontinued treatment against medical advice.Clinicaltrials.gov: NCT01925690.

Extensive evidence suggests that people use base rate information inconsistently in decision making. A classic example is the inverse base rate effect (IBRE), whereby participants classify ambiguous stimuli sharing features of both common and rare categories as members of the rare category. Computational models of the IBRE have posited that it arises either from associative similarity-based mechanisms or from dissimilarity-based processes that may depend on higher-level inference. Here we develop a hybrid model, which posits that similarity- and dissimilarity-based evidence both contribute to the IBRE, and test it using functional magnetic resonance imaging data collected from human subjects completing an IBRE task. Consistent with our model, multivoxel pattern analysis reveals that activation patterns on ambiguous test trials contain information consistent with dissimilarity-based processing. Further, trial-by-trial activation in left rostrolateral prefrontal cortex tracks model-based predictions for dissimilarity-based processing, consistent with theories positing a role for higher-level symbolic processing in the IBRE.

When weighing evidence for a decision, individuals are continually faced with the choice of whether to gather more information or act on what has already been learned. The present experiment employed a self-paced category learning task and fMRI to examine the neural mechanisms underlying stopping of information search and how they contribute to choice accuracy. Participants learned to classify triads of face, object, and scene cues into one of two categories using a rule based on one of the stimulus dimensions. After each trial, participants were given the option to explicitly solve the rule or continue learning. Representational similarity analysis (RSA) was used to examine activation of rule-relevant information on trials leading up to a decision to solve the rule. We found that activation of rule-relevant information increased leading up to participants' stopping decisions. Stopping was associated with widespread activation that included medial prefrontal cortex and visual association areas. Engagement of ventromedial prefrontal cortex (vmPFC) was associated with accurate stopping, and activation in this region was functionally coupled with signal in dorsolateral prefrontal cortex (dlPFC). Results suggest that activating rule information when deciding whether to stop an information search increases choice accuracy, and that the response profile of vmPFC during such decisions may provide an index of effective learning.

Pending further research, the SET, a brief, inexpensive, and nontechnical measure of speedy eye movement, may serve as a visual/oculomotor indicator of cognitive impairment in multiple sclerosis.

Visual attention studies have demonstrated that the shape of space-based selection can be governed by salient object contours: when a portion of an enclosed space is cued, the selected region extends to the full enclosure. Although this form of object-based attention (OBA) is well established, one continuing investigation focuses on whether this selection is obligatory or under voluntary control. We attempt to dissociate between these alternatives by interrogating the locus coeruleus-norepinephrine (LC-NE) system – known to fluctuate with top-down attention – during a classic two-rectangle paradigm in a sample of healthy human participants (N = 36). An endogenous spatial pre-cue directed voluntary space-based attention (SBA) to one end of a rectangular frame. We manipulated the reliability of the cue, such that targets appearing at an uncued location within the frame occurred at low or moderate frequencies. Phasic pupillary responses time-locked to the cue display served to noninvasively measure LC-NE activity, reflecting top-down processing of the spatial cue. If OBA is controlled analogously to SBA, then object selection should emerge only when it is behaviorally expedient and when LC-NE activity reflects a high degree of top-down attention to the cue display. Our results bore this out. Thus, we conclude that OBA was voluntarily controlled, and furthermore show that phasic norepinephrine may modulate attentional strategy.