The medial frontal cortex and adjacent orbitofrontal cortex have been the focus of investigations of decision-making, behavioral flexibility, and social behavior. We review studies conducted in ...humans, macaques, and rodents and argue that several regions with different functional roles can be identified in the dorsal anterior cingulate cortex, perigenual anterior cingulate cortex, anterior medial frontal cortex, ventromedial prefrontal cortex, and medial and lateral parts of the orbitofrontal cortex. There is increasing evidence that the manner in which these areas represent the value of the environment and specific choices is different from subcortical brain regions and more complex than previously thought. Although activity in some regions reflects distributions of reward and opportunities across the environment, in other cases, activity reflects the structural relationships between features of the environment that animals can use to infer what decision to take even if they have not encountered identical opportunities in the past.
The prefrontal cortex (PFC) provides high-level coordination of behavior but is not a homogeneous structure. In this review, Klein-Flügge et al. compare the function of several distinct PFC regions and connected subcortical nuclei in decision-making, behavioral flexibility, and social behavior.
Neural mechanisms that mediate the ability to make value-guided decisions have received substantial attention in humans and animals
. Experiments in animals typically involve long training periods. ...By contrast, choices in the real world often need to be made between new options spontaneously. It is therefore possible that the neural mechanisms targeted in animal studies differ from those required for new decisions, which are typical of human imaging studies. Here we show that the primate medial frontal cortex (MFC)
is involved in making new inferential choices when the options have not been previously experienced. Macaques spontaneously inferred the values of new options via similarities with the component parts of previously encountered options. Functional magnetic resonance imaging (fMRI) suggested that this ability was mediated by the MFC, which is rarely investigated in monkeys
; MFC activity reflected different processes of comparison for unfamiliar and familiar options. Multidimensional representations of options in the MFC used a coding scheme resembling that of grid cells, which is well known in spatial navigation
, to integrate dimensions in this non-physical space
during novel decision-making. By contrast, the orbitofrontal cortex held specific object-based value representations
. In addition, minimally invasive ultrasonic disruption
of MFC, but not adjacent tissue, altered the estimation of novel choice values.
Abstract Staying engaged is necessary to maintain goal-directed behaviors. Despite this, engagement exhibits continuous, intrinsic fluctuations. Even in experimental settings, animals, unlike most ...humans, repeatedly and spontaneously move between periods of complete task engagement and disengagement. We, therefore, looked at behavior in male macaques ( macaca mulatta) in four tasks while recording fMRI signals. We identified consistent autocorrelation in task disengagement. This made it possible to build models capturing task-independent engagement. We identified task general patterns of neural activity linked to impending sudden task disengagement in mid-cingulate gyrus. By contrast, activity centered in perigenual anterior cingulate cortex (pgACC) was associated with maintenance of performance across tasks. Importantly, we carefully controlled for task-specific factors such as the reward history and other motivational effects, such as response vigor, in our analyses. Moreover, we showed pgACC activity had a causal link to task engagement: transcranial ultrasound stimulation of pgACC changed task engagement patterns.
Animals learn from the past to make predictions. These predictions are adjusted after prediction errors, i.e., after surprising events. Generally, most reward prediction errors models learn the ...average expected amount of reward. However, here we demonstrate the existence of distinct mechanisms for detecting other types of surprising events. Six macaques learned to respond to visual stimuli to receive varying amounts of juice rewards. Most trials ended with the delivery of either 1 or 3 juice drops so that animals learned to expect 2 juice drops on average even though instances of precisely 2 drops were rare. To encourage learning, we also included sessions during which the ratio between 1 and 3 drops changed. Additionally, in all sessions, the stimulus sometimes appeared in an unexpected location. Thus, 3 types of surprising events could occur: reward amount surprise (i.e., a scalar reward prediction error), rare reward surprise, and visuospatial surprise. Importantly, we can dissociate scalar reward prediction errors-rewards that deviated from the average reward amount expected-and rare reward events-rewards that accorded with the average reward expectation but that rarely occurred. We linked each type of surprise to a distinct pattern of neural activity using functional magnetic resonance imaging. Activity in the vicinity of the dopaminergic midbrain only reflected surprise about the amount of reward. Lateral prefrontal cortex had a more general role in detecting surprising events. Posterior lateral orbitofrontal cortex specifically detected rare reward events regardless of whether they followed average reward amount expectations, but only in learnable reward environments.
The medial frontal cortex has been linked to voluntary action, but an explanation of why decisions to act emerge at particular points in time has been lacking. We show that, in macaques, decisions ...about whether and when to act are predicted by a set of features defining the animal’s current and past context; for example, respectively, cues indicating the current average rate of reward and recent previous voluntary action decisions. We show that activity in two brain areas—the anterior cingulate cortex and basal forebrain—tracks these contextual factors and mediates their effects on behavior in distinct ways. We use focused transcranial ultrasound to selectively and effectively stimulate deep in the brain, even as deep as the basal forebrain, and demonstrate that alteration of activity in the two areas changes decisions about when to act.
•Likelihood and timing of voluntary action in macaques can be partially predicted•Recent experience and present context influence when voluntary action occurs•A basal forebrain-cingulate circuit mediated effects of these factors on behavior•Stimulation of this circuit by ultrasound changed decisions about when to act
Deciding when to act is crucial for animals’ survival. Khalighinejad et al. used neuroimaging and ultrasound to identify a basal forebrain-cingulate circuit that tracks contextual factors in animals’ environments and mediates their effects on animals’ decisions about when to act.
When choosing, primates are guided not only by personal experience of objects but also by social information such as others’ attitudes toward the objects. Crucially, both sources of ...information—personal and socially derived—vary in reliability. To choose optimally, one must sometimes override choice guidance by personal experience and follow social cues instead, and sometimes one must do the opposite. The dorsomedial frontopolar cortex (dmFPC) tracks reliability of social information and determines whether it will be attended to guide behavior. To do this, dmFPC activity enters specific patterns of interaction with a region in the mid-superior temporal sulcus (mSTS). Reversible disruption of dmFPC activity with transcranial ultrasound stimulation (TUS) led macaques to fail to be guided by social information when it was reliable but to be more likely to use it when it was unreliable. By contrast, mSTS disruption uniformly downregulated the impact of social information on behavior.
•Macaques’ dmFPC activity changes with the reliability of social information•mSTS-dmFPC interaction occurs when social information influences behavior•Disruption of dmFPC decreases the impact of social information when it is reliable•Disruption of dmFPC increases the impact of social information when it is unreliable
Mahmoodi et al. identify a neural circuit in macaques that comprises dorsomedial frontopolar cortex (dmFPC) and mid-superior temporal sulcus (mSTS) for regulating the impact of social information according to its reliability. Disruption of dmFPC and mSTS produces distinct changes in social information use.
In this thesis the cognitive and neuro-computational bases of novel value-based decision-making in non-human primates are studied. Humans routinely perform choices among options that have not ...previously been experienced, using value expectations derived from their component attributes. Animal studies, however, are typically performed after extensive training ensuring familiarity with the task. Here we show how Rhesus macaques can readily perform value-guided choices among novel stimuli - if their components are known. An economic analysis of subjective biases is provided. Neuroimaging and causal techniques are then used to uncover a network centred in anterior medial frontal cortex (AMFC) underlying adaptive novel decisions. A first experiment, using fMRI with a binary decision task, reveals that orbitofrontal cortex is equally modulated by value in novel and familiar choices, but in contrast AMFC and dorsolateral prefrontal cortex (dlPFC) show a markedly different pattern of responses between conditions. A second experiment, using fMRI and single option trials, reveals how AMFC and dlPFC, but no other regions, encode representations of abstract value independent from its components (reward magnitude and probability), appearing across sessions with exposure to the novel options. Additionally, a pattern of hexagonal symmetry is found in AMFC activity, indicating a grid-like encoding of two-dimensional value space. Such a code provides a mechanistic explanation of how novel options' values may be computed. A last experiment confirms this by showing that transiently disrupting AMFC with focused transcranial ultrasound impairs the use of an integrated representation of value when novel decisions are made. Together, these experiments bridge neuroscientific studies in humans and monkeys and reveal a neural basis for novel decision-making that has not previously been investigated in either species.
To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis.
Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. ...Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale NIHSS ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale mRS ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death.
Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio OR 1.68, 95% confidence interval CI 1.26-2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11-1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18-2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19-0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28-0.82; p = 0.007).
Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome.
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