Bryan A. Strange

Automatic and intentional brain responses during evaluation of trustworthiness of faces

Successful social interaction partly depends on appraisal of others from their facial appearance. A critical aspect of this appraisal relates to whether we consider others to be trustworthy. We determined the neural basis for such trustworthiness judgments using event-related functional magnetic resonance imaging. Subjects viewed faces and assessed either trustworthiness or age. In a parametric factorial design, trustworthiness ratings were correlated with BOLD signal change to reveal task-independent increased activity in bilateral amygdala and right insula in response to faces judged untrustworthy. Right superior temporal sulcus (STS) showed enhanced signal change during explicit trustworthiness judgments alone. The findings extend a proposed model of social cognition by highlighting a functional dissociation between automatic engagement of amygdala versus intentional engagement of STS in social judgment.

Encoding of emotional memories depends on amygdala and hippocampus and their interactions

We have studied patients with variable degrees of left hippocampal and amygdala pathology who performed a verbal encoding task during functional magnetic resonance imaging (fMRI) to assess the impact of pathology on emotional-memory performance and encoding-evoked activity. The severity of left hippocampal pathology predicted memory performance for neutral and emotional items alike, whereas the severity of amygdala pathology predicted memory performance for emotional items alone. Encoding-related hippocampal activity for successfully remembered emotional items correlated with the degree of left amygdala pathology. Conversely, amygdala-evoked activity with respect to subsequently remembered emotional items correlated with the degree of left hippocampal pathology. Our data indicate a reciprocal dependence between amygdala and hippocampus during the encoding of emotional memories.

An emotion-induced retrograde amnesia in humans is amygdala- and beta-adrenergic-dependent.

The influence of emotion on human memory is associated with two contradictory effects in the form of either emotion-induced enhancements or decrements in memory. In a series of experiments involving single word presentation, we show that enhanced memory for emotional words is strongly coupled to decrements in memory for items preceding the emotional stimulus, an effect that is more pronounced in women. These memory effects would appear to depend on a common neurobiological substrate, in that enhancements and decrements are reversed by propranolol, a β-adrenergic antagonist, and abolished by selective bilateral amygdala damage. Thus, our findings suggest that amygdala-dependent β-adrenergic modulation of episodic encoding has costs as well as benefits.

Information theory, novelty and hippocampal responses: unpredicted or unpredictable?

Shannons information theory provides a principled framework for the quantitative analysis of brain responses during the encoding and representation of event streams. In particular, entropy measures the expected uncertainty of events in a given context. This contextual uncertainty or unpredictability may, itself, be important for balancing [bottom-up] sensory information and [top-down] prior expectations during perceptual synthesis. Using event-related functional magnetic resonance imaging (fMRI), we found that the anterior hippocampus is sensitive to the entropy of a visual stimulus stream. In contrast, activity in an extensive bilateral cortico-thalamic network was dictated by the surprise or information associated with each particular stimulus. In short, we show that the probabilistic structure or context in which events occur is an important predictor of hippocampal activity.

Memory fMRI in left hippocampal sclerosis: optimizing the approach to predicting postsurgical memory.

Background: An optimal technique for clinical memory fMRI is not established. Previous studies suggest activity in right parahippocampal gyrus and right hippocampus shows the strongest difference between left hippocampal sclerosis (HS) patients and normal control subjects and that the difference in activity between left and right hippocampus predicts postoperative memory change. Methods: The authors studied 30 patients with mesial temporal lobe epilepsy (mTLE) and left HS, 12 of whom subsequently underwent surgery, and 13 normal control subjects. The patients who had surgery underwent neuropsychometric evaluation pre- and postoperatively. All subjects underwent a verbal memory encoding event-related fMRI study. Activation maps were assessed visually. Subsequently, the brain regions involved in the memory task were revealed by group averaging; these regions were used to determine regions of interest (ROIs) for subsequent analysis. By use of stepwise discriminant function and stepwise multiple regression, the ROIs that optimally discriminated between patients and normal control subjects and that optimally predicted postoperative verbal memory outcome were determined. Results: Visual inspection of individual patient activation statistic maps revealed noisy data that did not afford visual interpretation. Stepwise discriminant function revealed the difference between left and right hippocampal activity best discriminated between patients and normal control subjects. Stepwise multiple regression revealed left hippocampal activity was the strongest predictor of postoperative verbal memory outcome; greater left hippocampal activity predicted a greater postoperative decline in memory. Conclusions: Patients with left hippocampal sclerosis (HS) differ from normal control subjects in the distribution of memory-encoding activity between left and right hippocampus. Functional adequacy of left hippocampus best predicts postoperative memory outcome in left HS.

Preserved verbal memory function in left medial temporal pathology involves reorganisation of function to right medial temporal lobe

The left hippocampus and related structures mediate verbal memory function. The mechanism underlying preserved verbal memory function in patients with left hippocampal damage is unknown. Temporal lobe epilepsy, a common disease, is frequently the consequence of a characteristic hippocampal pathology termed hippocampal sclerosis, which may also affect the amygdala. In this setting, mapping the sites of memory function is a vital component of planning for surgical treatment for epilepsy. Using event-related functional magnetic resonance imaging, we studied 24 right-handed nonamnesic patients with left hippocampal sclerosis and 12 normal controls, performing a verbal encoding task. The patients were subdivided into two groups according to presence or absence of additional left amygdala pathology. Analysis of the data employed a two-level random-effects design, examining the main effects of subsequent memory in each group, as well as the differences between the groups. Additional effects of emotionality of the remembered words were also examined. Verbal memory encoding involved activation of left hippocampus in normals, but was associated with reorganisation to right hippocampus and parahippocampal gyrus in the patients. The additional presence of left amygdala sclerosis resulted in reorganisation for encoding of emotional verbal material to right amygdala. Retained verbal memory function in the presence of left medial temporal lobe pathology is mediated by recruitment of a parallel system in the right hemisphere consistent with adaptive functional reorganisation. The findings indicate a high degree of plasticity in medial temporal lobe structures.

Prefrontal-Occipitoparietal Coupling Underlies Late Latency Human Neuronal Responses to Emotion

Enhanced late positive potentials (LPPs) evoked by highly arousing unpleasant and pleasant stimuli have been consistently observed in event-related potential experiments in humans. Although the psychological factors modulating the LPP have been studied in detail, the neurobiological underpinnings of this response remain poorly understood. Current models suggest that the LPP is a product of both an automatic facilitation of perceptual activity, as well as postperceptual processing under cognitive control. Here we applied magnetoencephalography (MEG) and beamformer analysis combined with Granger causality measures to provide a mechanistic account for LPP generation that reconciles these two models. We demonstrate that the magnetic homolog of the LPP, mLPP, is localized within bilateral occipitoparietal and right prefrontal cortex. Critically, directed functional connectivity analysis between these brain regions, indexed by Granger causality, demonstrates stronger bidirectional influences between frontal and occipitoparietal cortex for high arousing emotional relative to low arousing neutral pictures. Thus, both bottom-up and top-down accounts of the late latency response to emotion derived from psychological studies can be explained by a reciprocal codependency between activity in prefrontal and occipitoparietal cortex.

A fast pathway for fear in human amygdala

A fast, subcortical pathway to the amygdala is thought to have evolved to enable rapid detection of threat. This pathways existence is fundamental for understanding nonconscious emotional responses, but has been challenged as a result of a lack of evidence for short-latency fear-related responses in primate amygdala, including humans. We recorded human intracranial electrophysiological data and found fast amygdala responses, beginning 74-ms post-stimulus onset, to fearful, but not neutral or happy, facial expressions. These responses had considerably shorter latency than fear responses that we observed in visual cortex. Notably, fast amygdala responses were limited to low spatial frequency components of fearful faces, as predicted by magnocellular inputs to amygdala. Furthermore, fast amygdala responses were not evoked by photographs of arousing scenes, which is indicative of selective early reactivity to socially relevant visual information conveyed by fearful faces. These data therefore support the existence of a phylogenetically old subcortical pathway providing fast, but coarse, threat-related signals to human amygdala.

An electroconvulsive therapy procedure impairs reconsolidation of episodic memories in humans

Despite accumulating evidence for a reconsolidation process in animals, support in humans, especially for episodic memory, is limited. Using a within-subjects manipulation, we found that a single application of electroconvulsive therapy following memory reactivation in patients with unipolar depression disrupted reactivated, but not non-reactivated, memories for an emotional episode in a time-dependent manner. Our results provide evidence for reconsolidation of emotional episodic memories in humans.

Dissociating intentional learning from relative novelty responses in the medial temporal lobe

The establishment of a role for medial temporal lobe (MTL) structures in episodic memory has led to an investigative focus on the specific contributions and interactions between constituent MTL regions, including the hippocampus and surrounding medial temporal cortices. By dissociating an intentional stimulus-category learning condition from a passive viewing condition, we demonstrate, using fMRI, that novelty- and familiarity-driven responses in human anterior and posterior hippocampus, respectively, only occur during intentional learning. With increasing familiarity of stimulus-category associations, there is a shift in neuronal responses from anterior to posterior hippocampal regions. This anterior/posterior response gradient may reflect a weighting of functional hippocampal architecture related to encoding of novel and retrieval of familiar information. By contrast, perirhinal cortex is engaged by novel stimuli irrespective of task, highlighting this region as a component of a generic familiarity discrimination system. By introducing distinct stimulus types, we further demonstrate that these MTL responses are independent of stimulus complexity. Different patterns of activity for intentional learning vs. passive viewing indicate that intentional encoding/retrieval of stimulus-category associations and automatic novelty/familiarity assessment of stimuli are processed in anatomically dissociable neuronal ensembles within the MTL memory system.