J. S. Morris

Neural activity associated with episodic memory for emotional context

To address the question of which brain regions subserve retrieval of emotionally-valenced memories, we used event-related fMRI to index neural activity during the incidental retrieval of emotional and non-emotional contextual information. At study, emotionally neutral words were presented in the context of sentences that were either negatively, neutrally or positively valenced. At test, fMRI data were obtained while participants discriminated between studied and unstudied words. Recognition of words presented in emotionally negative relative to emotionally neutral contexts was associated with enhanced activity in right dorsolateral prefrontal cortex, left amygdala and hippocampus, right lingual gyrus and posterior cingulate cortex. Recognition of words from positive relative to neutral contexts was associated with increased activity in bilateral prefrontal and orbitofrontal cortices, and left anterior temporal lobe. These findings suggest that neural activity mediating episodic retrieval of contextual information and its subsequent processing is modulated by emotion in at least two ways. First, there is enhancement of activity in networks supporting episodic retrieval of neutral information. Second, regions known to be activated when emotional information is encountered in the environment are also active when emotional information is retrieved from memory.

Crossmodal binding of fear in voice and face

In social environments, multiple sensory channels are simultaneously engaged in the service of communication. In this experiment, we were concerned with defining the neuronal mechanisms for a perceptual bias in processing simultaneously presented emotional voices and faces. Specifically, we were interested in how bimodal presentation of a fearful voice facilitates recognition of fearful facial expression. By using event-related functional MRI, that crossed sensory modality (visual or auditory) with emotional expression (fearful or happy), we show that perceptual facilitation during face fear processing is expressed through modulation of neuronal responses in the amygdala and the fusiform cortex. These data suggest that the amygdala is important for emotional crossmodal sensory convergence with the associated perceptual bias during fear processing, being mediated by task-related modulation of face-processing regions of fusiform cortex.

Saying it with feeling: neural responses to emotional vocalizations

To determine how vocally expressed emotion is processed in the brain, we measured neural activity in healthy volunteers listening to fearful, sad, happy and neutral non-verbal vocalizations. Enhanced responses to emotional vocalizations were seen in the caudate nucleus, as well as anterior insular, temporal and prefrontal cortices. The right amygdala exhibited decreased responses to fearful vocalizations as well as fear-specific inhibitory interactions with left anterior insula. A region of the pons, implicated in acoustic startle responses also showed fear-specific interactions with the amygdala. The data demonstrate: firstly, that processing of vocal emotion involves a bilaterally distributed network of brain regions; and secondly, that processing of fear-related auditory stimuli involves context-specific interactions between the amygdala and other cortical and brainstem regions implicated in fear processing.

Involvement of Human Amygdala and Orbitofrontal Cortex in Hunger-Enhanced Memory for Food Stimuli

We used positron emission tomography to measure regional cerebral blood flow (rCBF) in 10 healthy volunteers performing a recognition memory task with food and non-food items. The biological salience of the food stimuli was manipulated by requiring subjects to fast before the experiment and eat to satiation at fixed time points during scanning. All subjects showed enhanced recognition of food stimuli (relative to non-food) in the fasting state. Satiation significantly reduced the memory advantage for food. Left amygdala rCBF covaried positively with recognition memory for food items, whereas rCBF in right anterior orbitofrontal cortex covaried with overall memory performance. Right posterior orbitofrontal rCBF covaried positively with hunger ratings during presentation of food items. Regression analysis of the neuroimaging data revealed that left amygdala and right lateral orbitofrontal rCBF covaried as a function of stimulus category (i.e., food vs non-food). These results indicate the involvement of amygdala and discrete regions of orbitofrontal cortex in the integration of perceptual (food), motivational (hunger), and cognitive (memory) processes in the human brain.

Covariation of activity in habenula and dorsal raphe nuclei following tryptophan depletion

Abnormal serotonergic function is implicated in the pathogenesis of affective disorders. We induced transient depressive relapses in volunteer patients by rapidly depleting plasma tryptophan, the precursor of serotonin (5-HT), and measured neural activity during different cognitive tasks using positron emission tomography (PET). Neural activity in several 5-HT-related brain areas, e.g., dorsal raphé, habenula, septal region, amygdala, and orbitofrontal cortex, covaried significantly with plasma levels of tryptophan and ratings of depressed mood. Task-specific responses in left amygdala and left anterior cingulate were attenuated by tryptophan depletion. We used these PET data to test the hypothesis that projections from the habenula modulate dorsal raphé activity and that this modulation is enhanced in patients experiencing a profound mood change following serotonergic challenge. A strong linear correlation (r(2) > 0.5) between habenula and raphé activity was observed in subjects with postdepletion ratings >/=10 on a modified Hamilton depression scale, whereas subjects experiencing milder changes in mood had weaker habenula-raphé coupling (r(2) < 0.5). These data support a model of the serotonergic system in which the habenula projection to the raphé represents a convergent feedback pathway that controls the release of 5-HT throughout the brain. In our experiment we were able to engage this system in patients who were sensitive to tryptophan depletion.

Parallel neural responses in amygdala subregions and sensory cortex during implicit fear conditioning.

We used event-related fMRI to measure neural activity in volunteer subjects during acquisition of an implicit association between a visual conditioned stimulus (CS+) (angry face) and an auditory unconditioned stimulus (UCS) (aversive, loud noise). Three distinct functional regions were identified within left amygdala: a UCS (noise)-related lateral region, a CS+-related ventral region, and a dorsal region where CS+-related responses changed progressively across the learning session. Differential neural responses to the visual CS+ were also evoked in extrastriate and auditory cortices. Our results indicate that learning an association between biologically salient stimuli of different sensory modalities involves parallel changes of neural activity in segregated amygdala subregions and unimodal sensory cortices.

Human amygdala responses to fearful eyes

Fearful facial expressions evoke increased neural responses in human amygdala. We used event-related fMRI to investigate whether eye or mouth components of a fearful face are critical in evoking this increased amygdala activity. In addition to prototypical fearful (FF) and neutral (NN) faces, subjects viewed two types of chimerical face: fearful eyes combined with a neutral mouth (FN), and neutral eyes combined with a fearful mouth (NF). FE faces evoked specific responses in left anterior amygdala. FN faces evoked responses in bilateral posterior amygdala and superior colliculus. Responses in right amygdala, superior colliculus, and pulvinar exhibited significant time x condition interactions with respect to faces with fearful eyes (FF, FN) vs neutral eyes (NF, NN). These data indicate that fearful eyes alone are sufficient to evoke increased amygdala activity. In addition, however, left amygdala displayed discriminatory responses to fearful eyes in different configural contexts (i.e., in FF and FN faces). These results suggest, therefore, that human amygdala responds to both feature-specific and configural aspects of fearful facial expressions.

Experience–dependent modulation of tonotopic neural responses in human auditory cortex

Experience–dependent plasticity of receptive fields in the auditory cortex has been demonstrated by electrophysiological experiments in animals. In the present study we used PET neuroimaging to measure regional brain activity in volunteer human subjects during discriminatory classical conditioning of high (8000 Hz) or low (200 Hz) frequency tones by an aversive 100 dB white noise burst. Conditioning–related, frequency–specific modulation of tonotopic neural responses in the auditory cortex was observed. The modulated regions of the auditory cortex positively covaried with activity in the amygdala, basal forebrain and orbitofrontal cortex, and showed context–specific functional interactions with the medial geniculate nucleus. These results accord with animal single–unit data and support neurobiological models of auditory conditioning and value–dependent neural selection.

Neural responses to salient visual stimuli

The neural mechanisms involved in the selective processing of salient or behaviourally important stimuli are uncertain. We used an aversive conditioning paradigm in human volunteer subjects to manipulate the salience of visual stimuli (emotionally expressive faces) presented during positron emission tomography (PET) neuroimaging. Increases in salience, and conflicts between the innate and acquired value of the stimuli, produced augmented activation of the pulvinar nucleus of the right thalamus. Furthermore, this pulvinar activity correlated positively with responses in structures hypothesized to mediate value in the brain–right amygdala and basal forebrain (including the cholinergic nucleus basalis of Meynert). The results provide evidence that the pulvinar nucleus of the thalamus plays a crucial modulatory role in selective visual processing, and that changes in perceptual salience are mediated by value–dependent plasticity in pulvinar responses.