Lizabeth M. Romanski

Extinction of emotional learning: contribution of medial prefrontal cortex.

Stimuli associated with painful or otherwise unpleasant events acquire aversive emotional properties in animals and humans. Subsequent presentation of the stimulus alone (in the absence of the unpleasant event) leads to the eventual extinction of the aversive reaction. Although the neural basis of emotional learning has been studied extensively, considerably less is known about the neural basis of emotional extinction. In the present study, we show that the medial prefrontal cortex plays an important role in the regulation of fear extinction in rats, a finding that may help elucidate the mechanisms and, possibly, the treatment of disorders of uncontrolled fear, such as anxiety, phobic, panic and posttraumatic stress disorders in humans.

Auditory belt and parabelt projections to the prefrontal cortex in the rhesus monkey.

Recent anatomical and electrophysiological studies have expanded our knowledge of the auditory cortical system in primates and have described its organization as a series of concentric circles with a central or primary auditory core, surrounded by a lateral and medial belt of secondary auditory cortex with a tertiary parabelt cortex just lateral to this belt. Because recent studies have shown that rostral and caudal belt and parabelt cortices have distinct patterns of connections and acoustic responsivity, we hypothesized that these divergent auditory regions might have distinct targets in the frontal lobe. We, therefore, placed discrete injections of wheat germ agglutinin‐horseradish peroxidase or fluorescent retrograde tracers into the prefrontal cortex of macaque monkeys and analyzed the anterograde and retrograde labeling in the aforementioned auditory areas. Injections that included rostral and orbital prefrontal areas (10, 46 rostral, 12) labeled the rostral belt and parabelt most heavily, whereas injections including the caudal principal sulcus (area 46), periarcuate cortex (area 8a), and ventrolateral prefrontal cortex (area12vl) labeled the caudal belt and parabelt. Projections originating in the parabelt cortex were denser than those arising from the lateral or medial belt cortices in most cases. In addition, the anterior third of the superior temporal gyrus and the dorsal bank of the superior temporal sulcus were also labeled after prefrontal injections, confirming previous studies. The present topographical results suggest that acoustic information diverges into separate streams that target distinct rostral and caudal domains of the prefrontal cortex, which may serve different acoustic functions. J. Comp. Neurol. 403:141–157, 1999.

Somatosensory and auditory convergence in the lateral nucleus of the amygdala

Previous studies have shown that the lateral nucleus of the amygdala (AL) is essential in auditory fear conditioning and that neurons in the AL respond to auditory stimuli. The goals of the present study were to determine whether neurons in the AL are also responsive to somatosensory stimuli and, if so, whether single neurons in the AL respond to both auditory and somatosensory stimulation. Single-unit activity was recorded in the AL in anesthetized rats during the presentation of acoustic (clicks) and somatosensory (footshock) stimuli. Neurons in the dorsal subdivision of the AL responded to both somatosensory and auditory stimuli, whereas neurons in the ventrolateral AL responded only to somatosensory stimuli and neurons in the ventromedial AL did not respond to either stimuli. These findings indicate that the dorsal AL is a site of auditory and somatosensory convergence and may therefore be a locus of convergence of conditioned and unconditioned stimuli in auditory fear conditioning.

TOPOGRAPHIC ORGANIZATION OF MEDIAL PULVINAR CONNECTIONS WITH THE PREFRONTAL CORTEX IN THE RHESUS MONKEY

The medial nucleus of the pulvinar complex (PM) has widespread connections with association cortex. We investigated the connections of the PM with the prefrontal cortex (PFC) in macaque monkeys, with tracers placed into the PM and the PFC, respectively.

Overlapping projections to the amygdala and striatum from auditory processing areas of the thalamus and cortex

The purpose of this study was to advance our understanding of the anatomical organization of sensory projections to the amygdala, and specifically to identify potential interactions within the amygdala between thalamic and cortical sensory projections of a single sensory modality. Thus, interconnections between the amygdala and acoustic processing areas of the thalamus and cortex were examined in the rat using WGA-HRP as an anterograde and a retrograde axonal tracer. Injections placed in medial aspects of the medial geniculate body (MGB) produced anterograde transport to the lateral nucleus of the amygdala and to adjacent areas of the striatum. Injections of primary auditory cortex (TE1) produced no transport to amygdala. In contrast, injections ventral to TE1 involving TE3 and perirhinal periallocortex (PRh) produced anterograde transport in the subcortical forebrain that was indistinguishable from that produced by the MGB injections. The TE3 and PRh injections also resulted in retrograde transport to primary auditory cortex and to MGB, thus confirming the involvement of these ventral cortical areas in auditory functions. Injections of the lateral nucleus of the amygdala resulted in retrograde transport back to the medial areas of MGB and to temporal cortical areas PRh, TE3, and the ventral most part of TE1. Thus, auditory processing regions of the thalamus and cortex give rise to overlapping (possibly convergent) projections to the lateral nucleus of the amygdala. These projections may allow diverse auditory signals to act on common ensembles of amygdaloid neurons and may therefore play a role in the integration of sensory messages leading to emotional reactions.

Involvement of cortical and thalamic auditory regions in retention of differential bradycardiac conditioning to acoustic conditioned stimuli in rabbits

Our previous findings indicate that lesions in the medial division of the medial geniculate nucleus (mMGN) prevent the acquisition of differential conditioning of bradycardia to acoustic stimuli in rabbits. In the present experiment, the effect of lesions in mMGN on retention of differential bradycardiac conditioning was examined. In addition, the possible involvement of auditory cortex in differential conditioning was investigated. Electrodes were chronically implanted in mMGN, the ventral division of the medial geniculate nucleus (vMGN), or auditory cortex. After 7 days of recovery, animals received one differential Pavlovian conditioning session. At the end of the session, lesions were produced through the implanted electrodes. All animals demonstrated differential bradycardiac conditioning during the prelesion session. Animals with vMGN lesions also demonstrated differential conditioning during the postlesion session. However, mMGN and auditory cortex lesion animals failed to demonstrate differential conditioning during the postlesion session due to an increased response magnitude to the unpaired tone (CS-). These data support the hypothesis that mMGN plays a role in differential conditioning of bradycardia to tonal stimuli. In addition, these findings suggest that a possible corticothalamic pathway may be involved in the inhibition of the response to the CS-.

The Primate Cortical Auditory System and Neural Representation of Conspecific Vocalizations

Over the past decade, renewed interest in the auditory system has resulted in a surge of anatomical and physiological research in the primate auditory cortex and its targets. Anatomical studies have delineated multiple areas in and around primary auditory cortex and demonstrated connectivity among these areas, as well as between these areas and the rest of the cortex, including prefrontal cortex. Physiological recordings of auditory neurons have found that species-specific vocalizations are useful in probing the selectivity and potential functions of acoustic neurons. A number of cortical regions contain neurons that are robustly responsive to vocalizations, and some auditory responsive neurons show more selectivity for vocalizations than for other complex sounds. Demonstration of selectivity for vocalizations has prompted the question of which features are encoded by higher-order auditory neurons. Results based on detailed studies of the structure of these vocalizations, as well as the tuning and information-coding properties of neurons sensitive to these vocalizations, have begun to provide answers to this question. In future studies, these and other methods may help to define the way in which cells, ensembles, and brain regions process communication sounds. Moreover, the discovery that several nonprimary auditory cortical regions may be multisensory and responsive to vocalizations with corresponding facial gestures may change the way in which we view the processing of communication information by the auditory system.

Bilateral destruction of neocortical and perirhinal projection targets of the acoustic thalamus does not disrupt auditory fear conditioning

The present study examined whether complete bilateral destruction of auditory cortex would interfere with auditory fear conditioning in rats. Complete destruction of auditory cortex required lesions of temporal neocortical and perirhinal periallocortical areas. Fear conditioning was assessed by measuring freezing and arterial pressure responses elicited by an acoustic stimulus after pairing with footshock. Animals with complete bilateral lesions of auditory cortex showed conditioned arterial pressure and freezing responses comparable to those of unoperated controls. In contrast, bilateral destruction of the acoustic thalamus interfered with the conditioning of both responses. These results demonstrate that the auditory cortex is not required for the conditioning of fear responses to simple acoustic stimuli and add to the growing body of evidence that fear conditioning can be mediated by subcortical (amygdaloid) projections of the acoustic thalamus.

Domain specificity in the primate prefrontal cortex

Experimental studies in nonhuman primates and functional imaging studies in humans have underlined the critical role played by the prefrontal cortex (PFC) in working memory. However, the precise organization of the frontal lobes with respect to the different types of information operated upon is a point of controversy, and several models of functional organizations have been proposed. One model, developed by Goldman-Rakic and colleagues, postulates a modular organization of working memory based on the type of information processing (the domain specificity hypothesis). Evidence to date has focused on the encoding of the locations of visual objects by the dorsolateral PFC, whereas the ventrolateral PFC is suggested to be involved in processing the features and identity of objects. In this model, domain should refer to any sensory modality that registers information relevant to that domain—for example, there would be visual and auditory input to a spatial information processing region and a feature analysis system. In support of this model, recent studies have described pathways from the posterior and anterior auditory association cortex that target dorsolateral spatial-processing regions and ventrolateral object-processing regions, respectively. In addition, physiological recordings from the ventrolateral PFC indicate that some cells in this region are responsive to the features of complex sounds. Finally, recordings in adjacent ventrolateral prefrontal regions have shown that the features of somatosensory stimuli can be discriminated and encoded by ventrolateral prefrontal neurons. These discoveries argue that two domains, differing with respect to the type of information being processed, and not with respect to the sensory modality of the information, are specifically localized to discrete regions of the PFC and embody the domain specificity hypothesis, first proposed by Patricia Goldman-Rakic.

Integration of faces and vocalizations in ventral prefrontal cortex: Implications for the evolution of audiovisual speech

The integration of facial gestures and vocal signals is an essential process in human communication and relies on an interconnected circuit of brain regions, including language regions in the inferior frontal gyrus (IFG). Studies have determined that ventral prefrontal cortical regions in macaques [e.g., the ventrolateral prefrontal cortex (VLPFC)] share similar cytoarchitectonic features as cortical areas in the human IFG, suggesting structural homology. Anterograde and retrograde tracing studies show that macaque VLPFC receives afferents from the superior and inferior temporal gyrus, which provide complex auditory and visual information, respectively. Moreover, physiological studies have shown that single neurons in VLPFC integrate species-specific face and vocal stimuli. Although bimodal responses may be found across a wide region of prefrontal cortex, vocalization responsive cells, which also respond to faces, are mainly found in anterior VLPFC. This suggests that VLPFC may be specialized to process and integrate social communication information, just as the IFG is specialized to process and integrate speech and gestures in the human brain.