Edited by: Enrique Saldaña, Universidad de Salamanca, Spain
Reviewed by: Jon H. Kaas, Vanderbilt University, USA; Marcello G. Rosa, Monash University, Australia
*Correspondence: Monica M. Munoz-Lopez, Human Neuroanatomy Laboratory, Department of Health Sciences, School of Medicine, University of Castilla-La Mancha, Ave. Almansa, 14,02006 Albacete, Spain. e-mail:
This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Episodic memory or the ability to store context-rich information about everyday events depends on the hippocampal formation (entorhinal cortex, subiculum, presubiculum, parasubiculum, hippocampus proper, and dentate gyrus). A substantial amount of behavioral-lesion and anatomical studies have contributed to our understanding of the organization of how visual stimuli are retained in episodic memory. However, whether auditory memory is organized similarly is still unclear. One hypothesis is that, like the “visual ventral stream” for which the connections of the inferior temporal gyrus with the perirhinal cortex are necessary for visual recognition in monkeys, direct connections between the auditory association areas of the superior temporal gyrus and the hippocampal formation and with the parahippocampal region (temporal pole, perhirinal, and posterior parahippocampal cortices) might also underlie recognition memory for sounds. Alternatively, the anatomical organization of memory could be different in audition. This alternative “indirect stream” hypothesis posits that, unlike the visual association cortex, the majority of auditory information makes one or more synapses in intermediate, polymodal areas, where they may integrate information from other sensory modalities, before reaching the medial temporal memory system. This review considers anatomical studies that can support either one or both hypotheses – focusing on anatomical studies on the primate brain, primarily in macaque monkeys, that have reported not only direct auditory association connections with medial temporal areas, but, importantly, also possible indirect pathways for auditory information to reach the medial temporal lobe memory system.
The aim of this review is to consider the anatomical substrate of auditory memory. We explore two possible questions. First, in analogy with the classic view of visual processing (Mishkin and Ungerleider,
Anatomical studies cannot, on their own, differentiate these two views; they do, however, reveal both opportunities and constraints on the manner by which sensory information reaches brain regions involved in memory processing (Figure
Episodic memory refers to the ability to store information about everyday events and encompasses a complex system of hippocampo–cortical and hippocampo–subcortical connections (Aggleton and Brown,
Episodic memory has been attributed almost exclusively to humans (Suddendorf and Corballis,
One of the challenges in animal research has been to design behavioral tasks that are as close as possible to the episodic memory tests used in neuropsychological assessment with humans. Such tasks are critical to study the anatomical and functional organization of episodic-like memory in animals. In non-human primates and rodents, episodic memory is often evaluated using trial-unique tasks in which animals have to remember a specific stimulus during a single trial. Each trial requires memory of a different object or image, in a similar way that we experience unique events in everyday life. There is a wide breadth of fascinating tasks, but to describe all of them here would exceed the aim of this review. We summarize one of the critical paradigms from which many different variants have emerged – namely a test of recognition memory. Remembering that you have seen/heard someone or something before is a critical component of episodic memory.
The recognition paradigm extensively used in the study of visual memory is the delayed non-matching to sample task (DNMS). Each trial in this type of task consists in a
Back in the seventies, one of the pioneering memory studies in monkeys showed that only lesions that include the hippocampus, amygdala, and the adjacent entorhinal and posterior parahippocampal cortices impaired memory in a visual version of the DNMS task (Mishkin,
Research since then has shown that amongst the areas included in the original lesion (Mishkin,
We now know from retrograde tract tracing studies that the perirhinal cortex receives the majority of its input from visual areas in the inferior temporal cortex (Suzuki and Amaral,
These neuroanatomical studies reveal the main flow of information underlying visual recognition, but one of the central features of episodic memory is that our memories of events are formed by information received via different sensory modalities (olfactory, somatosensory, auditory as well as visual) and, consequently, episodic memory is often said to be multimodal. Neuroanatomical tract-tracing studies show that, although some sensory-specific information reaches the medial temporal cortex directly (primarily olfactory and visual, as well as, although to a lesser extent, somatosensory and auditory), the great bulk of incoming connections originate in polymodal areas of the neocortex (see review in Mohedano-Moriano et al.,
The possibility of multimodal inputs to the episodic-like memory system raises the question of how well matched is the picture emerging from anatomical and behavioral-lesion studies. To address this question, one study showed that lesions including areas 35 and 36 of the perirhinal cortex and the posterior parahippocampal cortex (areas TH and TF of Von Bonin and Bailey,
At about the same time, an anatomical study showed that a higher order somatosensory area in the granular insular cortex sends projections directly to area 35 of the perirhinal cortex, and suggested that this pathway might be one direct link between the somatosensory and limbic systems (Schneider et al.,
It appeared, then, that the perirhinal cortex mediates the storage of information in a multimodal way and hence satisfies one of the critical features of episodic memory. The perirhinal cortex became therefore one of the best candidate areas for episodic-like memory in non-human primates. There are important subtleties to this assertion such as whether the perirhinal cortex is involved in
Why is more difficult for monkeys to hold in mind auditory information than visual? Do humans have also more difficulties to store auditory information compared to visual? |
Medial frontal cortex, especially area 25, is part of the limbic system that is associated with episodic memory. Is this area also important for auditory memory in primates and humans? |
Is there an analogue of the perirhinal cortex important for auditory recognition memory? |
Anterior cingulate area 24, prelimbic area 32, and area 25 of the infralimbic cortex may be involved in the production of monkey calls. What is their role in auditory processing? |
Are motor patterns, such as those related with the articulation of sounds, important for auditory memory? |
In monkeys, the dorsal part of the temporal pole receives its major input from the most rostral part of the superior temporal gyrus, but it also receives afferents from multimodal areas. What is the nature of its involvement in the processing of monkey calls? |
What areas the similarities and differences of the auditory processing areas in humans and non-human primates? |
What is the role of the amygdalar connections with hippocampal formation and the superior temporal gyrus? And how do they contribute to auditory memory? |
Does auditory memory store in the same way as in the visual and somatosensory modalities? Are perirhinal and entorhinal cortices necessary for the formation of auditory memory as they are for visual and tactile memory? It is clear that auditory memory depends on medial temporal areas in humans (Prisko,
However, medial temporal lobe resections, that leave working memory intact in vision in human and non-human primates, critically impair this type of short-term memory in audition (Fritz et al.,
To better understand the anatomical organization of auditory memory we consider here a number of major tract tracing studies in the non-human primate brain. These studies reveal evidence for direct (monosynaptic) and indirect connections (two synapses) that finally link the STG with the medial temporal lobe memory system, comprising the hippocampal formation (dentate gyrus, hippocampal fields CA1–3, subiculum, presubiculum, parasubiculum, and EC), and the parahippocampal region (temporal pole, areas 35 and 36 of the perirhinal cortex, and the posterior parahippocampal cortex areas TH and TF of Von Bonin and Bailey,
Like in vision or touch, direct connections of the auditory cortex with the medial temporal cortex may be critical for the long-term storage of auditory information (Engelien et al.,
The amalgam of architectonic divisions comprising the STG and the medial temporal cortex; areas which interaction might be critical for the storage of auditory information are shown in Figure
In rhesus monkeys, the STG was described in depth by Pandya et al. (Pandya and Sanides,
In the
The cytoarchitectonic areas RTL, RT, and RTM, as defined by Kaas and Hackett (
Core (primary) and belt (secondary) areas of the auditory cortex in monkeys are characterized by a high density of reciprocal cortico–cortical connections (Hackett et al.,
Apart from the better understood core and belt areas of the auditory cortex (Hackett,
The study by Romanski et al. (
Evidence for the rostral STG projection to EC comes primarily from two retrograde tracer studies. The first one, having placed retrograde tracer injections in EC (Amaral et al.,
Perirhinal and posterior parahippocampal cortices receive their densest input from higher order processing visual areas TE and TEO of the inferior temporal cortex, and the rest from multiple polymodal processing areas of the neocortex; i.e. the dorsal bank of the superior temporal sulcus (area TPO), the opercular area of the STG (TAa), to a lesser extent, from insular, anterior cingulate, medial and orbitofrontal cortex (Suzuki and Amaral,
In relation with auditory afferents, the rostral part of the STG (areas Ts1–3), including the TP, projects to areas 35 and 36 of the perirhinal cortex and to areas TH and TF of the posterior parahippocampal cortex. A restricted area of the caudal STG, which appears to include the caudal lateral parabelt area of the auditory cortex and area Tpt (see Figure 11 in Suzuki and Amaral,
Furthermore, in humans, this area contributes substantially to the enlargement of the left planum temporale on the left hemisphere and it is considered part of Wernicke's area (Galaburda et al.,
The temporal pole has been considered part of the parahippocampal region both in humans and non-human primates (Insausti et al.,
Anatomical studies with wallerian degeneration techniques showed that early auditory and visual processing areas send projections to progressively more rostral portions of the STG and subsequently to TP (Jones and Powell,
On the other hand, the dorsal lateral TP receives input from medial, orbitofrontal, and insular cortex (Mesulam,
The participation of TP in memory in humans has been shown in fMRI studies, and critically, by its involvement in semantic dementia (Olson et al.,
In sum, the cortex of the rostral part of the STG, including the dorsal part of TP and, to a lesser extent, areas Ts1–3 of the auditory parabelt project directly to EC, the rostral part of areas 35 and 36 of the perirhinal cortex, and areas TH and TF of the posterior parahippocampal cortex. There is an additional projection from the caudal STG to area TH. The auditory projections to EC are, however, very meager in comparison with its polymodal input (Mohedano-Moriano et al.,
Neurons in the operculum and the dorsal bank of the superior temporal sulcus in the non-human primate – the superior temporal polysensory area STP – show responses to stimuli from different sensory modalities such as auditory, visual, and somatosensory (Bruce et al.,
A possible pathway, and probably the densest route of indirect projections from the auditory areas of the STG to the medial temporal cortex, would start in the rostral divisions of the lateral parabelt through a series of synaptic relays:
Areas Ts1–Ts2 of the gyral surface of the STG (Figure
Area TAa of the STG (Figure
Areas PGa and TPO (Figure
In summary, one of the routes for auditory afferents to reach the hippocampal formation, perirhinal, and posterior parahippocampal cortices might be through polymodal areas of the dorsal bank of the superior temporal sulcus (Figure
One of the sources of auditory information to the insula (Figure
Auditory–insular connections have received little attention, but a recent study reported that auditory-related areas located in the medial and lateral subdivisions of the caudal belt receive somatosensory information from retroinsular and granular insular cortex (Smiley et al.,
The agranular and disgranular divisions of the insula send dense projections to the rostromedial division of EC (Insausti et al.,
Area 32 (Barbas,
The STG-medial frontal projections in rhesus monkeys are organized topographically, in such a manner that the density of the projection decreases progressively from rostral to caudal in the STG. The lateral portion of TP and area Ts1 are the origin of the densest projection to areas 25, 32, and to a lesser extent to area 24, whereas the density of the projection decreases progressively from area Ts2 to Ts3 (Vogt and Pandya,
Areas 32, 24, and 25 have been associated with the production of calls in squirrel monkeys (Jürgens and Pratt,
Ventral medial frontal areas 24, 32, and 25 have, on the other hand, lead the frontal projections with medial temporal cortex. In fact, among all the architectonic areas that form the frontal cortex, areas 25 and 32 have the densest connections with CA1/Subiculum and, and therefore, have a very direct access to the medial temporal memory system (Barbas and Blatt,
Although the role of these regions of the medial frontal cortex in working or long-term memory in audition is still puzzling, removals that include area 25 impair visual long-term recognition memory in monkeys (Bachevalier and Mishkin,
In sum, the complex anatomical and physiological organization of the medial frontal cortex suggests that areas 24, 25, and 32 are involved in some motor aspects of monkey call production, amongst other functions. In addition, they interact with auditory and medial temporal cortices and therefore, they may modulate auditory memory function. Emotional modulation of auditory memory might be mediated possibly by way of interactions via connections with the amygdala (Aggleton et al.,
Superior temporal gyrus projections to area 23 of the caudal cingulate cortex and to areas 29 and 30 have been described by in retrograde tracer experiments, but they have been reported as very modest and arising primarily from the dorsal bank of the superior temporal sulcus, rather than from auditory processing areas (Vogt and Pandya,
However, there might be a modest contribution of auditory projections to caudal cingulate (area 23) and retrosplenial cortex (area 29) as well as caudal presubiculum (Yukie,
Area 29 of the retrosplenial cortex and area 23 of the posterior cingulate cortex are important sources of cortical afferents to the caudal entorhinal cortex, the posterior parahippocampal areas TH and TF, and to a lesser extent, to perirhinal cortex areas 35 and 36.
The intraparietal sulcus is involved in spatial auditory processing (Cohen and Andersen,
Some studies have failed to find direct connections between auditory areas of the STG and the intraparietal sulcus (Cavada and Goldman-Rakic,
Tract tracing studies indicate that the medial part of area Tpt in the caudal STG sends projections to the ventral intraparietal area, an area that has been involved in neuroanatomical networks functionally related to visual, vestibular, somatomotor, and auditory processing (Lewis and Van Essen,
In sum, this pathway arises in the caudal parabelt areas and projects via inferior pariental cortex (area 7a) to areas TH and TF of the posterior parahippocampal cortex (Suzuki and Amaral,
The amygdaloid complex, a group of nuclei with dense cortical and hypothalamic connections, is important in emotion, motivation, memory, and social behavior.
Connections between auditory-related areas of the rostral half of the STG and the amygdala in monkeys have been reported previously (Nauta,
The lateral nucleus of the amygdala provides the densest input to EC, with additional projections also originating in the basal and accessory basal nucleus (Insausti et al.,
The amygdala, therefore, may influence EC, and moreover has further access to the hippocampus. Many of the amygdalar nuclei, primarily basal, lateral basal, medial basal, cortical nucleus and cortical–amygdaloid area send direct projections to the molecular layer of the amygdalo–hippocampal area and stratum lacunosum moleculare of the uncal portions of CA3 and less densely to CA1, and the CA1/Subiculum area, also called prosubiculum. Additional projections terminate in the presubiculum, parasubiculum, and layers I–III of the rostral one-half of EC (Rosene and Van Hoesen,
In non-human primates, there is a direct thalamo–amygdaloid pathway that seems to be relatively minor. Among the multiple thalamic nuclei, only the peripeduncular nucleus was found to project substantially to the lateral amygdaloid nucleus (Jones et al.,
Classical degeneration and more modern neuronal tracer techniques have been employed to discover and describe the thalamic connections to auditory areas (De Vito and Simmons,
In the thalamus, the medial nucleus of the pulvinar, an area of multimodal convergence (Cappe et al.,
The primary aim of this review has been to draw attention to the complexity of additional indirect connections by which auditory information can get to memory processing areas of the medial temporal lobes. Specifically, the anatomical studies reviewed here indicate that, unlike the strong, direct and reciprocal connections of visual association areas between the inferior temporal cortex and areas 35 and 36 of the perirhinal and areas TH and TF of the posterior parahippocampal cortex, direct connections from auditory processing areas of the STG with medial temporal cortex appear to be considerably more modest. Thus, whereas the visual “ventral stream” of processing in the Mishkin and Ungerleider (
The entry of auditory information to the medial temporal cortex might be, therefore, more indirect in audition than in vision. In addition to the cortical direct and indirect pathways, auditory information may enter the medial temporal cortex via subcortical structures, like the lateral and basal nuclei of the amygdala and the thalamus, with possibly an especial role for the medial pulvinar. The direct connections of the amygdala with the hippocampus points to a possible role of emotion in auditory long-term memory.
It cannot be ruled out the contribution of other subcortical nuclei in the diencephalon or brainstem, although little or no neuroanatomical evidence exists. It is foreseeable that the auditory memory involves much more intricate and complex neural networks and that all this information may be translated to clinical practice.
The projections of neurons in auditory processing areas of the STG seem to reach memory-related areas of the medial temporal cortex and diencephalon via indirect connections with polysensory areas (Figure
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
7a, area 7a of the inferior parietal cortex; 23, area 23 (Brodmann,