Voice cells in the primate temporal lobe

Communication signals are important for social interactions and survival and are thought to receive specialized processing in the visual and auditory systems. Whereas the neural processing of faces by face clusters and face cells has been repeatedly studied [1-5], less is known about the neural representation of voice content. Recent functional magnetic resonance imaging (fMRI) studies have localized voice-preferring regions in the primate temporal lobe [6, 7], but the hemodynamic response cannot directly assess neurophysiological properties. We investigated the responses of neurons in an fMRI-identified voice cluster in awake monkeys, and here we provide the first systematic evidence for voice cells. "Voice cells" were identified, in analogy to "face cells," as neurons responding at least 2-fold stronger to conspecific voices than to "nonvoice" sounds or heterospecific voices. Importantly, whereas face clusters are thought to contain high proportions of face cells [4] responding broadly to many faces [1, 2, 4, 5, 8-10], we found that voice clusters contain moderate proportions of voice cells. Furthermore, individual voice cells exhibit high stimulus selectivity. The results reveal the neurophysiological bases for fMRI-defined voice clusters in the primate brain and highlight potential differences in how the auditory and?visual systems generate selective representations of communication signals.     

A neural code for egocentric spatial maps in the human medial temporal lobe

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PTEN levels in Alzheimer's disease medial temporal cortex

Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) is a dual (protein tyrosine and lipid) phosphatase one of the functions of which is to dephosphorylate phosphatidylinositol 3,4,5-trisphosphate to phosphatidylinositol-3,4-biphosphate thereby inhibiting phosphoinositide-dependent kinase activation of the cell survival kinase Akt. Akt activity is up regulated in Alzheimer's disease (AD) brain in parallel to the progression of neurofibrillary pathology. The present study determined whether altered expression of PTEN occurs in Alzheimer's disease brain. Western immunoblotting revealed no significant changes of PTEN protein levels in nuclear and membrane fractions of medial temporal cortex from a series of Alzheimer's disease and control cases. Similarly, no changes in PTEN protein levels, as determined by dot-blotting, were seen in temporal cortex homogenates from a separate series of Alzheimer's disease and control brains. A small but significant decrease in the levels of Ser(380) p-PTEN was seen in homogenates of Alzheimer's disease temporal cortex. Immunohistochemistry revealed PTEN immunoreactivity in a number of brain structures including neurons, capillaries and structures resembling oligodendrocytes and astrocytes. The majority of temporal cortex pyramidal neurons (93-100%) were PTEN immunopositive. The Alzheimer's disease cases had significantly lower numbers of total ( approximately 12% loss, P<0.02) and PTEN immunopositive ( approximately 15% loss, P<0.01) pyramidal neurons as compared to the control cases.     

A quantitative morphometric comparative analysis of the primate temporal lobe

Given their importance in language comprehension, the human temporal lobes and/or some of their component structures might be expected to be larger than allometric predictions for a nonhuman anthropoid brain of human size. Whole brain, T1-weighted MRI scans were collected from 44 living anthropoid primates spanning 11 species. Easyvision software (Philips Medical Systems, The Netherlands) was used to measure the volume of the entire brain, the temporal lobes, the superior temporal gyri, and the temporal lobe white matter. The surface areas of both the entire temporal lobe and the superior temporal gyrus were also measured, as was temporal cortical gyrification.Allometric regressions of temporal lobe structures on brain volume consistently showed apes and monkeys to scale along different trajectories, with the monkeys typically lying at a higher elevation than the apes. Within the temporal lobe, overall volume, surface area, and white matter volume were significantly larger in humans than predicted by the ape regression lines. The largest departure from allometry in humans was for the temporal lobe white matter volume which, in addition to being significantly larger than predicted for brain size, was also significantly larger than predicted for temporal lobe volume. Among the nonhuman primate sample, Cebus have small temporal lobes for their brain size, and Macaca and Papio have large superior temporal gyri for their brain size. The observed departures from allometry might reflect neurobiological adaptations supporting species-specific communication in both humans and old world monkeys.     

Shaping of object representations in the human medial temporal lobe based on temporal regularities

Regularities are gradually represented in cortex after extensive experience [1], and yet they can influence behavior after minimal exposure [2, 3]. What kind of representations support such rapid statistical learning? The medial temporal lobe (MTL) can represent information from even a single experience [4], making it a good candidate system for assisting in initial learning about regularities. We combined anatomical segmentation of the MTL, high-resolution fMRI, and multivariate pattern analysis to identify representations of objects in cortical and hippocampal areas of human MTL, assessing how these representations were shaped by exposure to regularities. Subjects viewed a continuous visual stream containing hidden temporal relationships-pairs of objects that reliably appeared nearby in time. We compared the pattern of blood oxygen level-dependent activity evoked by each object before and after this exposure, and found that perirhinal cortex, parahippocampal cortex, subiculum, CA1, and CA2/CA3/dentate gyrus (CA2/3/DG) encoded regularities by increasing the representational similarity of their constituent objects. Most regions exhibited bidirectional associative shaping, whereas CA2/3/DG represented regularities in a forward-looking predictive manner. These findings suggest that object representations in MTL come to mirror the temporal structure of the environment, supporting rapid and incidental statistical learning.     

Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration

Chronic stress produces deficits in cognition accompanied by alterations in neural chemistry and morphology. For example, both stress and chronic administration of corticosterone produce dendritic atrophy in hippocampal neurons (Woolley C, Gould E, McEwen BS. 1990. Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 531:225–231; Watanabe Y, Gould E, McEwen BS, 1992b. Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 588:341–345). Prefrontal cortex is also a target for glucocorticoids involved in the stress response (Meaney MJ, Aitken DH. 1985. [³H]Dexamethasone binding in rat frontal cortex. Brain Res 328:176–180); it shows neurochemical changes in response to stress (e.g., Luine VN, Spencer RL, McEwen BS. 1993. Effect of chronic corticosterone ingestion on spatial memory performance and hippocampal serotonergic function. Brain Res 616:55–70; Crayton JW, Joshi I, Gulati A, Arora RC, Wolf WA. 1996. Effect of corticosterone on serotonin and catecholamine receptors and uptake sites in rat frontal cortex. Brain Res 728:260–262; Takao K, Nagatani T, Kitamura Y, Yamawaki S. 1997. Effects of corticosterone on 5‐HT_1A and 5‐HT₂ receptor binding and on the receptor‐mediated behavioral responses of rats. Eur J Pharmacol 333:123–128; Sandi C, Loscertales M. 1999. Opposite effects on NCAM expression in the rat frontal cortex induced by acute vs. chronic corticosterone treatments. Brain Res 828:127–134), and mediates many of the behaviors that are altered by chronic corticosterone administration (e.g., Lyons DM, Lopez JM, Yang C, Schatzberg AF. 2000. Stress‐level cortisol treatment impairs inhibitory control of behavior in monkeys. J Neurosci 20:7816–7821). To determine if glucocorticoid‐induced morphological changes also occur in medial prefrontal cortex, the effects of chronic corticosterone administration on dendritic morphology in this corticolimbic structure were assessed. Adult male rats received s.c. injections of either corticosterone (10 mg in 250 μL sesame oil; n = 8) or vehicle (250 μL; n = 8) daily for 3 weeks. A third group of rats served as intact controls (n = 4). Brains were stained using a Golgi‐Cox procedure and pyramidal neurons in layer II‐III of medial prefrontal cortex were drawn; dendritic morphology was quantified in three dimensions. Sholl analyses demonstrated a significant redistribution of apical dendrites in corticosterone‐treated animals: the amount of dendritic material proximal to the soma was increased relative to intact rats, while distal dendritic material was decreased relative to intact animals. Thus, chronic glucocorticoid administration dramatically reorganized apical arbors in medial prefrontal cortex. This reorganization likely reflects functional changes and may contribute to stress‐induced changes in cognition. © 2001 John Wiley & Sons, Inc. J Neurobiol 49: 245–253, 2001     

Midbrain activity shapes high-level visual properties in the primate temporal cortex

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Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration.

Chronic stress produces deficits in cognition accompanied by alterations in neural chemistry and morphology. For example, both stress and chronic administration of corticosterone produce dendritic atrophy in hippocampal neurons (Woolley C, Gould E, McEwen BS. 1990. Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 531:225-231; Watanabe Y, Gould E, McEwen BS, 1992b. Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 588:341-345). Prefrontal cortex is also a target for glucocorticoids involved in the stress response (Meaney MJ, Aitken DH. 1985. [(3)H]Dexamethasone binding in rat frontal cortex. Brain Res 328:176-180); it shows neurochemical changes in response to stress (e.g., Luine VN, Spencer RL, McEwen BS. 1993. Effect of chronic corticosterone ingestion on spatial memory performance and hippocampal serotonergic function. Brain Res 616:55-70; Crayton JW, Joshi I, Gulati A, Arora RC, Wolf WA. 1996. Effect of corticosterone on serotonin and catecholamine receptors and uptake sites in rat frontal cortex. Brain Res 728:260-262; Takao K, Nagatani T, Kitamura Y, Yamawaki S. 1997. Effects of corticosterone on 5-HT(1A) and 5-HT(2) receptor binding and on the receptor-mediated behavioral responses of rats. Eur J Pharmacol 333:123-128; Sandi C, Loscertales M. 1999. Opposite effects on NCAM expression in the rat frontal cortex induced by acute vs. chronic corticosterone treatments. Brain Res 828:127-134), and mediates many of the behaviors that are altered by chronic corticosterone administration (e.g., Lyons DM, Lopez JM, Yang C, Schatzberg AF. 2000. Stress-level cortisol treatment impairs inhibitory control of behavior in monkeys. J Neurosci 20:7816-7821). To determine if glucocorticoid-induced morphological changes also occur in medial prefrontal cortex, the effects of chronic corticosterone administration on dendritic morphology in this corticolimbic structure were assessed. Adult male rats received s.c. injections of either corticosterone (10 mg in 250 microL sesame oil; n = 8) or vehicle (250 microL; n = 8) daily for 3 weeks. A third group of rats served as intact controls (n = 4). Brains were stained using a Golgi-Cox procedure and pyramidal neurons in layer II-III of medial prefrontal cortex were drawn; dendritic morphology was quantified in three dimensions. Sholl analyses demonstrated a significant redistribution of apical dendrites in corticosterone-treated animals: the amount of dendritic material proximal to the soma was increased relative to intact rats, while distal dendritic material was decreased relative to intact animals. Thus, chronic glucocorticoid administration dramatically reorganized apical arbors in medial prefrontal cortex. This reorganization likely reflects functional changes and may contribute to stress-induced changes in cognition.     

A model of cardinality blindness in inferotemporal cortex

A classifier is cardinality invariant if it can classify more than one token of a single type at a time. We present a convolutional neural network (CNN) model of inferotemporal cortex (IT) and show that it is cardinality invariant. While the CNN is designed with translation invariance in mind, cardinality invariance is an emergent property. We speculate that translation invariance may lead to cardinality invariance in general, and particularly in IT. Recent investigations have shown that cells in IT are indeed cardinality blind. We also explore the implications of a cardinality blind classifier for vision overall, concentrating on visual attention and search.     

Patchy organization and asymmetric distribution of the neural correlates of face processing in monkey inferotemporal cortex

BACKGROUND: It is believed that a face-specific system exists within the primate ventral visual pathway that is separate from a domain-general nonface object coding system. In addition, it is believed that hemispheric asymmetry, which was long held to be a distinct feature of the human brain, can be found in the brains of other primates as well. We show here for the first time by way of a functional imaging technique that face- and object-selective neurons form spatially distinct clusters at the cellular level in monkey inferotemporal cortex. We have used a novel functional mapping technique that simultaneously generates two separate activity profiles by exploiting the differential time course of zif268 mRNA and protein expression. RESULTS: We show that neurons activated by face stimulation can be visualized at cellular resolution and distinguished from those activated by nonface complex objects. Our dual-activity maps of face and object selectivity show that face-selective patches of various sizes (mean, 22.30 mm2; std, 32.76 mm2) exist throughout the IT cortex in the context of a large expanse of cortical territory that is responsive to visual objects. CONCLUSIONS: These results add to recent findings that face-selective patches of various sizes exist throughout area IT and provide the first direct anatomical evidence at cellular resolution for a hemispheric asymmetry in favor of the right hemisphere. Together, our results support the notion that human and monkey brains share a similarity in both anatomical organization and distribution of function with respect to high-level visual processing.     

Object memory and perception in the medial temporal lobe: an alternative approach

The medial temporal lobe (MTL) includes several structures--the hippocampus, and the adjacent perirhinal, entorhinal and parahippocampal cortices--that have been associated with memory for at least the past 50 years. These components of the putative 'MTL memory system' are thought to operate together in the service of declarative memory--memory for facts and events--having little or no role in other functions such as perception. Object perception, however, is thought to be independent of the MTL, and instead is usually considered to be the domain of the ventral visual stream (VVS) or 'what' pathway. This 'textbook' view fits squarely into the prevailing paradigm of anatomical modularisation of psychological function in the brain. Recent studies, however, question this view, indicating that first, the MTL is functionally heterogeneous, and second, structures in the MTL might have a role in perception. Furthermore, the specific contributions of the individual structures within the MTL are being elucidated. These new findings indicate that it might no longer be useful to assume a strict functional dissociation between the MTL and the VVS, and that psychological functions might not be modularised in the way usually assumed. We propose an alternative approach to understanding the functions of these brain regions in terms of what computations they perform, and what representations they contain.     

Distribution of TRPC1 and TRPC5 in medial temporal lobe structures of mice

The transient receptor potential (TRP) superfamily comprises a group of non-selective cation channels that have been implicated in both receptor and store-operated channel functions. The family of the classical TRPs (TRPCs) consists of seven members (TRPC1-7). The presence of TRPC1 and TRPC5 mRNA in the brain has previously been demonstrated by real-time polymerase chain reaction. However, the distribution of these receptors within different brain areas of mice has not been investigated in detail. We have used antibodies directed against TRPC1 and TRPC5 to study the distribution and localization of these channels in murine medial temporal lobe structures. Both TRPC1 and TRPC5 channels are present in the various nuclei of the amygdala, in the hippocampus, and in the subiculum and the entorhinal cortex. We have found that TRPC1 channels are primarily expressed on cell somata and on dendrites, whereas TRPC5 channels are exclusively located on cell bodies. Moreover, TRPC1 channels are selectively expressed by neurons, whereas TRPC5 channels are mainly expressed by neurons, but also by non-neuronal cells. The expression of TRPC1 and TRPC5 channels in mammalian temporal lobe structures suggests their involvement in neuronal plasticity, learning and memory. This work was supported by the DFG (SFB 636/A5).     

Changes in the electrical activity of the medial septal region, piriform cortex and amygdala during epileptogenesis in the model of temporal lobe epilepsy

Local field potentials (EEGs) in the medial septal area, amygdala and piriform cortex were recorded in waking guinea pigs in the control and during epileptogenesis in the model of chronic temporal lobe epilepsy (lithium-pilocarpin model of status epilepticus). Analysis of changes in rhythmical activity and interstructural relations was carried out at different stages of epileptogenesis. Increased frequency of rhythmic activity in delta, theta, and alphabands was observed during epileptogenesis. Correlation relations between the activities of the medical septum with the piriform cortex and amygdala clearly decreased to 5 months after development of status epilepticus. Changes in the frequency of oscillations and structural correlations developed in time from two months on and reached a maximum 5 months after the status epilepticus development. It point to intensification of the pathological changes during formation of the epileptic focus. A possible role of the observed EEG changes in the formation of a pathological centre is discussed.     

Distinct neuronal types contribute to hybrid temporal encoding strategies in primate auditory cortex

Studies of the encoding of sensory stimuli by the brain often consider recorded neurons as a pool of identical units. Here, we report divergence in stimulus-encoding properties between subpopulations of cortical neurons that are classified based on spike timing and waveform features. Neurons in auditory cortex of the awake marmoset (Callithrix jacchus) encode temporal information with either stimulus-synchronized or nonsynchronized responses. When we classified single-unit recordings using either a criteria-based or an unsupervised classification method into regular-spiking, fast-spiking, and bursting units, a subset of intrinsically bursting neurons formed the most highly synchronized group, with strong phase-locking to sinusoidal amplitude modulation (SAM) that extended well above 20 Hz. In contrast with other unit types, these bursting neurons fired primarily on the rising phase of SAM or the onset of unmodulated stimuli, and preferred rapid stimulus onset rates. Such differentiating behavior has been previously reported in bursting neuron models and may reflect specializations for detection of acoustic edges. These units responded to natural stimuli (vocalizations) with brief and precise spiking at particular time points that could be decoded with high temporal stringency. Regular-spiking units better reflected the shape of slow modulations and responded more selectively to vocalizations with overall firing rate increases. Population decoding using time-binned neural activity found that decoding behavior differed substantially between regular-spiking and bursting units. A relatively small pool of bursting units was sufficient to identify the stimulus with high accuracy in a manner that relied on the temporal pattern of responses. These unit type differences may contribute to parallel and complementary neural codes.

Neurons in auditory cortex show highly diverse responses to sounds. This study suggests that neuronal type inferred from baseline firing properties accounts for much of this diversity, with a subpopulation of bursting units being specialized for precise temporal encoding.     

Active maintenance of associative mnemonic signal in monkey inferior temporal cortex

We investigated the contribution of the inferior temporal (IT) cortical neurons to the active maintenance of internal representations. The activity of single neurons in the IT cortex was recorded while the monkeys performed a sequential-type associative memory task in which distractor stimuli interrupted the delay epoch between the cue and target (paired-associate) stimuli. For each neuron, information about each stimulus conveyed by the delay activity was estimated as a coefficient of multiple regression analysis. We found that target information derived from long-term memory (LTM) persisted despite the distractors. By contrast, cue information derived from the visual system was attenuated and frequently replaced by distractor information. These results suggest that LTM-derived information required for upcoming behavior is actively maintained in the IT neurons, whereas visually derived information tends to be updated irrespective of behavioral relevance.     

Medial temporal lobe projections to the retrosplenial cortex of the macaque monkey

The projections to the retrosplenial cortex (areas 29 and 30) from the hippocampal formation, the entorhinal cortex, perirhinal cortex, and amygdala were examined in two species of macaque monkey by tracking the anterograde transport of amino acids. Hippocampal projections arose from the subiculum and presubiculum to terminate principally in area 29. Label was found in layer I and layer III(IV), the former seemingly reflecting both fibers of passage and termination. While the rostral subiculum mainly projects to the ventral retrosplenial cortex, mid and caudal levels of the subiculum have denser projections to both the caudal and dorsal retrosplenial cortex. Appreciable projections to dorsal area 30 [layer III(IV)] were only seen following an extensive injection involving both the caudal subiculum and presubiculum. This same case provided the only example of a light projection from the hippocampal formation to posterior cingulate area 23 (layer III). Anterograde label from the entorhinal cortex injections was typically concentrated in layer I of 29a-c, though the very caudal entorhinal cortex appeared to provide more widespread retrosplenial projections. In this study, neither the amygdala nor the perirhinal cortex were found to have appreciable projections to the retrosplenial cortex, although injections in either medial temporal region revealed efferent fibers that pass very close or even within this cortical area. Finally, light projections to area 30V, which is adjacent to the calcarine sulcus, were seen in those cases with rostral subiculum and entorhinal injections. The results reveal a particular affinity between the hippocampal formation and the retrosplenial cortex, and so distinguish areas 29 and 30 from area 23 within the posterior cingulate region. The findings also suggest further functional differences within retrosplenial subregions as area 29 received the large majority of efferents from the subiculum. ? 2012 Wiley Periodicals, Inc.     

The role of medial temporal lobe structures in implicit learning: an event-related FMRI study

The medial temporal lobe (MTL) has been associated with declarative learning of flexible relational rules and the basal ganglia with implicit learning of stimulus-response mappings. It remains an open question of whether MTL or basal ganglia are involved when learning flexible relational contingencies without awareness. We studied learning of an explicit stimulus-response association with fMRI. Embedded in this explicit task was a hidden structure that was learnt implicitly. Implicit learning of the sequential regularities of the "hidden rule" activated the ventral perirhinal cortex, within the MTL, whereas learning the fixed stimulus-response associations activated the basal ganglia, indicating that the function of the MTL and the basal ganglia depends on the learned material and not necessarily on the participants' awareness.     

A single-neuron correlate of change detection and change blindness in the human medial temporal lobe

Observers are often unaware of changes in their visual environment when attention is not focused at the location of the change . Because of its rather intriguing nature, this phenomenon, known as change blindness, has been extensively studied with psychophysics as well as with fMRI . However, whether change blindness can be tracked in the activity of single cells is not clear. To explore the neural correlates of change detection and change blindness, we recorded from single neurons in the human medial temporal lobe (MTL) during a change-detection paradigm. The preferred pictures of the visually responsive units elicited significantly higher firing rates on the attended trials when subjects correctly identified a change (change detection) compared to the unattended trials when they missed it (change blindness). On correct trials, the firing activity of individual units allowed us to predict the occurrence of a change, on a trial-by-trial basis, with 67% accuracy. In contrast, this prediction was at chance for incorrect, unattended trials. The firing rates of visually selective MTL cells thus constitute a neural correlate of change detection.