Resting state functional connectivity in patients with chronic hallucinations

Auditory verbal hallucinations (AVH) are not only among the most common but also one of the most distressing symptoms of schizophrenia. Despite elaborate research, the underlying brain mechanisms are as yet elusive. Functional MRI studies have associated the experience of AVH with activation of bilateral language-related areas, in particular the right inferior frontal gyrus (rIFG) and the left superior temporal gyrus (lSTG). While these findings helped to understand the neural underpinnings of hearing voices, they provide little information about possible brain mechanisms that predispose a person to experience AVH, i.e. the traits to hallucinate. In this study, we compared resting state connectivity between 49 psychotic patients with chronic AVH and 49 matched controls using the rIFG and the lSTG as seed regions, to identify functional brain systems underlying the predisposition to hallucinate. The right parahippocampal gyrus showed increased connectivity with the rIFG in patients as compared to controls. Reduced connectivity with the rIFG in patients was found for the right dorsolateral prefrontal cortex. Reduced connectivity with the lSTG in patients was identified in the left frontal operculum as well as the parietal opercular area. Connectivity between the lSTG and the left hippocampus was also reduced in patients and showed a negative correlation with the severity of hallucinations. Concluding, we found aberrant connectivity between the seed regions and medial temporal lobe structures which have a prominent role in memory retrieval. Moreover, we found decreased connectivity between language-related areas, indicating aberrant integration in this system potentially including corollary discharge mechanisms.     

Resting-state EEG source localization and functional connectivity in schizophrenia-like psychosis of epilepsy

Background

It is unclear whether, like in schizophrenia, psychosis-related disruption in connectivity between certain regions, as an index of intrinsic functional disintegration, occurs in schizophrenia-like psychosis of epilepsy (SLPE). In this study, we sought to determine abnormal patterns of resting-state EEG oscillations and functional connectivity in patients with SLPE, compared with nonpsychotic epilepsy patients, and to assess correlations with psychopathological deficits.

Methodology/Principal Findings

Resting EEG was recorded in 21 patients with focal epilepsy and SLPE and in 21 clinically-matched non-psychotic epilepsy controls. Source current density and functional connectivity were determined using eLORETA software. For connectivity analysis, a novel nonlinear connectivity measure called “lagged phase synchronization” was used. We found increased theta oscillations in regions involved in the default mode network (DMN), namely the medial and lateral parietal cortex bilaterally in the psychotic patients relative to their nonpsychotic counterparts. In addition, patients with psychosis had increased beta temporo-prefrontal connectivity in the hemisphere with predominant seizure focus. This functional connectivity in temporo-prefrontal circuits correlated with positive symptoms. Additionally, there was increased interhemispheric phase synchronization between the auditory cortex of the affected temporal lobe and the Broca''s area correlating with auditory hallucination scores.

Conclusions/Significance

In addition to dysfunction of parietal regions that are part of the DMN, resting-state disrupted connectivity of the medial temporal cortex with prefrontal areas that are either involved in the DMN or implicated in psychopathological dysfunction may be critical to schizophrenia-like psychosis, especially in individuals with temporal lobe epilepsy. This suggests that DMN deficits might be a core neurobiological feature of the disorder, and that abnormalities in theta oscillations and beta phase synchronization represent the underlying neural activity.     

Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity

Functional magnetic resonance imaging (fMRI) can provide maps of brain activation with millimeter spatial resolution but is limited in its temporal resolution to the order of seconds. Here, we describe a technique that combines structural and functional MRI with magnetoencephalography (MEG) to obtain spatiotemporal maps of human brain activity with millisecond temporal resolution. This new technique was used to obtain dynamic statistical parametric maps of cortical activity during semantic processing of visually presented words. An initial wave of activity was found to spread rapidly from occipital visual cortex to temporal, parietal, and frontal areas within 185 ms, with a high degree of temporal overlap between different areas. Repetition effects were observed in many of the same areas following this initial wave of activation, providing evidence for the involvement of feedback mechanisms in repetition priming.     

Modality-specific control of strategic spatial attention in parietal cortex

The neural basis of selective spatial attention presents a significant challenge to cognitive neuroscience. Recent neuroimaging studies have suggested that regions of the parietal and temporal cortex constitute a "supramodal" network that mediates goal-directed attention in multiple sensory modalities. Here we used transcranial magnetic stimulation (TMS) to determine which cortical subregions control strategic attention in vision and touch. Healthy observers undertook an orienting task in which a central arrow cue predicted the location of a subsequent visual or somatosensory target. To determine the attentional role of cortical subregions at different stages of processing, TMS was delivered to the right hemisphere during cue or target events. Results indicated a critical role of the inferior parietal cortex in strategic orienting to visual events, but not to somatosensory events. These findings are inconsistent with the existence of a supramodal attentional network and instead provide direct evidence for modality-specific attentional processing in parietal cortex.     

Effects of the Neurogranin Variant rs12807809 on Thalamocortical Morphology in Schizophrenia

Although the genome wide supported psychosis susceptibility neurogranin (NRGN) gene is expressed in human brains, it is unclear how it impacts brain morphology in schizophrenia. We investigated the influence of NRGN rs12807809 on cortical thickness, subcortical volumes and shapes in patients with schizophrenia. One hundred and fifty six subjects (91 patients with schizophrenia and 65 healthy controls) underwent structural MRI scans and their blood samples were genotyped. A brain mapping algorithm, large deformation diffeomorphic metric mapping, was used to perform group analysis of subcortical shapes and cortical thickness. Patients with risk TT genotype were associated with widespread cortical thinning involving frontal, parietal and temporal cortices compared with controls with TT genotype. No volumetric difference in subcortical structures (hippocampus, thalamus, amygdala, basal ganglia) was observed between risk TT genotype in patients and controls. However, patients with risk TT genotype were associated with thalamic shape abnormalities involving regions related to pulvinar and medial dorsal nuclei. Our results revealed the influence of the NRGN gene on thalamocortical morphology in schizophrenia involving widespread cortical thinning and thalamic shape abnormalities. These findings help to clarify underlying NRGN mediated pathophysiological mechanisms involving cortical-subcortical brain networks in schizophrenia.     

Differential neural responses to food images in women with bulimia versus anorexia nervosa

Background

Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known.

Methods

We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI).

Results

In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area.

Conclusions

Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.     

Symmetrical distribution of amino acid neurotransmitters in the right and left cerebral cortex of the rat

The level and activity of seven amino acids were examined in both the right and left areas of the cerebral cortex of the rat in order to determine their respective symmetrical distribution. In the first experiment, alanine, glycine, threonine, serine, GABA, aspartate, and glutamate were measured in six different regions of the cortex: medial, sulcal, and dorsal prefrontal as well as parietal, temporal, and occipital. The differences in the level of these amino acids in symmetrical regions of either side of the cortex were not statistically significant. In the second experiment, the in vivo synthesis from the [¹⁴C]glucose precursor of three amino acids, glutamate, glutamine, and GABA was measured using the cortical push-pull perfusion technique in the freely moving rat. Although differences in synthesis were found between the prefrontal and parietal areas of the cortex, no changes occurred between right and left hemispheres. These results indicate that for the resting levels of the amino acids examined in this study, no differential asymmetric distribution exists between right or left cortical regions of the rat's brain.     

Cortical Surface Area Correlates with STON2 Gene Ser307Pro Polymorphism in First-Episode Treatment-Na?ve Patients with Schizophrenia

Background

Evidence shows that STON2 gene is associated with synaptic function and schizophrenia. This study aims to explore the relationship between two functional polymorphisms (Ser307Pro and Ala851Ser) of STON2 gene and the cortical surface area in first-episode treatment-naïve patients with schizophrenia and healthy controls.

Methodology/Principal Findings

Magnetic resonance imaging of the whole cortical surface area, which was computed by an automated surface-based technique (FreeSurfer), was obtained from 74 first-episode treatment-naïve patients with schizophrenia and 55 healthy controls. Multiple regression analysis was performed to investigate the effect of genotype subgroups on the cortical surface area. A significant genotype-by-diagnosis effect on the cortical surface area was observed. Pro-allele carriers of Ser307Pro polymorphism had larger right inferior temporal surface area than Ser/Ser carriers in the patients with schizophrenia; however, no significant difference was found in the same area in the healthy controls. The Ala851Ser polymorphism of STON2 gene was not significantly associated with the cortical surface area in patients with schizophrenia and healthy controls.

Conclusions/Significance

The present study demonstrated that the functional variant of the STON2 gene could alter cortical surface area on the right inferior temporal and contribute to the pathogenesis of schizophrenia.     

Origins of spatial working memory deficits in schizophrenia: an event-related FMRI and near-infrared spectroscopy study

Abnormal prefrontal functioning plays a central role in the working memory (WM) deficits of schizophrenic patients, but the nature of the relationship between WM and prefrontal activation remains undetermined. Using two functional neuroimaging methods, we investigated the neural correlates of remembering and forgetting in schizophrenic and healthy participants. We focused on the brain activation during WM maintenance phase with event-related functional magnetic resonance imaging (fMRI). We also examined oxygenated hemoglobin changes in relation to memory performance with the near-infrared spectroscopy (NIRS) using the same spatial WM task. Distinct types of correct and error trials were segregated for analysis. fMRI data indicated that prefrontal activation was increased during WM maintenance on correct trials in both schizophrenic and healthy subjects. However, a significant difference was observed in the functional asymmetry of frontal activation pattern. Healthy subjects showed increased activation in the right frontal, temporal and cingulate regions. Schizophrenic patients showed greater activation compared with control subjects in left frontal, temporal and parietal regions as well as in right frontal regions. We also observed increased 'false memory' errors in schizophrenic patients, associated with increased prefrontal activation and resembling the activation pattern observed on the correct trials. NIRS data replicated the fMRI results. Thus, increased frontal activity was correlated with the accuracy of WM in both healthy control and schizophrenic participants. The major difference between the two groups concerned functional asymmetry; healthy subjects recruited right frontal regions during spatial WM maintenance whereas schizophrenic subjects recruited a wider network in both hemispheres to achieve the same level of memory performance. Increased "false memory" errors and accompanying bilateral prefrontal activation in schizophrenia suggest that the etiology of memory errors must be considered when comparing group performances. Finally, the concordance of fMRI and NIRS data supports NIRS as an alternative functional neuroimaging method for psychiatric research.     

Is the Cerebellum the Optimal Reference Region for Intensity Normalization of Perfusion MR Studies in Early Alzheimer’s Disease?

The cerebellum is the region most commonly used as a reference when normalizing the intensity of perfusion images acquired using magnetic resonance imaging (MRI) in Alzheimer’s disease (AD) studies. In addition, the cerebellum provides unbiased estimations with nuclear medicine techniques. However, no reports confirm the cerebellum as an optimal reference region in MRI studies or evaluate the consequences of using different normalization regions. In this study, we address the effect of using the cerebellum, whole-brain white matter, and whole-brain cortical gray matter in the normalization of cerebral blood flow (CBF) parametric maps by comparing patients with stable mild cognitive impairment (MCI), patients with AD and healthy controls. According to our results, normalization by whole-brain cortical gray matter enables more sensitive detection of perfusion abnormalities in AD patients and reveals a larger number of affected regions than data normalized by the cerebellum or whole-brain white matter. Therefore, the cerebellum is not the most valid reference region in MRI studies for early stages of AD. After normalization by whole-brain cortical gray matter, we found a significant decrease in CBF in both parietal lobes and an increase in CBF in the right medial temporal lobe. We found no differences in perfusion between patients with stable MCI and healthy controls either before or after normalization.     

Structural Alteration of the Dorsal Visual Network in DLB Patients with Visual Hallucinations: A Cortical Thickness MRI Study

Visual hallucinations (VH) represent one of the core features in discriminating dementia with Lewy bodies (DLB) from Alzheimer’s Disease (AD). Previous studies reported that in DLB patients functional alterations of the parieto-occipital regions were correlated with the presence of VH. The aim of our study was to assess whether morphological changes in specific cortical regions of DLB could be related to the presence and severity of VH. We performed a cortical thickness analysis on magnetic resonance imaging data in a cohort including 18 DLB patients, 15 AD patients and 14 healthy control subjects. Relatively to DLB group, correlation analysis between the cortical thickness and the Neuropsychiatric Inventory (NPI) hallucination item scores was also performed. Cortical thickness was reduced bilaterally in DLB compared to controls in the pericalcarine and lingual gyri, cuneus, precuneus, superior parietal gyrus. Cortical thinning was found bilaterally in AD compared to controls in temporal cortex including the superior and middle temporal gyrus, part of inferior temporal cortex, temporal pole and insula. Inferior parietal and supramarginal gyri were also affected bilaterally in AD as compared to controls. The comparison between DLB and AD evidenced cortical thinning in DLB group in the right posterior regions including superior parietal gyrus, precuneus, cuneus, pericalcarine and lingual gyri. Furthermore, the correlation analysis between cortical thickness and NPI hallucination item scores showed that the structural alteration in the dorsal visual regions including superior parietal gyrus and precuneus closely correlated with the occurrence and severity of VH. We suggest that structural changes in key regions of the dorsal visual network may play a crucial role in the physiopathology of VH in DLB patients.     

Right or left ear reference changes the voltage of frontal and parietal somatosensory evoked potentials

Short-latency cortical somatosensory evoked potentials (SEPs) to left median nerve stimulation were recorded with either the left or right earlobe as reference. With a right earlobe reference the voltage of the parietal N20 and P27 was reduced while the voltage of the frontal P20 and N30 was enhanced. The effects were consistent, but their size varied with the SEP component considered and also among the subjects. Analysis of SEPs at different scalp sites and at either earlobe suggested that the ear contralateral to the side stimulated picked up transient potential differences, depending a.o. on side asymmetry and geometry of the neural generators as disclosed in topographic mapping. For example, the right ear potential can be shifted negatively by the right N20 field evoked by left median nerve stimulation. The changes involve the absolute potential values, but not the time features of the gradients of potential fields. Scalp current density (SCD) maps are not affected. The results are pertinent for current discussions about which reference to use and document the practical recommendation of recording short-latency cortical SEPs with a reference at the ear ipsilateral (not contralateral) to the side of stimulation.     

Neural activity in the human brain relating to uncertainty and arousal during anticipation

We used functional magnetic resonance neuroimaging to measure brain activity during delay between reward-related decisions and their outcomes, and the modulation of this delay activity by uncertainty and arousal. Feedback, indicating financial gain or loss, was given following a fixed delay. Anticipatory arousal was indexed by galvanic skin conductance. Delay-period activity was associated with bilateral activation in orbital and medial prefrontal, temporal, and right parietal cortices. During delay, activity in anterior cingulate and orbitofrontal cortices was modulated by outcome uncertainty, whereas anterior cingulate, dorsolateral prefrontal, and parietal cortices activity was modulated by degree of anticipatory arousal. A distinct region of anterior cingulate was commonly activated by both uncertainty and arousal. Our findings highlight distinct contributions of cognitive uncertainty and autonomic arousal to anticipatory neural activity in prefrontal cortex.     

Altered Neural Basis of the Reality Processing and Its Relation to Cognitive Insight in Schizophrenia

It has been reported that reality evaluation and recognition are impaired in patients with schizophrenia and these impairments are related to the severity of psychotic symptoms. The current study aimed to investigate the neural basis of impairments in reality evaluation and recognition and their relationships with cognitive insight in schizophrenia. During functional magnetic resonance imaging, 20 patients with schizophrenia and 20 healthy controls performed a set of reality evaluation and recognition tasks, in which subjects judged whether scenes in a series of drawings were real or unreal and whether they were familiar or novel. During reality evaluation, patients showed decreased activity in various regions including the inferior parietal lobule, retrosplenial cortex and parahippocampal gyrus, compared with controls. Particularly, parahippocampal gyrus activity was correlated with the severity of positive symptoms in patients. During recognition, patients also exhibited decreased activity in various regions, including the dorsolateral prefrontal cortex, inferior parietal lobule and posterior cingulate cortex. Particularly, inferior parietal lobule activity and posterior cingulate cortex activity were correlated with cognitive insight in patients. These findings provide evidence that neural impairments in reality evaluation and recognition are related to psychotic symptoms. Anomalous appraisal of context by dysfunctions in the context network may contribute to impairments in the reality processing in schizophrenia, and abnormal declarative memory processes may be involved in cognitive insight in patients with schizophrenia.     

Retinotopic organization of striate and extrastriate visual cortex in the golden hamster (Mesocricetus auratus).

The visual topography within striate and lateral extrastriate visual cortices was studied in adult hamsters. The cortical areas 17 and 18a in the left hemisphere were electrophysiologically mapped upon stimulation of the right eye, correlating receptive field positions in the visual field with cortical recording sites. Reference lesions were placed at selected cortical sites. Like in rats and other mammals, the lateral extrastriate cortex contained multiple representations of the visual field. Rostral area 18a contained the rostrolateral maps, with medial and lateral divisions. More caudally and sharing a common border with V1, maps in lateromedial, posterolateral and posterior areas were found. More laterally and forming a "third tier" of visual maps, anterolateral, laterolateral-anterior, laterolateral and laterolateral-posterior areas were found. There was also an indication of a possible pararhinal map. The plan so defined is virtually identical to that of rats. The results may be useful to understand a basic mammalian plan in the organization of the visual cortex.     

Copying You Copying Me: Interpersonal Motor Co-Ordination Influences Automatic Imitation

Moving in a co-ordinated fashion with another individual changes our behaviour towards them; we tend to like them more, find them more attractive, and are more willing to co-operate with them. It is generally assumed that this effect on behaviour results from alterations in representations of self and others. Specifically, through neurophysiological perception-action matching mechanisms, interpersonal motor co-ordination (IMC) is believed to forge a neural coupling between actor and observer, which serves to blur boundaries in conceptual self-other representations and causes positive views of the self to be projected onto others. An investigation into this potential neural mechanism is lacking, however. Moreover, the specific components of IMC that might influence this mechanism have not yet been specified. In the present study we exploited a robust behavioural phenomenon – automatic imitation – to assess the degree to which IMC influences neural action observation-execution matching mechanisms. This revealed that automatic imitation is reduced when the actions of another individual are perceived to be synchronised in time, but are spatially incongruent, with our own. We interpret our findings as evidence that IMC does indeed exert an effect on neural perception-action matching mechanisms, but this serves to promote better self-other distinction. Our findings demonstrate that further investigation is required to understand the complex relationship between neural perception-action coupling, conceptual self-other representations, and social behaviour.     

The Selective Impairment of Resting-State Functional Connectivity of the Lateral Subregion of the Frontal Pole in Schizophrenia

Objective

Although extensive resting-state functional connectivity (rsFC) changes have been reported in schizophrenia, rsFC changes of the frontal pole (FP) remain unclear. The FP contains several subregions with different connection patterns; however, it is unknown whether the FP subregions are differentially affected in schizophrenia. To explore this possibility, we compared rsFC differences of the FP subregions between schizophrenia patients and healthy controls.

Method

One hundred healthy controls and 91 patients with schizophrenia underwent resting-state functional MRI with a sensitivity-encoded spiral-in (SENSE-SPIRAL) imaging sequence to reduced susceptibility-induced signal loss and distortion. The FP was subdivided into the orbital (FPo), medial (FPm), and lateral (FPl) subregions. Mean fMRI time series were extracted for each FP subregion and entered into a seed-based rsFC analysis.

Results

The FP subregions exhibited differential rsFC patterns in both healthy controls and schizophrenia patients. Direct comparison between groups revealed reduced rsFCs between the bilateral FPl and several cognitive-related regions, including the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex/precuneus, temporal cortex and inferior parietal lobule in schizophrenia. Although the FPl exhibited obvious atrophy, rsFC changes were unrelated to volumetric atrophy in the FPl, to duration of illness, and to antipsychotic medication dosage. No significant differences were observed in the rsFCs of other FP subregions.

Conclusion

These findings suggest a selective (the lateral subregion) functional disconnection of the FP subregions in schizophrenia.     

Altered Oscillation and Synchronization of Default-Mode Network Activity in Mild Alzheimer’s Disease Compared to Mild Cognitive Impairment: An Electrophysiological Study

Some researchers have suggested that the default mode network (DMN) plays an important role in the pathological mechanisms of Alzheimer’s disease (AD). To examine whether the cortical activities in DMN regions show significant difference between mild AD from mild cognitive impairment (MCI), electrophysiological responses were analyzed from 21 mild Alzheimer’s disease (AD) and 21 mild cognitive impairment (MCI) patients during an eyes closed, resting-state condition. The spectral power and functional connectivity of the DMN were estimated using a minimum norm estimate (MNE) combined with fast Fourier transform and imaginary coherence analysis. Our results indicated that source-based EEG maps of resting-state activity showed alterations of cortical spectral power in mild AD when compared to MCI. These alterations are characteristic of attenuated alpha or beta activities in the DMN, as are enhanced delta or theta activities in the medial temporal, inferior parietal, posterior cingulate cortex and precuneus. With regard to altered synchronization in AD, altered functional interconnections were observed as specific connectivity patterns of connection hubs in the precuneus, posterior cingulate cortex, anterior cingulate cortex and medial temporal regions. Moreover, posterior theta and alpha power and altered connectivity in the medial temporal lobe correlated significantly with scores obtained on the Mini-Mental State Examination (MMSE). In conclusion, EEG is a useful tool for investigating the DMN in the brain and differentiating early stage AD and MCI patients. This is a promising finding; however, further large-scale studies are needed.     

Large-Scale Information Flow in Conscious and Unconscious States: an ECoG Study in Monkeys

Consciousness is an emergent property of the complex brain network. In order to understand how consciousness is constructed, neural interactions within this network must be elucidated. Previous studies have shown that specific neural interactions between the thalamus and frontoparietal cortices; frontal and parietal cortices; and parietal and temporal cortices are correlated with levels of consciousness. However, due to technical limitations, the network underlying consciousness has not been investigated in terms of large-scale interactions with high temporal and spectral resolution. In this study, we recorded neural activity with dense electrocorticogram (ECoG) arrays and used the spectral Granger causality to generate a more comprehensive network that relates to consciousness in monkeys. We found that neural interactions were significantly different between conscious and unconscious states in all combinations of cortical region pairs. Furthermore, the difference in neural interactions between conscious and unconscious states could be represented in 4 frequency-specific large-scale networks with unique interaction patterns: 2 networks were related to consciousness and showed peaks in alpha and beta bands, while the other 2 networks were related to unconsciousness and showed peaks in theta and gamma bands. Moreover, networks in the unconscious state were shared amongst 3 different unconscious conditions, which were induced either by ketamine and medetomidine, propofol, or sleep. Our results provide a novel picture that the difference between conscious and unconscious states is characterized by a switch in frequency-specific modes of large-scale communications across the entire cortex, rather than the cessation of interactions between specific cortical regions.     

Extensive cochleotopic mapping of human auditory cortical fields obtained with phase-encoding FMRI

The primary sensory cortices are characterized by a topographical mapping of basic sensory features which is considered to deteriorate in higher-order areas in favor of complex sensory features. Recently, however, retinotopic maps were also discovered in the higher-order visual, parietal and prefrontal cortices. The discovery of these maps enabled the distinction between visual regions, clarified their function and hierarchical processing. Could such extension of topographical mapping to high-order processing regions apply to the auditory modality as well? This question has been studied previously in animal models but only sporadically in humans, whose anatomical and functional organization may differ from that of animals (e.g. unique verbal functions and Heschl''s gyrus curvature). Here we applied fMRI spectral analysis to investigate the cochleotopic organization of the human cerebral cortex. We found multiple mirror-symmetric novel cochleotopic maps covering most of the core and high-order human auditory cortex, including regions considered non-cochleotopic, stretching all the way to the superior temporal sulcus. These maps suggest that topographical mapping persists well beyond the auditory core and belt, and that the mirror-symmetry of topographical preferences may be a fundamental principle across sensory modalities.