Amygdala lesions do not compromise the cortical network for false-belief reasoning

The amygdala plays an integral role in human social cognition and behavior, with clear links to emotion recognition, trust judgments, anthropomorphization, and psychiatric disorders ranging from social phobia to autism. A central feature of human social cognition is a theory-of-mind (ToM) that enables the representation other people''s mental states as distinct from one''s own. Numerous neuroimaging studies of the best studied use of ToM—false-belief reasoning—suggest that it relies on a specific cortical network; moreover, the amygdala is structurally and functionally connected with many components of this cortical network. It remains unknown whether the cortical implementation of any form of ToM depends on amygdala function. Here we investigated this question directly by conducting functional MRI on two patients with rare bilateral amygdala lesions while they performed a neuroimaging protocol standardized for measuring cortical activity associated with false-belief reasoning. We compared patient responses with those of two healthy comparison groups that included 480 adults. Based on both univariate and multivariate comparisons, neither patient showed any evidence of atypical cortical activity or any evidence of atypical behavioral performance; moreover, this pattern of typical cortical and behavioral response was replicated for both patients in a follow-up session. These findings argue that the amygdala is not necessary for the cortical implementation of ToM in adulthood and suggest a reevaluation of the role of the amygdala and its cortical interactions in human social cognition.The amygdala is considered a critical node of the “social brain” that contributes to myriad social behaviors exhibited by primates (1–4). Neurons in both the monkey (5) and human amygdala (6) respond prominently to faces, and lesions of the monkey amygdala result in complex impairments in social behavior (7, 8). Rare bilateral lesions of the amygdala in human patients impair the ability to infer emotions from facial expressions (9, 10), to make more complex social judgments from faces (11), and to guide appropriate social behaviors (12).A core social ability of humans that emerges early in childhood has been long studied under the name of “theory-of-mind” (ToM), an ability to impute mental states to other people. Amygdala lesions can impair the ability to impute such mental states spontaneously to animated geometric shapes (13, 14) as well as other complex expressions of ToM (15). These impairments in social cognition following amygdala lesions also have been compared with the intensively studied impairments in mental-state understanding observed in autism spectrum disorder (16, 17). Indeed, the amygdala has been implicated in emotional and social dysfunction in a number of psychiatric disorders (18).Neuroimaging studies of ToM-related abilities, on the other hand, have focused largely on cortical networks (19, 20). One of these networks, based on using a localizer requiring subjects to infer false beliefs from written stories (the “False-Belief Localizer”) (21, 22) has become so well established that it is commonly referred to as the “ToM network” and prominently includes the temporoparietal junction as well as medial frontoparietal and anterior temporal cortices (23–28).If the amygdala plays a critical role in social cognition, why is it not regularly identified in neuroimaging studies of ToM? One answer may be that these studies have been focused more on cortical networks, and possible amygdala activations are either underreported or underdiscussed. A second answer may be that the blood oxygenation level-dependent (BOLD) response is more difficult to evoke in the amygdala than in cortex (29, 30). However, the amygdala’s vast connectivity with most of the neocortex (31), prominently including some of the key nodes of the false-belief network such as the medial prefrontal cortex (32, 33), together with its role in social cognition reviewed above, justifies a strong hypothesis. That hypothesis is that the cortical false-belief network should include or be modulated by the amygdala. The clear prediction from this hypothesis is that lesions of the amygdala should alter the functional response of cortical regions critical to ToM.To test this prediction in the most direct way, we used functional MRI (fMRI) in two rare patients with bilateral amygdala lesions and closely interrogated BOLD responses within the amygdala in a large group of neurologically healthy controls. The patients with amygdala lesions had developmental-onset calcifications of the amygdala resulting from Urbach–Wiethe disease (34) (raising interesting further questions about the possible developmental contributions of the amygdala to the false-belief reasoning network, issues we take up in Discussion). To evoke false-belief network activation, each patient performed the well-established False-Belief Localizer twice in separate MRI sessions. The False-Belief Localizer (often called simply the “ToM Localizer”) developed by Rebecca Saxe and colleagues (21, 22) uses brief verbal narratives to manipulate the demand to represent another person''s false belief about reality.At the outset, we clarify that the False-Belief Localizer does not exhaustively represent the range and complexity of the human capacity to reason about mental states (35). In fact, many different behavioral tasks have been used to manipulate mental-state reasoning in previous neuroimaging studies (23, 26), and recent evidence has demonstrated convincingly that these various tasks are not interchangeable manipulations of a single ToM capacity but rather modulate dissociable cortical networks (28, 36). Nonetheless, several reasons justify our decision to focus here on the False-Belief Localizer. First, given that false-belief representation historically has been considered the most unequivocal expression of ToM (37), theory and research on ToM has long maintained a central focus on the capacity to represent false beliefs (38, 39). Second, the focus of ToM research on false-belief reasoning has remained strong in neuroimaging studies of social cognition, in large part because of the efforts of Saxe and colleagues (21, 22) to optimize and make publicly available an efficient protocol for this purpose. Because this same basic protocol has been used in numerous neuroimaging studies of neurologically healthy adults, it is now possible to generate large empirical distributions against which new data points can be compared (40). Therefore, the present study tests the hypothesis that cortical function during false-belief reasoning would show abnormalities in the absence of the amygdala, using this same false-belief neuroimaging task.     

A Neural Basis for the Retrieval of Words for Actions

Although much has been learned in recent years about the neural basis for retrieving words denoting concrete entities, the neural basis for retrieving words denoting actions remains poorly understood. We addressed this issue by testing two specific anatomical hypotheses. (1) Naming of actions depends not only on the classical implementation structures of the left frontal operculum, but also on mediational structures located in left premotor/prefrontal areas. (2) The neural systems subserving naming of actions and naming of concrete entities are segregated. The study used the lesion method and involved 75 subjects with focal, stable lesions in the left or right hemispheres, whose magnetic resonance data were analysed with a three-dimensional reconstruction method. The experimental tasks were standardised procedures for measuring action and object naming. The findings offered partial support for the hypotheses, in that: (1) lesions related to impaired action naming overlapped maximally in the left frontal operculum and in the underlying white matter and anterior insula; and (2) lesions of the left anterior temporal and inferotemporal regions, which produce impairments in naming of concrete entities, did not cause action naming deficits. A follow-up analysis indicated that action naming impairments, especially when they were disproportionate relative to concrete entity naming impairments, were not only associated with premotor/prefrontal lesions, but also with lesions of the left mesial occipital cortex and of the paraventricular white matter underneath the supramarginal and posterior temporal regions.     

Orienting to social stimuli differentiates social cognitive impairment in autism and schizophrenia

Both autism and schizophrenia feature deficits in aspects of social cognition that may be related to amygdala dysfunction, but it is unclear whether these are similar or different patterns of impairment. We compared the visual scanning patterns and emotion judgments of individuals with autism, individuals with schizophrenia and controls on a task well characterized with respect to amygdala functioning. On this task, eye movements of participants are recorded as they assess emotional content within a series of complex social scenes where faces are either included or digitally erased. Results indicated marked abnormalities in visual scanning for both disorders. Controls increased their gaze on face regions when faces were present to a significantly greater degree than both the autism or schizophrenia groups. While the control and the schizophrenia groups oriented to face regions faster when faces were present compared to when they were absent, the autism group oriented at the same rate in both conditions. The schizophrenia group, meanwhile, exhibited a delay in orienting to face regions across both conditions, although whether anti-psychotic medication contributed to this effect is unclear. These findings suggest that while processing emotional information in social scenes, both individuals with autism and individuals with schizophrenia fixate faces less than controls, although only those with autism fail to orient to faces more rapidly based on the presence of facial information. Autism and schizophrenia may therefore share an abnormality in utilizing facial information for assessing emotional content in social scenes, but differ in the ability to seek out socially relevant cues from complex stimuli. Impairments in social orienting are discussed within the context of evidence suggesting the role of the amygdala in orienting to emotionally meaningful information.     

EMPATH: a neural network that categorizes facial expressions

There are two competing theories of facial expression recognition. Some researchers have suggested that it is an example of "categorical perception." In this view, expression categories are considered to be discrete entities with sharp boundaries, and discrimination of nearby pairs of expressive faces is enhanced near those boundaries. Other researchers, however, suggest that facial expression perception is more graded and that facial expressions are best thought of as points in a continuous, low-dimensional space, where, for instance, "surprise" expressions lie between "happiness" and "fear" expressions due to their perceptual similarity. In this article, we show that a simple yet biologically plausible neural network model, trained to classify facial expressions into six basic emotions, predicts data used to support both of these theories. Without any parameter tuning, the model matches a variety of psychological data on categorization, similarity, reaction times, discrimination, and recognition difficulty, both qualitatively and quantitatively. We thus explain many of the seemingly complex psychological phenomena related to facial expression perception as natural consequences of the tasks' implementations in the brain.     

Amygdala damage impairs emotion recognition from scenes only when they contain facial expressions

Bilateral damage to the human amygdala impairs recognition of negatively valenced emotions from facial expressions, but it is unclear if this finding generalizes to richer visual stimuli that contain cues in addition to faces. We investigated this issue in 4 subjects with bilateral amygdala damage, 23 with unilateral amygdala damage, 22 brain-damaged controls and 16 normal individuals. Subjects were shown two blocks of complex social scenes; all stimuli in the two blocks were identical, except that the first block had all facial expressions in the image erased. While control subjects were more accurate in recognizing emotions when facial expressions were present, subjects with bilateral amygdala damage did not show the same benefit for negative emotions, often performing equivalently across the two conditions. Most striking, subjects with bilateral amygdala damage were more accurate in recognizing scenes showing anger with faces erased than with faces present, an effect resulting in part from highly abnormal recognition of certain angry facial expressions. All four subjects with bilateral amygdala damage were impaired in recognizing angry faces shown in isolation, and frequently mistook expressions of anger for smiles, a mistake never made by any control subject. Bilateral amygdala damage thus disproportionately impairs recognition of certain emotions from complex visual stimuli when subjects utilize information from facial expressions.     

Chemoimmune prophylaxis of superficial bladder tumors: Results after treatment of 130 patients in 4 years

Since January 1978 we performed chemoimmune prophylaxis in 130 patients with superficial transitional cell carcinoma of the bladder. After complete tumor resection and exclusion of an urinary tract infection as well as an impaired global immune competence treatment consisted of one intravenous application of 700 mg Cyclophosphamide (CTX)/m2 followed by 6 intravesical instillations of 120 mg BCG/50 ml saline together with BCG skin scarifications. In a total of 12.3% of the treated patients tumor recurrences were observed until the 18th month. These results compared favourably with the high recurrence rate in a group of 80 patients without CTX/BCG prophylaxis. In 48 patients with a history of recurrent tumors statistically significant treatment effects were noted after CTX/BCG (p less than 0.01) using the Wilcoxontest. In 10% of the cases, inflammatory tumor-like lesions developed. Side effects of the treatment were generally well tolerable. From the presented data it is concluded that chemoimmune prophylaxis effectively prevents recurrences in superficial bladder cancer.     

Biological behavior of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide induced carcinoma of the transitional epithelium in the rat.

30 female Wistar rats weighing between 70 and 90 g were fed for 8 months with 0,188% N-[4-(5-nitro-2-furyl)-2-thiazolyl] Formamide (FANFT). After this period a papillary tumor of the urinary bladder was demonstrable in each animal. Histological examination always revealed a transitional cell carcinoma with prevailing medium tumor stages; no distant metastases were found. The grade of malignancy was classified as medium and high. No significant statistical relationship could be ascertained between tumor stage and grade or between grade and weight, but a correlation was established between tumor stage and weight. After 12 months, 36/60 kidneys were found to be normal, whereas in 20/60 dysplasias and in 2/60 transitional cell carcinomas of the renal pelvis were observed; secondary hydronephrosis due to bladder tumors occured 4 times. Other organ changes were not noticeable.     

Harnwegsinfektionen nach Prostataoperationen

Zusammenfassung Prostata-Adenom-Patienten mit präoperativem Harnwegsinfekt und Patienten ohne Infekt wurden im Hinblick auf Schweregrad und Verlauf der postoperativen Bakteriurie vergleichend untersucht. Während die Ausheilungstendenz des Harnwegsinfektes in beiden Gruppen etwa gleich ist, wird bei Patienten mit präoperativem Harnwegsinfekt in der postoperativen Phase ein signifikant häufigeres Auftreten von mehrfachresistenten Keimen registriert. Ein Vergleich zwischen 100 Resektions- und 100 Ektomie-Patienten läßt keine Unterschiede in bezug auf Schweregrad und Verlauf des postoperativen Harnwegsinfektes erkennen.

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Urinary tract infection following prostatic surgery

Summary A comparative study was conducted on the severity and course of postoperative urinary infections in prostatic adenoma patients with preoperative bacteriuria and patients without infection. In both groups urinary infections showed a similar tendency to resolve, whereas a significant increase of polyresistant bacterial strains was noted in patients with preoperative bacteriuria. A comparison of 100 patients who had undergone transurethral resection and 100 patients who had undergone prostatectomy showed that severity and course of the postoperative urinary tract infection did not differ.

     

Decoding Face Information in Time, Frequency and Space from Direct Intracranial Recordings of the Human Brain

Faces are processed by a neural system with distributed anatomical components, but the roles of these components remain unclear. A dominant theory of face perception postulates independent representations of invariant aspects of faces (e.g., identity) in ventral temporal cortex including the fusiform gyrus, and changeable aspects of faces (e.g., emotion) in lateral temporal cortex including the superior temporal sulcus. Here we recorded neuronal activity directly from the cortical surface in 9 neurosurgical subjects undergoing epilepsy monitoring while they viewed static and dynamic facial expressions. Applying novel decoding analyses to the power spectrogram of electrocorticograms (ECoG) from over 100 contacts in ventral and lateral temporal cortex, we found better representation of both invariant and changeable aspects of faces in ventral than lateral temporal cortex. Critical information for discriminating faces from geometric patterns was carried by power modulations between 50 to 150 Hz. For both static and dynamic face stimuli, we obtained a higher decoding performance in ventral than lateral temporal cortex. For discriminating fearful from happy expressions, critical information was carried by power modulation between 60–150 Hz and below 30 Hz, and again better decoded in ventral than lateral temporal cortex. Task-relevant attention improved decoding accuracy more than10% across a wide frequency range in ventral but not at all in lateral temporal cortex. Spatial searchlight decoding showed that decoding performance was highest around the middle fusiform gyrus. Finally, we found that the right hemisphere, in general, showed superior decoding to the left hemisphere. Taken together, our results challenge the dominant model for independent face representation of invariant and changeable aspects: information about both face attributes was better decoded from a single region in the middle fusiform gyrus.     

Intact recognition of emotional prosody following amygdala damage.

Bilateral damage to the amygdala in a variety of animal species can impair emotional reactions to stimuli in several sensory modalities. Such damage in humans impairs visual recognition of emotion in facial expressions, but possible impairments in modalities other than vision have not been sufficiently explored. We examined two subjects with complete bilateral amygdala damage, and seven with unilateral amygdala damage, on a standardized task of emotional prosody recognition. The data were compared to those from 15 brain-damaged and from 14 normal control subjects. One of the bilateral amygdala subjects, whose lesions were restricted to the amygdala, was entirely normal in recognizing emotion in prosody on all tasks, the other, whose damage included substantial lesions also in extra-amygdalar structures, especially in right hemisphere, was normal on most, albeit not all, measures of emotional prosody recognition. We suggest that the human amygdala's role in recognizing emotion in prosody may not be as critical as it is for facial expressions, and that extra-amygdalar structures in right hemisphere may be more important for recognizing emotional prosody. It remains possible that recognition of emotion in classes of auditory stimuli other than prosody will require the amygdala.