Posterior Temporal Lobe Research Articles

Resting State BOLD Variability of the Posterior Medial Temporal Lobe Correlates with Cognitive Performance in Older Adults with and without Risk for Cognitive Decline.

Local brain signal variability [SD of the BOLD signal (SDBOLD]] correlates with age and cognitive performance, and recently differentiated Alzheimer’s disease (AD) patients from healthy controls. However, it is unknown whether changes to SDBOLD precede diagnosis of AD or mild cognitive impairment. We compared ostensibly healthy older adult humans who scored below the recommended threshold on the Montreal cognitive assessment (MoCA) and who showed reduced medial temporal lobe (MTL) volume in a previous study (“at-risk” group, n = 20), with healthy older adults who scored within the normal range on the MoCA (“control” group, n = 20). Using multivariate partial least-squares analysis we assessed the correlations between SDBOLD and age, MoCA score, global fractional anisotropy, global mean diffusivity, and four cognitive factors. Greater SDBOLD in the MTL and occipital cortex positively correlated with performance on cognitive control/speed tasks but negatively correlated with memory scores in the control group. These relations were weaker in the at-risk group. A post hoc analysis assessed associations between MTL volumes and SDBOLD in both groups. This revealed a negative correlation, most robust in the at-risk group, between MTL SDBOLD and MTL subregion volumetry, particularly the entorhinal and parahippocampal regions. Together, these results suggest that the association between SDBOLD and cognition differs between the at-risk and control groups, which may be because of lower MTL volumes in the at-risk group. Our data indicate relations between MTL SDBOLD and cognition may be helpful in understanding brain differences in individuals who may be at risk for further cognitive decline.

Spatial metabolic profiles to discriminate dementia with Lewy bodies from Alzheimer disease.

To differentiate dementia with Lewy bodies (DLB) from Alzheimer disease (AD) using a single imaging modality is challenging, because of their common hypometabolic findings. Scaled subprofile modeling/principal component analysis (SSM/PCA), an unsupervised artificial intelligence, has the potential to offer an alternative to image analysis. We aimed to produce spatial metabolic profiles to discriminate DLB from AD and to identify the characteristics of the profiles. Fifty individuals each with DLB, AD, and normal cognition (NL) underwent 18F-FDG-PET and MRI. The spatial metabolic profile to differentiate DLB from AD (DLB-AD discrimination profile) was determined using SSM/PCA with tenfold cross validation. For comparison, we also produced disease-related profiles that can discriminate AD and DLB from NL (AD- and DLB-related profiles, respectively). The DLB-AD discrimination profile significantly differentiated DLB from AD with comparable accuracy to that of discriminating DLB and AD from NL. The AD- and DLB-related profiles comprised metabolic imaging features typical of each pathology. In contrast, the DLB-AD discrimination profile emphasized preservation in the posterior cingulate cortex (cingulate island sign) and medial temporal lobe, and occipital hypometabolism. Common hypometabolic findings between DLB and AD were less noticeable in the profile. The DLB-related profile significantly correlated with cognitive function and three core features of DLB, whereas the DLB-AD discrimination profile did not. Spatial metabolic profile that could discriminate DLB from AD emphasized different imaging features and eliminated common findings between DLB and AD. Neither cognitive function nor core features were associated with the profile.

Associations between lesion size, lesion location and aphasia in acute stroke

ABSTRACT Background: The localization and organization of language has been an ongoing research interest ever since the early findings of Paul Broca. The emergence of neuroimaging the past 20 years has given us new insights on the anatomical and structural organization of the brain. Lesion studies on patients with aphasia can provide knowledge on where and how specific language functions are organized in the brain.Aims: The primary objective of the study was to investigate the relationships between aphasia severity, aphasic symptoms, lesion location and lesion volume in patients with left hemispheric stroke in the acute phase (within one week post-stroke). Using a voxel-based lesion-symptom mapping method (VLSM), we hypothesized that lesions associated with speech comprehension deficits mainly would involve regions within the posterior superior and middle temporal lobe, and lesions associated with speech production deficits would mainly be associated to the inferior frontal areas of the left hemisphere.Methods & procedures: Findings from diffusion-weighted magnetic resonance imaging (DWI-MRI) and patients’ scores from the Norwegian Basic Aphasia Assessment (NBAA) were used to investigate our research questions. We did a whole group analysis of descriptive statistics, lesion localization and lesion volume. We thereafter divided the patients into two groups based on their median scores on the NBAA, one high comprehension group and one low comprehension group. We used VLSM to investigate the associations between the patients’ lesions and the results from the NBAA.Outcomes & Results:Lesion volume was significantly associated with all subtest from the NBAA. Our initial analysis of the whole group showed that difficulties in naming was associated with lesions within the rolandic operculum. We also found that difficulties in repetition was associated with lesions within the rolandic operculum, and in addition, the superior temporal gyrus. In the group of patients with high comprehension scores lesions within Broca’s area, insula, the superior temporal gyrus (STG) and Heschl’s gyrus were found to be associated with difficulties with overall aphasia severity, repetition, naming, and reading out loud from the NBAA. Conclusions: Lesion volume is strongly associated with aphasia severity in the acute stages of stroke. Further, lesions within Broca’s area, the insula, the STG and Heschl’s gyrus were found to be crucial areas in language comprehension and production. This confirms current views that speech and language processes depend on the integrity of the entire network comprising both cortical structures and their interconnected fibre tracts.

Isolating syntax in natural language: MEG evidence for an early contribution of left posterior temporal cortex

Although the construction of syntactic structures is considered a fundamental component of language processing, insights concerning its neurobiological basis have remained elusive. This may be due, in part, to the inherent difficulty of isolating incremental syntax from other components of language, such as semantic composition. However, while pure manipulations of syntax are challenging to design, natural language grammars do have a sparse set of constructions presenting the possibility. Here we examined one such case, English post-nominal adjectives (mountain TALL enough for a strenuous hike), which were contrasted with semantically parallel but structurally simpler noun-adjective sequences in an MEG experiment. We observed a sharp activity increase in the left posterior temporal lobe (PTL) when syntactic composition was more straightforward, approximately 200 msec after adjective onset. The semantic fit between the noun and adjective was also varied, but this affected anterior temporal cortex, consistent with prior work. These findings offer a unique demonstration of the relevance of posterior temporal cortex for syntactic processing in natural language. We also present connectivity evidence that the syntax-related PTL responses were relayed to ipsilateral inferior frontal and anterior temporal regions. The combined results draw an initial picture of the rapid spatio-temporal dynamics of the syntactic and semantic composition network in sentence processing.

Alpha Rhythms Reveal When and Where Item and Associative Memories Are Retrieved.

Memories for past experiences can range from vague recognition to full-blown recall of associated details. Electroencephalography has shown that recall signals unfold a few hundred milliseconds after simple recognition, but has only provided limited insights into the underlying brain networks. Functional magnetic resonance imaging (fMRI) has revealed a “core recollection network” (CRN) centered on posterior parietal and medial temporal lobe regions, but the temporal dynamics of these regions during retrieval remain largely unknown. Here we used Magnetoencephalography in a memory paradigm assessing correct rejection (CR) of lures, item recognition (IR) and associative recall (AR) in human participants of both sexes. We found that power decreases in the alpha frequency band (10–12 Hz) systematically track different mnemonic outcomes in both time and space: Over left posterior sensors, alpha power decreased in a stepwise fashion from 500 ms onward, first from CR to IR and then from IR to AR. When projecting alpha power into source space, the CRN known from fMRI studies emerged, including posterior parietal cortex (PPC) and hippocampus. While PPC showed a monotonic change across conditions, hippocampal effects were specific to recall. These region-specific effects were corroborated by a separate fMRI dataset. Importantly, alpha power time courses revealed a temporal dissociation between item and associative memory in hippocampus and PPC, with earlier AR effects in hippocampus. Our data thus link engagement of the CRN to the temporal dynamics of episodic memory and highlight the role of alpha rhythms in revealing when and where different types of memories are retrieved.SIGNIFICANCE STATEMENT Our ability to remember ranges from the vague feeling of familiarity to vivid recollection of associated details. Scientific understanding of episodic memory thus far relied upon separate lines of research focusing on either temporal (via electroencephalography) or spatial (via functional magnetic resonance imaging) dimensions. However, both techniques have limitations that have hindered understanding of when and where memories are retrieved. Capitalizing on the enhanced temporal and spatial resolution of magnetoencephalography, we show that changes in alpha power reveal both when and where different types of memory are retrieved. Having access to the temporal and spatial characteristics of successful retrieval provided new insights into the cross-regional dynamics in the hippocampus and parietal cortex.

Using Nonlinear Dynamics and Multivariate Statistics to Analyze EEG Signals of Insomniacs with the Intervention of Superficial Acupuncture.

Objective As a noninvasive and nonpharmacological therapeutic approach, superficial acupuncture (SA) is a special method of acupuncture. In this study, using nonlinear dynamics and multivariate statistics, we studied the electroencephalography (EEG) of primary insomnia under SA intervention to investigate how brain regions change. Method This study included 30 adults with primary insomnia. They underwent superficial acupuncture at the Shangen acupoint. The EEG signals were collected for 10 minutes at each state, including the resting state, the intervention state, and the postintervention state. The data were conducted using nonlinear dynamics (including approximate entropy (ApEn) and correlation dimension (CD)) and multivariate statistics. Result The repeated-measures ANOVA results showed that both ApEn and CD values were not significantly different at the three states (p > 0.05). The paired t-test results showed that the ApEn values of electrodes O2 (the right occipital lobe) at the postintervention state have decreased, compared with the resting state (p < 0.05), and no difference was detected in CD (p > 0.05). The cluster analysis results of ApEn showed that patients' EEG has changed from the right prefrontal lobe (electrode Fp2) to the right posterior temporal lobe (electrode T6) and finally to the right occipital lobe (electrode O2), before, during, and after the SA intervention. In addition, the factor analysis results of CD revealed that patients' EEG of all brain regions except for the occipital lobes has changed to the frontal lobes and anterior temporal and frontal lobes from pre- to postintervention. Conclusion SA activated the corresponding brain regions and reduced the complexity of the brain involved. It is feasible to use nonlinear dynamics analysis and multivariate statistics to examine the effects of SA on the human brain.

Posterior Quadrant Disconnection for Sub-Hemispheric Drug Refractory Epilepsy

The posterior quadratic epilepsy (PQE) is a form of a multilobar epilepsy, involving the temporal-parietal and occipital lobes. Basically, epilepsies with localized networks to the posterior temporal, posterior parietal, and occipital lobes can benefit from this type of surgery. Gliosis due to perinatal insult and cortical dysplasis and angiomas in Sturge Weber syndrome involving the PQ have often been cited in the literature as the etiology for PQE. However, before considering surgery, it is important to localize the epileptogenic focus through a complete pre operative work up involving; EEG (Electro-Encephalo-Graphy), video EEG, single photon emission computed tomography (SPECT), positron emission tomography (PET), and magneto encephalography (MEG). Historically, these pathologies were dealt with multi-lobar resections, which were associated with high morbidity and mortality, owing to blood loss, especially in young children, hydrocephalus, and hemosiderosis. Based on the theory of networks involved in epileptogenesis, the concept of disconnection in epilepsy surgery was introduced. Delalande and colleagues, described the technique of hemispheric disconnection (functional hemispherectomy) for pathologies like: hemimegalencephaly, rasmussens encephalitis involving the entire hemisphere. The technique has evolved with time, moving towards minimally invasive endoscopic vertical hemispherotomy, described by Chandra and colleagues.[1],[2] The posterior quadrant disconnection (PQD) evolved as a tailored disconnection on similar lines as hemispherotomy, for managing refractory epilepsy arising from the posterior quadrant.[3] The technique and principles involved in the PQD surgery are similar to the those of peri-insular hemispherotomy and has been described in the literature by few authors.[3],[4],[5],[6] The technique of performing PQD will be described here in a step-wise fashion with illustrations supplemented by a surgical video.

Immunologic and Brain Bases of Neurotoxicity Associated with CAR T-Cell Therapy

Introduction: CD19-directed chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment for B-cell acute lymphoblastic leukemia (ALL), inducing complete remission in 70-90% of highly refractory patients. Unfortunately, CAR-T cell therapy is associated with immune effector cell-associated neurotoxicity syndrome (ICANS) in 40% of patients, which presents as confusion, memory impairment, aphasia, altered level of consciousness and/or delirium. The neurobiological and immune bases of ICANS remain poorly understood, and identifying them will help develop strategies for early intervention to mitigate ICANS. Methods: From an ongoing prospective, longitudinal study, we report on the first 7 patients with relapsed ALL (age 5-19 years, 5 males) who underwent comprehensive assessments at baseline before lympho-depleting (LD) chemotherapy (fludarabine and cyclophosphamide) and infusion of CD19-directed CAR T-cells, and post-infusion, on days 10 and 28. These assessments included multimodal magnetic resonance imaging (MRI) of the brain (anatomical, perfusion, diffusion tensor imaging and MR spectroscopy), neuropsychological testing, serum measures of blood-brain barrier permeability and cytokines, and immune cell profiles in peripheral blood using mass cytometry by time-of-flight (CyTOF). We also acquired multimodal MRI and neuropsychological testing in 9 healthy controls (age 5-20 years, 7 males), once, at baseline. MRI data were acquired on a 3T Philips MR scanner using a 32 channel head coil without the use of sedatives or contrast agents and were processed blind to the diagnosis and order of data acquisition. Results: In our cohort of 7 patients, 5 developed cytokine release syndrome and 4 developed ICANS. Brain imaging findings are demonstrated in figures 1 (cortical thickness) and 2 (blood perfusion). Prior to CAR T-cell infusion patients relative to healthy controls had thinner cortex bilaterally across large portions of the brain. By post-infusion day 10, cortical thickness decreased in the postcentral gyrus (PoG) and posterior temporal lobe (pTL). Subsequently, by post-infusion day 28, cortex thickened in the PoG but continued thinning in the pTL. Patients relative to controls had lower regional cerebral blood flow (rCBF) in the thalamus, insular cortex, and cingulate gyrus, and higher rCBF in the genu of the corpus callosum (gCC). By post-infusion day 10, rCBF increased in the thalamus and decreased in the putamen and gCC. By post-infusion day 28, rCBF in the thalamus decreased and reverted towards baseline values, whereas rCBF in gCC continued to decrease away from baseline values. CyTOF analyses, as expected, showed expansion of monocytes and myeloid-derived suppressor cells by post-infusion day 10. Furthermore, in these immune cells, phosphorylation of key signaling proteins (e.g. extracellular-signal regulated kinase, ERK1/2) increased in response to external stimulation. Conclusions: Patients had widespread brain abnormalities at baseline compared to controls, likely because of prior therapies and/or underlying ALL. Post LD chemotherapy and CAR T-cell infusion, several brain abnormalities worsened by day 10 and then reverted toward baseline values by day 28. These temporal changes are generally consistent with clinically reported development of ICANS by day 10, which largely resolves by day 28. However, in certain regions brain measures progressively deviated from baseline and control values through day 28, suggesting some abnormalities associated with CAR T therapy may persist. Preliminary immune cell profiling implicates monocytes as a possible source of elevated cytokines following CAR T-cell infusion. Analysis for correlation of these findings with symptomatic ICANS and neuropsychological measures is ongoing. Patients on this study will also be followed at 6 months and 1 year to evaluate for long term neurological effects of CAR T-cell therapy. Figure 1: Cortical Thickness abnormalities in patients relative to healthy controls (1st panel); within-patient changes post-infusion (2nd, 3rd, &amp; 4th panel). Blue &amp; violet show decreases and orange &amp; red show increases in cortical thickness. Figure 2: Blood perfusion abnormalities in patients relative to healthy controls (1st panel); within patient changes post infusion (2nd, 3rd, &amp; 4th panel). Blue &amp; violet show decreases and orange &amp; red show increases in regional cerebral blood flow. Disclosures Pulsipher: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Other: Education for employees; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Miltenyi: Research Funding; Bellicum: Consultancy; Amgen: Other: Lecture; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Medac: Honoraria. Wayne:Spectrum Pharmaceuticals: Consultancy, Research Funding; AbbVie: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Servier: Consultancy.

A case report of multiple cerebral abscess formation complicating serogroup B Neisseria meningitidis meningitis

BackgroundInvasive meningococcal disease (IMD) presenting with meningitis causes significant mortality and morbidity. Suppurative complications of serogroup B meningococcal sepsis are rare and necessitate urgent multidisciplinary management to mitigate long-term morbidity or mortality.Case presentationWe present a rare case of invasive meningococcal disease in a 28-month old boy complicated by multiple abscess formation within a pre-existing antenatal left middle cerebral artery territory infarct. Past history was also notable for cerebral palsy with right hemiplegia, global developmental delay and West syndrome (infantile spasms). Two craniotomies were performed to achieve source control and prolonged antimicrobial therapy was necessary. The patient was successfully discharged following extensive multidisciplinary rehabilitation.ConclusionsLongstanding areas of encephalomalacia in the left MCA distribution may have facilitated the development of multiple meningococcal serogroup B abscess cavities in the posterior left frontal, left parietal and left temporal lobes following an initial period of cerebritis and meningitis. A combination of chronic cerebral hypoperfusion and some degree of pre-existing necrosis in these areas, may also have facilitated growth of Neisseria meningitidis, leading ultimately to extensive cerebral abscess formation following haematogenous seeding during meningococcemia. In this case report we review similar cases of cerebral abscess or subdural empyema complicating serogroup B meningococcal meningitis.

On the neural model of paraphasia: Examining the lesion data

Paraphasia refers to phonologically and/or semantically altered productions of target words that are commonly observed in aphasia and other neurogenic disorders of language. The neural processes involved in the production of both phonological and semantic paraphasia were discussed within the dual stream model of language processing (Hickok, 2012., Hickok & Poeppel, 2007). According to this model, the dorsal stream is involved in phonological production and the ventral stream provides interface between sound and meaning. The objective of the present study is to further verify the prediction that lesions involving the dorsal stream will produce phonological paraphasia and lesions in the ventral stream will result in semantic paraphasia. Brain lesions that encompass both streams will result in both phonological and semantic types of paraphasia. Method. Subjects. Three aphasic cases, with an age range of 66-74 years, served as subjects: JL, PP, and RW. All three had similar, but not identical, lesions in the left parietal lobe including supramarginal and angular gyri and in posterior temporal lobe (See Figures 1-3) Two tests were administered: Boston Diagnostic Aphasia Examination, and 2) Boston Naming Test. All paraphasic responses were derived from the confrontation naming responses. These were broadly classified into phonologic, semantic and mixed types of paraphasia As predicted, all three subjects produced both phonologic and semantic types of paraphasia. This pattern of performance is probably the result of lesions both in the dorsal and ventral streams. Discussed further is the variability in the performance of the subjects.

Abnormal functional connectivity strength in first-episode, drug-naïve adult patients with major depressive disorder

BackgroundThe pathogenesis of major depressive disorder (MDD) is complicated and equivocal. Previous studies have found an incidence of abnormal changes of neural networks, with plentiful evidence pointing the finger of suspicion firmly at the default mode network (DMN) and cortico-limbic networks. The aim of the present study was to use the approach of functional connectivity strength (FCS) to directly investigate the features of spontaneous brain activity in the case of first-episode, drug-naïve adult patients with MDD at rest. MethodsResting-state functional magnetic resonance imaging (MRI) scans were performed on 23 first-episode drug-naïve major depressive disorder (MDD) patients and 20 healthy controls (HCs). In this study, using graph-theory approaches(FCS), we computed the characteristics of brain connectivity. Simultaneously, we used a series of validated test procedures to evaluate the patients' cognitive function. Subsequently, the results were compared with the peak of FCS value and a correlation analysis was conducted. ResultsCompared with the HCs group, MDD patients showed significantly decreased FCS in bilateral posterior cingulate cortex (PCC)/precuneus and bilateral prefrontal cortex(PFC) and increased FCS in right posterior central gyrus, left thalamus and left temporal lobe. These brain regions belongs to the default-mode network and cortico-limbic networks. Finally, the correlation analyses showed the negative correlation of the FCS values in the left posterior cingulate cortex (PCC)/precuneus and Hamilton Anxiety Rating Scale (HAMA, r = −0.472, p = .023), Stroop Color Word Test-A(SCWT-A, r = −0.451, p = .031), Stroop Color Word Test-B(SCWT-B, r = −0.588, p = .003).Meanwhile, there was negative correlation between the FCS values in the left thalamus and SCWT-A(r = −0.473, p = .023), SCWT-B(r = −0.465, p = .025), SCWTC(r = −0.524, p = .010).In addition, the FCS values in the right PCC has negative correlation with Montgomery Asberg Depression Rating Scale (MADRS) (r = −0.433, p = .039). ConclusionsDMN is an important node of MDD. FCS within the default mode network and cortico-limbic networks in patients with major depressive disorder has been changed in the early stage of MDD. FCS can provide favourable and additional evidence in the investigation of brain pathophysiology and therapy in depression.

Multimodality Language Mapping Using Cortical Stimulation in Paediatric Patients With Epilepsy

Abstract INTRODUCTION Pediatric patients with epilepsy often undergo language mapping using electrical cortical stimulation. Previous studies have shown general localization of auditory naming in the anterior temporal lobe and visual naming in the posterior parietal and temporal lobe. No probabilistic map exists, however, that quantifiably details the location of the different language modalities for pediatric patients with epilepsy. METHODS A series of 41 consecutive pediatric patients underwent cortical language mapping (24 female; range 5.2-18.5 yr; mean age 13.8 yr), either extraoperative (n = 34) or intraoperative (n = 7), prior to epileptic focus resection. The exact location of where an error occurred was recorded and transposed on a cortical parcellation system. Statistical analysis used a binomial one sided exact test with a cut off set at 60%. RESULTS Results show an increased range of sites for both visual and auditory naming as compared to adults. Cortical stimulation language testing was conducted 2102 times; 1201 visual and 901 auditory. Visual naming sites extended into the anterior temporal lobe. Auditory naming sites extended from the anterior temporal lobe to the middle temporal and posterior temporal gyrus. CONCLUSION The anterior temporal lobe is a commonly resected region, often felt to be of minimal risk. Knowledge of how these 2 language modalities extend into the temporal lobe in addition to how they differ from adults provides insight into which areas are safe to resect and which areas to spare during pediatric epilepsy surgery.

Neural Mechanisms for Monitoring and Halting of Spoken Word Production.

During conversation, speakers monitor their own and others' output so they can alter their production adaptively, including halting it if needed. We investigated the neural mechanisms of monitoring and halting in spoken word production by employing a modified stop signal task during fMRI. Healthy participants named target pictures and withheld their naming response when presented with infrequent auditory words as stop signals. We also investigated whether the speech comprehension system monitors inner (i.e., prearticulatory) speech via the output of phonological word form encoding as proposed by the perceptual loop theory [Levelt, W. J. M. Speaking: From intention to articulation. Cambridge, MA: MIT Press, 1989] by presenting stop signals phonologically similar to the target picture name (e.g., cabbage-CAMEL). The contrast of successful halting versus naming revealed extensive BOLD signal responses in bilateral inferior frontal gyrus, preSMA, and superior temporal gyrus. Successful versus unsuccessful halting of speech was associated with increased BOLD signal bilaterally in the posterior middle temporal, frontal, and parietal lobes and decreases bilaterally in the posterior and left anterior superior temporal gyrus and right inferior frontal gyrus. These results show, for the first time, the neural mechanisms engaged during both monitoring and interrupting speech production. However, we failed to observe any differential effects of phonological similarity in either the behavioral or neural data, indicating monitoring of inner versus external speech might involve different mechanisms.

Brain metabolic connectome classify mild cognitive impairment into Alzheimer's dementia.

Identifying whether patients with mild cognitive impairment (MCI) are converting to Alzheimer's disease (AD) is clinically important, but there are still controversies and doubts. We aimed to develop a novel connectome approach which could accurately and precisely predict whether MCI patients are converted to AD using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). In our study, FDG-PET images were acquired from 84 patients with MCI who converted to AD within 48 months and 109 patients with MCI without conversion within 48 months from the Alzheimer's Disease Neuroimaging Initiative database. The experimental results showed that the classification performance about whether an MCI patient would convert to AD were 92.1%, 87.1%, 94.4% and 0.95 (Accuracy, Sensitivity, Specificity and AUC). The abnormality of functional connection was located at Middle frontal gyrus, Posterior cingulate gyrus, Precentral gyrus, Precuneus and Temporal lobe. These finding showed the brain connectome as a practical approach for developing predictive neuroimaging biomarker.

Characteristic asymmetric limbic and anterior temporal atrophy in demented patients with pathologically confirmed argyrophilic grain disease.

The purpose of this study is to clarify the characteristic structural magnetic resonance imaging (MRI) findings in demented patients with pathologically confirmed argyrophilic grain disease (AGD). Nine pathologically confirmed AGD patients with cerebral three-dimensional T1-weighted MRI were evaluated in this study. In addition to visual rating scales of atrophic and asymmetric changes in the limbic and temporal lobes, voxel-based morphometry (VBM) was performed to assess group difference between pathologically confirmed AGD and Alzheimer's disease (AD) patients. On visual analyses of AGD patients, the medial temporal, anterior temporal, and posterior temporal atrophy scores were 3.3 ± 0.7, 1.7 ± 0.5, and 1.0 ± 0.7, respectively. Asymmetric scores of the hippocampus and parahippocampal gyrus, amygdala and ambient gyrus, anterior temporal, and posterior temporal lobes were rated as 1.1 ± 0.7, 1.6 ± 0.5, 1.3 ± 0.8, and 0.4 ± 0.7, respectively. In spite of no statistical differences in atrophic scores, AGD patients showed the higher score and proportion of anterior temporal asymmetric score than AD (p = 0.03 and 0.02). Compared with controls, VBM analysis revealed left dominant asymmetric atrophy predominantly in the limbic and anterior temporal lobe in AGD patients. By contrast, there was no significant gray matter reduction between AGD and AD patients. Asymmetric atrophy relatively localized to the anterior temporal and limbic lobes including the amygdala and ambient gyrus is a characteristic MRI finding of AGD. For the precise antemortem diagnosis, especially to differentiation from AD, it is important to pay attention to this asymmetric change.

High-Dimensional Mapping of Cognition to the Brain Using Voxel-Based Morphometry and Subcortical Shape Analysis.

It is increasingly recognized that the complex functions of human cognition are not accurately represented by arbitrarily-defined anatomical brain regions. Given the considerable functional specialization within such regions, more fine-grained studies of brain structure could capture such localized associations. However, such analyses/studies in a large community-dwelling population are lacking. To perform a fine-mapping of cognitive ability to cortical and subcortical grey matter on magnetic resonance imaging (MRI). In 3,813 stroke-free and non-demented persons from the Rotterdam Study (mean age 69.1 (±8.8) years; 55.8% women) with cognitive assessments and brain MRI, we performed voxel-based morphometry and subcortical shape analysis on global cognition and separate tests that tapped into memory, information processing speed, fine motor speed, and executive function domains. We found that the different cognitive tests significantly associated with grey matter density in differential but also overlapping brain regions, primarily in the left hemisphere. Clusters of significantly associated voxels with global cognition were located within multiple anatomic regions: left amygdala, hippocampus, parietal lobule, superior temporal gyrus, insula and posterior temporal lobe. Subcortical shape analysis revealed associations primarily within the head and tail of the caudate nucleus, putamen, ventral part of the thalamus, and nucleus accumbens, more equally distributed among the left and right hemisphere. Within the caudate nucleus both positive (head) as well as negative (tail) associations were observed with global cognition. In a large population-based sample, we mapped cognitive performance to cortical and subcortical grey matter density using a hypothesis-free approach with high-dimensional neuroimaging. Leveraging the power of our large sample size, we confirmed well-known associations as well as identified novel brain regions related to cognition.

Dyadic interaction processing in the posterior temporal cortex

Recent behavioural evidence shows that visual displays of two individuals interacting are not simply encoded as separate individuals, but as an interactive unit that is 'more than the sum of its parts'. Recent functional magnetic resonance imaging (fMRI) evidence shows the importance of the posterior superior temporal sulcus (pSTS) in processing human social interactions, and suggests that it may represent human-object interactions as qualitatively 'greater' than the average of their constituent parts. The current study aimed to investigate whether the pSTS or other posterior temporal lobe region(s): 1) Demonstrated evidence of a dyadic information effect - that is, qualitatively different responses to an interacting dyad than to averaged responses of the same two interactors, presented in isolation, and; 2) Significantly differentiated between different types of social interactions.Multivoxel pattern analysis was performed in which a classifier was trained to differentiate between qualitatively different types of dyadic interactions. Above-chance classification of interactions was observed in 'interaction selective' pSTS-I and extrastriate body area (EBA), but not in other regions of interest (i.e. face-selective STS and mentalizing-selective temporo-parietal junction). A dyadic information effect was not observed in the pSTS-I, but instead was shown in the EBA; that is, classification of dyadic interactions did not fully generalise to averaged responses to the isolated interactors, indicating that dyadic representations in the EBA contain unique information that cannot be recovered from the interactors presented in isolation. These findings complement previous observations for congruent grouping of human bodies and objects in the broader lateral occipital temporal cortex area.

Remote spatial and autobiographical memory in cases of episodic amnesia and topographical disorientation

A number of theories have postulated that there is a strong relationship between episodic memory and spatial processes mediated by the hippocampus. Evidence for episodic amnesia following damage to the medial temporal lobes is extensive, but less is known about the types of spatial memory affected by damage to these regions. In this study, we compared episodic memory with detailed scene memory, landmark recognition and schematic (map-based) spatial memory in a group of individuals with amnesia related to damage to the medial temporal lobes (MTL) including the hippocampus. We compared their performance to matched controls, and to an individual with topographical disorientation, a selective spatial memory deficit relating to more posterior temporal and occipital lobe damage. For individuals with MTL lesions, impairments to scene memory were comparable to those in episodic memory. Landmark recognition was impaired only for less familiar landmarks, and schematic spatial memory was not impaired compared to controls. Despite the absence of hippocampal damage, the individual with topographical disorientation, like the MTL amnesic patients, demonstrated impairments to scene memory and recognition of less familiar landmarks, and intact schematic spatial memory, but with less severe episodic memory loss. These results highlight the similarities between detailed scene memory and episodic memory, including their reliance on the medial temporal lobe, and suggest that more schematic forms of spatial memory may be unaffected by medial temporal damage. In addition, the results suggest that damage to more posterior temporal or occipital regions that leads to spatial memory deficits may entail some impairment to episodic memory even if the hippocampus is spared.

Segmentation of medial temporal subregions reveals early right-sided involvement in semantic variant PPA

BackgroundSemantic variant of primary progressive aphasia (svPPA) is a subtype of frontotemporal dementia characterized by asymmetric temporal atrophy.MethodsWe investigated the pattern of medial temporal lobe atrophy in 24 svPPA patients compared to 72 controls using novel approaches to segment the hippocampal and amygdalar subregions on MRIs. Based on semantic knowledge scores, we split the svPPA group into 3 subgroups of early, middle and late disease stage.ResultsEarly stage: all left amygdalar and hippocampal subregions (except the tail) were affected in svPPA (21–35% smaller than controls), together with the following amygdalar nuclei in the right hemisphere: lateral, accessory basal and superficial (15–23%). On the right, only the temporal pole was affected among the cortical regions. Middle stage: the left hippocampal tail became affected (28%), together with the other amygdalar nuclei (22–26%), and CA4 (15%) on the right, with orbitofrontal cortex and subcortical structures involvement on the left, and more posterior temporal lobe on the right. Late stage: the remaining right hippocampal regions (except the tail) (19–24%) became affected, with more posterior left cortical and right extra-temporal anterior cortical involvement.ConclusionsWith advanced subregions segmentation, it is possible to detect early involvement of the right medial temporal lobe in svPPA that is not detectable by measuring the amygdala or hippocampus as a whole.

SUN-LB099 Hashimoto's Encephalopathy: The Needle in the Haystack

Background: Hashimoto’s encephalopathy (HE) is a rare heterogeneous disorder first described in 1966 and presents with variable neuropsychiatric dysfunction, including cognitive decline, seizures, myoclonus, and psychiatric manifestations. HE is likely an autoimmune vasculitis rather than a thyroid dysfunction, and is steroid responsive. Clinical case: A 64-year-old Caucasian female with a past history of tobacco abuse presents with altered level of consciousness, left frontal headache, and a mechanical fall resulting in a radial fracture. No chest pain or syncopal episode. She was noted to have persistent confusion and flu-like symptoms for three days. Review of systems were otherwise negative. Patient does not take any medications. Surgical and social histories were unremarkable. Vital signs: BP 131/59, HR 97, RR 16, Tmax 103.4, Sat 97%. Neurologic examination revealed episodes of confusion with paraphasic speech errors. She was unable to correctly recall her name. No dysarthria, facial asymmetry, or motor deficits. Laboratories: WBC 19,100uL (4,000-10,000uL). Chemistries revealed normal electrolytes and hepatic function, coagulation studies, urinalysis, B12, TSH, and toxicology. Autoimmune and paraneoplastic etiologies were excluded. Lumbar puncture revealed elevated protein 102.7mg/dL (15-45mg/dL) and WBC 54/uL (0-10/uL) with 100% mononuclear predominance. Head CT revealed low attenuation in the right posterior temporal lobe. MRI brain without/with contrast revealed chronic ischemic vessel disease. EEG noted mild generalized slowing and disorganization. Patient was initially treated for viral encephalitis until CSF PCR analyses for a broad spectrum of pathogens was negative. Further serum studies including thyroglobulin antibody and thyroid peroxidase antibody were sent, noting values of 63.8U/mL (<60U/mL) and >1300U/mL (<60U/mL), respectively. She was treated with Methylprednisolone 250mg IV daily for three days and transitioned to a Prednisone 60mg daily taper. She had immediate and complete resolution of her symptoms within the first 24 hours of corticosteroid therapy. Conclusion: Hashimoto's encephalopathy is a diagnosis of exclusion as it can mimic meningitis, encephalitis, psychiatric disorders, stroke, vasculitis, and migraines. Persistent confusion and fevers may cause a delay in diagnosis. HE affects women predominantly in the 5-6th decade. Diagnosis can be made with an elevated anti-thyroid peroxidase antibody and/or antithyroglobulin antibody. Severity does not correspond with serum levels. HE responds well to corticosteroids, including 50-150mg Prednisone daily, with 90-98% response rate, and may take months for complete resolution of symptoms. Refractory cases may require immunosuppressive agents. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.