Memory impairment and Alzheimer's disease pathology in individuals with MCI who underestimate or overestimate their decline.

OBJECTIVES: The aim of this study was to examine whether the discrepancy between participant and informant estimation of memory decline can predict MCI prognosis. METHODS: Analyses involved data from individuals with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who filled the Everyday Cognition questionnaire. Participants who underestimated (N = 112) and overestimated (N = 157) their memory decline were compared on memory tasks, brain volume, and cerebrospinal markers, at study entry and after 24 months. RESULTS: Individuals who underestimated their memory decline performed more poorly on memory tests, had smaller hippocampus volume, and greater Alzheimer's disease pathology than did individuals who overestimated their cognitive decline. Longitudinal comparisons demonstrated that individuals who underestimated their decline deteriorated more significantly in memory and in brain measures. CONCLUSIONS: Underestimation of memory decline should raise clinicians' suspicion of the existence of AD pathology in individuals with MCI.

Dissociation in awareness of memory and language decline in Alzheimer's disease.

OBJECTIVES: The aim of this study was to examine awareness of decline in memory and in language in individuals with Alzheimer's disease (AD), by comparing participant and informant ratings, as well as these ratings and actual test performance. METHODS: We analyzed data from 149 individuals with AD enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who filled the Everyday Cognition questionnaire and performed memory and language tasks. RESULTS: Participants provided significantly lower assessments of decline than did informants for both memory and language. There was a negative association between informant ratings and memory test scores but no association between participant ratings and memory test scores. Both participant and informant ratings correlated negatively with performance on the language tests. Informant, but not participant, ratings contributed to the prediction of one memory variable beyond demographic factors. Participant ratings contributed to the prediction of language scores beyond demographic factors more than did informant ratings. CONCLUSIONS: The findings reflect better awareness of decline in language than of decline in memory in individuals with AD.

Downwards Vertical Attention Bias in Conversion Disorder vs Controls: A Pilot Study.

BACKGROUND: Conversion disorder (CD) is a largely enigmatic disorder, one that requires a thorough ruling-out process. Prior research suggests that metaphors and conceptualization are rooted in physical experience, and that we interpret our affective world through metaphors. Spatial metaphors (interaction of affect and vertical space) are a prominent example of the grounding of metaphors. This is a relatively unpaved direction of research of CD. OBJECTIVES: The present pilot study sought to explore this view by investigating the "healthy is up, sick is down" spatial metaphors (e.g., "fell ill" and "top shape") in patients with CD, examining the correlation between the processing of bodily-related words, CD, and vertical space. We hypothesized that patients with CD, who experience their bodies as ill, will demonstrate a downwards bias when processing bodily-related words; corresponding to the "healthy is up, sick is down" spatial metaphor. METHODS: A total of 8 female patients (ages M-38.13 SD-10.44) and 42 female controls (ages M-36.4 SD-14.57) performed a visual attention task. Participants were asked to identify a spatial probe at the top or the bottom of a screen, following either a bodily related (e.g., arm) or non-bodily related (e.g., clock) prime word. RESULTS: As predicted, when processing bodily-related words, patients with CD demonstrated a downwards attention bias. Moreover, the higher the patient's level of somatization, the faster the patient detected lower (vs upper) spatial targets. CONCLUSIONS: This study suggests that the changed health paradigm of patients with CD is grounded in sensorimotor perception. Further research could propose new diagnostic and treatment options for CD.

Neuroscientific account of Guilt- and Shame-Driven PTSD phenotypes.

Background: Guilt and Shame, two core self-related emotions, often emerge following trauma and play an important role in the development and maintenance of post-traumatic stress disorder (PTSD). Importantly, Guilt and Shame exhibit specific focal and non-specific global impacts of trauma on self-perception, respectively.Objective and Methods: Integrating psychological theories with neuroscientific knowledge, we suggest a scheme of two diverging clinical phenotypes of PTSD, associated with distinct self-related processes and differential functionality of relevant neural networks.Proposal: The Guilt-driven phenotype is characterized by preoccupation with negative self-attributes of one's actions in the traumatic event. It involves altered functionality of both the salience network (SN) and the default-mode network (DMN), associated with heightened interoceptive signalling and ruminative introspection which may lead to hyperarousal and intrusive symptoms, respectively. On the contrary, the Shame-driven phenotype is characterized by global, identity-related negative self-attributions. It involves altered functionality of both the SN and the DMN, associated with blunted interoceptive signalling and diminished introspection which may result in withdrawal and anhedonia symptoms together with dissociative experiences, respectively.Conclusion: The proposed PTSD phenotypes may inform neuropsychological therapeutic interventions (e.g. self-focused psychotherapy and neuromodulation) aiming to restore the function of large-scale self-related neural processing.

Guilt and Shame are two self-related emotions that often emerge following traumatic events and may contribute to the clinical profile of post-traumatic stress disorder (PTSD).Our framework suggests Guilt and Sham driven phenotypes of post-traumatic psychopathology, associated with two self-processing deficiencies related to specific action or global identity, respectively.The proposed phenotypes may inform neuropsychological treatments aiming to restore dysfunctional neural networks, later to be evident in alleviating Guilt and Shame and improving clinical outcomes.

Preserved morphological processing in semantic dementia.

Individuals with semantic dementia (SD) show progressive worsening of lexical-conceptual single word knowledge alongside preservation of nonsemantic aspects of language. The current study examines morphological processing in SD. S.H.S., a Hebrew-speaking person with SD, completed eight tasks that tested inflection, linear derivation, and nonlinear derivation at three time points over six and a half years. S.H.S. correctly produced plural nouns and judged the grammaticality of noun-verb and noun-adjective inflectional agreement. A steeper decline was seen in the ability to judge irregularly versus regularly inflected forms. S.H.S. judged nationality suffixes accurately and produced diminutive and agentive suffixes successfully. He also relied on morphological decomposition when performing lexical decision. Judgement of sentences consisting of derived verbal participles was intact with regard to morphological considerations alone, but impaired when semantic considerations determined grammaticality. S.H.S.'s performance suggests that structural aspects of word knowledge might be functional in the face of a severe semantic impairment.

Body Structural Description Impairment in Complex Regional Pain Syndrome Type I.

Background: Complex Regional Pain Syndrome (CRPS) is a clinical syndrome composed of chronic pain, motor impairment, and autonomic dysfunction, usually affecting a limb. Although CRPS seems to be a peripheral disorder, it is accompanied by parietal alterations leading to body schema impairments (the online representations of the body). Impairments to body structural description (the topographical bodily map) were not assessed systematically in CRPS. A patient we encountered with severe disruption to her bodily structural description led us to study this domain further. Aims: To document aberrant body structural description in subjects with CRPS using an object assembly task. Methods: Body Schema Study: 6 subjects with CRPS-I and six age and sex-matched healthy controls completed visual puzzles taken from WAIS-III and WAIS-R. The puzzles were either related to the human body or non-human body objects. Mann-Whitney U-tests were performed to compare groups' performances. Results: The CRPS group received relatively lower scores compared to controls for human body objects (u = 3, p < 0.05), whereas the non-human object scoring did not reveal significant differences between groups (u = 9, p > 0.05). Conclusion: CRPS subjects suffer from impaired body structural description, taking the form of body parts disassembly and body parts discontinuity. This impairment can serve as a nidus for aberrant psychological representation of the body.

Interaction of Temporal Lobe Epilepsy and Posttraumatic Stress Disorder: Network Analysis of a Single Case.

In this case study, we present a 21 years old female with long-standing Temporal Lobe Epilepsy (TLE) who, following a sexual assault, also developed Posttraumatic Stress Disorder (PTSD), leading to a change in her seizure semiology. The new seizures seemed to be a re-enactment of the sexual assault and accordingly were at first thought to be Psychogenic Non-Epileptic Seizures (PNES). Nevertheless, electroencephalography (EEG) recording at the Epilepsy Monitoring Unit (EMU) revealed ictal epileptic brain activity during these new attacks. In order to further explore the nature of the relation between epileptic seizures and PTSD symptomatology, a functional MRI (fMRI) scan was conducted focusing on neural response to threat (fearful faces). The results indicated that the response to threat elicited bilateral amygdala activation, as well as enhanced amygdala connectivity with the insula and anterior cingulate cortex (ACC), all central nodes of the fear circuitry. Accordingly, we suggest that this unique presentation of "pseudo" PNES might stem from the anatomical proximity of the epileptic network in this patient (temporal-insular-frontal) to the fear circuitry, allowing abnormal epileptic activity to "exploit" or activate the fear circuit or vice versa. We further propose that the traumatic experience may have changed the patient's ictal semiology by modifying the course of the spread of the ictal activity toward the PTSD network.

Enhanced pain modulation capacity among individuals with borderline personality disorder: A possible mechanism underlying their hypoalgesia.

BACKGROUND: Ample evidence suggests that individuals with borderline personality disorder (BPD) exhibit hyposensitivity to pain. Since the underlying mechanism of the pain hyposensitivity is unknown, we tested here for the first time whether this hyposensitivity is pain specific or exists also for innocuous sensation, and whether it is associated with enhanced descending pain modulation capabilities. METHODS: Participants were 55 women; 22 patients with BPD and 33 matched healthy controls. Testing included the measurement of warmth sensation threshold (WST), heat-pain threshold (HPT), pain adaptation, conditioned pain modulation (CPM) and temporal summation of heat-pain (TSP). The level of dissociation was also evaluated. RESULTS: Women with BPD had higher WST and HPT compared with healthy controls. Moreover, women with BPD had greater magnitude of pain adaptation and CPM as well as higher dissociation level compared to controls. In neither the BPD nor the control group did WST and HPT correlate with pain adaptation, CPM or dissociation. In the BPD group only, HPT inversely correlated with the magnitude of TSP. CONCLUSIONS: Women with BPD present generalized hyposensitivity to both innocuous and noxious stimuli. Furthermore, women with BPD exhibit more efficient pain inhibition capabilities than healthy controls. While efficient pain modulation may underlie pain hyposensitivity in BPD, both traits may exist independently from each other, or may be moderated by another factor such as dissociation. SIGNIFICANCE: On the basis of testing pronociceptive and antinociceptive components among individuals with BPD and healthy controls, this study reveals enhanced ability to inhibit pain among woman with borderline personality disorder (BPD) which may underlie hyposensitivity to both noxious and innocuous stimuli and perhaps also self-injurious behaviour among these individuals. The study contributes novel information on possible mechanisms involved in BPD manifestations.

Proximity Bias Following Affective Metaphors in Patients With Depression-Psychoanalytic Considerations.

Background: Many languages use spatial metaphors to describe affective states such as an upward bias to denote positive mood, a downward bias to denote negative mood, a body proximity bias to denote personal relatedness concern, and a right-left bias to denote negative or positive valence. These biases might be related to experiential traces related to these affective states. If this is the case, depressed subjects would show either a downward spatial bias, a body proximity bias, or a right-left shift in attention. We evaluated the occurrence of such biases in subjects with depression compared to healthy controls. Methods: Subjects: 10 subjects with depression (5F:5M; age = 47.2 ± 15.2) and 10 healthy controls (5F:5M; age = 45.8 ± 14.5). Experimental task: line bisection task. Lines were presented in three spatial orientations [vertical (up-down), horizontal (right-left), radial (proximal-distal)] and were either blank, composed with words (negative/positive/neutral), or with smileys (negative/positive/neutral). There were 21 line types, and each was presented eight times, reaching a total of 168 lines. Results: Compared with healthy controls, subjects with depression bisected radial lines significantly closer to their body. There were no significant differences for either horizontal or vertical lines. Conclusion: The proximity spatial bias observed in subjects with depression suggests that depression might activate neural spatial networks. We argue that these networks could be dynamically activated through narcissistic mechanisms as implied in "Mourning and Melancholia" where Freud postulates a narcissistic mediated bias in depression according to which the depressed subjects withdraw from the outside world.

[Lipman Halpern--the 70th anniversary of the Department of Neurology at the Hadassah Hebrew University Medical Center].

The paper describes the establishment of the Department of Neurology at the Hadassah Hospital in Jerusalem, as well as the department's early activity, emphasizing the role of Dr. Lipman Halpern, one the founders. The paper further illustrates the neurological and psychiatric infrastructure in Palestine of the 1930's, as well as major professional and organizational issues faced by Dr. Halpern, particularly the relationship between psychiatry and neurology. Thus, the paper claims, not only did Dr. Halpern's German neuro-psychiatric training influence his personal and professional choices, but it had also shaped the department of neurology in its early days. Furthermore, Dr. Halpern's training had an impact on the neuro-psychiatric community in Palestine, one of the main features of which was the strong interaction between psychiatry and neurology.

Patients with motor conversion disorder use early developmental motor patterns.

OBJECTIVE: To assess psychological factors of individuals suffering from conversion disorder/Functional Neurological Disorder (CD/FND) as observed through their motor behavior. METHODS: We analyzed the psychomotor behavior of 6 patients (all male, average age - 52.8 years) with CD/FND in a specialized clinic using a binary motor - psychological developmental paradigm (Emotorics - Emotive Body Movement Mind Paradigm [Emotorics-EBMMP]). RESULTS: All patients showed dominance of an early developmental prototype (P0) characterized by flexed postures resembling the infant held by his caregivers and relative paucity of a more developed prototype (P1) characterized by erect position typical for a face to face interaction. CONCLUSIONS: The P0 preponderance suggests impingement on the core self and regression to/or fixation in an early developmental stage.

Pain Perception and Body Awareness Among Individuals With Borderline Personality Disorder.

Studies indicate that individuals with borderline personality disorder (BPD) often demonstrate attenuated pain perception, termed hypoalgesia. This study examines the hypothesis that body awareness moderates the association between BPD and pain perception. Participants consisted of 46 women diagnosed with BPD and 47 healthy controls. Sensory testing included the measurement of heat-pain thresholds, ratings of suprathreshold stimuli, measurement of temperature evoking moderate pain, and temporal summation of noxious mechanical stimuli. Body awareness was assessed by a self-report questionnaire. As hypothesized, among subjects with low levels of body awareness, those with BPD demonstrated hypoalgesia as manifested in their lower suprathreshold pain ratings and moderate pain evoked by higher temperature, in comparison with the controls. Among those with high levels of body awareness, BPD subjects demonstrated increased reactivity to pain as manifested in their higher pain ratings and moderate pain evoked by lower temperature, in comparison with the controls.

Unique persistent neurological sequelae of heat stroke.

Heat stroke is a rare clinical phenomenon, characterized by systemic heat and cytokine-induced organ damage. Permanent neurological deficits rarely develop following heat strokes, and cerebellar dysfunction predominates among these rare cases. We report a case of severe heat stroke with recovery from severe multiorgan failure but with persistent neurological manifestations. These included a combination of resolving right-sided signs as well as persistent frontal subcortical dysfunction, with minimal, if any, cerebellar involvement. This combination and the absence of cerebellar involvement is an unusual neurological sequelae of heat stroke.

Category specific dysnomia after thalamic infarction: a case-control study.

Category specific naming impairment was described mainly after cortical lesions. It is thought to result from a lesion in a specific network, reflecting the organization of our semantic knowledge. The deficit usually involves multiple semantic categories whose profile of naming deficit generally obeys the animate/inanimate dichotomy. Thalamic lesions cause general semantic naming deficit, and only rarely a category specific semantic deficit for very limited and highly specific categories. We performed a case-control study on a 56-year-old right-handed man who presented with language impairment following a left anterior thalamic infarction. His naming ability and semantic knowledge were evaluated in the visual, tactile and auditory modalities for stimuli from 11 different categories, and compared to that of five controls. In naming to visual stimuli the patient performed poorly (error rate>50%) in four categories: vegetables, toys, animals and body parts (average 70.31+/-15%). In each category there was a different dominating error type. He performed better in the other seven categories (tools, clothes, transportation, fruits, electric, furniture, kitchen utensils), averaging 14.28+/-9% errors. Further analysis revealed a dichotomy between naming in animate and inanimate categories in the visual and tactile modalities but not in response to auditory stimuli. Thus, a unique category specific profile of response and naming errors to visual and tactile, but not auditory stimuli was found after a left anterior thalamic infarction. This might reflect the role of the thalamus not only as a relay station but further as a central integrator of different stages of perceptual and semantic processing.

Reduced endogenous control in alien hand syndrome: evidence from naturalistic action.

Patients with alien hand (AH) syndrome from medial frontal lesions exhibit involuntary but seemingly purposeful contralesional upper limb movements. Two observations about AH patients have received little, if any, experimental confirmation. The first is that AH is triggered opportunistically by nearby objects. The second is that AH behaviors are increased in conditions of fatigue or anxiety, i.e. under reduced attentional control. A prominent account explains AH as reduced intention-driven (endogenous) executive control. This account predicts that erroneous AH behaviors should be driven by environmental (i.e. exogenous) factors, such as distractor proximity to the hand. AH errors should be less influenced by the intention or action plan (i.e. endogenous factors), such as the semantic relatedness of distractors to targets. Moreover, due to capacity limitations of the endogenous controller, AH behaviors should increase under conditions of secondary task load. We tested these predictions with an AH patient in two experiments using a naturalistic coffee-making task. Experiment 1 demonstrated that the affected hand was highly perseverative and strongly influenced by exogenous but not endogenous factors. The non-alien hand made fewer errors. Experiment 2 showed that there was a disproportionate increase in perseverations and exogenous errors of the affected hand under secondary task load. The non-alien hand was significantly less disrupted by dual task conditions. These data provide experimental support for previous anecdotal observations about AH behavior in naturalistic settings, and are consistent with a unilateral defect in endogenous control.

Frontotemporal dementia and parkinsonism with the P301S tau gene mutation in a Jewish family.

BACKGROUND: Frontotemporal dementia with parkinsonism linked to chromosome 17q21-22 (FTDP-17) is an autosomal dominant tauopathy manifested by a variable combination of personality changes, cognitive decline and hypokinetic-rigid movement disorder. Significant clinical and pathological heterogeneity of FTDP-17 is related in part to more than 20 different pathogenic mutations identified in the tau gene. Among others, the P301S mutation has been previously reported in three families of European and one of Japanese origin presenting with different clinical phenotypes. OBJECTIVES: To report a three-generation family of Jewish-Algerian origin with FTDP-17 due to the P301S tau mutation. METHODS: Clinical, neuropsychological and neuroimaging evaluation of 3 patients, tau genotyping, and pathological study of the proband. RESULTS: The 3 affected family members had a fairly stereotyped clinical course with early personality changes from their late 30s followed within a period of 1-2 years by a progressive cognitive and motor deterioration eventually leading to a state of akinetic mutism or death 3-5 years after the initial symptoms. The main clinical manifestations included severe dementia and hypokinetic-rigid movement disorder associated with supranuclear gaze impairment, pyramidal signs and frontal release signs. Brain imaging disclosed a variable degree of frontotemporal atrophy, ventriculomegaly and regional cerebral hypoperfusion or glucose hypometabolism. Frontal lobe biopsy in the proband revealed weak tau immunoreactivity in a few cortical neurons, in rare neurites and in some glial cells with no neurofibrillary tangles. Molecular DNA analysis identified a P301S mutation in exon 10 of the tau gene. CONCLUSIONS: The observed clinical features further expand the reported P301S phenotype and confirm a more aggressive course of the disease than in the other known tau mutations.

Depression with anosognosia following a left subcortical stroke.

Controversy exists about whether depression following stroke represents a biologically mediated change or a psychological reaction to the deficits. We present a patient with an acute isolated personality change and depression following a lacunar infarct of the left internal capsule, who was unaware of his affective change. His anosognosia for the depression, which was abrupt and not accompanied by cognitive impairments, suggests that post stroke depression, at least in this case, is better explained by a biological than a psychological model.

The alien hand syndrome: What makes the alien hand alien?

The alien hand syndrome is a deeply puzzling phenomenon in which brain-damaged patients experience their limb performing seemingly purposeful acts without their intention. Furthermore, the limb may interfere with the actions of their normal limb. We report a case of alien hand syndrome following a left medial frontal and corpus callosum ischemic lesion. From our clinical observations and the patient's performances on experimental tasks, we postulate that three factors contribute to the sense of alienness: First, the errant limb must be disinhibited and disproportionately reactive to external environmental stimuli. Second, the limb is under less volitional control and produces perseverative movements in which motor stereotypies are concatenated. Consequently, the disinhibited limb perseverates on external stimuli and appears purposeful, despite not being engaged in true goal-directed intentions. Finally, the patient needs to have a relatively intact action-monitoring system to be aware of the abnormal movements as they are occurring.