Temporal Lobe Dysfunction Research Articles

Long-term consolidation of declarative memory: insight from temporal lobe epilepsy

Several experiments carried out with a subset of patients with temporal lobe epilepsy have demonstrated normal memory performance at standard delays of recall (i.e. minutes to hours) but impaired performance over longer delays (i.e. days or weeks), suggesting altered long-term consolidation mechanisms. These mechanisms were specifically investigated in a group of five adult-onset pharmaco-sensitive patients with temporal lobe epilepsy, exhibiting severe episodic memory complaints despite normal performance at standardized memory assessment. In a first experiment, the magnitude of autobiographical memory loss was evaluated using retrograde personal memory tasks based on verbal and visual cues. In both conditions, results showed an unusual U-shaped pattern of personal memory impairment, encompassing most of the patients' life, sparing however, periods of the childhood, early adulthood and past several weeks. This profile was suggestive of a long-term consolidation impairment of personal episodes, adequately consolidated over 'short-term' delays but gradually forgotten thereafter. Therefore, in a subsequent experiment, patients were submitted to a protocol specifically devised to investigate short and long-term consolidation of contextually-bound experiences (episodic memory) and context-free information (semantic knowledge and single-items). In the short term (1 h), performance at both contextually-free and contextually-bound memory tasks was intact. After a 6-week delay, however, contextually-bound memory performance was impaired while contextually-free memory performance remained preserved. This effect was independent of task difficulty and the modality of retrieval (recall and recognition). Neuroimaging studies revealed the presence of mild metabolic changes within medial temporal lobe structures. Taken together, these results show the existence of different consolidation systems within declarative memory. They suggest that mild medial temporal lobe dysfunction can impede the building and stabilization of episodic memories but leaves long-term semantic and single-items mnemonic traces intact.

Normative Data for Rey's Auditory Verbal Learning Test in Individuals with Schizophrenia

Deficits in episodic memory, related to medial temporal lobe dysfunction, are a core component of schizophrenia. Rey's Auditory Verbal Learning Test (RAVLT) is one of the most widely used neuropsychological memory tasks in clinical practice but normative data are limited. Over the last 15 years, the RAVLT has been used to assess verbal episodic memory performance as part of the Western Australian Family Study of Schizophrenia (WAFSS). This study aims to provide RAVLT norms, derived from the WAFSS, for individuals meeting DSM-IV and ICD-10 diagnostic criteria for schizophrenia or schizophrenia-spectrum disorder, for use in clinical settings. Performance on three immediate and one delayed recall trials, and additional measures of encoding and forgetting, is presented for 492 patients and 260 healthy community controls. Results indicated that age and sex (both groups) and IQ (schizophrenia group only) significantly influenced performance. Norms are presented, as means and standard deviations, stratified accordingly. Additional between-groups analysis clearly shows a significant memory deficit in schizophrenia even when patients are matched on IQ, age, and sex with healthy controls.

Rapid Cycling Associated With Menstrual Periods in an Adolescent: Electrophysiological Underpinnings for Bipolarity

Rapid Cycling Associated With Menstrual Periods in an Adolescent: Electrophysiological Underpinnings for Bipolarity

How localized is localization-related epilepsy?

The most common localization-related epilepsy is temporal lobe epilepsy (TLE). Traditionally, TLE has been considered a localized disorder given the focal mesial temporal onset of seizures, hippocampal atrophy and sclerosis, and therapeutic response to focal resection of the anteromedial temporal lobe. However, there is growing evidence of more diffuse anatomic and functional abnormalities. Patients with TLE exhibit dysfunction of the anterior temporal lobe (e.g., memory formation and naming), but they also can exhibit abnormal cognitive functions not associated with focal dysfunction of the anterior temporal lobes. The reason for these unanticipated cognitive findings is becoming clearer. MRI studies have provided evidence for reduced volumes in multiple brain regions in TLE including extrahippocampal temporal, frontal, parietal, and occipital lobes, and diverse subcortical structures, which involve not only the hippocampus and parahippocampal gyrus, but also the thalamus, caudate, amygdala, and cerebellum.1 Diffuse abnormalities of the cortical mantle also occur, including markers of gray matter complexity and thickness in temporal lobe and in extratemporal regions ipsilateral and contralateral to the side of temporal lobe seizure onset.2 Positron …

Use of complex three-dimensional objects to assess visuospatial memory in healthy individuals and patients with unilateral amygdalohippocampectomy

Because many visuospatial memory tests do not reliably detect right medial temporal lobe (MTL) dysfunction, we developed a novel object recognition test using complex three-dimensional stimuli. To influence encoding strategy, half the stimuli were multicolored (color towers) and accompanied by verbally based instructions, and half were gray (gray towers) and accompanied by visuospatially based instructions. In Experiment 1, healthy subjects completed the test while performing verbal or visuospatial interference tasks or without interference. In Experiment 2, patients with unilateral amygdalohippocampectomies for intractable epilepsy completed the test without interference. Results suggest that color tower recognition was partially dependent on verbal processing and sensitive to MTL lesions in general. Recognition of gray towers was reliant on visuospatial processing, and the decay in accuracy after a delay was sensitive and specific to right MTL lesions. These findings suggest that test stimuli such as three-dimensional objects can be useful in assessing right MTL dysfunction.

Frontal and temporal lobe involvement on verbal fluency measures in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) has been associated with changes in frontal and temporal lobe-mediated cognitive and behavioral functions. Verbal fluency, a sensitive measure to these changes, was utilized to investigate phonemic and semantic abilities in 49 ALS patients and 25 healthy controls (HCs). A subset of the ALS patients was classified as ALS-intact, ALS with mild cognitive impairments (ALS-mild), and ALS with fronto-temporal dementia (ALS-FTD) based on a comprehensive neuropsychological evaluation. Clustering and switching, the underlying component processes of verbal fluency, were analyzed using Troyer's (Troyer, Moscovitch, & Winocur, 1997) and Abwender's (Abwender, Swan, Bowerman, & Connolly, 2001) scoring systems. ALS patients exhibited decreased fluency versus HCs. For phonemic fluency, the intact ALS sample generated fewer clusters and more switches than the ALS-mild and ALS-FTD patients using both scoring systems. This suggests temporal involvement in ALS patients, with increasing frontal lobe involvement in patients with greater cognitive dysfunction. For semantic fluency, similar results were obtained with a greater emphasis on declines in clustering or increased temporal lobe dysfunction. These results suggest that verbal fluency measures identify frontal and temporal lobe involvement in the cognitive decline associated with ALS, particularly when the component processes are evaluated. The clinical utility of these scoring systems with ALS patients is also discussed.

Medial temporal lobe dysfunction during encoding and retrieval of episodic memory in non-demented APOE ε4 carriers

Presence of the apolipoprotein E (APOE) ε4 allele is linked to an increased risk to develop Alzheimer's dementia (AD). However, there are controversial data concerning the impact of the APOE genotype on cognitive functioning and brain activity in healthy subjects. We used event-related functional magnetic resonance imaging (fMRI) to investigate the effects of APOE genotype on spatial contextual memory encoding and retrieval success in healthy older adults. Eighteen subjects (eight APOE4 heterozygotes (ε4+) and 10 non-carriers (ε4−), mean age 60.0±5.0 years) were included in the present analysis. Behaviorally, ε4+ subjects performed significantly worse than ε4− subjects in item memory and spatial context retrieval. fMRI data revealed that ε4+ subjects, compared to ε4-subjects, predominantly showed an increase of neural activity specific to encoding of items and their spatial context in prefrontal, temporal and parietal regions. In contrast, ε4+ subjects showed activity decreases in the right amygdala during successful item recognition and in the prefrontal cortex bilaterally during spatial context retrieval when compared to ε4− subjects. While the activity increases during encoding may reflect compensatory activity in the attempt to maintain normal performance, the decreases during retrieval indicate incipient neural decline in ε4+ subjects. These data highlight that preclinical ApoE-related changes in neural activity are not unidirectional but dissociate depending on the memory phase, i.e., encoding or retrieval.

Paroxysmal Dyskinesia With Deja Vu Aura

Paroxysmal Dyskinesia With Deja Vu Aura

P02-243 - Neurocognition and temperament in borderline and schizotypal personality disorder

ObjectiveExplore the neurocognitive and temperament profile of borderline personality disorder (BPD) and schizotypal personality disorder (SPD) to better understand their underlying neurobiology for improved treatment.Methods17 BPD, 16 SPD, and 15 healthy controls (HCs) were given a comprehensive neuropsychological battery (CANTAB), the Iowa Gambling Task, a time perception task, and questionnaires of impulsivity, temperament, emotion, and frontal behavior (measures orbitofrontal cortex (OFC) dysfunction).ResultsBPD and SPD patients performed significantly worse on the delayed match to sample (DMS) task compared to HCs, but had preserved function on decision-making, planning, time perception and attention tasks. SPD patients performed significantly worse on spatial working memory (SWM) tasks, and had higher religious commitment scores than HC and BPD groups, which correlated with their SWM deficits. BPD patients had significantly more frontal behaviors and emotions than both groups, which correlated with their emotionality, impulsivity, BPD symptoms, and temperament traits.ConclusionsBoth BPD and SPD groups had a deficit on the DMS task, sensitive to medial temporal lobe (MTL) dysfunction, but only SPD patients had SWM deficits, indicative of dorsolateral frontal cortex (DLFC) dysfunction, which correlated with their high religious commitment in line with their odd beliefs and magical thinking. Only BPD patients had frontal behavior deficits, related to OFC dysfunction, which positively correlated with their emotionality, impulsivity, and temperament traits. While both disorders may have a deficit in MTL function, DLFC dysfunction may contribute to SPD symptoms, and OFC dysfunction to BPD symptoms, suggesting treatment should target unique prefrontal cortex regions respectively.

Superior temporal lobe dysfunction and frontotemporal dysconnectivity in subjects at risk of psychosis and in first‐episode psychosis

Superior temporal lobe dysfunction is a robust finding in functional neuroimaging studies of schizophrenia and is thought to be related to a disruption of fronto-temporal functional connectivity. However, the stage of the disorder at which these functional alterations occur is unclear. We addressed this issue by using functional MRI (fMRI) to study subjects in the prodromal and first episode phases of schizophrenia. Subjects with an at risk mental state (ARMS) for psychosis, a first psychotic episode (FEP), and controls were studied using fMRI while performing a working memory task. Activation in the superior temporal gyrus (STG) was assessed using statistical parametric mapping, and its relationship to frontal activation was examined using dynamic causal modeling. The STG was differentially engaged across the three groups. There was deactivation of this region during the task in controls, whereas subjects with FEP showed activation and the response in subjects with ARMS was intermediately relative to the two other groups. There were corresponding differences in the effective connectivity between the STG and the middle frontal gyrus across the three groups, with a negative coupling between these areas in controls, a positive coupling in the FEP group, and an intermediate value in the ARMS group. A failure to deactivate the superior temporal lobe during tasks that engage prefrontal cortex is evident at the onset of schizophrenia and may reflect a disruption of fronto-temporal connectivity. Qualitatively similar alterations are evident in people with prodromal symptoms of the disorder.

The clinical utility of the Warrington Recognition Memory Test in people with a low IQ

The sensitivity of the Warrington Recognition Memory for Faces (RMF) to reliably localize temporal lobe dysfunction in surgical epilepsy candidates is not as strong as that of the Recognition Memory for Words (RMW). Previous research has indicated that its diagnostic utility is improved in patients with lower IQs. Data from 114 patients with unilateral hippocampal sclerosis was retrospectively examined to explore the accuracy of both subtests in patients with IQs within the low average/borderline impaired and intellectual disability ranges. In our group, the RMF did not discriminate between right and left hippocampal sclerosis, whilst the RMW did. However, many patients functioning within the intellectual disability range are unable to complete the RMW. There is a need to develop neuropsychological protocols appropriate for this group.

Pathogenesis and Neuropsychological Sequelae in Cysticercosis: A Case Study

Cysticercosis is a disease that occurs via the dissemination of the larvae form of the pork tapeworm Taenia solium to various organ systems, including the central nervous system. Sequelae may include seizures and neuropsychological impairment. The present case study involves a 45-year-old Caucasian female executive diagnosed with neurocysticercosis. Evaluation methods consisted of neuropsychological and electrophysiological assessment. Both neuropsychological evaluation and electrophysiological testing suggested right temporal and right parietal lobe dysfunction. Comparison of neuropsychological and quantitative electroencephalogram (QEEG) test results yielded high agreement in terms of site of lesion as documented by magnetic resonance imaging (MRI) and computed tomography scan (CT scan) findings. Neuropsychological findings are described in detail, as well as a description of subsequent neurocognitive rehabilitation. Serial assessment is delineated and compared with the baseline evaluation. This case study serves to underscore the clinical utility of neuropsychological assessment and neurocognitive rehabilitation in infectious disease consultations, specifically in neurocysticercosis.

Dissociation of long-term verbal memory and fronto-executive impairment in first-episode psychosis

BackgroundVerbal memory is frequently and severely affected in schizophrenia and has been implicated as a mediator of poor clinical outcome. Whereas encoding deficits are well demonstrated, it is unclear whether retention is impaired. This distinction is important because accelerated forgetting implies impaired consolidation attributable to medial temporal lobe (MTL) dysfunction whereas impaired encoding and retrieval implicates involvement of prefrontal cortex.MethodWe assessed a group of healthy volunteers (n=97) and pre-morbid IQ- and sex-matched first-episode psychosis patients (n=97), the majority of whom developed schizophrenia. We compared performance of verbal learning and recall with measures of visuospatial working memory, planning and attentional set-shifting, and also current IQ.ResultsAll measures of performance, including verbal memory retention, a memory savings score that accounted for learning impairments, were significantly impaired in the schizophrenia group. The difference between groups for delayed recall remained even after the influence of learning and recall was accounted for. Factor analyses showed that, in patients, all variables except verbal memory retention loaded on a single factor, whereas in controls verbal memory and fronto-executive measures were separable.ConclusionsThe results suggest that IQ, executive function and verbal learning deficits in schizophrenia may reflect a common abnormality of information processing in prefrontal cortex rather than specific impairments in different cognitive domains. Verbal memory retention impairments, however, may have a different aetiology.

Clinical, neuropsychological, neurophysiologic, and genetic features of a new Italian pedigree with familial cortical myoclonic tremor with epilepsy

We studied the clinical, neuropsychological, neurophysiologic, and genetic features of an Italian family with familial cortical myoclonic tremor with epilepsy (FCMTE). Clinically affected members of the family had limb and voice tremor, seizures, and myoclonus involving the eyelids during blinking. Neuropsychological testing disclosed visuospatial impairment, possibly due to temporal lobe dysfunction. Neurophysiologic findings suggested increased primary motor cortex excitability with normal sensorimotor integration. Linkage analysis excluded the 8q24 locus, where patients shared a common haplotype spanning 14.5 Mb in the pericentromeric region of chromosome 2.

Psychomotor epilepsy and psychosis

The EEG findings in waking, sleep, and sphenoidal electrode recordings in 96 patients with partial epileptic seizures with complex symptoms, who, after a median interval of 18 years developed paranoid/hallucinatory psychosis, were compared with the findings from a group of patients without psychosis, who had had the same type of epilepsy in median 24 years. There were no significant differences between the two groups with regard to median age at onset of epilepsy or complex partial seizures, age, or duration of epilepsy at time of examination. The psychotic patients had a significant preponderance of temporal medio-basal spike foci, recorded on the sphenoidal electrode, indicating deep temporal lobe dysfunction as an important factor in the pathogenesis of psychosis. A significant higher frequency of bilateral and multiple spike foci, together with a significant frequency of slow-wave admixture to the waking background EEG activity, indicated more extensive and severe epileptogenic lesions in the psychotic patients. There was no correlation between psychosis and unilateral EEG-foci in either temporal lobe.

Attention impairment in temporal lobe epilepsy: A neurophysiological approach via analysis of the P300 wave

Attention is often impaired in temporal lobe epilepsy (TLE). The P300 wave (an endogenous, event-related potential) is a correlate of attention which is usually recorded during an "oddball paradigm," where the subject is instructed to detect an infrequent target stimulus presented amongst frequent, standard stimuli. Modifications of the P300 wave's latency and amplitude in TLE have been suggested, but it is still not known whether the source regions also differ. Our hypothesis was that temporal lobe dysfunction would modify the P3 source regions in TLE patients. A comparative, high density, 128-channel electroencephalographic analysis of the characteristics of P300 (P3b latency and amplitude) was performed in 10 TLE patients and 10 healthy controls during auditory and visual oddball paradigms. The P3b sources were localized on individual 3D MR images using the LORETA method and intergroup statistical comparisons were performed using SPM2(R) software. Our main results (in both individual analyses and intergroup comparisons) revealed a reduction in temporal (and more particularly mesiotemporal) sources and, to a lesser extent, frontal sources in TLE patients, compared with controls. This reduction may reflect direct, local cortical dysfunction caused by the epileptic focus or more complex interference between epileptic networks and normal attentional pathways.

Tracking progression in frontotemporal lobar degeneration

Semantic dementia is a sporadic neurodegenerative disorder characterized by the progressive erosion of semantic processing and is one of the canonical subtypes of frontotemporal lobar degeneration. This study aimed to characterize the pattern of global and regional longitudinal brain atrophy in semantic dementia and to identify imaging biomarkers that could underpin therapeutic trials. Twenty-one patients with semantic dementia (including eight pathologically confirmed cases) underwent whole-brain and region-of-interest analyses on volumetric brain MRI scans at two time points. Sample size estimates for trials were subsequently calculated using these data. Mean (SD) whole-brain atrophy rate was 39.6 (31.9) mL/y [3.2 (12.0) mL/y in controls], with ventricular enlargement of 8.9 (4.4) mL/y [1.0 (1.0) mL/y in controls]. All patients had a smaller left temporal lobe at baseline [left mean 31.9 (6.9) mL, right mean 49.2 (9.5) mL; p < 0.0001]; however, the mean rate of atrophy was significantly greater in the right temporal lobe [right 3.9 (1.7) mL/y, left 2.8 (1.2) mL/y; p = 0.02]. Similarly, whereas the left hippocampus was smaller at baseline, the mean atrophy rate was significantly greater in the right hippocampus. Using the atrophy rates generated, sample size requirements for clinical trials were found to be smallest for temporal lobe measurement. These findings show that the rate of tissue loss in the right temporal lobe overtakes the left temporal lobe as semantic dementia evolves, consistent with the later development of symptoms attributable to right temporal lobe dysfunction. Furthermore, our findings demonstrate that MRI measures of temporal lobe volume loss could provide a feasible and sensitive index of disease progression in semantic dementia.

Neurobehavioral Profile and Brain Imaging Study of the 22q13.3 Deletion Syndrome in Childhood

The 22q13.3 deletion syndrome (Online Mendelian Inheritance in Man No. 606232) is a neurodevelopmental disorder that includes hypotonia, severely impaired development of speech and language, autistic-like behavior, and minor dysmorphic features. Although the number of reported cases is increasing, the 22q13.3 deletion remains underdiagnosed because of failure in recognizing the clinical phenotype and detecting the 22qter deletion by routine chromosome analyses. Our goal is to contribute to the description of the neurobehavioral phenotype and brain abnormalities of this microdeletional syndrome. We assessed neuromotor, sensory, language, communication, and social development and performed cerebral MRI and study of regional cerebral blood flow measured by positron emission tomography in 8 children carrying the 22q13.3 deletion. Despite variability in expression and severity, the children shared a common developmental profile characterized by hypotonia, sleep disorders, and poor response to their environment in early infancy; expressive language deficit contrasting with emergence of social reciprocity from ages approximately 3 to 5 years; sensory processing dysfunction; and neuromotor disorders. Brain MRI findings were normal or showed a thin or morphologically atypical corpus callosum. Positron emission tomography study detected a localized dysfunction of the left temporal polar lobe and amygdala hypoperfusion. The developmental course of the 22q13.3 deletion syndrome belongs to pervasive developmental disorders but is distinct from autism. An improved description of the natural history of this syndrome should help in recognizing this largely underdiagnosed condition.

Episodic, but not semantic, autobiographical memory is reduced in amnestic mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) is characterized by decline in anterograde memory as measured by the ability to learn and remember new information. We investigated whether retrograde memory for autobiographical information was affected by aMCI. Eighteen control (age 66–84 years) and 17 aMCI (age 66–84 years) participants described a personal event from each of the five periods across the lifespan. These events were transcribed and scored according to procedures that separate episodic (specific happenings) from semantic (general knowledge) elements of autobiographical memory. Although both groups generated protocols of similar length, the composition of autobiographical recall differentiated the groups. The aMCI group protocols were characterized by reduced episodic and increased semantic information relative to the control group. Both groups showed a similar pattern of recall across time periods, with no evidence that the aMCI group had more difficulty recalling recent, rather than remote, life events. These results indicate that episodic and semantic autobiographical memories are differentially affected by the early brain changes associated with aMCI. Reduced autobiographical episodic memories in aMCI may be the result of medial temporal lobe dysfunction, consistent with multiple trace theory, or alternatively, could be related to dysfunction of a wider related network of neocortical structures. In contrast, the preservation of autobiographical semantic memories in aMCI suggests neural systems, such as lateral temporal cortex, that support these memories, may remain relatively intact.

IC-P2-130: Profiles of longitudinal brain atrophy in semantic dementia

Semantic dementia (SD) is a sporadic neurodegenerative disorder characterized clinically by progressive erosion of semantic processing in verbal and nonverbal domains and pathologically by the presence of ubiquitin-positive, TDP-43 positive neuronal inclusions. Brain imaging typically shows asymmetrical antero-inferior temporal lobe atrophy more severe on the left. Within the spectrum of the frontotemporal lobar degenerations (FTLD), the uniform and specific clinico-pathological signature of SD makes it the leading candidate FTLD subtype for trials of disease-modifying therapy. The aims of this study were to characterise in detail the pattern of global and regional longitudinal brain atrophy in SD and to identify imaging biomarkers of SD that could underpin therapeutic trials. In a cohort of 21 patients with SD (including 8 with pathological confirmation) we performed whole brain and region of interest analyses on volumetric brain MRI scans at two time-points. Mean whole brain atrophy rate measured using the boundary shift integral (BSI) was 2.5% per year (0.4% per year in controls) with ventricular enlargement at 6.2ml per year (0.6ml per year in controls). In regional analyses, all patients had a smaller left temporal lobe at baseline (left mean 31.9ml, right mean 49.2ml), however the mean rate of atrophy was significantly greater in the right temporal lobe (right 3.9ml per year, left 2.8ml per year). Similarly, whereas the left hippocampus was smaller at baseline (left mean 1.92ml, right mean 2.41ml) mean atrophy rate was significantly greater in the right hippocampus (right 0.17ml per year, left 0.10 ml per year). These findings suggest that as SD evolves, atrophy is initially more prominent on the left but then the rate of loss in the right temporal lobe overtakes the left, consistent with the later development of symptoms attributable to right temporal lobe dysfunction in SD. Our findings show that MRI measures of temporal lobe volume loss would provide a feasible and sensitive index of disease progression in SD: whereas whole-brain and hippocampal volume measures have been advanced as candidate biomarkers in other degenerative dementias, in SD temporal lobe volumetry would require fewer patients to detect the same level of effect.