Medial Temporal Structures Research Articles

Presence of cerebral amyloid modulates phenotype and pattern of neurodegeneration in early Parkinson's disease

ObjectiveTo evaluate the frequency of cerebral amyloid in early Parkinson's disease (ePD) and provide a multimodal assessment of the influence of cerebral amyloid on disease phenotype.MethodsWe performed a multicentre cohort...

Occurrence predictors of the temporal interictal epileptic discharges in epilepsy patients with extratemporal lesions: A prospective cohort study

ObjectiveElectrical kindling models of epilepsy suggest that medial temporal structures are more prone to be irritated. The aim of this study is to investigate the occurrence rate of temporal interictal epileptic discharges (TIEDs) in the epilepsy patients with extratemporal lesions (ETLs), and to determine the predictive factors for TIEDs in this cohort. MethodsTotally 221 patients were admitted for presurgical evaluation, and focal ETL were found in all of them by MRI examination. The occurrence rates of TIEDs in several groups with different brain lobe locations, durations; of epilepsy, seizure frequencies, and onset ages stages were assessed. We also evaluated the surgical outcome of; resection in this cohort. ResultsThe total occurrence rate of TIEDs in this cohort was 29.9%. The occurrence rate of TIEDs in the patients with longer durations (>5 or 10 years) was significantly higher than those with shorter duration (<1 year). These; patients with lower seizure frequency (<1 seizure/month) had a significantly decreased incidence of TIEDs; compared with those with higher frequency (>1 seizure/month or week). In the terms of the brain lobe locations; and age at onset, there were no differences between the groups. Furthermore, there were no differences in terms of the surgical outcomes between the patients with TIEDs and other patients in this series. ConclusionsTIEDs were frequently recorded in these patients with ETLs, and the predictive factors for TIEDs included the epilepsy duration and seizure frequency. SignificanceThis study is instrumental for the presurgical EEG interpretationand the counseling of these ETLs patients considered for epilepsy surgery.

Neuroanatomical Networks Supporting Memory and Their Relation to Amnesia; a View from the Thalamus

The anterior and mediodorsal thalamic nuclei form neuroanatomical networks supporting memory along with the mammillary body, medial temporal structures, prefrontal cortices and posterior cingulate cortex. In this review article, we discuss human diencephalic amnesic syndromes, including Wernicke-Korsakoff syndrome and amnesia associated with thalamic infarcts, and animal neuropsychological studies from a neuroanatomical network perspective. In addition, we suggest future research directions for understanding the functional roles of the anterior and mediodorsal thalamic nuclei in memory function based on findings from recent animal studies.

Structural MRI Biomarkers of Mild Cognitive Impairment from Young Elders to Centenarians.

Underpinnings of mild cognitive impairment (MCI) change with increasing age. We hypothesize that MRI signatures of mild cognitive impairment (MCI) would be different at a higher age compared to younger elders. 244 participants (71-103 years) from the Sydney Memory and Ageing Study and the Sydney Centenarian Study were categorized as amnestic MCI (aMCI), non-amnestic MCI (naMCI) or cognitively normal (CN). Brain "atrophy" and white matter hyper-intensities (WMHs) associated with MCI subtypes and age effects were examined by general linear models, controlling for confounding factors. Reduced logistic regressions were performed to determine structures that best discriminated aMCI from CN in individuals <85 and those ≥85 years. aMCI was associated with smaller volumes of overall cortex, medial temporal structures, anterior corpus callosum, and select frontal and parietal regions compared to CN; such associations did not significantly change with age. Structures that best discriminated aMCI from CN differed however in the <85 and ≥85 age groups: cortex, putamen, parahippocampal, precuneus and superior frontal cortices in <85 years, and the hippocampus, pars triangularis and temporal pole in ≥85 years. Differences between naMCI and CN were small and non-significant in the sample. WMHs were not significantly associated with MCI subtypes. Structural MRI distinguishes aMCI, but not naMCI, from CN in elderly individuals. The structures that best distinguish aMCI from CN differ in those <85 from those ≥85, suggesting different neuropathological underpinnings of cognitive impairment in the very old.

Different effects of anterior temporal lobectomy and selective amygdalohippocampectomy on verbal memory performance of patients with epilepsy.

The advantage of selective amygdalohippocampectomy (SAH) over anterior temporal lobectomy (ATL) for the treatment of temporal lobe epilepsy (TLE) remains controversial. Because ATL is more extensive and involves the lateral and medial parts of the temporal lobe, it may be predicted that its impact on memory is more important than SAH, which involves resection of medial temporal structures only. However, several studies do not support this assumption. Possible explanations include task-specific factors such as the extent of semantic and syntactic information to be memorized and failure to control for main confounders. We compared preoperative vs. postoperative memory performance in 13 patients with SAH with 26 patients who underwent ATL matched on side of surgery, IQ, age at seizure onset, and age at surgery. Memory function was assessed using the Logical Memory subtest from the Wechsler Memory Scales - 3rd edition (LM-WMS), the Rey Auditory Verbal Learning Test (RAVLT), the Digit Span subtest from the Wechsler Adult Intelligence Scale, and the Rey-Osterrieth Complex Figure Test. Repeated measures analyses of variance revealed opposite effects of SAH and ATL on the two verbal learning memory tests. On the immediate recall trial of the LM-WMS, performance deteriorated after ATL in comparison with that after SAH. By contrast, on the delayed recognition trial of the RAVLT, performance deteriorated after SAH compared with that after ATL. However, additional analyses revealed that the latter finding was only observed when surgery was conducted in the right hemisphere. No interaction effects were found on other memory outcomes. The results are congruent with the view that tasks involving rich semantic content and syntactical structure are more sensitive to the effects of lateral temporal cortex resection as compared with mesiotemporal resection. The findings highlight the importance of task selection in the assessment of memory in patients undergoing TLE surgery.

Structural covariance mapping delineates medial and medio-lateral temporal networks in déjà vu.

Déjà vu (DV) is an eerie phenomenon experienced frequently as an aura of temporal lobe epilepsy, but also reported commonly by healthy individuals. The former pathological manifestation appears to result from aberrant neural activity among brain structures within the medial temporal lobes. Recent studies also implicate medial temporal brain structures in the non-pathological experience of DV, but as one element of a diffuse neuroanatomical correlate; it remains to be seen if neural activity among the medial temporal lobes also underlies this benign manifestation. The present study set out to investigate this. Due to its unpredictable and infrequent occurrence, however, non-pathological DV does not lend itself easily to functional neuroimaging. Instead, we draw on research showing that brain structure covaries among regions that interact frequently as nodes of functional networks. Specifically, we assessed whether grey-matter covariance among structures implicated in non-pathological DV differs according to the frequency with which the phenomenon is experienced. This revealed two diverging patterns of structural covariation: Among the first, comprised primarily of medial temporal structures and the caudate, grey-matter volume becomes more positively correlated with higher frequency of DV experience. The second pattern encompasses medial and lateral temporal structures, among which greater DV frequency is associated with more negatively correlated grey matter. Using a meta-analytic method of co-activation mapping, we demonstrate a higher probability of functional interactions among brain structures constituting the former pattern, particularly during memory-related processes. Our findings suggest that altered neural signalling within memory-related medial temporal brain structures underlies both pathological and non-pathological DV.

Abnormal spindle-like microcephaly-associated (ASPM) mutations strongly disrupt neocortical structure but spare the hippocampus and long-term memory

Autosomal recessive primary microcephaly results from abnormal brain development linked to proliferation defects in neural progenitors. The most frequent form, caused by ASPM mutations, is usually defined by a reduced brain volume and is associated with intellectual disability. Although many ASPM cases have now been reported, structural brain abnormalities and their link with cognitive disabilities have rarely been investigated. In this study, we used high resolution T1-weighted magnetic resonance imaging in seven patients with ASPM mutations and 39 healthy age-matched controls to quantify regional volumes, thickness, surface area, gyrification index and white matter volumes of 30 cortical regions. We observed a consistent reduction of 50% or more in the volume and surface area of all cortical regions except for the hippocampus and surrounding medial temporal structures, which were significantly less reduced. Neuropsychologic assessment indicated significant impairments of cognitive abilities. However, these impairments were associated with normal mnesic abilities, in keeping with the relative preservation of the hippocampus and medial temporal structures. These results show that, contrary to current opinion, the cortical volume and surface area of patients with ASPM mutations is reduced depending on a regionally specific fashion and their cognitive profile reflects this heterogeneity. The precise characterization of the cortical map and cognitive abilities of patients with ASPM mutations should allow developing more focused reeducative interventions well-suited to their real abilities.

Regional Cortical Surface Area in Adolescents: A Preliminary MRI Twin Study of Genetic and Environmental Contributions.

Cortical surface area (CSA) has particular relevance for understanding development, behavior, and the connection between brain structure and function. Little is known about genetic and environmental determinants of CSA during development. We utilized bivariate twin methods to identify global and regionally specific genetic factors which influence CSA in a preliminary sample of typically-developing adolescents, with hypotheses based on findings in middle-aged adults. Similar to previous findings, we observed high heritability for total CSA. There was also significant evidence for genetic influences on regional CSA, particularly when these were not adjusted for total CSA, with highest heritability in frontal cortex and relatively fewer genetic contributions to medial temporal cortical structures. Adjustment for total CSA reduced regional CSA heritability dramatically, but a moderate influence of genetic factors remained in some regions. Both global and regionally-specific genetic factors influence regional CSA during adolescence.

Neuromagnetic evidence for hippocampal modulation of auditory processing

The hippocampus is well known to be involved in memory, as well as in perceptual processing. To date, the electrophysiological process by which unilateral hippocampal lesions, such as hippocampal sclerosis (HS), modulate the auditory processing remains unknown. Auditory-evoked magnetic fields (AEFs) are valuable for evaluating auditory functions, because M100, a major component of AEFs, originates from auditory areas. Therefore, AEFs of mesial temporal lobe epilepsy (mTLE, n=17) with unilateral HS were compared with those of healthy (HC, n=17) and disease controls (n=9), thereby determining whether AEFs were indicative of hippocampal influences on the auditory processing. Monaural tone-burst stimuli were presented for each side, followed by analysis of M100 and a previously less characterized exogenous component (M400: 300–500ms). The frequency of acceptable M100 dipoles was significantly decreased in the HS side. Beam-forming-based source localization analysis also showed decreased activity of the auditory area, which corresponded to the inadequately estimated dipoles. M400 was found to be related to the medial temporal structure on the HS side. Volumetric analysis was also performed, focusing on the auditory-related areas (planum temporale, Heschl's gyrus, and superior temporal gyrus), as well as the hippocampus. M100 amplitudes positively correlated with hippocampal and planum temporale volumes in the HC group, whereas they negatively correlated with Heschl's gyrus volume in the mTLE group. Interestingly, significantly enhanced M400 component was observed in the HS side of the mTLE patients. In addition, the M400 component positively correlated with Heschl's gyrus volume and tended to positively correlate with disease duration. M400 was markedly diminished after hippocampal resection. Although volumetric analysis showed decreased hippocampal volume in the HS side, the planum temporale and Heschl's gyrus, the two major sources of M100, were preserved. These results suggested that HS significantly influenced AEFs. Therefore, we concluded that the hippocampus modulates auditory processing differently under normal conditions and in HS.

Seizure Frequency Can Alter Brain Connectivity: Evidence from Resting-State fMRI.

The frequency of seizures is an important factor that can alter functional brain connectivity. Analysis of this factor in patients with epilepsy is complex because of disease- and medication-induced confounders. Because patients with hot-water epilepsy generally are not on long-term drug therapy, we used seed-based connectivity analysis in these patients to assess connectivity changes associated with seizure frequency without confounding from antiepileptic drugs. Resting-state fMRI data from 36 patients with hot-water epilepsy (18 with frequent seizures [>2 per month] and 18 with infrequent seizures [≤2 per month]) and 18 healthy age- and sex-matched controls were analyzed for seed-to-voxel connectivity by using 106 seeds. Voxel wise paired t-test analysis (P < .005, corrected for false-discovery rate) was used to identify significant intergroup differences between these groups. Connectivity analysis revealed significant differences between the 2 groups (P < .001). Patients in the frequent-seizure group had increased connectivity within the medial temporal structures and widespread areas of poor connectivity, even involving the default mode network, in comparison with those in the infrequent-seizure group. Patients in the infrequent-seizure group had focal abnormalities with increased default mode network connectivity and decreased left entorhinal cortex connectivity. The results of this study suggest that seizure frequency can alter functional brain connectivity, which can be visualized by using resting-state fMRI. Imaging features such as diffuse network abnormalities, involvement of the default mode network, and recruitment of medial temporal lobe structures were seen only in patients with frequent seizures. Future studies in more common epilepsy groups, however, will be required to further establish this finding.

Human hippocampus represents space and time during retrieval of real-world memories

Memory stretches over a lifetime. In controlled laboratory settings, the hippocampus and other medial temporal lobe brain structures have been shown to represent space and time on the scale of meters and seconds. It remains unclear whether the hippocampus also represents space and time over the longer scales necessary for human episodic memory. We recorded neural activity while participants relived their own experiences, cued by photographs taken with a custom lifelogging device. We found that the left anterior hippocampus represents space and time for a month of remembered events occurring over distances of up to 30 km. Although previous studies have identified similar drifts in representational similarity across space or time over the relatively brief time scales (seconds to minutes) that characterize individual episodic memories, our results provide compelling evidence that a similar pattern of spatiotemporal organization also exists for organizing distinct memories that are distant in space and time. These results further support the emerging view that the anterior, as opposed to posterior, hippocampus integrates distinct experiences, thereby providing a scaffold for encoding and retrieval of autobiographical memories on the scale of our lives.

Scene construction impairments in Alzheimer's disease – A unique role for the posterior cingulate cortex

Episodic memory dysfunction represents one of the most prominent and characteristic clinical features of patients with Alzheimer's disease (AD), attributable to the degeneration of medial temporal and posterior parietal regions of the brain. Recent studies have demonstrated marked impairments in the ability to envisage personally relevant events in the future in AD. It remains unclear, however, whether AD patients can imagine fictitious scenes free from temporal constraints, a process that is proposed to rely fundamentally upon the integrity of the hippocampus. The objective of the present study was to investigate the capacity for atemporal scene construction, and its associated neural substrates, in AD. Fourteen AD patients were tested on the scene construction task and their performance was contrasted with 14 age- and education-matched healthy older Control participants. Scene construction performance was strikingly compromised in the AD group, with significant impairments evident for provision of contextual details, spatial coherence, and the overall richness of the imagined experience. Voxel-based morphometry analyses based on structural MRI revealed significant associations between scene construction capacity and atrophy in posterior parietal and lateral temporal brain structures in AD. In contrast, scene construction performance in Controls was related to integrity of frontal, parietal, and medial temporal structures, including the parahippocampal gyrus and posterior hippocampus. The posterior cingulate cortex (PCC) emerged as the common region implicated for scene construction performance across participant groups. Our study highlights the importance of regions specialised for spatial and contextual processing for the construction of atemporal scenes. Damage to these regions in AD compromises the ability to construct novel scenes, leading to the recapitulation of content from previously experienced events.

An in vivo morphometry study on the standard transsylvian trajectory for mesial temporal lobe epilepsy surgery.

A safe and appropriate surgical approach to the medial temporal structure is a prerequisite to perform surgeries for temporal lobe epilepsy. We used in vivo morphometry to identify the standard direction for entry into the inferior horn of the lateral ventricle via the Sylvian fissure: an important initial step in performing transsylvian selective amygdalohippocampectomy. 3D magnetic resonance images obtained from 28 patients without intra-parenchymal lesions were re-oriented to demonstrate all points in the Talairach space of the brain. The limen insulae and the midpoint between the hippocampal sulcus and the innominate sulcus on the coronal slice through the posterior edge of the amygdala were defined as the start and target points, respectively. We evaluated the direction of the vector between these two points and its validity in the brain of 12 patients with temporal lobe epilepsy. The direction of the mean approach vector was 52.4° posteriorly and 16.2° inferiorly. The mean approach vector on the axial plane showed the approximate parallelism with the sphenoid ridge in individual cases. The computer simulation revealed that our average approach vector correctly entered the inferior horn of the lateral ventricle in all temporal lobe epilepsy brains. In vivo morphometry may contribute to the further development of safe and minimally-invasive neurosurgical procedures.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-015-1198-x) contains supplementary material, which is available to authorized users.

Increased frequency of brain pathology in inmates of a high-security forensic institution: a qualitative CT and MRI scan study.

This study aimed to assess whether brain pathology might be more abundant in forensic inpatients in a high-security setting than in non-criminal individuals. By using a previously used reliable approach, we explored the frequency and extent of brain pathology in a large group of institutionalized offenders who had not previously been considered to be suffering from structural brain damage and compare it to healthy, non-offending subjects. MRI and CT brain scans from 148 male inpatients of a high-security mental health institution (offense type: 51 sex, 80 violent, 9 arson, and 8 nonviolent) that were obtained due to headache, vertigo, or psychological complaints during imprisonment were assessed and compared to 52 non-criminal healthy controls. Brain scans were assessed qualitatively with respect to evidence of structural brain damage. Each case received a semiquantitative rating of "normal" (=0), "questionably abnormal" (=1), or "definitely abnormal" (=2) for the lateral ventricles, frontal/parietal cortex, and medial temporal structures bilaterally as well as third ventricle. Forensic inpatients displayed signs of brain damage to a significantly higher degree than healthy controls (p<0.001). Even after adjustment for age, in the patients, being younger than the controls (p<0.05), every offender type group displayed a higher proportion of subjects with brain regions categorized as definitely abnormal than the non-criminal controls. Within the forensic inpatients, offense type groups did not significantly differ in brain pathology. The astonishingly high prevalence of brain pathology in institutionalized inmates of a high-security mental health institution who previously had not been considered to be suffering from an organic brain syndrome raises questions on whether such neuroradiological assessment might be considered as a routine procedure in newly admitted patients. Furthermore, it highlights that organic changes, detectable under clinical routine conditions, may play a role in the development of legally relevant behavioral disturbances which might be underestimated.

Nonlinear cerebral atrophy patterns across the Alzheimer's disease continuum: impact of APOE4 genotype

The progression of Alzheimer's disease (AD) is characterized by complex trajectories of cerebral atrophy that are affected by interactions with age and apolipoprotein E allele ε4 (APOE4) status. In this article, we report the nonlinear volumetric changes in gray matter across the full biological spectrum of the disease, represented by the AD-cerebrospinal fluid (CSF) index. This index reflects the subject's level of pathology and position along the AD continuum. We also evaluated the associated impact of the APOE4 genotype. The atrophy pattern associated with the AD-CSF index was highly symmetrical and corresponded with the typical AD signature. Medial temporal structures showed different atrophy dynamics along the progression of the disease. The bilateral parahippocampal cortices and a parietotemporal region extending from the middle temporal to the supramarginal gyrus presented an initial increase in volume which later reverted. Similarly, a portion of the precuneus presented a rather linear inverse association with the AD-CSF index whereas some other clusters did not show significant atrophy until index values corresponded to positive CSF tau values. APOE4 carriers showed steeper hippocampal volume reductions with AD progression. Overall, the reported atrophy patterns are in close agreement with those mentioned in previous findings. However, the detected nonlinearities suggest that there may be different pathological processes taking place at specific moments during AD progression and reveal the impact of the APOE4 allele.

Violence: heightened brain attentional network response is selectively muted in Down syndrome

BackgroundThe ability to recognize and respond appropriately to threat is critical to survival, and the neural substrates subserving attention to threat may be probed using depictions of media violence. Whether neural responses to potential threat differ in Down syndrome is not known.MethodsWe performed functional MRI scans of 15 adolescent and adult Down syndrome and 14 typically developing individuals, group matched by age and gender, during 50 min of passive cartoon viewing. Brain activation to auditory and visual features, violence, and presence of the protagonist and antagonist were compared across cartoon segments. fMRI signal from the brain’s dorsal attention network was compared to thematic and violent events within the cartoons between Down syndrome and control samples.ResultsWe found that in typical development, the brain’s dorsal attention network was most active during violent scenes in the cartoons and that this was significantly and specifically reduced in Down syndrome. When the antagonist was on screen, there was significantly less activation in the left medial temporal lobe of individuals with Down syndrome. As scenes represented greater relative threat, the disparity between attentional brain activation in Down syndrome and control individuals increased. There was a reduction in the temporal autocorrelation of the dorsal attention network, consistent with a shortened attention span in Down syndrome. Individuals with Down syndrome exhibited significantly reduced activation in primary sensory cortices, and such perceptual impairments may constrain their ability to respond to more complex social cues such as violence.ConclusionsThese findings may indicate a relative deficit in emotive perception of violence in Down syndrome, possibly mediated by impaired sensory perception and hypoactivation of medial temporal structures in response to threats, with relative preservation of activity in pro-social brain regions. These findings indicate that specific genetic differences associated with Down syndrome can modulate the brain’s response to violence and other complex emotive ideas.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-015-9112-y) contains supplementary material, which is available to authorized users.

Technical note on hemispherotomy.

Complications both peri and postoperative and surgical difficulties during anatomical hemispherectomies motivated Rasmussen, in 1974, to describe a new technique, the Functional Hemispherectomy [1]. The main argument at that time was that by performing a complete disconnection with preservation of brain tissue in the affected hemisphere, it would generate the same long-term results as the old technique. After that brilliant proposal, several other techniques appeared in the literature [2] depicting refinements of the original technique converging finally to the description of the hemispherotomies. This one almost immediately had some technical variants concerning either a vertical [3] or lateral approach [4–7]. All these techniques have in common the opening of the lateral ventricle which is typically exposed in its totality, from the frontal to the temporal horn, crossing the atrium. Anatomical landmarks are key to this procedure irrespective of small variations in the technique depending on the experience and technical skill of the surgeon. In this context, I read with interest the paper Vertical Extraventricular Functional Hemispherotomy: a New Variant for Hemispheric Disconnection. Technical Notes and Results in Three Patients, by Giordano et al., and I have some comments on this technique. The authors claim that their technique reduces the probability of hydrocephalus because of the reduced amount of brain tissue resected and minimal opening of CSF spaces. Nevertheless, they applied the technique in only three patients and the traditional techniques, both the lateral [7] and the vertical approaches [3] with a much longer experience, have very low incidence of hydrocephalus and minimal resection of brain tissue [8]. Moreover, age at surgery (under 1 year of age) seems to be an important factor responsible for the occurrence of hydrocephalus in the postoperative period associated eventually with other factors as severity of the disease itself (as in hemimegalencephaly) [9]. One other point is that the technique described contrary to the traditional ones is very challenging because it does not rely on anatomical landmarks and corridors familiar to the neurosurgeons (peri-insular region, ventricles, medial temporal structures, fornices, etc.) but a very long route crossing the hemisphere through the white matter relying only in neuronavigation, which is sometimes very defiant due to known or unknown facts (brain shift, eventual malfunction, or error of the system). In conclusion, proposing a new surgical technique or a variant of a popular one requires convincing feasibility and/ or a clear reduction of morbidity/mortality and better results, which is not the case in my view.

1-A-D-9. Auditory evoked magnetic fields reflect pathological auditory processing caused by hippocampal sclerosis

Hippocampal sclerosis (HS) caused the amplitude reduction of a major peak evoked 100 ms (N100) after the onset of auditory stimulation. Task-unrelated auditory responses with peak latency at around 400 ms have been reported in normal hippocampus. In this study, we examined the effects of HS on M100 and M400 of auditory-evoked magnetic fields (AEFs) in mesial temporal lobe epilepsy (mTLE, n = 17) with unilateral HS and compared these data with those of healthy controls (HC, n = 17). Monaural tone-burst stimuli were presented for each side. Volumetric analysis was also performed, focusing on the hippocampus. Frequency of acceptable M100 dipoles was significantly decreased in the HS side. M100 amplitudes positively correlated with hippocampal volumes in HC, but not in mTLE. Interestingly, significantly enhanced M400 component was observed in mTLE, particularly in the HS side. Beam-forming-based source localization analysis suggested M400 was related to the medial temporal structure on the HS side. These results suggested that HS significantly influenced AEFs. Therefore, we concluded that the HS disturbs normal auditory processing and is involved with compensatory M400 generation.

Amnesia in an actor: Learning and re-learning of play passages despite severe autobiographical amnesia

We describe the case of an accomplished actor, whom we term AB, who suffered severe amnesia following a cardiac arrest and hypoxic brain damage, affecting medial temporal and thalamic structures. His performance on standard episodic memory tests, and on measures of retrograde amnesia, including autobiographical memory, was severely impaired. When presented with passages from plays he had not appeared in, AB showed a severe impairment at the first learning trial, but thereafter showed a ‘normal’ learning curve for this semantically and syntactically complex material. On being presented with passages from plays he had performed in the past, AB did not show any recognition of them whatsoever, as one might expect from his severe episodic memory impairment. However, AB showed a striking benefit (savings score) in relearning passages he had previously performed, compared with new passages, despite not having any autobiographical recall of having performed the relearned passages before. Moreover, although his initial recall performance in learning these passages was impaired compared with healthy control actors of similar age and experience, AB demonstrated the same incremental learning rate on subsequent learning trials of the passages as did the controls. We conclude that, although severely impaired at the first learning trial (on both ‘new’ and ‘old’ passages), AB was able to employ his long-established semantic and procedural skills to attempt the task, and that thereafter he showed a ‘normal’ rate of incremental learning from a lower baseline.

Verbal memory impairment in new onset bipolar disorder: Relationship with frontal and medial temporal morphology

Objectives. Verbal memory (VM) impairment is a trait feature of bipolar I disorder (BDI) that is present at illness onset and associated with functional outcome. However, little is known about the morphological abnormalities underlying this deficit early in the disease course. This study examined the neurobiological correlates of VM impairment in euthymic newly diagnosed patients, with attention to frontal and medial temporal (MT) structures known to contribute to VM. Methods. Euthymic patients with BDI recently recovered from their first episode of mania (n = 42) were compared with healthy subjects (n = 37) using measures of the California Verbal Learning Test (CVLT-II) associated with frontal and MT functioning. A subset of participants had 3T MRI scan (n = 31 patient group, n = 30 healthy subject group). Hippocampal and prefrontal volumes were analyzed using FreeSurfer 5.1 and correlated with their corresponding CVLT-II subscores. Results. Patients showed decreased performance in total learning as well as short and long delay verbal recall. Consistent with MT dysfunction, they also showed deficits in recognition discriminability and learning slope. In the patient group only, left hippocampal volumes were negatively correlated with these measures. Conclusions. These results suggest that anomalous MT functioning is involved with VM impairment early in the course of BDI.