Interlimb Transfer of Reach Adaptation Does Not Require an Intact Corpus Callosum: Evidence from Patients with Callosal Lesions and Agenesis.

Generalization of sensorimotor adaptation across limbs, known as interlimb transfer, is a well-demonstrated phenomenon in humans, yet the underlying neural mechanisms remain unclear. Theoretical models suggest that interlimb transfer is mediated by interhemispheric transfer of information via the corpus callosum. We thus hypothesized that lesions of the corpus callosum, especially to its midbody connecting motor, supplementary motor, and premotor areas of the two cerebral hemispheres, would impair interlimb transfer of sensorimotor adaptation. To test this hypothesis, we recruited three patients: two rare stroke patients with recent, extensive callosal lesions including the midbody and one patient with complete agenesis. A prismatic adaptation paradigm involving unconstrained arm reaching movements was designed to assess interlimb transfer from the prism-exposed dominant arm (DA) to the unexposed non-dominant arm (NDA) for each participant. Baseline results showed that spatial performance of each patient did not significantly differ from controls, for both limbs. Further, each patient adapted to the prismatic perturbation, with no significant difference in error reduction compared with controls. Crucially, interlimb transfer was found in each patient. The absolute magnitude of each patient's transfer did not significantly differ from controls. These findings show that sensorimotor adaptation can transfer across limbs despite extensive lesions or complete absence of the corpus callosum. Therefore, callosal pathways connecting homologous motor, premotor, and supplementary motor areas are not necessary for interlimb transfer of prismatic reach adaptation. Such interlimb transfer could be mediated by transcallosal splenium pathways (connecting parietal, temporal and visual areas), ipsilateral cortico-spinal pathways or subcortical structures such as the cerebellum.

Extremely long-term memory and familiarity after 12 years.

In 2006 Mitchell demonstrated that implicit memory was robust to decay. He showed that the ability to identify fragments of pictures seen 17 years before was significantly higher than for new stimuli. Is this true only for implicit memory? In this study, we tested whether explicit memory was still possible for drawings (n = 144) that had been presented once or three times, two seconds each time on average, approximately 12 years earlier. Surprisingly, our data reveal that our participants were able to recognize pictures above chance level. Preserved memory was mainly observed in the youngest subjects, for stimuli seen three times. Despite the fact that confidence judgments were low, reports suggest that recognition could be based on a strong sense of familiarity. These data extend Mitchell's findings and show that familiarity can also be robust to decay.

Alien Hand, Restless Brain: Salience Network and Interhemispheric Connectivity Disruption Parallel Emergence and Extinction of Diagonistic Dyspraxia.

Diagonistic dyspraxia (DD) is by far the most spectacular manifestation reported by sufferers of acute corpus callosum (CC) injury (so-called "split-brain"). In this form of alien hand syndrome, one hand acts at cross purposes with the other "against the patient's will". Although recent models view DD as a disorder of motor control, there is still little information regarding its neural underpinnings, due to widespread connectivity changes produced by CC insult, and the obstacle that non-volitional movements represent for task-based functional neuroimaging studies. Here, we studied patient AM, the first report of DD in patient with complete developmental CC agenesis. This unique case also offers the opportunity to study the resting-state connectomics of DD in the absence of diffuse changes subsequent to CC injury or surgery. AM developed DD following status epilepticus (SE) which resolved over a 2-year period. Whole brain functional connectivity (FC) was compared (Crawford-Howell [CH]) to 16 controls during the period of acute DD symptoms (Time 1) and after remission (Time 2). Whole brain graph theoretical models were also constructed and topological efficiency examined. At Time 1, disrupted FC was observed in inter-hemispheric and intra-hemispheric right edges, involving frontal superior and midline structures. Graph analysis indicated disruption of the efficiency of salience and right frontoparietal (FP) networks. At Time 2, after remission of diagnostic dyspraxia symptoms, FC and salience network changes had resolved. In sum, longitudinal analysis of connectivity in AM indicates that DD behaviors could result from disruption of systems that support the experience and control of volitional movements and the ability to generate appropriate behavioral responses to salient stimuli. This also raises the possibility that changes to large-scale functional architecture revealed by resting-state functional magnetic resonance imaging (fMRI) (rs-fMRI) may provide relevant information on the evolution of behavioral syndromes in addition to that provided by structural and task-based functional imaging.

Fast, but not slow, familiarity is preserved in patients with amnestic mild cognitive impairment.

Recognition memory--affected early in the course of Alzheimer Disease (AD)--is supposed to rely on two processes: recollection (i.e., retrieval of details from the encoding episode) and familiarity (i.e., acontextual sense of prior exposure). Recollection has repeatedly been shown to be impaired in patients with amnestic Mild Cognitive Impairment (aMCI)--known to be at high risk for AD. However, studies that evaluated familiarity in these patients have reported conflicting results. Here, we assessed familiarity in single-domain aMCI patients (n = 19) and healthy matched controls (n = 22). All participants underwent a classic yes/no recognition memory paradigm with confidence judgements, allowing an estimation of familiarity and recollection similar to the approach used in previous studies. In addition, they underwent a novel speeded recognition memory task, the Speed and Accuracy Boosting procedure, based on the idea that familiarity is fast and hence that fast answers rely on familiarity. On the classic yes/no task, aMCI patients were found to have impaired performance, reaction times, recollection and familiarity. However, performance and reaction times of aMCI patients did not differ from that of controls in the speeded task. This is noteworthy since this task was comparatively difficult for control subjects. This dissociation within familiarity suggests that a very basic component of declarative memory, probably at the interface between implicit and explicit memory, may be preserved, or possibly released, in patients with aMCI. It is suggested that early subprocesses (e.g., fluency based familiarity) could be preserved in aMCI patients, while delayed ones (e.g., conceptual fluency, post-retrieval monitoring, confidence assessment, or even access to awareness) may be impaired. These findings may provide support for recent suggestions that familiarity may result from the combination of a set of subprocesses, each with its specific temporal signature.

Clinical, neuropsychological, and metabolic characteristics of transient epileptic amnesia syndrome.

OBJECTIVE: Transient epileptic amnesia (TEA) is a recently individualized syndrome occurring in adult patients that includes epileptic seizures with amnestic features and interictal memory disturbances. METHODS: We investigated the clinical, neuropsychological, and 18F-FDG positron emission tomography (18F-FDG-PET) features of 30 consecutive cases of TEA in our center. RESULTS: The mean age of onset of amnestic seizures was 59 years. Pure acute amnesia was the only epileptic manifestation in 17% of cases. Interictal electroencephalography (EEG) abnormalities were present in 57% on awake recording and in most patients in whom sleep EEG was performed (96%). Nine of 30 patients showed anterograde memory deficit and six of 30 exhibited mild executive functioning impairment. On the autobiographical memory interview (AMI), patients showed a significant deficit for the recent period of the episodic subscale. Outcome under treatment was favorable in the majority of cases. A significant improvement was noted on recollection of autobiographical memory. 18F-FDG-PET (22 cases) showed positive correlations between left mesial temporal metabolism levels and anterograde and retrograde memory scores. SIGNIFICANCE: TEA is an emerging epileptic syndrome that likely remains misidentified and misdiagnosed. Neurometabolic data support a dysfunction of a hippocampal-neocortical network sustaining episodic memory.

Impaired visual recognition memory predicts Alzheimer's disease in amnestic mild cognitive impairment.

BACKGROUND: In the common form of Alzheimer's disease (AD), neurofibrillary tangles, which are associated with cognitive dysfunction, initially develop in the anterior subhippocampal (perirhinal/entorhinal) cortex before reaching the hippocampus. This area plays a key role in visual recognition memory (VRM). Impaired VRM could therefore be an early marker of AD. METHODS: An extensive neuropsychological assessment including VRM tasks was performed in 26 patients with single-domain amnestic mild cognitive impairment at baseline. We evaluated the diagnostic accuracy of neuropsychological tests using ROC curve analyses in a prospective longitudinal study until conversion to probable AD or with a follow-up of at least 6 years. RESULTS: VRM performance predicted conversion to AD with a sensitivity of 80% and a specificity of 90.9%. Combining the assessment of VRM with a verbal memory task increased diagnostic accuracy. CONCLUSIONS: Cognitive 'biomarkers' evaluating the function of brain areas that are the target of degenerative change should be considered for the early diagnosis of AD.

Alteration of autobiographical memory in amnestic mild cognitive impairment.

The concept of amnestic mild cognitive impairment (aMCI) concerns a population of older individuals at high risk of developing probable Alzheimer's disease. Although anterograde memory deficits have been largely documented in patients with aMCI, little is known about the integrity of their autobiographical memory (AuM). This study aimed at evaluating AuM in aMCI individuals and at investigating whether their ability to retrieve AuMs varied as a function of whether the tests used required recognition or effortful retrieval processes. Fourteen aMCI patients and 14 matched controls underwent a standard neuropsychological evaluation and an extensive autobiographical assessment. AuM was explored using verbal material, the Autobiographical Memory Interview, and a visual task of personal photographs. Together, these tests tapped the semantic and episodic components of AuM and different cognitive processes involved in retrieval (recall and recognition). Results indicate that AuM is altered in aMCI patients. This impairment affects both episodic and semantic components of AuM, and is characterized by a general difficulty in recollecting personal episodes covering the entire lifespan, along with a loss of recognition of recently experienced episodes. Furthermore, recollection of personal episodes was correlated with scores on tests requiring retrieval abilities, while recognition of familiar photographs was correlated with scores on tests assessing encoding/storage of new information. Results suggest that the AuM deficit in aMCI patients may result from the combination of two mechanisms, an anterograde memory impairment impeding the storage of newly experienced events, and a global alteration of recollection affecting the recall of AuM covering all periods of life. Alteration of these processes may possibly be related to the progression and distribution of the neuropathological lesions in medial temporal and frontal lobe structures found in Alzheimer's disease.

Which memory system is impaired first in Alzheimer's disease?

Diagnosis of Alzheimer's disease (AD) in its earliest stages becomes increasingly important as disease modifying agents are being developed. In this area of research, many clinical and neuroimaging studies focus on markers of hippocampal dysfunction. However, during the "transentorhinal stage" of AD, neurofibrillary tangles (NFT), related to tau protein pathology, develop in the anterior subhippocampal (perirhinal/entorhinal) cortex before the hippocampus. NFT are tightly correlated with clinical symptoms. Therefore, an accurate understanding of the behavioral correlate of transentorhinal dysfunction could critically contribute to the early diagnosis of the disease. Recent findings from studies in animals and human brain-damaged patients suggest that the anterior subhippocampal region, functionally integrated into an anterior mesiotemporal network, is involved in object based context-free memory. In this article, we evaluate the hypothesis according to which tau deposition in the anterior subhippocampal region during the earliest stages of the most common form of AD, with predominant MTL dysfunction, will lead to dysfunction of neural networks implicated in context-free memory. We challenge the view that impaired episodic memory is the hallmark of early AD. Instead, a model that integrates the localization and temporal sequence of NFT within the mesial temporal lobe (MTL) is proposed. Paralleling the development of NFT in anterior subhippocampal areas, impaired context-free, object-based, memory could be the first detectable sign in AD. In a subsequent, "hippocampal" stage, context-rich, episodic and spatial memory, becomes altered as well. The question as to the "episodic" nature of "episodic memory tasks" is also addressed.

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.

Hypo-retrieval and hyper-suppression mechanisms in functional amnesia.

Functional amnesia (FA) is characterized by an extensive retrograde memory loss in the absence of detectable structural brain damage. The two main hypotheses put forward to explain this disturbance involve a global retrieval deficit (affecting both pre- and post-onset memories) and a selective inability to explicitly retrieve pre-onset memories. Here, we extensively examined P.P., a patient with FA, with a view to obtaining additional insights into the cognitive and neural mechanisms underlying this disorder. In Experiments 1 and 2, post-onset memories were assessed using tasks focusing on the state of consciousness associated with their retrieval. Although subtle deficits in the ability to recollect post-onset personal events were detected, P.P.'s performances were normal when the encoding of the event was monitored in a laboratory setting. In Experiment 3, implicit recognition of pre-onset memories was tested using skin conductance responses. Results showed that P.P. responded implicitly to photographs of personal pre-onset events that were not explicitly recognized. In Experiment 4, designed to assess the patient's ability to suppress newly acquired information, P.P. suppressed more items than controls. Additionally, while no grey matter loss was evidenced with voxel-based morphometry, magnetic resonance spectroscopy and magnetization transfer imaging showed significant metabolic and structural changes within the white matter of the right prefrontal lobe. In conclusion, our results suggest that FA may result from a combination between two processes, a "hypo-retrieval" of pre-onset memories, tentatively due to white matter tract damage, and a "hyper-suppression" mechanism, concomitantly preventing the retrieval of pre-onset memories.

Persistent cognitive functioning deficits in operating rooms: two cases.

BACKGROUND: To date, chronic toxic encephalopathy (CTE) has never been described in operating room personnel. CASE REPORT: We report two cases of anaesthetists who developed this pathology. They have both used anaesthetic gases for many years in paediatric surgery. Air conditioning was deficient during three years in operating rooms and atmospheric anaesthetics concentration was high (N(2)O mean concentration: 311 ppm, peak levels 1,600 ppm; halogenated: 16 ppm, peak levels: 1,600 ppm). CLINICAL SYMPTOMS: Mood troubles and non-specific neuropsychic deficits gradually evolved until they had to stop working. Neuropsychological assessment showed important deficits in attention, executive functioning, short-term memory and visuo-spatial organization. Blood tests, VEPs, MRI, neuroSPECT and cardiovascular exams were normal. Troubles had slowly improved after cessation of exposure and sequels still remain. CONCLUSION: These CTE cases seem to be the consequence of a long-term exposure to important levels of anaesthetic gases, and particularly nitrous oxide. It points out the importance of preventive measures in operating rooms, where occupational hazards are varied.

Pure progressive amnesia: An atypical amnestic syndrome?

We report on M.S., an 83-year-old patient with isolated pure progressive amnesia. This rare, recently identified, form of amnesia has been described in elderly patients. Neuropathological studies suggest that this syndrome is an atypical clinical presentation of Alzheimer's disease. The aim of our study was to characterize the neuropsychological pattern of pure progressive amnesia in comparison with other amnestic syndromes and memory dissociations reported in the literature. Our results indicate that pure progressive amnesia is characterized by a highly unusual dissociation in the realm of memory, with severe deficits on tests based on recognition and recall of verbal and visual single items, contrasting with relatively preserved anterograde autobiographical and spatial memory and normal recall of complex material such as stories. These findings suggest that memory for single items could depend on an independent system. One hypothesis is that M.S.'s unusual memory profile results from relative dysfunction of the ventral medial temporal lobe pathway. An alternative explanation implicates cognitive reserve. Further studies are required in order to progress on this matter. In any case, pure progressive amnesia is a clinical syndrome that may provide further insight into the organization of declarative memory.