The recent ability to inactivate specific genes in mice has significantly accelerated our understanding of molecular, cellular, and even behavioral aspects of normal and disease processes. However, this ability has also demonstrated the extreme complexity of genetic determination in mammals, in particular, that genes in the same family or pathway can be functionally redundant and that a given gene often has multiple roles. Thus, inactivation of a gene often does not indicate its complete spectrum of functions. To circumvent this problem, (...) many new tools and novel applications of classic techniques have been developed to place spatial and temporal restrictions on the genomic alterations. These approaches include chimera and mosaic studies, organ transplantation, complementation assays, dominant negative mutants, conditional gene knockouts, and lineage-specific gene rescue. Not only has this opened up more sophisticated ways to make genomic alterations, but it has provided the opportunity to create animal models for sporadic human genetic diseases. BioEssays 20:200–208, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

In the verbal domain, there is only very weak evidence favoring the view that working memory is an active state of long-term memory. We strengthen existing evidence by reviewing two recent fMRI studies of verbal working memory, which clearly demonstrate activation in the superior temporal lobe, a region known to be involved in processing speech during comprehension tasks.

Purpose: Some enigmatic remarks and behaviors of Socrates have been a subject of debate among scholars. We investigated the possibility of underlying epilepsy in Socrates by analyzing pathographic evidence in ancient literature from the viewpoint of the current understanding of seizure semiology. Methods: We performed a case study from a literature survey. Results: In 399 BCE, Socrates was tried and executed in Athens on the charge of “impiety.” His charges included the “introduction of new deities” and “not believing in the (...) gods of the state,” because he publicly claimed that he was periodically and personally receiving a “divine sign,” or daimonion, that directed him in various actions. We found textual evidence that his daimonion was probably a simple partial seizure (SPS) of temporal lobe origin. It was a brief voice that usually prohibited Socrates from initiating certain actions. It started when he was a child, and it visited Socrates unpredictably. Moreover, we found at least two descriptions of Socrates’ unique behavior that are consistent with complex partial seizures (CPSs). The fact that Socrates had been experiencing both SPSs and CPSs periodically since childhood makes the diagnosis of temporal lobe epilepsy (TLE) likely. Conclusions: We hypothesize that Socrates had a mild case of TLE without secondary generalization. This is the first report in 2,400 years to present a pathographic diagnosis of TLE in Socrates based on specific diagnostic features in the ancient textual evidence. Our study demonstrates that the knowledge of modern epileptology could help understand certain behaviors of historic figures. (shrink)

Recent studies have revealed that the temporal lobe, a cortical region thought to be in charge of episodic and semantic memory, is involved in creative insight. This work examines the contributions of discrete temporal regions to insight. Activity in the medial temporal regions is indicative of novelty recognition and detection, which is necessary for the formation of novel associations and the “Aha!” experience. The fusiform gyrus mainly affects the formation of gestalt-like representation and perspective taking. The (...) anterior and posterior middle temporal gyri are individually associated with extensive semantic processing and inhibiting salient or routine word associations, which are necessary to form non-salient, novel and remote associations. The anterior and posterior superior temporal gyri are individually responsible for integrating/binding and accessing various types of available conceptual representations. Based on the current knowledge, an integrated model of the temporal lobe's role in insight and some future directions are proposed. (shrink)

Using fMRI, we investigated how right temporal lobe gliomas affecting the posterior superior temporal sulcus alter neural processing observed during speech perception and production tasks. Behavioural language testing showed that three pre-operative neurosurgical patients with grade 2, grade 3 or grade 4 tumours had the same pattern of mild language impairment in the domains of object naming and written word comprehension. When matching heard words for semantic relatedness (a speech perception task), these patients showed under-activation in the (...) tumour infiltrated right superior temporal lobe compared to 61 neurotypical participants and 16 patients with tumours that preserved the right postero-superior temporal lobe, with enhanced activation within the (tumour-free) contralateral left superior temporal lobe. In contrast, when correctly naming objects (a speech production task), the patients with right postero-superior temporal lobe tumours showed higher activation than both control groups in the same right postero-superior temporal lobe region that was under-activated during auditory semantic matching. The task dependent pattern of under-activation during the auditory speech task and over-activation during object naming was also observed in eight stroke patients with right hemisphere infarcts that affected the right postero-superior temporal lobe compared to eight stroke patients with right hemisphere infarcts that spared it. These task-specific and site-specific cross-pathology effects highlight the importance of the right temporal lobe for language processing and motivate further study of how right temporal lobe tumours affect language performance and neural reorganisation. These findings may have important implications for surgical management of these patients, as knowledge of the regions showing functional reorganisation may help to avoid their inadvertent damage during neurosurgery. (shrink)

Religiosity is a prominent feature of the Geschwind syndrome, a behavioural pattern found in some cases of temporal lobe epilepsy. Since the 1950s, when Wilder Penfield induced spiritual feelings by experimental manipulation of the temporal lobes, development of brain imaging technology has revealed neural correlates of intense emotional states, spurring the growth of neurotheology. In their secular empiricism, psychiatry, neurology and psychology are inclined to pathologise deviant religious expression, thereby reinforcing the dualism of objective and phenomenal worlds. (...) Considering theological perspectives and the idea of cosmic consciousness, the authors urge a holistic approach to the spiritual events of epileptic aura, potentially leading to a deeper understanding of the mind and its transcendent potential. (shrink)

In this systematic review, we aim to describe the association between temporal lobe epilepsy and sleep, with bidirectional links in mechanisms and therapeutic aspects. Sleep stages may variably impact seizure occurrence, secondary generalization and the development, frequency and distribution of interictal epileptiform discharges. Conversely, epilepsy affects sleep micro- and macroarchitecture. TLE, the most frequent form of drug resistant epilepsy, shares an enduring relationship with sleep, with some intriguing potential mechanisms specific to anatomic localization, linking the two. Sleep characteristics (...) of TLE may also inform localizing properties in persons with DRE, since seizures arising from the temporal lobe seem to be more common during wakefulness, compared to seizures of extratemporal origin. Polysomnographic studies indicate that persons with TLE may experience excessive daytime somnolence, disrupted sleep architecture, increased wake after sleep onset, frequent shifts in sleep stages, lower sleep efficiency, decreased rapid eye movement sleep, and possibly, increased incidence of sleep apnea. Limited literature suggests that effective epilepsy surgery may remedy many of these objective and subjective sleep-related concerns, via multipronged effects, apart from reduced seizure frequency. Additionally, sleep abnormalities also seem to influence memory, language and cognitive-executive function in both medically controlled and refractory TLE. Another aspect of the relationship pertains to anti-seizure medications, which may contribute significantly to sleep characteristics and abnormalities in persons with TLE. Literature focused on specific aspects of TLE and sleep is limited, and heterogeneous. Future investigations are essential to understand the pathogenetic mechanisms linking sleep abnormalities on epilepsy outcomes in the important sub-population of TLE. (shrink)

Episodic memories are shaped by the representational format of their contents. These formats are not only determined by medial temporal lobe areas, but essentially also by the neocortical regions which these areas control. The representational formats of medial temporal lobe and neocortex are sufficient to determine both, memory contents and subjective memory qualities, without the further need for an attribution system.

Research investigating the brain basis of language comprehension has associated the left anterior temporal lobe with sentence-level combinatorics. Using magnetoencephalography, we test the parsing strategy implemented in this brain region. The number of incremental parse steps from a predictive left-corner parsing strategy that is supported by psycholinguistic research is compared with those from a less-predictive strategy. We test for a correlation between parse steps and source-localized MEG activity recorded while participants read a story. Left-corner parse steps correlated with (...) activity in the left ATL around 350–500 ms after word onset. No other correlations specific to sentence comprehension were observed. These data indicate that the left ATL engages in combinatoric processing that is well characterized by a predictive left-corner parsing strategy. (shrink)

To define the determinants of impaired facial emotion recognition (FER) in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS), we examined 76 patients with unilateral MTLE-HS, 36 prior to antero-mesial temporal lobectomy (AMTL) and 40 after AMTL, and 28 healthy control subjects with a FER test consisting of 60 items (20 each for anger, fear, and happiness). Mean percentages of the accurate responses were calculated for different subgroups: right vs. left MTLE-HS, early (age at (...) onset <6 years) vs. late-onset, and before vs. after AMTL. After controlling for years of education, duration of epilepsy and number of antiepileptic drugs (AEDs) taken, on multivariate analysis, fear recognition was profoundly impaired in early-onset right MTLE-HS patients compared to other MTLE patients and control subjects. Happiness recognition was significantly better in post-AMTL MTLE-HS patients compared to pre-AMTL patients while anger and fear recognition did not differ. We conclude that patients with right MTLE-HS with age at seizure onset <6 years are maximally predisposed to impaired fear recognition. In them, right AMTL does not further worsen FER abilities. Longitudinal studies comparing FER in the same patients before and after AMTL will be required to refine and confirm our cross-sectional observations. (shrink)

Objective: The aim of the current study was to investigate the alterations in the neural networks of patients with temporal lobe epilepsy during working memory encoding.Methods: Patients with TLE and healthy volunteers completed a WM task, during which 34-channel electroencephalogram signals were recorded. The neural networks during WM encoding were calculated in TLE patients with and without WM deficits.Results: Functional connectivity strength decreased, and the theta network was altered in the TLE-WM group, although no significant differences in clinical (...) features were observed between the TLE-N and TLE-WM groups.Conclusions: Not all patients with TLE present with cognitive impairments and alterations in the theta network were identified in TLE patients with functional cognitive deficits.Significance: The theta network may represent a sensitive measure of cognitive impairment and could predict cognitive outcomes among patients with TLE. (shrink)

BackgroundTemporal lobe epilepsy is the most prevalent refractory focal epilepsy and is more likely accompanied by cognitive impairment. The fully understanding of the neuronal activity underlying TLE is of great significance.ObjectiveThis study aimed to comprehensively explore the potential brain activity abnormalities affected by TLE and detect whether the changes were associated with cognition.MethodsSix static intrinsic brain activity indicators [amplitude of low-frequency fluctuation, fractional ALFF, regional homogeneity, degree centrality, global signal correlation, and voxel-mirrored homotopic connectivity ] and their corresponding dynamic (...) indicators, such as dynamic ALFF, dynamic fALFF, dynamic ReHo, dynamic DC, dynamic VMHC, and dynamic GSCorr, in 57 patients with unilateral TLE and 42 healthy volunteers were compared. Correlation analyses were also performed between these indicators in areas displaying group differences and cognitive function, epilepsy duration, and severity.ResultsMarked overlap was present among the abnormal brain regions detected using various static and dynamic indicators, primarily including increased ALFF/dALFF/fALFF in the bilateral medial temporal lobe and thalamus, decreased ALFF/dALFF/fALFF in the frontal lobe contralateral to the epileptogenic side, decreased fALFF, ReHo, dReHo, DC, dDC, GSCorr, dGSCorr, and VMHC in the temporal neocortex ipsilateral to the epileptogenic foci, decreased dReHo, dDC, dGSCorr, and dVMHC in the occipital lobe, and increased ALFF, fALFF, dfALFF, ReHo, and DC in the supplementary motor area ipsilateral to the epileptogenic foci. Furthermore, most IBA indicators in the abnormal brain region significantly correlated with the duration of epilepsy and several cognitive scale scores.ConclusionThe combined application of static and dynamic IBA indicators could comprehensively reveal more real abnormal neuronal activity and the impairment and compensatory mechanisms of cognitive function in TLE. Moreover, it might help in the lateralization of epileptogenic foci and exploration of the transmission and inhibition pathways of epileptic activity. (shrink)

We highlight recent progress in neuroimaging and neuropsychological research on memory mechanisms in the medial temporal lobe that speaks to the involuntary nature of memory retrieval processes. We suggest that evidence form these studies supports Barzykowski and Moulin's proposal that memory signals involved in experiences of familiarity and déjà vu can be generated in the absence of retrieval intentionality.

Preoperative mapping of language and declarative memory functions in temporal lobe epilepsy patients is essential since they frequently encounter deterioration of these functions and show variable degrees of cerebral reorganization. Due to growing evidence on language and declarative memory interdependence at a neural and neuropsychological level, we propose the GE2REC protocol for interactive language-and-memory network mapping. GE2REC consists of three inter-related tasks, sentence generation with implicit encoding and two recollection memory tasks: recognition and recall. This protocol has previously (...) been validated in healthy participants, and in this study, we showed that it also maps the LMN in the left TLE. Compared to healthy controls, left TLE showed widespread inter- and intra-hemispheric reorganization of the LMN through reduced activity of regions engaged in the integration and the coordination of this meta-network. We also illustrated how this protocol could be implemented in clinical practice individually by presenting two case studies of LTLE patients who underwent efficient surgery and became seizure-free but showed different cognitive outcomes. This protocol can be advantageous for clinical practice because it is short and easy to perform; allows brain mapping of essential cognitive functions, even at an individual level; engages language-and-memory interaction allowing to evaluate the integrative processes within the LMN; provides a more comprehensive assessment by including both verbal and visual modalities, as well as various language and memory processes. Based on the available postsurgical data, we presented preliminary results obtained with this protocol in LTLE patients that could potentially inform the clinical practice. This implies the necessity to further validate the potential of GE2REC for neurosurgical planning, along with two directions, guiding resection and describing LMN neuroplasticity at an individual level. (shrink)

Aggleton & Brown predict that recognition and episodic recall depend on different brain systems and can thus be dissociated from one another. However, intact recall with impaired recognition has not yet been demonstrated if the same type of information is used in both tests. Current evidence suggests that processes underlying familiarity-based recognition are redundant with processes underlying episodic memory.