Silke Lux

Chronic Epilepsy and Cognition: A Longitudinal Study in Temporal Lobe Epilepsy

It remains unclear whether uncontrolled epilepsy causes mental decline. This longitudinal study contrasts change of memory and nonmemory functions in 147 surgically and 102 medically treated patients with temporal lobe epilepsy. All participants were evaluated at baseline (T1) and after 2 to 10 years (T3). Surgical patients underwent additional testing 1 year postoperatively (T2). Data were analyzed on an individual and group level. Sixty‐three percent of the surgical and 12% of the medically treated patients were seizure‐free at T3. Fifty percent of the medically treated and 60% of the surgical patients showed significant memory decline at T3 with little change in nonmemory functions (difference not significant). Surgery anticipated the decline seen in the medically treated group and exceeded it when surgery was performed on the left, or if seizures continued postoperatively. Seizure‐free surgical patients showed recovery of nonmemory functions at T2 (p < 0.001) and of memory functions at T3 (T3, p = 0.03). Multiple regression indicated retest interval, seizure control, and mental reserve capacity as predictors of performance changes. In addition, psychosocial outcome was better when seizures were controlled. In conclusion, chronic temporal lobe epilepsy is associated with progressive memory impairment. Surgery, particularly if unsuccessful, accelerates this decline. However, memory decline may be stopped and even reversed if seizures are fully controlled. Ann Neurol 2003;54:425–432

Depression in patients with temporal lobe epilepsy is related to mesial temporal sclerosis

Depression is a frequent psychiatric symptom in epilepsy and has been related to epilepsy of temporal origin, especially of left-sided foci. No study differentiated the precise localization of the epileptogenic lesion within the temporal lobe. Regarding this issue, we evaluated depression assessed by the Beck Depression Inventory in 60 patients with temporal lobe epilepsy, with particular consideration of morphological abnormalities within the temporal lobe (mesial temporal sclerosis (MTS) versus neocortical lesions) and lateralization of the lesion. Multivariate analyses indicated significant higher depression scores in MTS independent of the lateralization of the lesion. Depression was a good indicator for MTS but not vice versa. Hence, MTS can be discussed as a predisposing factor for the development of mood disorders in focal epilepsy.

Long-term seizure outcome and antiepileptic drug treatment in surgically treated temporal lobe epilepsy patients: a controlled study.

Summary:  Purpose: To evaluate the long‐term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE).

Specific role of medial prefrontal cortex in retrieving recent autobiographical memories: An fMRI study of young female subjects

Episodic-autobiographical memory (AM) is characterized by self-conscious reflection, emotional connotation and mental time travel. Semantic memory (SM) contains context and emotion free general knowledge. The present study specifically aimed at exploring the effect of time on the neural substrates of autobiographical and semantic memory retrieval by studying memories from different life periods in young female participants using functional brain imaging. Recent compared to early childhood events activated retrosplenial cortex. More importantly, medial prefrontal cortex (MPFC) was specifically engaged in the retrieval of recent AMs. The data show time-modulated neural substrates during recent and remote memories in women and suggest that a specific MPFC activation underlies the autonoetic, emotional and self-related character of recent AMs.

Altered neural network supporting declarative long-term memory in mild cognitive impairment

Autobiographical episodic memory represents a subsystem of declarative long-term memory and largely depends on combining information from multiple sources. The purpose of this study was to assess neural correlates of declarative long-term memory in patients with amnestic mild cognitive impairment (MCI) and controls using fMRI and a task requiring autobiographical and semantic memory retrieval. Comparison of the network supporting episodic autobiographical and semantic memory irrespective of remoteness (recent and remote) revealed significant activations in right parietal cortex and precuneus bilaterally in the patients. Autobiographical episodic versus semantic memory retrieval in the controls led to significant bilateral activations of the parietal-temporal junction, left temporal pole, anterior cingulate, retrosplenial cortex and cerebellum. In contrast, MCI patients activated left supplementary motor area, left premotor and superior temporal cortex. In MCI patients compared to controls a dysfunction of the retrosplenial cortex during memory retrieval was revealed by a lack of differential activation in relation to recency of memories and memory type. Our data suggest that MCI leads to a loss of specificity in the neural network supporting declarative long-term memory.

Differential processing of hierarchical visual stimuli in young and older healthy adults: Implications for pathology

Hierarchical figures in which large (global) forms are constructed from smaller (local) forms (Navon, 1977) have proved valuable in studies of perceptual organisation and hemispheric specialisation in both healthy volunteers and a wide range of neurological and psychiatric patients. In studies using Navon figures, normal young adults typically identify global forms faster than local forms. When the global and local forms are incongruent (e.g., a large E made of smaller Rs), global forms often interfere with local form identification more than vice versa. In two conditions on the same subjects, we contrasted the performance of young (mean age 22 years) and older (mean age 58 years) healthy volunteers on global and local processing. In the directed attention task, subjects were instructed to detect a target letter that occurred at the prespecified local or global level. The young subjects showed, as expected, faster reaction times (RTs) to detect global targets. In contrast, the older subjects showed significantly faster RTs to the local targets. Likewise, in a divided attention task, in which subjects were instructed to detect a target letter that could occur at either the local or the global level, the young adults were slightly quicker to detect the global targets and the older subjects were significantly quicker to detect the local targets. Error rates were generally low and there was no significant speed/accuracy trade-off in either condition. The observed local precedence effects in healthy older subjects were unexpected and are discussed in reference to previous work on differential hemispheric aging. That work has suggested that the left hemisphere is preferentially biased toward local processing and ages relatively slowly while the right hemisphere is biased toward global processing and ages relatively quickly. The implications of such putative differential aging for the interpretation of pathological local/global processing in neurological and psychiatric diseases are also emphasised.

Neural mechanisms associated with attention to temporal synchrony versus spatial orientation: an fMRI study.

Previous neuropsychological and functional imaging studies have suggested that the right hemisphere is crucially involved in spatial cognition. By contrast, much less is known about the putative left hemisphere specialization for aspects of temporal cognition. Accordingly, we studied with functional magnetic resonance imaging the neural mechanisms underlying attention to stimulus onset synchrony or orientational congruence with identical pairs of geometric figures. In each trial, two rhombuses were presented, each 4 degrees peripheral to a central fixation cross, in the left and right visual hemifields. In half of the trials, subjects were asked to judge and indicate via button presses whether the rhombuses appeared simultaneously. In the other half of the trials, subjects indicated whether the orientation of the rhombuses was the same (Factor 1, task, temporal synchrony, orientation). In half of the trials, subjects responded with their right hand and in the other half with their left hand (Factor 2, hand, right, left). Data were analyzed using SPM99 and a random-effects model. Attention to orientation differentially activated right temporo-occipital cortex. Attention to stimulus onset synchrony activated left anterior superior temporal gyrus, left inferior parietal cortex, left medial frontal gyrus, and right operculum. Activation of right temporo-occipital cortex for attention to stimulus orientation is in good agreement with previous functional neuroimaging studies of stimulus orientation. More importantly, activation of a predominantly left-hemispheric network with attention to stimulus onset synchrony extends the results of previous functional imaging, psychophysical, and neuropsychological studies of temporal processing.

Processing the spatial configuration of complex actions involves right posterior parietal cortex : An fMRI study with clinical implications

The left hemispheric dominance for complex motor behavior is undisputed. Clinical observations of complex motor deficits in patients with right hemispheric lesions, however, suggest an additional contribution of the right hemisphere to higher motor control. We assessed, using functional MRI (fMRI), which brain regions are implicated in processing the spatial aspects of complex, object‐related actions. Using a blocked, factorial design, 17 healthy volunteers were asked to detect either spatial or sequential errors (factor ERROR) in complex activities of daily living, presented as video sequences with the appropriate object(s) or as pantomimes (factor STIMULUS). Observing complex actions (irrespective of stimulus type) activated a bilateral frontoparietal network. Observing actions with objects (relative to pantomimes) differentially increased neural activity in the fusiform gyrus and inferior occipital cortex bilaterally. Observing pantomimes, i.e., the same actions but without any object, differentially activated right prefrontal cortex, anterior cingulate cortex, the precuneus, and left cerebellum. The left cingulate cortex was differentially activated when subjects assessed the sequencing of actions. By contrast, assessing the spatial configuration of complex actions differentially increased neural activity in right posterior parietal cortex. A significant interaction of ERROR and STIMULUS was revealed for the right inferior parietal cortex only. These findings suggest a specific role of the right hemisphere, especially of right posterior parietal cortex, in processing spatial aspects of complex actions and thus provide a physiological basis for the observed apraxic motor deficits in patients with right hemispheric damage. Hum Brain Mapp, 2006.

Gestalt perception and the decline of global precedence in older subjects.

Our visual world is hierarchically organized. Hierarchical processing is frequently investigated using Navon figures (large letters made up of smaller ones). In young adults, many studies reported faster reaction times (RT) to target letters presented at the global level [i.e., global precedence (GP)]. Furthermore, an age-related decline of this GP has been reported. We tested whether deficits in perceptual grouping via Gestalt laws (Gestalt principles of Proximity and Continuity) might contribute to this decline. In a directed attention task with valid and invalid cues, 20 young (mean age 22) and 20 older (mean age 57) male subjects had to indicate whether a target letter appeared at the global or local level of a Navon figure. The number of local letters forming the global figure was modulated in 5 steps. As expected, during valid trials, young adults showed a GP that linearly increased with increasing numbers of local letters (i.e., GP enhancement). This suggests that GP is related to perceptual grouping via Gestalt laws. By contrast, the group of older subjects demonstrated no precedence effect in RT and a non-significant trend toward GP in error rates (ER). No GP enhancement with an increasing number of local elements was observed. Exploratory analysis revealed that individual insensitivity to the modulation of matrix density, as revealed by a lack of global RT acceleration, was restricted to subjects that showed an overall local precedence (LP). Because older subjects tended to more frequently display an insensitivity to matrix modulation and an LP, we conclude that deficient Gestalt detection as indicated by non-enhanced global RT might contribute to the RT-related decline of GP with age.

Crossed cerebral lateralization for verbal and visuo-spatial function in a pair of handedness discordant monozygotic twins: MRI and fMRI brain imaging.

To examine the nature of hemispheric lateralization for neural processes underlying verbal fluency and visuo‐spatial attention, we investigated a single pair of handedness discordant monozygotic (MzHd) twins. Imaging of the brain was undertaken using magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) in combination with manual performance tasks. The twins were discordant for MRI anatomical asymmetries of the pars triangularis and planum temporale, whose asymmetry was consistent with verbal laterality on fMRI. Thus, the right‐handed twin had left lateralized verbal with right lateralized visuo‐spatial attention, while the left‐handed twin had right lateralized verbal with left lateralized visuo‐spatial activation; these data lend further support for to the conclusions of Sommer et al.