Material specific lateralization of medial temporal lobe function: An fMRI investigation

The theory of material specific lateralization of memory function posits that left and right MTL regions are asymmetrically involved in mnemonic processing of verbal and nonverbal material respectively. Lesion and functional imaging (fMRI) studies provide robust evidence for a left MTL asymmetry in the verbal memory domain. Evidence for a right MTL/nonverbal asymmetry is not as robust. A handful of fMRI studies have investigated this issue but have generally utilised nonverbal stimuli which are amenable to semantic elaboration. This fMRI study aimed to investigate the neural correlates of recognition memory processing in 20 healthy young adults (mean age = 26 years) for verbal stimuli and nonverbal stimuli that were specifically designed to minimize verbalisation. Analyses revealed that the neural correlates of recognition memory processing for verbal and nonverbal stimuli were differentiable and asymmetrically recruited the left and right MTL respectively. The right perirhinal cortex and hippocampus were preferentially involved in successful recognition memory of items devoid of semantic information. In contrast, the left anterior hippocampus was preferentially involved in successful recognition memory of stimuli which contained semantic meaning. These results suggest that the left MTL is preferentially involved in mnemonic processing of verbal/semantic information. In contrast, the right MTL is preferentially involved in visual/non‐semantic mnemonic processing. We propose that during development, the left MTL becomes specialised for verbal mnemonic processing due to its proximity with left lateralised cortical language processing areas while visual/non‐semantic mnemonic processing gets ‘crowded out’ to become predominantly, but not completely, the domain of the right MTL. Hum Brain Mapp 37:933–941, 2016. © 2015 Wiley Periodicals, Inc .     

Functional neuroimaging predicts individual memory outcome after amygdalohippocampectomy

We examined memory-related activity within to-be-resected medial temporal lobe (MTL) structures in 12 epilepsy patients with PET before amygdalohippocampectomy and studied the reallocation of memory functions to the contralateral MTL before and after surgery. Learning tasks were designed to activate predominantly the right or left MTL. Those patients who significantly activated to-be-resected ipsilateral MTL structures during the ipsilateral learning task (i.e. the left MTL during verbal learning or the right MTL during nonverbal learning) experienced a postoperative memory decline. Preoperative activation in the contralateral MTL during the ipsilateral learning task positively correlated with the postoperative outcome for ipsilateral memory. There was no significant postoperative reallocation of ipsilateral memory functions to the contralateral MTL.     

Material-specific lateralization of working memory in the medial temporal lobe

Mnemonic deficits in patients with medial temporal lobe (MTL) damage arising from temporal lobe epilepsy (TLE) are traditionally constrained to long-term episodic memory, sparing short-term and working memory (WM). This view of WM as being independent of MTL structures has recently been challenged by a small number of patient and neuroimaging studies, which have focused primarily on visual and visuospatial WM. In the present study we investigated material-specific lateralization of WM in 96 patients with unilateral damage to MTL stemming from TLE (56 left) and 30 control subjects using a pair of matched verbal and visuospatial supraspan tasks. Patients with unilateral TLE were impaired on both verbal and visuospatial WM tasks irrespective of the affected hemisphere. Patients with unilateral right TLE showed an additional deficit for visuospatial WM capacity when contrasted with patients with left TLE, whereas patients with unilateral left TLE showed increased intrusion errors on the verbal task when compared to patients with right TLE. These findings suggest a material-specific lateralization of WM in the MTL.     

Impairment of verbal recollection following ischemic damage to the right anterior hippocampus

Damage to the left medial temporal lobe (MTL) leads to an impairment of verbal recognition memory, affecting both the process of conscious recollection and familiarity-based recognition. Neuroimaging evidence, on the other hand, suggests a bilateral MTL contribution to verbal recollection. We investigated verbal recognition memory in three patients with focal ischemic lesions to the right MTL. The dual-process signal detection model and the process-dissociation procedure were applied to assess the contributions of recollection and familiarity to recognition memory. Compared to a group of 27 healthy age-matched controls, patients were impaired at recollection while familiarity was intact, and this effect was found for both estimation procedures. Detailed single-case analyses confirmed this pattern in two of the three right MTL patients. The findings suggest that, when task demands are high, as during recollective recognition, the right anterior hippocampus may also contribute to verbal recollection, thereby confirming neuroimaging evidence of a joint involvement of the left and the right MTL in verbal recollection.     

Reorganization of verbal and nonverbal memory in temporal lobe epilepsy due to unilateral hippocampal sclerosis

PURPOSE: Patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) often suffer from material-specific memory impairments. The purpose of this study was to use functional magnetic resonance imaging (fMRI) to study the organization of specific memory functions in these patients. METHODS: We report 14 patients with unilateral TLE and HS, and 10 controls, performing an fMRI memory paradigm of word, picture, and face encoding. RESULTS: Compared with controls, patients with left TLE demonstrated less left MTL and greater right MTL activation and patients with right TLE demonstrated less right MTL and greater left MTL activation. Correlations between fMRI activation and memory performance revealed greater activation in the damaged left hippocampus to be correlated with better verbal memory performance in left TLE patients and greater right hippocampal activation to be correlated with better nonverbal memory in right TLE patients. Conversely, greater fMRI activation in the contralateral hippocampus correlated with worse memory performance. CONCLUSIONS: Our findings suggest that memory function in unilateral TLE is better when it is sustained by activation within the damaged hippocampus and that reorganization to the undamaged MTL is an inefficient process, incapable of preserving memory function.     

Lateralization of hippocampal activation differs between left and right temporal lobe epilepsy patients and correlates with postsurgical verbal learning decrement

We addressed the question whether lateralization of memory-related medial temporal lobe (MTL) activity in medial temporal lobe epilepsy (MTLE) patients is determined by pathology or sex, differentiating between two MTL subregions implicated in visuospatial memory as regions-of-interest (ROI) - the hippocampus (Hc) and the parahippocampal place area (PPA). We further assessed the relation between lateralization of hippocampal activation and postsurgical memory decline regarding performance in standardized neuropsychological tests of verbal and visuospatial learning. Functional magnetic resonance imaging (fMRI) data were acquired from unilateral MTLE patients performing an object location memory task in a virtual environment. Individual lateralization indices (LI) based on memory-related brain activation patterns were calculated for each subject and ROI. Correlational analyses were computed between pre- to postsurgical changes in learning and asymmetry in hippocampal activation. Results revealed that lateralization of hippocampal, memory-related activity in patients with MTLE was determined by the side of seizure focus, not sex. Laterality of activation in the PPA was neither influenced by side of pathology nor sex. Lateralization of hippocampal activation was significantly correlated with decline in verbal learning after surgery. We were able to demonstrate that asymmetry of hippocampal fMRI-activation in unilateral MTLE patients is determined by the side of seizure focus, thus indicating the relative functional integrity of the hippocampi. This is corroborated by the finding that greater activation of the to-be-resected hippocampus leads to stronger verbal memory decline after surgery.     

Spontaneous ripples in the hippocampus correlate with epileptogenicity and not memory function in patients with refractory epilepsy

IntroductionHigh-frequency oscillations (HFOs, 80–500 Hz) are newly-described EEG markers of epileptogenicity. The proportion of physiological and pathological HFOs is unclear, as frequency analysis is insufficient for separating the two types of events. For instance, ripples (80–250 Hz) also occur physiologically during memory consolidation processes in medial temporal lobe structures. We investigated the correlation between HFO rates and memory performance.MethodsPatients investigated with bilateral medial temporal electrodes and an intellectual capacity allowing for memory testing were included. High-frequency oscillations were visually marked, and rates of HFOs were calculated for each channel during slow-wave sleep. Patients underwent three verbal and three nonverbal memory tests. They were grouped into severe impairment, some impairment, mostly intact, or intact for verbal and nonverbal memory. We calculated a Pearson correlation between HFO rates in the hippocampi and the memory category and compared HFO rates in each hippocampus with the corresponding (verbal — left, nonverbal — right) memory result using Wilcoxon rank-sum test.ResultsTwenty patients were included; ten had bilateral, five had unilateral, and five had no memory impairment. Unilateral memory impairment was verbal in one patient and nonverbal in four. There was no correlation between HFO rates and memory performance in seizure onset areas. There was, however, a significant negative correlation between the overall memory performance and ripple rates (r = − 0.50, p = 0.03) outside the seizure onset zone.ConclusionOur results suggest that the majority of spontaneous hippocampal ripples, as defined in the present study, may reflect pathological activity, taking into account the association with memory impairment. The absence of negative correlation between memory performance and HFO rates in seizure onset areas could be explained by HFO rates in the SOZ being generally so high that differences between areas with remaining and impaired memory function cannot be seen.     

Memory performance following unilateral electrical stimulation of the hippocampus in a child with right temporal lobe epilepsy

Verbal and visual memory performance was evaluated during unilateral stimulation of the hippocampus in an 11-year-old child with complex partial epilepsy associated with a right mesial temporal lobe focus. Memory was assessed during left and right hippocampal stimulation as well as preoperatively and 6-months postoperatively following anterior temporal lobe resection including removal of the anterior portion of the hippocampus. Stimulation of the left hippocampus resulted in a mild to moderate decrement in both verbal and visual memory performance as compared with a right hippocampal stimulation. In addition, stable or improved performance on memory assessment as well as general neuropsychological evaluation was noted 6 months postoperatively. Taken together, these data suggest that, in this child with early seizure onset (8 months of age), visual learning/memory functions shifted to the contralateral hippocampus and associated structures following damage to the right mesial temporal lobe structures. In addition, verbal learning/memory continues to be mediated by the left hippocampus, as expected. Thus, it appears that, as in the case of language lateralization, there may be a distinct subset of temporal lobe seizure patients (i.e., early seizure onset, high seizure frequency, chronic duration) in whom the brain has the capacity to shift material-specific memory functions to the contralateral mesial temporal lobe structures.     

Adaptive visual memory reorganization in right medial temporal lobe epilepsy

Purpose: We investigated functional reorganization mechanisms of the human medial temporal lobe (MTL) for episodic memory, in patients suffering from medial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS).
Methods: We used functional magnetic resonance imaging (fMRI) to measure brain activity changes during matched episodic encoding tasks of abstract words (Verbal) and line drawings (Visual), in patients with unilateral right MTLE undergoing presurgical evaluation and healthy controls.
Results: As expected, a significant interaction between material type and the side of MTL activity was present in the control group, with preferential involvement of the left hippocampus in verbal encoding and the right parahippocampal region in visual encoding. When compared with controls, right MTLE patients with intact performance activated a region in the left hippocampus more during visual encoding, which resulted in an interaction between group and hemisphere. Importantly, an effect of memory performance on visual encoding activity was observed in the patients, with greater engagement of the left MTL being associated with higher recognition scores. Interestingly, activity in the left MTL also depended on the epileptic seizure frequency, suggesting a role for this clinical parameter in the recruitment of contralateral regions.
Discussion: Taken together, these results indicate functional reorganization of the MTLs in right HS, through transfer of function from the right to the left hemisphere, and strongly suggest an adaptive role for such reorganization mechanism in supporting preserved visual memory.     

Electrical stimulation of the human hippocampus produces verbal intrusions during memory testing

Verbal memory testing was conducted during electrical stimulation of the human hippocampus in 12 epilepsy surgery candidates with unilateral temporal lobe seizure onset. Performance was assessed during baseline, left hippocampal stimulation and right hippocampal stimulation. Verbal intrusion errors were greater during electrical stimulation of the hippocampus contralateral to the seizure focus. These findings suggest that verbal intrusions are related to memory deficits, and that patients with cerebral disease who intrude words from an earlier portion of a learning test are likely to have bilateral cerebral dysfunction.     

Effect of age of onset of temporal lobe epilepsy on the severity and the nature of preoperative memory deficits

The nature and severity of pre-operative memory deficits observed in unilateral temporal lobe epilepsy depend upon a number of variables. Among these variables, age of seizure onset seems to be important. The age at which the lesion is sustained could modify the normal functional organization of the brain. Many studies have examined the effect of age of onset on the severity of memory deficits but have seldom focused on the nature of such deficits (verbal/nonverbal) as a function of epileptic focus laterality. This study investigates the effect of age of onset on the nature and severity of memory impairments. Fifty-six epileptics with unilateral temporal lobe epilepsy and 20 normal subjects were administered a neuropsychological evaluation. Four groups of patients were constituted: left or right temporal lobe epilepsy with early (0-5 years) or late (10 years and over) age of seizure onset. The early group showed major verbal and nonverbal memory deficits. The late group presented minor specific deficits: essentially verbal deficits with left temporal lobe seizures and nonverbal deficits with right temporal lobe seizures. These results may be interpreted in the framework of ontogenesis theories of hemispheric specialization.     

fMRI memory assessment in healthy subjects: a new approach to view lateralization data at an individual level

We present a comprehensive and clinically applicable fMRI test—including both a verbal and a visuospatial task—for assessment of hemispheric specific memory in the medial temporal lobe (MTL). fMRI data was collected from 15 healthy right-handed volunteers. Whole-brain activation was analyzed as well as activation in two regions of interest: the MTL and the anterior speech area. Laterality indices (LI) and LI-curves were calculated using the LI toolbox of Wilke and Lidzba, 2007. The fMRI paradigms successfully visualized memory-related activity in the MTL, the verbal memory measure also provided information of language lateralization. Eleven subjects showed left lateralized verbal encoding in the MTL, visuospatial memory activation was divided equally between left and right, and 14/15 subjects had left lateralized language. Lateralization data at the group level were consistent with previous studies, but a variety of activation effects were found at the individual level indicating differences in strategy during verbal and visuospatial processing. Further studies using the presented method are needed to determine its clinical usefulness.     

Dissociation of alpha and theta activity as a function of verbal and visuospatial tasks

EEG was recorded from P3 and P4 in 12 male subjects during a rest condition and while they performed a verbal and a visuospatial task. Power in the alpha and theta bands was derived from EEG epochs associated with task-related cognitive activity uncontaminated by response activity. Alpha power was significantly lower during performance on both tasks compared to the rest condition, but did not differ between tasks or hemispheres. Conversely, theta power was significantly higher during task performance, and, in the right hemisphere only, was higher in epochs recorded during the visuospatial as opposed to the verbal task. This difference between the tasks in right hemisphere theta correlated significantly with level of visuospatial performance as, to a lesser extent, did differences in left hemisphere theta. These results are discussed in terms of the sensitivity of different regions of the EEG spectrum to cognitive activity underlying performance on different types of task.     

Memory fMRI lateralizes temporal lobe epilepsy.

BACKGROUND: The assessment of mesial temporal lobe (MTL) function is important for the diagnosis and treatment of temporal lobe epilepsy (TLE) and other brain diseases. Declarative memory depends on the integrity of the MTL region. OBJECTIVE: To investigate hemispheric asymmetries of MTL activity in patients with symptomatic TLE. METHODS: With use of blood oxygenation level-dependent fMRI, hemispheric asymmetries in MTL activation of 30 individual patients with refractory symptomatic TLE and 17 healthy control subjects were studied. Activation was induced by a task employing mental navigation and recall of landmarks based on the retrieval of individually familiar visuospatial knowledge. RESULTS: The study demonstrated that the memory task used reliably activated MTL structures in individual control subjects and patients with refractory TLE including children, older subjects, and patients with low formal IQ. Interhemispheric differences in MTL activation lateralized the side of seizure onset in 90% of patients with symptomatic unilateral TLE. In contrast, healthy control subjects did not show a systematic asymmetry of MTL activation. Correlations between MTL activation and neuropsychological measures suggest that the fMRI-detectable MTL changes were specifically related to memory rather than to memory-independent visuospatial abilities. CONCLUSION: fMRI of memory-induced MTL activation lateralizes the side of seizure onset in patients with refractory symptomatic TLE and may provide complementary information for presurgical evaluation.     

Memory lateralization in medial temporal lobe epilepsy assessed by functional MRI

PURPOSE: To determine the utility of functional magnetic resonance imaging (fMRI) in preoperative lateralization of memory function in patients with medial temporal lobe epilepsy (MTLE). METHODS: Nine patients with MTLE underwent standard preoperative assessment including video-EEG and intracarotid amytal testing (IAT). fMRI was performed while subjects encoded four types of stimuli (patterns, faces, scenes, and words). Activation maps were created for each subject representing areas more active for novel than for repeated stimuli. Regions of interest were drawn around the MTL in individual subjects, suprathreshold voxels were counted, and an asymmetry index was calculated. RESULTS: In eight of nine subjects, lateralization of memory encoding by fMRI was concordant with that obtained from the IAT. Group-level analysis demonstrated greater activation in the MTL contralateral to the seizure focus such that in the left MTLE group, verbal encoding engaged the right MTL, whereas in the right MTLE group, nonverbal encoding engaged the left MTL. CONCLUSIONS: fMRI is a valid tool for assessing of memory lateralization in patients with MTLE and may therefore allow noninvasive preoperative evaluation of memory lateralization. FMRI revealed that memory encoding may be reorganized to the contralateral MTL in patients with MTLE.     

Material-specific memory changes after anterior temporal lobectomy as predicted by the intracarotid amobarbital test

Summary: Purpose: The intracarotid amobarbital test (IAT) has been shown to predict verbal memory changes after anterior temporal lobectomy (ATL). Seeking to extend these findings, we examined two questions: (a) What is the relationship between material‐specific aspects of IAT memory and material‐specific memory changes after ATL? and (b) Which IAT memory score(s) optimally predict memory changes after surgery, the memory score after injection ipsilateral to the seizure focus, the memory score after injection contralateral to the seizure focus, or the IAT asymmetry score, comprising the ipsilateral minus contralateral injection scores? Methods: Seventy left hemisphere language‐dominant patients undergoing ATL for treatment of medically refractory seizures were administered a verbal and visuospatial recognition memory test before surgery and 3 weeks after surgery. IAT memory recognition scores for words and designs were used to predict verbal and visuospatial memory changes after surgery. Results: After surgery, left ATL patients declined in verbal memory, whereas right ATL patients declined in visuospatial memory. IAT total recognition memory scores (collapsed across all types of materials) and IAT word memory scores were associated with postoperative verbal memory decline. This relationship was significant for the IAT ipsilateral injection memory scores and the IAT hemispheric asymmetry scores. IAT memory performances were not related to visuospatial memory changes. Conclusions: Results indicate IAT memory measures to be related to postoperative verbal, but not visuospatial, memory change. A specific relationship was found between postoperative verbal memory change and IAT verbal memory after injection ipsilateral to the seizure focus, when relying primarily on the contralateral hemisphere. This finding is consistent with the functional reserve model of memory change in ATL.     

Material specific learning during electrical stimulation of the human hippocampus

Material specific learning was assessed during unilateral electrical stimulation of the hippocampus through intracerebrally implanted electrodes in 30 patients with unilateral temporal lobe epilepsy (TLE). Verbal learning significantly decreased in patients with right TLE after stimulation of the left, but not the right, hippocampus. No verbal learning impairment was observed in left TLE patients following stimulation of either hippocampus. Visuospatial memory performance significantly decreased following stimulation of the right hippocampus regardless of the side of seizure onset. Results suggest that the contralateral "nonepileptic" hippocampus does not assume the material specific mnestic functions of the dysfunctional hippocampus associated with longstanding epilepsy.     

Seizures During Cognitive Testing in Patients with Temporal Lobe Epilepsy: Possibility of Seizure Induction by Cognitive Activation

In 18 of 185 patients under consideration for epilepsy surgery, 20 seizures were observed during neuropsychological evaluation. We wished to determine whether the task at seizure onset corresponded neuropsychologically to lateralization of the epileptic focus. The patients' characteristics and the circumstances of the seizures were as follows: Fourteen patients had right temporal lobe epilepsy (RTE) and four had left temporal lobe epilepsy (LTE). Although a wide range of cognitive functions had been tested, all but one seizure occurred during assessment of memory performance. In the RTE patients, 12 of 16 seizures occurred during visual memory testing. Two seizures were observed during a verbal memory task, and one seizure was observed during mental rotation. In two LTE patients, seizures were elicited during verbal memory testing. Two LTE patients with seizures during visual memory testing had speech dominance of the right hemisphere. This high correspondence between the eliciting performance and the focus localization suggests that cognitive performances ipsilateral to the epileptic focus may affect seizure threshold in focal epilepsies.     

Memory deficits after resection from left or right anterior temporal lobe in humans: a meta-analytic review

PURPOSE: Memory deficits in epileptic patients have been found in some, but not all studies assessing the effects of side of seizures and resection from a temporal lobe on cognitive performance. The purpose of this study was to provide a quantitative review of previous studies on this issue. METHODS: Based on conventional meta-analytic procedures, we identified 33 studies that assessed verbal and nonverbal memory performance before and after anterior temporal lobectomy. The Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale were used. These studies were then subjected to two levels of analyses: (a) vote-counting procedure, and (b) effect-size calculations and comparisons. RESULTS: Overall, the data confirmed previous findings that verbal memory tasks are sensitive to left hemisphere dysfunction. The efficacy of a "nonverbal" task for tapping function in the nondominant (right) hemisphere was not confirmed, although a trend supporting this speculation was observed. With regard to the comparison of changes in verbal and nonverbal memory before and after resection from a temporal lobe, a clear trend was observed for decline in verbal memory function after resection from the left, especially significant for immediate verbal recall. A trend for contralateral improvement on nonverbal memory also was observed. The pattern of memory change after resection from the right temporal lobe was less clear. CONCLUSIONS: The findings of this study suggest that side of epileptic seizure and surgical resection from a temporal lobe affect verbal memory functions. The relations between the laterality of epileptic seizure, surgical resection from the temporal lobe, and nonverbal memory are to be verified by further research.     

The effects of duration of intractable epilepsy on memory function

We assessed whether duration (time since diagnosis) of intractable epilepsy is associated with progressive memory loss in 250 individuals with left or right temporal lobe epilepsy and those diagnosed with psychogenic nonepileptic seizures. Verbal and nonverbal memory function was assessed using several memory assessment measures administered to all individuals as part of a larger neuropsychological assessment. Multivariate multiple regression analyses demonstrated that duration of temporal lobe epilepsy and age of seizure onset are significantly related to verbal memory deficits in patients with epilepsy. The interaction between duration of epilepsy and diagnostic group was nonsignificant, as was the interaction between age at spell onset and diagnostic group. As measured by several neuropsychological memory tests, duration of disease adversely affects verbal memory performance in patients diagnosed with temporal lobe epilepsy. Our study also supports the notion that age at seizure onset significantly affects verbal memory performance in this population. These results have implications for the strategy of treatment and counseling of patients with intractable temporal lobe epilepsy.