Severe amnesia: an usual late complication after temporal lobectomy

A patient developed the severe amnesic syndrome 8 years after temporal lobe surgery for epilepsy. He underwent left temporal lobectomy (6 cm, 43.5 g; hippocampal sclerosis) aged 19, and remained seizure free for 8 years until a convulsion followed a head injury. He became severely amnesic after a fourth convulsion 16 months later. He was right-handed, pre-operative IQ was average, verbal memory poor and non-verbal memory normal. Post-operatively, these were unchanged. After the first post-operative seizure he began professional training. After onset of amnesia IQ was unchanged, anterograde memory severely impaired and retrograde amnesia dense for at least 16 months. He died 2 years later. Magnetic resonance imaging before amnesia showed absence of anterior left temporal lobe, atrophy of left fornix and mamillary body, and normal right temporal lobe. Four months after onset of amnesia, right hippocampal volume had reduced by 36%. Autopsy showed: previous left temporal lobectomy with absence of left amygdala and hippocampus, atrophy of fornix and mamillary body; neuronal loss in the right hippocampus, severe in CA1 and CA4; intact right amygdala and parahippocampal gyrus; recent diffuse damage associated with cause of death. A convulsion can cause severe hippocampal damage in adult life. Hippocampal zones CA1 and/or CA4 are critical for maintaining memory and the amygdala and parahippocampal gyrus cortex alone cannot support acquisition of new memories.     

Declarative memory following anterior temporal lobectomy in humans.

Hypothesized that verbal memory decline following anterior temporal lobectomy (ATL) is associated with a lack of significant neuropathology in resected left, but not right, hippocampus and is limited to measures of episodic memory only. Tests of immediate (digit span), semantic (visual naming), and episodic memory as measured by the California Verbal Learning Test (CVLT) were administered before and 6 mo after resection of the anterior left (n?=?36) or right (n?=?26) temporal lobe. There were no effects of hippocampal pathology on measures of immediate or semantic memory for either ATL group or for episodic memory for the right ATL group. Left ATL patients who demonstrated no/mild hippocampal sclerosis exhibited significantly greater postoperative decline in episodic memory compared with those with moderate/marked hippocampal sclerosis on multiple CVLT indices (recall measures, learning characteristics, and contrast measures). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Monkeys with rhinal cortex damage or neurotoxic hippocampal lesions are impaired on spatial scene learning and object reversals

Rhesus monkeys (Macaca mulatta) with lesions of the rhinal cortex or parahippocampal gyrus (made by aspiration) or hippocampus (made with ibotenic acid) and unoperated controls were tested on object discrimination and reversal, place discrimination and reversal, and spatial scene learning to determine the contribution of these temporal lobe structures to these forms of learning and memory. Rhinal cortex lesions produced a severe deficit in object reversal learning; hippocampal lesions produced a milder deficit. Monkeys with rhinal cortex removals and those with hippocampal lesions were equally impaired on spatial scene learning. None of the lesions impaired place discrimination or reversal. These results argue against the idea that the mnemonic contributions of the rhinal cortex and hippocampus are limited to object and spatial domains, respectively.     

Observations on the relationship between verbal explicit and implicit memory and density of neurons in the hippocampus

The relationship between neuronal density and verbal memory in left and right hippocampal subfields was investigated in patients who underwent surgery for alleviation of temporal lobe epilepsy. The surgery consisted of unilateral partial removal of the hippocampus along with the anterior temporal lobe and amygdala. Study 1 looked at post-surgical explicit vs implicit verbal memory for lists of words while Study 2 looked at pre- and post-surgical explicit memory for word pairs. Left subfield CA1 appeared to be the most consistently involved in explicit and implicit memory. The results of the two studies confirm presence of hemispheric asymmetry in verbal memory. The notion that hippocampal control of memory is most apparent in post-surgical performance is discussed.     

Hippocampal, but not amygdala, activity at encoding correlates with long-term, free recall of nonemotional information

Participation of two medial temporal lobe structures, the hippocampal region and the amygdala, in long-term declarative memory encoding was examined by using positron emission tomography of regional cerebral glucose. Positron emission tomography scanning was performed in eight healthy subjects listening passively to a repeated sequence of unrelated words. Memory for the words was assessed 24 hr later with an incidental free recall test. The percentage of words freely recalled then was correlated with glucose activity during encoding. The results revealed a striking correlation (r = 0.91, P < 0.001) between activity of the left hippocampal region (centered on the dorsal parahippocampal gyrus) and word recall. No correlation was found between activity of either the left or right amygdala and recall. The findings provide evidence for hippocampal involvement in long-term declarative memory encoding and for the view that the amygdala is not involved with declarative memory formation for nonemotional material.     

Selective spatial memory impairment after right unilateral temporal lobectomy

Deficits in performance of both spatial and visual tasks are common following tissue loss in the right temporal lobe. Since spatial and visual attributes are frequently confounded in experimental tasks, we have studied patients following unilateral temporal lobectomy, in an attempt to determine which aspect mediates the observed deficits. Spatial and visual memory performance was compared in normal controls (n = 16), left temporal (LTL; n = 19) and right temporal (RTL; n = 19) lobectomy patients, by presentation of eight abstract designs in a spatial array for subsequent recall and recognition of the designs (visual memory) and recall of their spatial position (spatial memory). By varying the retention intervals for each group, all three groups were matched on both recall and recognition of the designs at sub-ceiling levels. In contrast, recall of the position of the designs (spatial memory), tested at equivalent delays to those of the visual memory tests, revealed a deficit in the RTL patients compared to both controls and LTL patients (p < 0.05). Magnetic resonance imaging (MRI) was used to quantify the extent of resection of the hippocampus and parahippocampal regions in the two patient groups and showed a significant correlation between hippocampal and parahippocampal removal and spatial memory in the RTL group only. These data support the notion of a disproportionately large involvement of the right hippocampus and adjacent regions in spatial memory.     

Dissociations in Hippocampal and Frontal Contributions to Episodic Memory Performance.

The hippocampus and frontal lobes both contribute to episodic memory performance. In the present study, the authors evaluated the relative contributions of hippocampus, frontal lobes, anterior temporal cortex, and posterior cortex to memory performance in neurodegenerative patients and normal older controls. Subjects (n = 42) were studied with structural MRI and a memory paradigm that measured delayed recall, semantic clustering during recall, recognition discriminability, and recognition response bias. Data were analyzed with multiple regression. Consistent with the authors' hypotheses, hippocampal volumes were the best predictor of delayed recall and recognition discriminability, whereas frontal volumes were the best predictor of semantic clustering and response bias. Smaller frontal volumes were associated with less semantic clustering during recall and a more liberal response bias. Results indicate that hippocampal and frontal contributions to episodic memory can be dissociated, with the hippocampus more important for memory accuracy, and frontal structures more important for strategic processing and decision making. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cloning and expression of a novel juvenile hormone-metabolizing epoxide hydrolase during larval-pupal metamorphosis of the cabbage looper, Trichoplusia ni

This study explored the pattern of memory functioning in 58 patients with chronic schizophrenia and compared their performance with 53 normal controls. Multiple domains of memory were assessed, including verbal and non-verbal memory span, verbal and non-verbal paired associate learning, verbal and visual long-term memory, spatial and non-spatial conditional associative learning, recognition memory and memory for temporal order. Consistent with previous studies, substantial deficits in long-term memory were observed, with relative preservation of memory span. Memory for temporal order and recognition memory was intact, although significant deficits were observed on the conditional associative learning tasks. There was no evidence of lateralized memory impairment. In these respects, the pattern of memory impairment in schizophrenia is more similar in nature to that found in patients with memory dysfunction following mesiotemporal lobe lesions, rather than that associated with focal frontal lobe damage.     

Spatial memory deficits in patients with lesions to the right hippocampus and to the right parahippocampal cortex

Spatial memory tasks, performance of which is known to be sensitive to hippocampal lesions in the rat, or to medial temporal lesions in the human, were administered in order to investigate the effects of selective damage to medial temporal lobe structures of the human brain. The patients had undergone thermo-coagulation with a single electrode along the amygdalo-hippocampal axis in an attempt to alleviate their epilepsy. With this surgical technique, lesions to single medial temporal lobe structures can be carried out. The locations of the lesions were assessed by means of digital high-resolution magnetic resonance imaging and software allowing a 3-D reconstruction of the brain. A break in the collateral sulcus, dividing it into the anterior collateral sulcus and the posterior collateral sulcus is reported. This division may correspond to the end of the entorhinal/perirhinal cortex and the start of the parahippocampal cortex. The results confirmed the role of the right hippocampus in visuo-spatial memory tasks (object location, Rey-Osterrieth Figure with and without delay) and the left for verbal memory tasks (Rey Auditory Verbal Learning Task with delay). However, patients with lesions either to the right or to the left hippocampus were unimpaired on several memory tasks, including a spatial one, with a 30 min delay, designed to be analogous to the Morris water maze. Patients with lesions to the right parahippocampal cortex were impaired on this task with a 30 min delay, suggesting that the parahippocampal cortex itself may play an important role in spatial memory.     

Traumatic brain injury and memory: The role of hippocampal atrophy.

In traumatically brain-injured (TBI) patients (n?=?83), memory performance was examined on the Warrington Recognition Memory Test, Rey-Osterrieth Complex Figure, and the Logical Memory and Visual Reproduction subtests of the Wechsler Memory Scale-Revised in relationship to time postinjury and structural changes based on MRI volumetry, including hippocampus volume. Significant trauma-induced changes were observed, including hippocampal atrophy. Structure-function relationships generally became significant only after 90 days postinjury. Memory tended to relate more to the degree of hippocampal atrophy, particularly left hippocampus, than to nonspecific indicators such as the temporal horns or the ventricle-to-brain ratio. A stronger relationship with left versus right hippocampus was evident for measures of verbal and supposedly nonverbal memory. These results are discussed with regard to the role the hippocampus may play in a neural system of memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Memory encoding and retrieval in frontotemporal dementia and Alzheimer's disease.

Memory encoding and retrieval strategies were assessed in patients with behavior-executive variant frontotemporal dementia (FTD), language variant FTD, and Alzheimer's disease (AD) using verbal and visuospatial supraspan learning tests. FTD patients obtained higher free recall, cued recall, and recognition scores than AD patients. Comparison of free recall scores with cued recall and recognition scores was similar in the 3 dementia groups. Groups did not differ in semantic clustering strategies during learning, but serial-order recall was more common in FTD patients. These data do not support the idea that FTD patients' poor memory is due to a selective retrieval disorder, though FTD patients may fail to implement sophisticated organizational strategies during learning. FTD patients' retained capacity for encoding new information into long-term declarative memory is likely due to relatively spared medial temporal lobe involvement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rhinal cortex lesions and object recognition in rats.

Tested 11 male rats with bilateral lesions of lateral entorhinal cortex and perirhinal cortex on a nonrecurring-items delayed nonmatching-to-sample (DNMS) task resembling the one that is commonly used to study object recognition (OR) in monkeys. The rats were tested at retention delays of 4, 15, 60, 120, and 600 sec before and after surgery. After surgery, they displayed a delay-dependent deficit: They performed normally at the 4-sec delay but were impaired at delays of 15 sec or longer. The addition of bilateral amygdala lesions did not increase their DNMS deficits. The present finding of a severe DNMS deficit following rhinal cortex damage is consistent with the authors' previous finding that bilateral lesions of the hippocampus cause only mild DNMS deficits in rats unless there is also damage to rhinal cortex (D. G. Mumby et al, 1992). These findings add to accumulating evidence that the rhinal cortex, but not the amygdala, plays a critical role in OR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Strategic processing and memory for temporal order in patients with frontal lobe lesions.

This study evaluated whether deficits in memory for temporal order in patients with frontal lobe lesions result from impaired automatic encoding of temporal information or are secondary to deficits in effortful processes, such as the use of organizational strategies and control of interference. Patients with lesions in the dorsolateral prefrontal cortex and control participants were tested on temporal order reconstruction of semantically related and unrelated word lists learned under intentional or incidental conditions. Memory for temporal order in patients with frontal lobe lesions was sensitive to semantic relatedness but not to intention to learn. Tests of item free recall and recognition using similar encoding manipulations indicated that order performance in these patients was dissociable from item memory. Results indicate that automatic processing of temporal information is intact in patients with frontal lobe lesions but that strategic processing of this information is impaired. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intact perceptual and conceptual priming in temporal lobe epilepsy: Neuroanatomical and methodological implications.

Explicit memory appears to be supported by medical temporal lobe structures, whereas separate neocortical regions may mediate perceptual and conceptual implicit memory. Children and adults with temporal lobe epilepsy (TLE) and matched controls were administered experimental verbal memory tests. Performance on implicit tests--word identification and word generation--was contrasted with explicit recognition and recall. Encoding conditions emphasized either conceptual or perceptual aspects of study words and were crossed with presentation modality. The priming performance of participants with TLE did not differ from controls, but participants with TLE did show deficits on recognition and recall measures. Thus, intact left temporal cortex does not appear to be necessary for normal implicit memory performance, even when conceptual processing is emphasized at study or test. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling hippocampal and neocortical contributions to recognition memory: A complementary-learning-systems approach.

The authors present a computational neural-network model of how the hippocampus and medial temporal lobe cortex (MTLC) contribute to recognition memory. The hippocampal component contributes by recalling studied details. The MTLC component cannot support recall, but one can extract a scalar familiarity signal from MTLC that tracks how well a test item matches studied items. The authors present simulations that establish key differences in the operating characteristics of the hippocampal-recall and MTLC-familiarity signals and identify several manipulations (e.g., target-lure similarity, interference) that differentially affect the 2 signals. They also use the model to address the stochastic relationship between recall and familiarity and the effects of partial versus complete hippocampal lesions on recognition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cloning and expression of a novel murine semaphorin with structural similarity to insect semaphorin I

Tests of facial recognition and spatial learning were administered to presurgical patients with unilateral temporal lobe EEG foci. Right temporal lobe patients obtained lower facial recognition scores than left temporal lobe patients. The groups performed equally on the spatial learning test. A factor analysis revealed two independent factors: a general visuospatial factor and a more specific facial identification factor. The findings provide support for the existence of two dissociable visual processing systems. Memory impairments associated with right temporal lobe dysfunction may be characterized as an impairment in a ventral visual processing system responsible for facial memory and pattern recognition.     

Interaction of frontal and perirhinal cortices in visual object recognition memory in monkeys

Monkeys were trained preoperatively in visual object recognition memory. The task was delayed matching-to-sample with lists of trial-unique randomly generated visual stimuli in an automated apparatus, and the stimuli were 2D visual objects made from randomly generated coloured shapes. We then examined the effect of either: (i) disconnecting the frontal cortex in one hemisphere from the perirhinal cortex in the contralateral hemisphere by crossed unilateral ablations; (ii) disconnecting the magnocellular portion of the mediodorsal (MDmc) thalamic nucleus in one hemisphere from the perirhinal cortex in the contralateral hemisphere; or (iii) bilaterally ablating first the amygdala, then adding fornix transection, then finally perirhinal cortex ablation. We found that both frontal/perirhinal and MDmc/perirhinal disconnection had a large effect on visual object recognition memory, whereas both amygdalectomy and the addition of fornix transection had only a mild effect. We conclude that the frontal lobe needs to interact with the perirhinal cortex within the same hemisphere for visual object recognition memory, but that routes through the amygdala and hippocampus are not of primary importance.     

Alumina gel injections into the temporal lobe of rhesus monkeys cause complex partial seizures and morphological changes found in human temporal lobe epilepsy

The goal of the present study was to determine whether alumina gel injections into temporal lobe structures cause complex partial seizures (CPS) and pathological changes observed in human temporal lobe epilepsy. Rhesus monkeys with alumina gel injections in the amygdala, perirhinal and entorhinal cortices, or Ammon's horn and dentate gyrus all initially displayed focal pathological electroencephalographic (EEG) slowing limited to the site of injection. After clinical seizures developed, they also displayed widespread pathological EEG slowing over both hemispheres, interictal and ictal epileptiform EEG abnormalities limited to the mesial-inferior temporal lobe on the side of injection, and different degrees of spread to other ipsilateral and contralateral structures. Noninjected control and nonepileptic monkeys with injections into the middle and inferior temporal gyri displayed no hippocampal neuronal loss or mossy fiber sprouting. When alumina gel was injected into the amygdala, CPS began within 3-6 weeks and degeneration of neurons and gliosis occurred in the perirhinal cortex or the hippocampus, with consequent sprouting of mossy fibers in the dentate gyrus. Dispersion of the granule cell layer was also observed. Other monkeys with alumina gel in the perirhinal and entorhinal cortices developed CPS within 2-3 weeks after the injections and displayed mossy fiber sprouting only after 4 weeks after the injections. Alumina gel in Ammon's horn and the dentate gyrus also induced CPS, but mossy fiber sprouting was limited to sites immediately adjacent to the injection, probably because none survived more than 4 weeks after the injections. This nonhuman primate model of CPS displayed similar anatomical, behavioral, and EEG features as observed in human temporal lobe epilepsy and provides opportunities to analyze the chronological sequence of epileptogenesis and to test potential therapies.     

Semantic knowledge and episodic memory for faces in semantic dementia.

Previous studies have documented poor recognition memory for faces in patients with semantic dementia. Preserved face recognition memory was found in this study, however, so long as atrophy was confined predominantly to the left temporal lobe. Patients with structural damage to the right temporal lobe were typically impaired, with the status of the hippocampus and parahippocampal gyrus (including the perirhinal cortex) on the right being critical. Two single-case studies of patients with predominantly left temporal lobe pathology confirmed good recognition memory for famous faces, even if semantic knowledge about the celebrities depicted was severely degraded. An effect of semantic knowledge on recognition memory became apparent only when perceptually different photographs of the famous people were used at study and test. These results support the view that new episodic learning typically draws on information from both perceptual and semantic systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A test of spatial memory and its clinical utility in the pre-surgical investigation of temporal lobe epilepsy patients

Deficits in memory for figurative detail, spatial composition and the spatial location of objects in a scene have been reported postoperatively in right temporal lobectomy patients. The aim of this study was to examine whether these deficits can be used as a sign of lateralised dysfunction in pre-surgical temporal lobe epilepsy (TLE) patients. Sixty-nine patients with lateralised TLE (27 right, 42 left) were assessed on a battery of neuropsychological tests, including tests of general intellectual functioning and psychomotor speed and standardised memory tests involving the learning and recall of verbal and non-verbal material. A new task, the "Aspects of Spatial Memory Test" (AoSMT), based on the experimental tasks developed by Pigott and Milner [39] was also administered. The RTLE and LTLE groups did not differ in their overall level of intellectual function or on measures of cognitive and motor speed. On the AoSMT the LTLE group recognised significantly more figurative detail changes than the RTLE group. In addition, the RTLE group took significantly longer than the LTLE group to identify changes in orientation, figurative detail and filled/unfilled spaces. Poor scores on the AoSMT were significantly correlated with quantitative MRI measures of right hippocampal pathology. The clinical and theoretical implications of these findings are discussed.