Medial Temporal Lobe Contributions to Episodic Future Thinking: Scene Construction or Future Projection?

Previous research has shown that the medial temporal lobes (MTL) are more strongly engaged when individuals think about the future than about the present, leading to the suggestion that future projection drives MTL engagement. However, future thinking tasks often involve scene processing, leaving open the alternative possibility that scene-construction demands, rather than future projection, are responsible for the MTL differences observed in prior work. This study explores this alternative account. Using functional magnetic resonance imaging, we directly contrasted MTL activity in 1) high scene-construction and low scene-construction imagination conditions matched in future thinking demands and 2) future-oriented and present-oriented imagination conditions matched in scene-construction demands. Consistent with the alternative account, the MTL was more active for the high versus low scene-construction condition. By contrast, MTL differences were not observed when comparing the future versus present conditions. Moreover, the magnitude of MTL activation was associated with the extent to which participants imagined a scene but was not associated with the extent to which participants thought about the future. These findings help disambiguate which component processes of imagination specifically involve the MTL.

Does the hippocampus keep track of time?

In the present study, we examined the role of the medial temporal lobe (MTL) in prospective time estimation at short and long timescales using a novel behavioral paradigm adapted from rodent work. Amnesic patients with MTL damage and healthy control participants estimated the duration of nature-based video clips that were either short (≤ 90 s) or long (more than 4 min). Consistent with previous work in rodents, we found that amnesic patients were impaired at making estimations for long, but not for short durations. Critically, these effects were observed in patients who had lesions circumscribed to the hippocampus, suggesting that the pattern observed was not attributable to the involvement of extra-hippocampal structures. That the MTL, and more specifically the hippocampus, is critical for prospective temporal estimation only at long intervals suggests that multiple neurobiological mechanisms support prospective time estimation.

BDNF genotype is associated with hippocampal volume in mild traumatic brain injury.

The negative long-term effects of mild traumatic brain injury (mTBI) have been a growing concern in recent years, with accumulating evidence suggesting that mTBI combined with additional vulnerability factors may induce neurodegenerative-type changes in the brain. However, the factors instantiating risk for neurodegenerative disease following mTBI are unknown. This study examined the link between mTBI and brain-derived neurotrophic factor (BDNF) genotype, which has previously been shown to regulate processes involved in neurodegeneration including synaptic plasticity and facilitation of neural survival through its expression. Specifically, we examined nine BDNF single-nucleotide polymorphisms (SNPs; rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850, rs11030107, rs7127507 and rs12273363) previously associated with brain atrophy or memory deficits in mTBI. Participants were 165 white, non-Hispanic Iraq and Afghanistan war veterans between the ages of 19 and 58, 110 of whom had at least one mTBI in their lifetime. Results showed that the BDNF SNP rs1157659 interacted with mTBI to predict hippocampal volume. Furthermore, exploratory analysis of functional resting state data showed that rs1157659 minor allele homozygotes with a history of mTBI had reduced functional connectivity in the default mode network compared to major allele homozygotes and heterozygotes. Apolipoprotein E (APOE) was not a significant predictor of hippocampal volume or functional connectivity. These results suggest that rs1157659 minor allele homozygotes may be at greater risk for neurodegeneration after exposure to mTBI and provide further evidence for a potential role for BDNF in regulating neural processes following mTBI.

Using future thinking to reduce temporal discounting: Under what circumstances are the medial temporal lobes critical?

The capacity to envision the future plays an important role in many aspects of cognition, including our ability to make optimal, adaptive choices. Past work has shown that the medial temporal lobe (MTL) is necessary for decisions that draw on episodic future thinking. By contrast, little is known about the role of the MTL in decisions that draw on semantic future thinking. Accordingly, the present study investigated whether the MTL contributes to one form of decision making, namely intertemporal choice, when such decisions depend on semantic consideration of the future. In an intertemporal choice task, participants must select either a smaller amount of money that is available in the present or a larger amount of money that would be available at a future date. Amnesic individuals with MTL damage and healthy control participants performed such a task in which, prior to making a choice, they engaged in a semantic generation exercise, wherein they generated items that they would purchase with the future reward. In experiment 1, we found that, relative to a baseline condition involving standard intertemporal choice, healthy individuals were more inclined to select a larger, later reward over a smaller, present reward after engaging in semantic future thinking. By contrast, amnesic participants were paradoxically less inclined to wait for a future reward following semantic future thinking. This finding suggests that amnesics may have had difficulty "tagging" the generated item(s) as belonging to the future. Critically, experiment 2 showed that when the generated items were presented alongside the intertemporal choices, both controls and amnesic participants shifted to more patient choices. These findings suggest that the MTL is not needed for making optimal decisions that draw on semantic future thinking as long as scaffolding is provided to support accurate time tagging. Together, these findings stand to better clarify the role of the MTL in decision making.

Response preparation and response inhibition after lesions of the medial frontal lobe.

Two patients with chronic unilateral medial frontal lobe lesions, including the supplementary motor area, were given tasks of response preparation and response inhibition. Whereas the patient with a left-sided lesion, like normal controls, did benefit from preparatory information regarding a subsequent response, the patient with a right-sided lesion did not. On a task requiring the inhibition of an inappropriate response, the patient with a left-sided lesion again performed normally. Conversely, the patient with a right-sided lesion had significant problems inhibiting the extremity contralateral to the lesion. We postulate that the medial frontal lobe may participate in response preparation and response inhibition by modulating the levels of excitability of the motor systems. Our findings also suggest that the right hemisphere may have a dominant role in mediating these processes.

Frontal verbal amnesia. Phonological amnesia.

Although aphasic patients with frontal lobe damage may demonstrate impaired retention of verbal material, significant anterograde memory disturbances have not, to our knowledge, been reported with a minor Broca's aphasia. We describe a patient with minor Broca's aphasia who exhibited an unusual and profound anterograde memory disturbance, especially for phonologically specified stimuli. We suggest that this disturbance is attributable to an impairment in the volitional, controlled search of stored phonological information.

Selective attention in hemispatial neglect.

To determine how increasing demands on visual selective attention affect the symptoms of hemispatial neglect, we studied patients with right hemispheric lesions on a cancellation task requiring various degrees of focused attention. In the target only condition, the patients were to cancel all stimuli. In the target-nontarget condition, discriminating targets from nontargets did not require close scrutiny, whereas in the target-foil condition, discriminating targets from foils required greater attention to detail. Our findings indicate that increasing demands on visual selective attention adversely affect both exploration of the left side of space and visual discrimination.

Changing attentional demands in left hemispatial neglect.

Seven variations of a letter cancellation test were used to examine how varying attentional demands affect hemispatial neglect in patients with right hemisphere lesions. While the 14 targets always remained in the same location, the number of distractors (zero, nine, 28, or 82) as well as their complexity (one letter or nine different letters) were varied. The percentage of targets canceled in the left hemispace was linearly related to the number of distractors. There were no differences between the complexity conditions. In a second study, the same 14 targets were presented but the distractors (zero, 14, or 41) were all placed on the right. Increasing the number of distractors on the right increased neglect on both sides of the space. Taken together, these results suggest that, while the limited attentional resources of the left hemisphere are biased toward the right hemispace, the absence of contralateral attentional demands allows these resources to be directed ipsilaterally.

Verbal memory function in mild aphasia.

Verbal material may be processed by semantic and phonologic systems. Damage to these language systems may also impair memory. We classified 16 mildly aphasic patients according to phonologic and lexicosemantic abilities, tested them on a variety of short- and long-term memory measures, and correlated behavioral deficits with lesion location. Aphasia impaired both short- and long-term memory. Phonologic impairment affected only digit span performance. Lexicosemantic deficits impaired self-organized encoding of word lists. Memory impairment was not associated with specific lesion locations. Persistent verbal-memory impairments accompanying even mild residual aphasia may be responsible for much of the difficulty mildly aphasic patients experience returning to vocational, academic, and social life. Co-occurrence of these deficits probably reflects their underlying dependence on similar processing systems.

Amnesia following traumatic bilateral fornix transection.

There is controversy regarding the effect of isolated fornix damage on human memory. We report a patient who suffered a traumatic penetrating head injury that resulted in a significant and persistent anterograde amnesia. CT revealed a lesion that involved the region of the proximal, posterior portion of both fornices without evidence of damage to other hippocampal pathways or to other structures known to be critical for memory, such as the hippocampus, thalamus, or basal forebrain. The unique location of the lesion in this patient provides evidence supporting the role of isolated fornix lesions in amnesia.

Effects of changes in stimulus contingency on visual extinction.

Left visual field (LVF) extinction during double simultaneous stimulation (DSS) is common in patients with right cerebral lesions. A postulate is that during DSS, the intact left hemisphere's limited attentional capacity is directed to right hemispace, resulting in LVF extinction. External cueing may help direct attention to the LVF and improve performance. In the present study, we varied patterns of unilateral stimulation preceding DSS in an attempt to redirect attention through expectancy. Nine patients (7 stroke, 2 tumor) with right hemisphere lesions each had 40 DSS trials with the distribution of unilateral stimulation trials systematically varied. Mean extinction percentages on DSS trials were 17% following 5 right unilateral trials, 30% following 1 right unilateral trial, 52% following 1 left unilateral trial, and 63% following 5 left unilateral trials. These findings indicate that the probability of extinction decreases following unilateral stimulation to the right visual field and increases following unilateral stimulation to the LVF. These results suggest that expectancy alters the attentional bias which mediates extinction.

Dissociable cognitive and neural mechanisms of unilateral visual neglect.

We administered two experimental tasks to 16 patients with neglect following unilateral right hemisphere strokes, designed to probe processing of information in the neglected left visual field. A semantic priming/lexical decision task examined implicit processing of stimuli presented to the neglected field, and a discrimination task required explicit recognition of the same stimuli. We grouped patients according to three patterns of performance: (1) poor discrimination in the left visual field but intact priming, (2) normal priming and discrimination in both fields, and (3) normal priming but poor discrimination in both fields. Although patients in group 1 had posterior lesions, patients in groups 2 and 3 had extensive deep anterior lesions. These results suggest that the clinical phenomenon of unilateral visual neglect can be the surface manifestation of deficits in two different and interacting processes--attentional processes (group 1) and intentional processes (group 2)--or it may be a global attentional disturbance superimposed on these deficits (group 3).

Lateralization of memory for the visual attributes of objects: evidence from the posterior cerebral artery amobarbital test.

We used the posterior cerebral artery amobarbital test to examine how each temporal lobe mediates memory for objects. Temporal lobectomy candidates were presented with four objects while one hemisphere was anesthetized. We assessed recall and recognition following recovery from the drug. Verbal recall was significantly better following object presentation to the left hemisphere when the left hemisphere was not the seizure focus. Recognition memory, tested with two identical objects, two objects that shared the same name but had different physical characteristics, and two foils, was superior following object presentation to the right hemisphere. Only the right hemisphere could discriminate identical objects from same-name foils. These data confirm that the left temporal lobe has an advantage in encoding the verbal representation of an object and suggest that the right temporal lobe is critical for memory of specific visual attributes of objects.

Fear recognition deficits after focal brain damage: a cautionary note.

OBJECTIVE: To test the hypothesis that fear recognition deficits in neurologic patients reflect damage to an emotion-specific neural network. BACKGROUND: Previous studies have suggested that the perception of fear in facial expressions is mediated by a specialized neural system that includes the amygdala and certain posterior right-hemisphere cortical regions. However, the neuropsychological findings in patients with amygdala damage are inconclusive, and the contribution of distinct cortical regions to fear perception has only been examined in one study. METHODS: We studied the recognition of six basic facial expressions by asking subjects to match these emotions with the appropriate verbal labels. RESULTS: Both normal control subjects (n = 80) and patients with focal brain damage (n = 63) performed significantly worse in recognizing fear than in recognizing any other facial emotion, with errors consisting primarily of mistaking fear for surprise. Although patients were impaired relative to control subjects in recognizing fear, we could not obtain convincing evidence that left, right, or bilateral lesions were associated with disproportionate impairments of fear perception once we adjusted for differences in overall recognition performance for the other five facial emotion categories. The proposed special role of the amygdala and posterior right-hemisphere cortical regions in fear perception was also not supported. CONCLUSIONS: Fear recognition deficits in neurologic patients may be attributable to task difficulty factors rather than damage to putative neural systems dedicated to fear perception.

Acquisition of novel semantic information in amnesia: effects of lesion location.

Two patients with severe global amnesia are described who differ in the extent to which they have acquired new semantic information. Patient SS, who has extensive medial temporal lobe damage including the hippocampus as well as surrounding cortical areas, has failed to acquire virtually any new information regarding vocabulary or famous faces that entered the public domain since the onset of his amnesia. In contrast, patient PS, who has a selective lesion of the hippocampus proper, has gained a sense of familiarity of novel vocabulary and famous people, even though her effortful retrieval of this new semantic knowledge remains impaired. These findings extend to amnesia of adult onset, the proposal of Vargha-Khadem and colleagues that in patients with selective hippocampal injury, cortical areas surrounding the hippocampus may play an important role in new semantic learning [Vargha-Khadem, F., Gadian, D.G., Watkins, K. E., Connelly, A., Van Paesschen, W. and Mishkin, M., regarding the importance of the subhippocampal cortices in the mediation of new semantic learning in children with hippocampal lesions, Science, 1997, 277, 376-380].

Hemispheric asymmetries in mediating intention, but not selective attention.

Heilman and Van Den Abell [Neuropsychologia 17, 315-321, 1979] reported a right hemisphere dominance for cerebral activation. In the present study, we further examined the nature of this finding in an experimental paradigm in which selective attention and intention (response readiness) were manipulated independently. Normal subjects were tested on a choice reaction time task in which they were given preliminary information about where a target stimulus would occur (selective attention) and which hand to use for responding (intention). Our findings indicate that at short foreperiod durations, the right hemisphere is superior for mediating intention. There was no evidence for a right hemisphere superiority for selective attention.

Attentional factors in the occurrence of stimulus-response compatibility effects.

Two major hypotheses have been advanced to account for stimulus-response compatibility effects in the situation in which the location of the target is irrelevant for choosing the correct response. According to the attentional hypothesis, compatibility effects reflect a response bias, favoring the effector on the same side as the stimulus. According to the coding hypothesis, compatibility effects result from a correspondence between the spatial codes of the stimulus and effector. In the present study, two components of attention--selective attention and intention--were independently manipulated by providing selective preparatory information before onset of a target stimulus. Attentional information indicated where the target stimulus would occur; intentional information indicated which hand would have to be used to respond. Compatibility effects were observed only in the condition in which intentional information, but no attentional information, was provided. These findings support the attentional hypothesis and indicate that a specific aspect of attention, namely a selective readiness to respond to the stimulus, is a necessary condition for compatibility effects to occur.

Preserved priming in auditory perceptual identification in Alzheimer's disease.

To examine the status of auditory perceptual priming in Alzheimer's disease (AD), this study examined the performance of AD patients in auditory perceptual identification of words. In Experiment 1, the processing operations required to perform the tasks at study and test were matched, whereas in Experiment 2, processing operations at study and test were mismatched. AD patients showed normal priming in both experiments, despite impaired recognition memory. These findings extend to the auditory domain the finding of intact perceptual implicit memory in AD. Preserved auditory priming in AD may reflect the operation of a pre-semantic, phonological representation system, localized to posterior neocortical areas that are functionally spared in AD.

Repetition effects in a lexical decision task: the role of episodic memory in the performance of alcoholic Korsakoff patients.

To examine the contribution of episodic memory to the successful verbal priming performance of Korsakoff patients, we adapted a lexical decision task which holds constant the processing demands during study and testing. Words and nonwords were repeated at a lag of 0, 1, 3, 8 and 15 items and the decrease in response latency was taken as a measure of priming. In Experiment 1, Korsakoff patients showed repetition priming of a magnitude similar to that obtained by alcoholic controls, even at a lag of 15 intervening items. Experiment 2 explored the effect of word frequency on repetition priming. Korsakoff patients again showed normal priming up to lags of 15, and, as expected, these repetition effects were larger for low frequency than for high frequency words. This outcome was felt to be more consistent with an episodically based familiarity account than with a semantic activation account. Finally, Korsakoff patients were found to be impaired in their ability to use episodic memory in an explicit memory task that used the same material under comparable presentation conditions (Experiment 3). Contemporary processing models of episodic memory are discussed as possible explanations for the successful implicit memory performance by amnesic patients on this task.

A further analysis of perceptual identification priming in alcoholic Korsakoff patients.

Alcoholic Korsakoff patients have been shown to have normal repetition priming for words, but impaired priming for pseudowords, on perceptual identification tasks. Because real words, but not pseudowords, have semantic representations, successful priming of real words has been attributed to semantic activation. Alternatively, however, priming might reflect the perceptual, i.e. orthographic and phonological familiarity associated with real words in comparison with pseudowords. In order to examine which of these factors accounts for normal priming by amnesics, Experiment 1 was designed to contrast perceptual identification priming for words, pseudowords and pseudohomonyms (e.g. "phaire"). On this task, Korsakoff patients showed normal priming for real words and for pseudohomonyms, but significantly impaired priming for pseudowords. It was felt that since pseudohomonyms are orthographically unfamiliar but could access semantics through their phonological route, activation of a semantic representation rather than perceptual familiarity might be the critical factor underlying successful priming. Experiment 2 was then designed to further explore the robustness of this semantically mediated priming by presenting different word types within the same study list. Under these conditions, Korsakoffs' pseudohomonym priming was consistently below normal. This suggests that priming in Korsakoff patients depends upon the conceptual salience of the stimuli and not solely on semantic activation.