The function of the anterior temporal lobe: a review of the empirical evidence.

Recent work on the anterior temporal lobe (ATL) has lead to substantively different theoretical branches, of its putative functions, that have in some part developed independently of one another. The ATL has dense connectivity with a number of sensory modalities. This has resulted in empirical evidence that supports different functionality dependent upon the variables under investigation. The main bodies of evidence have implicated the ATL as a domain-general semantic hub, whilst other evidence points to a domain-specific role in social or 'person-related' processing. A third body of evidence suggests that the ATLs underlie processing of unique entities. Primarily, research of the ATL has been based on lesion studies and from clinical populations such as semantic dementia or temporal lobe epilepsy patients. Although important, this neuropsychological evidence has a number of confounds, therefore techniques such as functional neuroimaging on healthy participants and the relatively novel use of non-invasive brain stimulation may be more useful to isolate specific variables that can discriminate between these different theories concerning 'normal' function. This review focuses on these latter types of studies and considers the empirical evidence for each perspective. The overall literature is integrated in an attempt to formulate a unifying theory and the functional sub-regions within the ATL are explored. It is concluded that a holistic integration of the theories is feasible in that the ATLs could process domain-general semantic knowledge but with a bias towards social information or stimuli that is personally relevant. Thus, it may be the importance of social/emotional information that gives it priority of processing in the ATL not an inherent property of the structure itself.

Evidence for a social function of the anterior temporal lobes: low-frequency rTMS reduces implicit gender stereotypes.

By nature, stereotypes require processes of categorization or semantic association, including social information about groups of people. There is empirical evidence that the anterior temporal lobe (ATL) processes domain-general semantic information, and supports social knowledge. A recent study showed that inhibitory repetitive transcranial magnetic stimulation (rTMS) to the ATL reduced racial stereotypes on an implicit association test (IAT). However, it was not determined whether this was caused by changes to specific social, or general semantic processing, or both. The current study addresses these theoretical issues. The design investigated the effect of rTMS to the left or right ATL, or a sham stimulation, on a social IAT (gender stereotypes), a non-social IAT (living versus non-living associations), and a non-semantic control (Stroop) task. The results showed that low-frequency rTMS to both left and right ATL significantly reduced D-scores on the gender IAT compared to the sham group; however, there were no differences on the non-social IAT or the Stroop. The findings show the ATL has a role in mediating stereotypes, and the decrease of bias after stimulation could be due to weakening of social stereotypical associations either within the ATL or via a network of brain regions connected with the ATL.

Noninvasive brain stimulation reduces prejudice scores on an implicit association test.

OBJECTIVE: Inhibiting the anterior temporal lobe (ATL) via repetitive transcranial magnetic stimulation (rTMS) appears to have deleterious effects on people's semantic conceptualization, and left ATL damage is associated with semantic dementia. However, little research has investigated whether rTMS can inhibit conceptual schemata that have potentially negative consequences. Our aim was to investigate whether rTMS to the ATLs could reduce scores on a standard measure of prejudice (implicit association test, IAT). METHOD: Forty (17 female; mean age 20.6) neurologically normal, right-handed undergraduates participated. Participants were randomly allocated into one of four rTMS stimulation conditions-left ATL, right ATL, control site (motor cortex, Cz), and sham stimulation. All participants completed a modified IAT, where "good" and "bad" words were replaced with "terrorist" and "law-abider" words, and, "Black" and "White" were replaced with "Arab" and "Non-Arab" words. Participants were then given 15 min of rTMS stimulation. Afterward, participants completed a parallel form of the IAT. RESULTS: To investigate the effects of rTMS on IAT scores, a one-way ANOVA on the difference between pre- and postscores was carried out revealing that there were significant between group differences (F3,36 = 3.57; p = .02). Planned contrasts revealed that both left and right ATL stimulation significantly reduced IAT scores poststimulation, indicating lower prejudice. CONCLUSION: We show that prejudice scores can be significantly reduced by inhibitory rTMS delivered to the bilateral ATLs. This may implicate this area in conceptual associations that lead to overgeneralization and stereotyping of social groups.

Low-frequency repetitive transcranial magnetic stimulation of the anterior temporal lobes does not dissociate social versus nonsocial semantic knowledge.

Social conceptual knowledge is imperative to communicate with, interact with, and interpret human society; however, little is known about the neural basis of social concepts. Previous research has predominantly suggested that the right anterior temporal lobe (ATL) may specifically represent social conceptual knowledge, whereas the left ATL is necessary for general semantic processing. However, this view has not always been supported by empirical studies. Employing a lateralized design and two different semantic tasks and a nonsemantic control task, we aimed to clarify some of these ambiguities by potentially dissociating left from right functionality and social from nonsocial concepts, using inhibitory repetitive transcranial magnetic stimulation (rTMS) coupled with a sham and control site stimulation (N = 56). The results showed that stimulation of the left ATL led to overall faster processing times without affecting accuracy, whilst the right ATL and control groups did not significantly change in reaction times or accuracy. No difference occurred between social and nonsocial concepts after stimulation. This study is the first to show that inhibition of the left temporal lobe may improve performance on a semantic task and provides evidence that the ATLs may be lateralized in conceptual processing. The results do not confirm that the right temporal lobe is crucial for social conceptual processing, as inhibition did not significantly affect performance for social concepts.

Temporal lobe cortical electrical stimulation during the encoding and retrieval phase reduces false memories.

A recent study found that false memories were reduced by 36% when low frequency repetitive transcranial magnetic stimulation (rTMS) was applied to the left anterior temporal lobe after the encoding (study) phase. Here we were interested in the consequences on a false memory task of brain stimulation throughout the encoding and retrieval task phases. We used transcranial direct current stimulation (tDCS) because it has been shown to be a useful tool to enhance cognition. Specifically, we examined whether tDCS can induce changes in a task assessing false memories. Based on our preliminary results, three conditions of stimulation were chosen: anodal left/cathodal right anterior temporal lobe (ATL) stimulation ("bilateral stimulation"); anodal left ATL stimulation (with a large contralateral cathodal electrode--referred as "unilateral stimulation") and sham stimulation. Our results showed that false memories were reduced significantly after the two active conditions (unilateral and bilateral stimulation) as compared with sham stimulation. There were no significant changes in veridical memories. Our findings show that false memories are reduced by 73% when anodal tDCS is applied to the anterior temporal lobes throughout the encoding and retrieval stages, suggesting a possible strategy for improving certain aspects of learning.

Reducing false memories by magnetic pulse stimulation.

False memories are ubiquitous and often to our detriment. Yet, certain pathologies, including anterior temporal lobe dementia and autism, can lead to literal recall and thus greater resistance to false memories. This inspired us to reduce false memories by temporarily inhibiting the left anterior temporal lobe, using low frequency magnetic pulse stimulation. This site has been implicated in semantic memory and conceptual labelling. After active stimulation, participants in the sham/TMS group had 36% fewer false memories than they had with sham stimulation, and intact veridical memory. This is comparable to the improvement that people with autism and semantic dementia show over "normal" individuals. This finding suggests a potential method for reducing certain types of false memories.

Delta9-THC reinstates beer- and sucrose-seeking behaviour in abstinent rats: comparison with midazolam, food deprivation and predator odour.

AIMS: Recent studies suggest that cannabinoid receptor agonists may promote relapse to drug-seeking behaviour after a period of abstinence. In this study, the ability of Delta(9)-tetrahydrocannabinol (THC) to reinstate previously reinforced responding for alcoholic and non-alcoholic beverages was assessed in rats using a novel lick-based paradigm. METHODS: Rats were initially given free access to beer (containing 4.5% ethanol v/v), near-beer (a beverage that looks and tastes like beer but contains <0.5% ethanol v/v) or isocaloric sucrose in their home cages for 3 weeks. They were then trained to lick at a tube to self-administer the pre-exposed beverage in operant chambers under a VR10 schedule in 30-min sessions daily. After approximately 3 weeks of such access, the rats underwent an extinction procedure, so that licking at the tube produced no reward. Once responding had ceased, the rats were subjected to various reinstatement tests. RESULTS: In Experiment 1, the cannabinoid receptor agonist Delta(9)-THC (1 mg/kg) significantly reinstated responding, previously reinforced with beer or near-beer. The effect was unlikely to be caused by increased appetite because 24 h food-deprivation had no such effect. Exposure to cat odour in the test chamber failed to reinstate responding for beer or near-beer and caused a complete inhibition of responding. In Experiment 2, Delta(9)-THC (0.3 and 1 but not 3 mg/kg) again reinstated beer-seeking behaviour while the 1 mg/kg dose also reinstated responding in sucrose trained animals. Midazolam (0.15 mg/kg but not 0.5 or 1.5 mg/kg) produced a modest reinstatement of beer-seeking but had no effect on sucrose-seeking behaviour. CONCLUSIONS: The finding that Delta(9)-THC can reinstate alcohol-seeking provides the impetus for further research into the involvement of the cannabinoid system in alcohol craving. However, the reinstatement of near-beer and sucrose-seeking behaviour caused by Delta(9)-THC suggests a relatively non-specific effect. This may perhaps be related to the stressor-like effects of cannabinoids, and their ability to activate key neural circuitry in the amygdala and bed nucleus of the stria terminalis.

Rats on the grog: novel pharmacotherapies for alcohol craving.

Current pharmacotherapies for alcohol dependence in humans (e.g., naltrexone, acamprosate) are meeting with only limited therapeutic success. The development of novel pharmacotherapies is urgently needed but is reliant upon the screening of large numbers of candidate "anticraving" drugs using appropriate animal models. The development of animal models is complex because (1) laboratory animals are often reluctant to consume large quantities of alcohol, (2) inducing a state of alcohol dependence, analogous to the human condition, may require many months of alcohol exposure, (3) concluding that a given drug selectively reduces alcohol craving requires very carefully controlled experiments, and (4) false positives and false negatives may result from the sometimes distinct physiology and psychology of the alcohol-addicted human and rat. To address some of these problems, our laboratory has recently developed the "beer model" of alcohol dependence and craving. Rats, like humans, have a prodigious appetite for beer and will drink much more beer than equivalent ethanol solutions in water. Beer consumption in rats leads to clear signs of intoxication, anxiety reduction, and signs of withdrawal when beer access is suddenly denied. We have found that beer craving in rats is selectively reduced by the cannabinoid receptor antagonist SR 141716 and the opioid receptor antagonist naltrexone. Combining these two drugs appears to have a synergistic anticraving effect. Other promising pharmacotherapies for the future are discussed.

Combined low dose treatment with opioid and cannabinoid receptor antagonists synergistically reduces the motivation to consume alcohol in rats.

RATIONALE: Opioid and cannabinoid CB(1) receptor antagonists reduce the motivation to consume alcohol when taken individually but their effectiveness in combination is not yet known. OBJECTIVE: The effects of naloxone/naltrexone and SR 141716 alone and in combination were examined on beer consumption in rats. METHODS: In a progressive ratio paradigm rats were trained to lick at a tube for either beer (4.5% ethanol v/v) or near-beer (beer containing <0.5% ethanol v/v) under a progressive ratio schedule of reinforcement. They were then tested with naloxone (0.3, 0.6 or 1.2 mg/kg i.p.), SR 141716 (0.15, 0.3 or 0.6 mg/kg i.p.) and their combination. In a continuous access paradigm, other rats were given beer or near-beer in their home cages for several weeks and the effects of repeated (4 day) administration of naltrexone (0.3, 0.6 or 1.2 mg/kg), SR 141716 (0.15, 0.3 or 0.6 mg/kg) and their combination were assessed. RESULTS: In the progressive ratio paradigm SR 141716, naloxone and their combination were more effective in reducing the break points for beer rather than near-beer. The two lowest dose combinations produced a synergistic reduction in break points. The highest dose combination reduced break points for both beer and near-beer and effects were more additive than synergistic. In the continuous access paradigm, the low doses of the drugs selectively reduced beer consumption in a synergistic fashion with higher doses having a less selective and more additive effect. CONCLUSIONS: The combined, low dose treatment has possible clinical efficacy in treating alcohol craving in humans.

The consequences of beer consumption in rats: acute anxiolytic and ataxic effects and withdrawal-induced anxiety.

RATIONALE: Rats avidly consume standard off-the-shelf beer; however, the behavioural consequences of beer consumption in rodents have hardly been studied. OBJECTIVES: The present study examined the acute anxiolytic and ataxic effects of beer consumption in rats and the anxiogenic effects of withdrawal from free access to beer. METHOD: In experiment 1, male Wistar rats received 30 min access to "near-beer" each day (a malt beverage that looks and tastes like beer but which contains <0.5% ethanol). On the test day, for some rats, ethanol (either 2% or 4% v/v) was added to the near-beer to make it resemble standard (ethanol-containing) beer of "light" (2.5% beer) or full strength (4.5% beer). Immediately after this, rats were tested on their response to a predatory cue (a fabric collar that had been worn by a cat) and on an accelerating rotarod. In experiment 2, rats were trained in the same drinking paradigm as above and then tested on a further battery of anxiety tests. In experiment 3, rats were given continuous home cage access to either 4.5% beer or near-beer for 35 days. Half of the rats were then denied access to beer or near-beer for 24 h and then tested on the same anxiety test battery as in experiment 2. RESULTS: Rats drinking 4.5% beer approached a predatory cue significantly more than those given near-beer, indicating an anxiolytic effect. In experiment 2, rats drinking 4.5% beer displayed less anxiety-like behaviour in the elevated plus maze and emergence tests but not in the social interaction test. Rats given 4.5% beer fell off the rotarod significantly faster than rats given near-beer, indicating an ataxic effect. Rats previously given 4.5% beer drank significantly less near-beer the following day, suggesting a moderate aversion the day after beer consumption. In experiment 3, rats denied access to 4.5% beer showed significantly less social interaction and took longer to emerge into an open field than controls. CONCLUSION: These results are the first to our knowledge to show that rats will consume beer at levels that produce clear effects on anxiety and on motor co-ordination, and that will eventually produce behavioural signs of withdrawal.