Increased sensorimotor activity during categorisation of emotionally ambiguous faces.

Actions are rarely devoid of emotional content. Thus, a more complete picture of the neural mechanisms underlying the mental simulation of observed actions requires more research using emotion information. The present study used high-density electroencephalography to investigate mental simulation associated with facial emotion categorisation. Alpha-mu rhythm modulation was measured at each frequency, from 8 Hz to 13 Hz, to infer the degree of sensorimotor simulation. Results suggest the sensitivity of the sensorimotor activity to emotional information, because (1) categorising static images of neutral faces as happy or sad was associated with stronger suppression in the central region than categorising clearly happy faces, (2) there was preliminary evidence indicating that the strongest suppression in the central region was in response to neutral faces, followed by sad and then happy faces and (3) in the control task, which required categorising images with the head oriented right, left, or forward as right or left, differences between conditions showed a pattern more indicative of task difficulty rather than sensorimotor engagement. Dissociable processing of emotional information in facial expressions and directionality information in head orientations was further captured in beta band activity (14-20 Hz). Stronger mu suppression to neutral faces indicates that sensorimotor simulation extends beyond crude motor mimicry. We propose that mu rhythm responses to facial expressions may serve as a biomarker for empathy circuit activation. Future research should investigate whether atypical or inconsistent mu rhythm responses to facial expressions indicate difficulties in understanding or sharing emotions.

Altered structural connectome of children with auditory processing disorder: a diffusion MRI study.

Auditory processing disorder (APD) is a listening impairment that some school-aged children may experience despite having normal peripheral hearing. Recent resting-state functional magnetic resonance imaging (MRI) has revealed an alteration in regional functional brain topology in children with APD. However, little is known about the structural organization in APD. We used diffusion MRI data to investigate the structural connectome of 58 children from 8 to 14 years old diagnosed with APD (n = 29) and children without hearing complaints (healthy controls, HC; n = 29). We investigated the rich-club organization and structural connection differences between groups. The APD group showed similar rich-club organization and edge-wise connection compared with the HC group. However, at the regional level, we observed increased average path length (APL) and betweenness centrality in the right inferior parietal lobule and inferior precentral gyrus, respectively, in the APD group. Only HCs demonstrated a positive association between APL and the listening-in-spatialized-noise-sentences task in the left orbital gyrus. In line with previous findings, the current results provide evidence for altered structural networks at the regional level in the APD group, suggesting the involvement of multimodal deficits and a role for structure-function alteration in the listening difficulties of children with APD.

The brain-derived neurotrophic factor Val66Met genotype does not influence the grey or white matter structures underlying recognition memory.

A single nucleotide polymorphism (SNP) in the gene coding for brain-derived neurotrophic factor (BDNF) has previously been associated with a reduction in recognition memory performance. While previous findings have highlighted that this SNP contributes to recognition memory, little is known about its influence on subprocesses of recognition, familiarity and recollection. Previous research has reported reduced hippocampal volume and decreased fractional anisotropy in carriers of the Met allele across a range of white matter tracts, including those networks that may support recognition memory. Here, in a sample of 61 healthy young adults, we used a source memory task to measure accuracy on each recognition subprocess, in order to determine whether the Val66Met SNP (rs6265) influences these equally. Additionally, we compared grey matter volume between these groups for structures that underpin familiarity and recollection separately. Finally, we used probabilistic tractography to reconstruct tracts that subserve each of these two recognition systems. Behaviourally, we found group differences on the familiarity measure, but not on recollection. However, we did not find any group difference on grey- or white-matter structures. Together, these results suggest a functional influence of the Val66Met SNP that is independent of coarse structural changes, and nuance previous research highlighting the relationship between BDNF, brain structure, and behaviour.

Atypical white matter microstructure in left-handed individuals.

Information regarding anatomical connectivity in the human brain can be gathered using diffusion tensor imaging (DTI). Fractional anisotropy (FA) is the most commonly derived value, and reflects how strongly directional are the underlying tracts. Differences in FA are thus associated with differences in the underlying microstructure of the brain. The relationships between these differences in microstructure and functional differences in corresponding regions have also been examined. Previous studies have found an effect of handedness on functional lateralization in the brain and corresponding microstructural differences. Here, using tract-based spatial statistics to analyse DTI-derived FA values, we further investigated the structural white matter architecture in the brains of right- and left-handed males. We found significantly higher FA values for left-handed, relatively to right-handed, individuals, in all major lobes, and in the corpus callosum. In support of previous suggestions, we find that there is a difference in the microstructure of white matter in left- and right-handed males that could underpin reduced lateralization of function in left-handed individuals.

Mu rhythm suppression demonstrates action representation in pianists during passive listening of piano melodies.

Musicians undergo extensive training which enhances established neural links between auditory and motor areas of the brain. Long-term training develops, strengthens and enables flexibility in these connections allowing proficiency in performance. Previous research has indicated that passive listening of trained music results in the recruitment of premotor areas. It has been argued that this sound-action representation may rely on activity in mirror neuron systems and that these systems are heavily dependent on actual sensorimotor experience. Action observation studies using electroencephalography have associated changes in mu rhythm activity with the mirror neuron system in the visuomotor domain. We aimed to investigate similar effects in the audiomotor domain. We utilised a mu suppression method in our action-listening study to detect involuntary motor coactivation when pianists passively listened to piano melodies. Wavelet analysis revealed sensorimotor mu rhythm suppression while pianists listened passively to piano melodies. Thus, we show that this spectral analysis method can also be used to demonstrate that auditory stimuli can activate the human mirror neuron system when sounds are linked to actions. Mu suppression could be a useful index for further research on action representation and training-induced plasticity.

Using fMRI to compare the effects of benzylpiperazine with dexamphetamine - Their differences during the Stroop paradigm.

RATIONALE: Benzylpiperazine (BZP) has been found to increase neural activation in the dorsal striatum when compared to placebo in response to a Stroop paradigm, in addition, subjective effects have been compared to dexamphetamine (DEX). Despite their similarities, the two have not been directly compared in respect to their effects on selective attention and inhibition. OBJECTIVES: To use a double-blind placebo-controlled crossover study to compare the acute effects of BZP and DEX on executive function using functional magnetic resonance imaging (fMRI) and an event-related Stroop task. METHODS: Eleven healthy participants aged 18-40 years undertook the Stroop task 90[Formula: see text]min after taking an oral dose of either BZP (200[Formula: see text]mg), DEX (20[Formula: see text]mg) or placebo. RESULTS: BZP induced a greater increase in activation than DEX in the inferior frontal gyrus (IFG) during the Stroop task. DEX increased BOLD signal in the thalamus and decreased it in the IFG in comparison to placebo. CONCLUSION: Despite BZP and DEX reportedly inducing similar subjective effects, there are different patterns of neural activation. We believe this differential activity is due to pharmacological differences in their receptor binding profiles and that subsequent inhibitory effects might be due to their direct effect on dopaminergic activity.

Influence of Physical Activity on Human Sensory Long-Term Potentiation.

A growing body of literature has explored the influence of physical activity on brain structure and function. While the mechanisms of this relationship remain largely speculative, recent research suggests that one of the effects of physical exercise is an increase in synaptic long-term potentiation (LTP). This has not yet been explored directly in humans due to the difficulty of measuring LTP non-invasively. However, we have previously established that LTP-like changes in visual-evoked potentials (VEPs) can be measured in humans. Here, we investigated whether physical fitness status affects the degree of visual sensory LTP. Using a self-report measure of physical activity, participants were split into two groups: a high-activity group, and a low-activity group. LTP was measured and compared between the two groups using the previously established electroencephalography-LTP paradigm, which assesses the degree to which the N1b component of the VEP elicited by a sine grating is potentiated (enhanced) following a rapid "tetanic" presentation of that grating. Both groups demonstrated increased negativity in the amplitude of the N1b component of the VEP immediately after presentation of the visual "tetanus," indicating potentiation. However, after a 30-min rest period, the N1b for the high-activity group remained potentiated while the N1b for the low-activity group returned to baseline. This study presents the first evidence for the impact of self-reported levels of physical activity on LTP in humans, and sheds light on potential neurological mechanisms underlying the relationship between physical fitness and cognition.

EEG Complexity Analysis of Brain States, Tasks and ASD Risk.

Autism spectrum disorder is an increasingly prevalent and debilitating neurodevelopmental condition and an electroencephalogram (EEG) diagnostic challenge. Despite large amounts of electrophysiological research over many decades, an EEG biomarker for autism spectrum disorder (ASD) has not been found. We hypothesized that reductions in complex dynamical system behaviour in the human central nervous system as part of the macroscale neuronal function during cognitive processes might be detectable in whole EEG for higher-risk ASD adults. In three studies, we compared the medians of correlation dimension, largest Lyapunov exponent, Higuchi's fractal dimension, multiscale entropy, multifractal detrended fluctuation analysis and Kolmogorov complexity during resting, cognitive and social skill tasks in 20 EEG channels of 39 adults over a range of ASD risk. We found heterogeneous complexity distribution with clusters of hierarchical sequences pointing to potential cognitive processing differences, but no clear distinction based on ASD risk. We suggest that there is indication of statistically significant differences between complexity measures of brain states and tasks. Though replication of our studies is needed with a larger sample, we believe that our electrophysiological and analytic approach has potential as a biomarker for earlier ASD diagnosis.

Acute exercise as a modifier of neocortical plasticity and aperiodic activity in the visual cortex.

Long-term potentiation (LTP) is a form of neuroplasticity commonly implicated in mechanistic models of learning and memory. Acute exercise can boost LTP in the motor cortex, and is associated with a shift in excitation/inhibition (E:I) balance, but whether this extends to other regions such as the visual cortex is unknown. We investigated the effect of a preceding bout of exercise on LTP induction and the E:I balance in the visual cortex using electroencephalography (EEG). Young adults (N = 20, mean age = 24.20) engaged in 20 min of high-intensity interval training (HIIT) exercise and rest across two counterbalanced sessions. LTP was induced using a high frequency presentation of a visual stimulus; a "visual tetanus". Established EEG markers of visual LTP, the N1b and P2 component of the visual evoked potential, and an EEG-derived measure of the E:I balance, the aperiodic exponent, were measured before and after the visual tetanus. As expected, there was a potentiation of the N1b following the visual tetanus, with specificity to the tetanised stimulus, and a non-specific potentiation of the P2. These effects were not sensitive to a preceding bout of exercise. However, the E:I balance showed a late shift towards inhibition following the visual tetanus. A preceding bout of exercise resulted in specificity of this E:I balance shift to the tetanised stimulus, that was not seen following rest. This novel finding suggests a possible exercise-induced tuning of the visual cortex to stimulus details following LTP induction.

Impaired categorical perception of lexical tones in Mandarin-speaking congenital amusics.

The degree to which cognitive resources are shared in the processing of musical pitch and lexical tones remains uncertain. Testing Mandarin amusics on their categorical perception of Mandarin lexical tones may provide insight into this issue. In the present study, a group of 15 amusic Mandarin speakers identified and discriminated Mandarin tones presented as continua in separate blocks. The tonal continua employed were from a high-level tone to a mid-rising tone and from a high-level tone to a high-falling tone. The two tonal continua were made in the contexts of natural speech and of nonlinguistic analogues. In contrast to the controls, the participants with amusia showed no improvement for discrimination pairs that crossed the classification boundary for either speech or nonlinguistic analogues, indicating a lack of categorical perception. The lack of categorical perception of Mandarin tones in the amusic group shows that the pitch deficits in amusics may be domain-general, and this suggests that the processing of musical pitch and lexical tones may share certain cognitive resources and/or processes (Patel 2003, 2008, 2012).

Altered brain network topology in children with auditory processing disorder: A resting-state multi-echo fMRI study.

Children with auditory processing disorder (APD) experience hearing difficulties, particularly in the presence of competing sounds, despite having normal audiograms. There is considerable debate on whether APD symptoms originate from bottom-up (e.g., auditory sensory processing) and/or top-down processing (e.g., cognitive, language, memory). A related issue is that little is known about whether functional brain network topology is altered in APD. Therefore, we used resting-state functional magnetic resonance imaging data to investigate the functional brain network organization of 57 children from 8 to 14 years old, diagnosed with APD (n = 28) and without hearing difficulties (healthy control, HC; n = 29). We applied complex network analysis using graph theory to assess the whole-brain integration and segregation of functional networks and brain hub architecture. Our results showed children with APD and HC have similar global network properties -i.e., an average of all brain regions- and modular organization. Still, the APD group showed different hub architecture in default mode-ventral attention, somatomotor and frontoparietal-dorsal attention modules. At the nodal level -i.e., single-brain regions-, we observed decreased participation coefficient (PC - a measure quantifying the diversity of between-network connectivity) in auditory cortical regions in APD, including bilateral superior temporal gyrus and left middle temporal gyrus. Beyond auditory regions, PC was also decreased in APD in bilateral posterior temporo-occipital cortices, left intraparietal sulcus, and right posterior insular cortex. Correlation analysis suggested a positive association between PC in the left parahippocampal gyrus and the listening-in-spatialized-noise -sentences task where APD children were engaged in auditory perception. In conclusion, our findings provide evidence of altered brain network organization in children with APD, specific to auditory networks, and shed new light on the neural systems underlying children's listening difficulties.

Task-Modulated Oscillation Differences in Auditory and Spoken Chinese-English Bilingual Processing: An Electroencephalography Study.

Neurophysiological research on the bilingual activity of interpretation or interpreting has been very fruitful in understanding the bilingual brain and has gained increasing popularity recently. Issues like word interpreting and the directionality of interpreting have been attended to by many researchers, mainly with localizing techniques. Brain structures such as the dorsolateral prefrontal cortex have been repeatedly identified during interpreting. However, little is known about the oscillation and synchronization features of interpreting, especially sentence-level overt interpreting. In this study we implemented a Chinese-English sentence-level overt interpreting experiment with electroencephalography on 43 Chinese-English bilinguals and compared the oscillation and synchronization features of interpreting with those of listening, speaking and shadowing. We found significant time-frequency power differences in the delta-theta (1-7 Hz) and gamma band (above 30 Hz) between motor and silent tasks. Further theta-gamma coupling analysis revealed different synchronization networks in between speaking, shadowing and interpreting, indicating an idea-formulation dependent mechanism. Moreover, interpreting incurred robust right frontotemporal gamma coactivation network compared with speaking and shadowing, which we think may reflect the language conversion process inherent in interpreting.

A callosal biomarker of behavioral intervention outcomes for autism spectrum disorder? A case-control feasibility study with diffusion tensor imaging.

Tentative results from feasibility analyses are critical for planning future randomized control trials (RCTs) in the emerging field of neural biomarkers of behavioral interventions. The current feasibility study used MRI-derived diffusion imaging data to investigate whether it would be possible to identify neural biomarkers of a behavioral intervention among people diagnosed with autism spectrum disorder (ASD). The corpus callosum has been linked to cognitive processing and callosal abnormalities have been previously found in people diagnosed with ASD. We used a case-control design to evaluate the association between the type of intervention people diagnosed with ASD had previously received and their current white matter integrity in the corpus callosum. Twenty-six children and adolescents with ASD, with and without a history of parent-managed behavioral intervention, underwent an MRI scan with a diffusion data acquisition sequence. We conducted tract-based spatial statistics and a region of interest analysis. The fractional anisotropy values (believed to indicate white matter integrity) in the posterior corpus callosum was significantly different across cases (exposed to parent-managed behavioral intervention) and controls (not exposed to parent-managed behavioral intervention). The effect was modulated by the intensity of the behavioral intervention according to a dose-response relationship. The current feasibility case-control study provides the basis for estimating the statistical power required for future RCTs in this field. In addition, the study demonstrated the effectiveness of purposely-developed motion control protocols and helped to identify regions of interest candidates. Potential clinical applications of diffusion tensor imaging in the evaluation of treatment outcomes in ASD are discussed.

Reproducibility and repeatability of magnetic resonance imaging in dementia.

PURPOSE: Individualised predictive models of cognitive decline require disease-monitoring markers that are repeatable. For wide-spread adoption, such markers also need to be reproducible at different locations. This study assessed the repeatability and reproducibility of MRI markers derived from a dementia protocol. METHODS: Six participants were scanned at three different sites with a 3T MRI scanner. The protocol employed: T1-weighted (T1w) imaging, resting state functional MRI (rsfMRI), arterial spin labelling (ASL), diffusion-weighted imaging (DWI), T2-weighted fluid attenuation inversion recovery (FLAIR), T2-weighted (T2w) imaging, and susceptibility weighted imaging (SWI). Participants were scanned repeatedly, up to six times over a maximum period of five years. One participant was also scanned a further three times on sequential days on one scanner. Fifteen derived metrics were computed from the seven different modalities. RESULTS: Reproducibility (coefficient of variation; CoV, across sites) was best for T1w derived grey matter, white matter and hippocampal volume (CoV < 1.5%), compared to rsfMRI and SWI derived metrics (CoV, 19% and 21%). For a given metric, long-term repeatability (CoV across time) was comparable to reproducibility, with short-term repeatability considerably better. CONCLUSIONS: Reproducibility and repeatability were assessed for a suite of markers calculated from a dementia MRI protocol. In general, structural markers were less variable than functional MRI markers. Variability over time on the same scanner was comparable to variability measured across different scanners. Overall, the results support the viability of multi-site longitudinal studies for monitoring cognitive decline.

Right frontal anxiolytic-sensitive EEG 'theta' rhythm in the stop-signal task is a theory-based anxiety disorder biomarker.

Psychiatric diagnoses currently rely on a patient's presenting symptoms or signs, lacking much-needed theory-based biomarkers. Our neuropsychological theory of anxiety, recently supported by human imaging, is founded on a longstanding, reliable, rodent 'theta' brain rhythm model of human clinical anxiolytic drug action. We have now developed a human scalp EEG homolog-goal-conflict-specific rhythmicity (GCSR), i.e., EEG rhythmicity specific to a balanced conflict between goals (e.g., approach-avoidance). Critically, GCSR is consistently reduced by different classes of anxiolytic drug and correlates with clinically-relevant trait anxiety scores (STAI-T). Here we show elevated GCSR in student volunteers divided, after testing, on their STAI-T scores into low, medium, and high (typical of clinical anxiety) groups. We then tested anxiety disorder patients (meeting diagnostic criteria) and similar controls recruited separately from the community. The patient group had higher average GCSR than their controls-with a mixture of high and low GCSR that varied with, but cut across, conventional disorder diagnosis. Consequently, GCSR scores should provide the first theoretically-based biomarker that could help diagnose, and so redefine, a psychiatric disorder.

Spatial variation of perfusion MRI reflects cognitive decline in mild cognitive impairment and early dementia.

Cerebral blood flow (CBF) measured with arterial spin labelling (ASL) magnetic resonance imaging (MRI) reflects cerebral perfusion, related to metabolism, and arterial transit time (ATT), related to vascular health. Our aim was to investigate the spatial coefficient of variation (sCoV) of CBF maps as a surrogate for ATT, in volunteers meeting criteria for subjective cognitive decline (SCD), amnestic mild cognitive impairment (MCI) and probable Alzheimer's dementia (AD). Whole-brain pseudo continuous ASL MRI was performed at 3 T in 122 participants (controls = 20, SCD = 44, MCI = 45 and AD = 13) across three sites in New Zealand. From CBF maps that included all grey matter, sCoV progressively increased across each group with increased cognitive deficit. A similar overall trend was found when examining sCoV solely in the temporal lobe. We conclude that sCoV, a simple to compute imaging metric derived from ASL MRI, is sensitive to varying degrees of cognitive changes and supports the view that vascular health contributes to cognitive decline associated with Alzheimer's disease.

Personalised predictive modelling with brain-inspired spiking neural networks of longitudinal MRI neuroimaging data and the case study of dementia.

BACKGROUND: Longitudinal neuroimaging provides spatiotemporal brain data (STBD) measurement that can be utilised to understand dynamic changes in brain structure and/or function underpinning cognitive activities. Making sense of such highly interactive information is challenging, given that the features manifest intricate temporal, causal relations between the spatially distributed neural sources in the brain. METHODS: The current paper argues for the advancement of deep learning algorithms in brain-inspired spiking neural networks (SNN), capable of modelling structural data across time (longitudinal measurement) and space (anatomical components). The paper proposes a methodology and a computational architecture based on SNN for building personalised predictive models from longitudinal brain data to accurately detect, understand, and predict the dynamics of an individual's functional brain state. The methodology includes finding clusters of similar data to each individual, data interpolation, deep learning in a 3-dimensional brain-template structured SNN model, classification and prediction of individual outcome, visualisation of structural brain changes related to the predicted outcomes, interpretation of results, and individual and group predictive marker discovery. RESULTS: To demonstrate the functionality of the proposed methodology, the paper presents experimental results on a longitudinal magnetic resonance imaging (MRI) dataset derived from 175 older adults of the internationally recognised community-based cohort Sydney Memory and Ageing Study (MAS) spanning 6 years of follow-up. SIGNIFICANCE: The models were able to accurately classify and predict 2 years ahead of cognitive decline, such as mild cognitive impairment (MCI) and dementia with 95% and 91% accuracy, respectively. The proposed methodology also offers a 3-dimensional visualisation of the MRI models reflecting the dynamic patterns of regional changes in white matter hyperintensity (WMH) and brain volume over 6 years. CONCLUSION: The method is efficient for personalised predictive modelling on a wide range of neuroimaging longitudinal data, including also demographic, genetic, and clinical data. As a case study, it resulted in finding predictive markers for MCI and dementia as dynamic brain patterns using MRI data.

Impaired sensorimotor integration in focal hand dystonia patients in the absence of symptoms.

BACKGROUND: Functional imaging studies of people with focal hand dystonia (FHD) have indicated abnormal activity in sensorimotor brain regions. Few studies however, have examined FHD during movements that do not provoke symptoms of the disorder. It is possible, therefore, that any differences between FHD and controls are confounded by activity due to the occurrence of symptoms. Thus, in order to characterise impairments in patients with FHD during movements that do not induce dystonic symptoms, we investigated the neural correlates of externally paced finger tapping movements. METHODS: Functional MRI (fMRI) was used to compare patients with FHD to controls with respect to activation in networks modulated by task complexity and hand used to perform simple and complex tapping movements. RESULTS: In the 'complexity network,' patients with FHD showed significantly less activity relative to controls in posterior parietal cortex, medial supplementary motor area (SMA), anterior putamen and cerebellum. In the 'hand network,' patients with FHD showed less activation than controls in primary motor (M1) and somatosensory (S1) cortices, SMA and cerebellum. Conjunction analysis revealed that patients with FHD demonstrated reduced activation in the majority of combined network regions (M1, S1 and cerebellum). CONCLUSION: Dysfunction in FHD is widespread in both complexity and hand networks, and impairments are demonstrated even when performing tasks that do not evoke dystonic symptoms. These results suggest that such impairments are inherent to, rather than symptomatic of, the disorder.

Testing the repression hypothesis: effects of emotional valence on memory suppression in the think - no think task.

It has been proposed that performance in the think - no think (TNT) task represents a laboratory analogue of the voluntary form of memory repression. The central prediction of this repression hypothesis is that performance in the TNT task will be influenced by emotional characteristics of the material to be remembered. This prediction was tested in two experiments by asking participants to learn paired associates in which the first item was either emotionally positive (e.g. joy) or emotionally negative (e.g. hatred). The second word was always emotionally neutral (e.g. socks). Consistent with the repression hypothesis, significant memory suppression was observed in both experiments following 'no think' instructions for memories associated with emotionally negative material. No suppression was observed for memories associated with emotionally positive information. Implications of these findings for the relationship between performance in the TNT task and the controversial notion of memory repression are considered.

Frontal-midline theta from the perspective of hippocampal "theta".

Electrical recordings from the surface of the skull have a wide range of rhythmic components. A major task of analysis of this EEG is to determine their source and functional significance. The hippocampal "theta rhythm" has been extensively studied in rats and its rhythmicity has recently been shown to be functionally significant, per se. Here, we use relevant aspects of the hippocampal literature to provide perspective on one of the most studied human EEG rhythms: frontal-midline theta. We review its electrographic features, localization, prevalence, age distribution, behavioural modulation (particularly in relation to working memory, spatial navigation, episodic memory, internalised attention and meditation), relationship to personality, drug interactions, neurochemical relationships, and coherence with rhythmic activity at other sites. We conclude that FM-theta, like hippocampal theta, appears to play a role in (or at least occur during) processing of memory and emotion. It is correlated with working memory and/or sustained attention; but this does not entail a role in function since clear behavioural correlates of hippocampal theta have been demonstrated that are not sensitive to hippocampal damage. FM-theta is increased by anxiolytic drug action and personality-related reductions in anxiety, whereas hippocampal theta is decreased by anxiolytic drugs. In animals, frontal theta and hippocampal theta can be phase-locked or independent, depending on behavioural state. So, the cognitive functions of FM-theta, and their relationship to hippocampal theta, are unclear and definitive evidence for functional involvement in cognitive or emotional processing is lacking. One possible solution to this problem is analysis of FM-theta in animals-provided homology can be determined. The issues of sporadicity and low incidence of FM-theta also need to be addressed in the future. Changes in functional connectivity, indicated by changes in coherence, are also a largely untapped resource. We suggest that the most hopeful path to assessing the functions of FM-theta will be through the use of drugs, and the variation of their effects depending on baseline levels of FM-theta. Finally, we review some theories of theta function. Despite the apparent richness of the current data, we conclude that it is difficult (and may ultimately be impossible) to formulate a theory that attributes a specific cognitive function to FM-theta. However, the theories share some general computational assumptions and these should be a useful guide to future work and, ultimately, a definite theory of the function or functions of FM-theta.