Gloria Roberts

Deficits in learning and memory: Parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users

The consumption of cannabis has been linked to impairments in human learning and memory, as well as aspects of executive functioning. Cannabis-related impairments in learning and memory in chronic cannabis users, it has been argued, are caused by the effects of cannabis on hippocampal functioning. The current study involved two experiments. Experiment 1 compared 35 current users of cannabis and 38 well-matched controls on a face-name task, previously shown to activate the hippocampal region. Based on the results of experiment 1, experiment 2 used fMRI and a modified version of the face-name task, to examine cortical and (para)hippocampal activity during learning and recall in 14 current users of cannabis and 14 controls. Results of experiment 1 showed that cannabis users were significantly worse with respect to learning, short and long-term memory performance. Experiment 2 showed that despite non-significant differences in learning and memory performance, cannabis users had significantly lower levels of BOLD activity in the right superior temporal gyrus, right superior frontal gyrus, right middle frontal gyrus and left superior frontal gyrus compared to controls during learning. Results also showed that cannabis users had significantly higher BOLD activity in the right parahippocampal gyrus during learning. Hypoactivity in frontal and temporal cortices, and relative hyperactivity in the parahippocampus identify functional deficits and compensatory processes in cannabis users.

Reduced Inferior Frontal Gyrus Activation During Response Inhibition to Emotional Stimuli in Youth at High Risk of Bipolar Disorder

BACKGROUND Functional brain imaging of young people at increased genetic risk for bipolar disorder provides a means of identifying potential endophenotypes for this condition. Dysfunctional neural mechanisms for the cognitive control of emotion are implicated in the genetic predisposition to bipolar disorder, with aberrant activity in frontocortical, striatal, and limbic brain regions previously reported in subjects with established bipolar disorder during inhibitory and emotion processing tasks. METHODS Functional brain activity during inhibition of emotional material in young people at increased genetic risk for bipolar disorder was investigated using a facial-emotion go/no-go task during functional magnetic resonance imaging. Data from 47 genetically high-risk individuals aged 18 to 30 years with at least one first-degree relative with bipolar disorder were compared with 49 control subjects (within the same age range but without a family history of bipolar disorder or other severe mental illness). RESULTS Whole-brain corrected analyses revealed a highly specific and significant lack of recruitment of the inferior frontal gyrus when inhibiting responses to fearful faces in the high-risk participants compared with control subjects (p = .011, family-wise error, peak voxel). CONCLUSIONS Impaired inhibitory function of the inferior frontal cortex may represent a trait marker of vulnerability to bipolar disorder. That this finding was revealed during inhibition of emotional material further implicates dysregulated frontolimbic brain networks as a potential neurocognitive endophenotype for bipolar disorder and provides evidence for pre-existing functional disturbances in those at high genetic risk for bipolar disorder.

The contribution of geometry to the human connectome.

The human connectome is a topologically complex, spatially embedded network. While its topological properties have been richly characterized, the constraints imposed by its spatial embedding are poorly understood. By applying a novel resampling method to tractography data, we show that the brains spatial embedding makes a major, but not definitive, contribution to the topology of the human connectome. We first identify where the brains structural hubs would likely be located if geometry was the sole determinant of brain topology. Empirical networks show a widespread shift away from this geometric center toward more peripheral interconnected skeletons in each hemisphere, with discrete clusters around the anterior insula, and the anterior and posterior midline regions of the cortex. A relatively small number of strong inter-hemispheric connections assimilate these intra-hemispheric structures into a rich club, whose connections are locally more clustered but globally longer than predicted by geometry. We also quantify the extent to which the segregation, integration, and modularity of the human brain are passively inherited from its geometry. These analyses reveal novel insights into the influence of spatial geometry on the human connectome, highlighting specific topological features that likely confer functional advantages but carry an additional metabolic cost.

Menstrual cycle phase modulates cognitive control over male but not female stimuli

Evolutionary selection pressures have been one of the factors proposed to underlie sex differences in inhibitory control. Consequently, inhibitory control may vary as a function of the menstrual cycle and may be modulated by the stimuli being processed if these stimuli are related to reproductive success. We used functional MRI to study womens brain activation across the menstrual cycle on a GO/NOGO response inhibition task using attractive male and female faces as stimuli. We detected brain activity changes for both successful inhibitions and errors of commission that were unique to the male stimuli during the follicular phase of the menstrual cycle. That is, when pregnancy was possible women had superior inhibitory brain function and heightened detection of inhibitory failures when processing male stimuli. Moreover, we show that individual differences between females in sexual desire and social risk taking negatively correlate with error-related brain activity to the male stimuli during the follicular phase of the menstrual cycle. These results suggest an interaction between hormonal influences and stimulus-specific effects in producing an endophenotypic outcome predicted by evolutionary psychology, and suggest that the functioning of the brains monitoring system can predict individual differences in both traits and real-world risk-taking behaviours.

Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task.

It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.

The organisation of the elderly connectome

Investigations of the human connectome have elucidated core features of adult structural networks, particularly the crucial role of hub-regions. However, little is known regarding network organisation of the healthy elderly connectome, a crucial prelude to the systematic study of neurodegenerative disorders. Here, whole-brain probabilistic tractography was performed on high-angular diffusion-weighted images acquired from 115 healthy elderly subjects (age 76-94 years; 65 females). Structural networks were reconstructed between 512 cortical and subcortical brain regions. We sought to investigate the architectural features of hub-regions, as well as left-right asymmetries, and sexual dimorphisms. We observed that the topology of hub-regions is consistent with a young adult population, and previously published adult connectomic data. More importantly, the architectural features of hub connections reflect their ongoing vital role in network communication. We also found substantial sexual dimorphisms, with females exhibiting stronger inter-hemispheric connections between cingulate and prefrontal cortices. Lastly, we demonstrate intriguing left-lateralized subnetworks consistent with the neural circuitry specialised for language and executive functions, whilst rightward subnetworks were dominant in visual and visuospatial streams. These findings provide insights into healthy brain ageing and provide a benchmark for the study of neurodegenerative disorders such as Alzheimers disease (AD) and frontotemporal dementia (FTD).

Bipolar disorder in a national survey using the World Mental Health Version of the Composite International Diagnostic Interview: the impact of differing diagnostic algorithms

Mitchell PB, Johnston AK, Frankland A, Slade T, Green MJ, Roberts G, Wright A, Corry J, Hadzi‐Pavlovic D. Bipolar disorder in a national survey using the World Mental Health Version of the Composite International Diagnostic Interview: the impact of differing diagnostic algorithms.

Network dysfunction of emotional and cognitive processes in those at genetic risk of bipolar disorder

The emotional and cognitive vulnerabilities that precede the development of bipolar disorder are poorly understood. The inferior frontal gyrus-a key cortical hub for the integration of cognitive and emotional processes-exhibits both structural and functional changes in bipolar disorder, and is also functionally impaired in unaffected first-degree relatives, showing diminished engagement during inhibition of threat-related emotional stimuli. We hypothesized that this functional impairment of the inferior frontal gyrus in those at genetic risk of bipolar disorder reflects the dysfunction of broader network dynamics underlying the coordination of emotion perception and cognitive control. To test this, we studied effective connectivity in functional magnetic resonance imaging data acquired from 41 first-degree relatives of patients with bipolar disorder, 45 matched healthy controls and 55 participants with established bipolar disorder. Dynamic causal modelling was used to model the neuronal interaction between key regions associated with fear perception (the anterior cingulate), inhibition (the left dorsolateral prefrontal cortex) and the region upon which these influences converge, namely the inferior frontal gyrus. Network models that embodied non-linear, hierarchical relationships were the most strongly supported by data from our healthy control and bipolar participants. We observed a marked difference in the hierarchical influence of the anterior cingulate on the effective connectivity from the dorsolateral prefrontal cortex to the inferior frontal gyrus that is unique to the at-risk cohort. Non-specific, non-hierarchical mechanisms appear to compensate for this network disturbance. We thus establish a specific network disturbance suggesting dysfunction in the processes that support hierarchical relationships between emotion and cognitive control in those at high genetic risk for bipolar disorder.

Consistency-based thresholding of the human connectome

Abstract Densely seeded probabilistic tractography yields weighted networks that are nearly fully connected, hence containing many spurious fibers. It is thus necessary to prune spurious connections from probabilistically‐derived networks to obtain a more reliable overall estimate of the connectivity. A standard method is to threshold by weight, keeping only the strongest edges. Here, by measuring the consistency of edge weights across subjects, we propose a new thresholding method that aims to reduce the rate of false‐positives in group‐averaged connectivity matrices. Close inspection of the relationship between consistency, weight, and distance suggests that the most consistent edges are in fact those that are strong for their length, rather than simply strong overall. Hence retaining the most consistent edges preserves more long‐distance connections than traditional weight‐based thresholding, which penalizes long connections for being weak regardless of anatomy. By comparing our thresholded networks to mouse and macaque tracer data, we also show that consistency‐based thresholding exhibits the species‐invariant exponential decay of connection weights with distance, while weight‐based thresholding does not. We also show that consistency‐based thresholding can be used to identify highly consistent and highly inconsistent subnetworks across subjects, enabling more nuanced analyses of group‐level connectivity than just the mean connectivity. HighlightsThresholding is a common method for pruning networks.We developed a novel method for thresholding networks by intersubject consistency.Consistent edges tend to be those that are strong for their length, rather than strong overall.Our method replicates in an independent dataset.Consistent edges have similar distance dependence to mouse and macaque tracer data.

Neuropsychological and social cognitive function in young people at genetic risk of bipolar disorder

BACKGROUND Impairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives. METHOD Neurocognitive and social cognitive ability was examined in 99 young people (age range 16-30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD. RESULTS Only verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs. CONCLUSIONS Selective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.