Alterations to functional connectivity following a traumatic brain injury (TBI) may lead to impai... more Alterations to functional connectivity following a traumatic brain injury (TBI) may lead to impaired cognitive performance and major depressive disorder (MDD). In particular, functional gamma band connectivity is thought to reflect information binding important for working memory. The objective of this study was to determine whether altered functional gamma connectivity may be a factor in MDD following TBI (TBI-MDD). This study assessed individuals with TBI-MDD, as well as individuals with TBI alone and MDD alone using electroencephalographic recordings while participants performed a working memory task to assess differences in functional connectivity between these groups. Functional connectivity was compared using the debiased weighted phase lag index (wPLI). wPLI was measured from a group of healthy controls (n = 31), participants with MDD (n = 17), participants with TBI (n = 20) and participants with TBI-MDD (n = 15). Contrary to the predictions, this study found both the groups ...
Ultrasound (US) at diagnostic frequency and power is known to alter nerve potentials; however, th... more Ultrasound (US) at diagnostic frequency and power is known to alter nerve potentials; however, the precise mechanism of action is unknown. We investigated whether US alters resting nerve potential to lower the threshold for magnetic nerve stimulation. Seventeen healthy subjects were recruited. For each subject, a 1.5 MHz US imaging probe was placed onto the elbow with the beam directed at the ulnar nerve. The probe was coupled to the skin using standard acoustic coupling gel as would be done for a routine clinical US scan. Ulnar nerve stimulation was performed simultaneously with magnetic stimulation (MS). Successful magnetic stimulation of the ulnar nerve was confirmed with nerve potentials measured by electromyography. There was no significant change in electromyography signal when MS was performed during US exposure. US at the diagnostic frequency and power tested does not alter nerve thresholds with MS. Testing at other frequencies is required, however, before US is negated as a...
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, Jan 15, 2016
The impact of stressful life events (SLEs) on brain anatomy is poorly understood, particularly it... more The impact of stressful life events (SLEs) on brain anatomy is poorly understood, particularly its long-term neural consequences. We tested the hypothesis that a serious SLE (repatriation of French citizens living in Algeria in 1962) is associated with changes in brain regions previously implicated in psychopathology (hippocampus, amygdala, corpus callosum, prefrontal cortex, anterior, posterior and isthmus cingulate cortex (ICC)) in a large elderly population. Structural magnetic resonance imaging was used to acquire anatomical scans from 82 subjects repatriated from Algeria and 339 subjects without this experience or any other trauma. We derived quantitative regional estimates of subcortical volume using FreeSurfer Software. The General Linear Model was used to test the association between repatriation and changes in brain volume adjusted for confounders (gender, age, education, total brain volume, traumatic brain injury, Mini Mental State Examination score at baseline, current an...
Recent neuroimaging studies in body dysmorphic disorder (BDD) have implicated abnormal structure ... more Recent neuroimaging studies in body dysmorphic disorder (BDD) have implicated abnormal structure and function of occipito-temporal and fronto-limbic regions in the potential pathophysiology of the disorder. To date, morphometric investigations have yielded inconsistent results, and have suggested that clinical symptoms may mediate structural brain abnormalities in BDD. We measured Grey Matter (GM) cortical thickness in 20 participants with BDD and 20 healthy control participants matched on age, gender, estimated IQ and handedness. We observed cortical thinning in BDD patients compared with healthy control participants within the left middle temporal and left inferior parietal gyrus. No significant relationships between cortical thickness and BDD symptom severity, insight, social anxiety and depression were observed within the BDD group. Thinning within left temporal and left inferior parietal regions supports the involvement of these regions in the pathophysiology of BDD.
Episodic memory (EM) impairments in schizophrenia (SZ) are predictive of functional outcome and a... more Episodic memory (EM) impairments in schizophrenia (SZ) are predictive of functional outcome and are a potential endophenotype of the disorder. The current study investigated the neuroanatomical correlates of EM encoding and retrieval in SZ with structural magnetic resonance and diffusion tensor imaging (DTI) measures in 22 patients with SZ and 22 age- and gender-matched healthy controls. Tract-based Spatial Statistics (TBSS) was used to investigate microstructural alterations in white matter (WM), while FreeSurfer surface-based analysis was used to determine abnormalities in grey matter (GM) and WM volumetrics and cortical thickness. Compared to controls, patients demonstrated GM deficits in temporal and parietal regions and lower fractional anisotropy (FA) of WM in diffuse brain regions. Patients also demonstrated reduced functioning in both encoding and retention of auditory-verbal EM. Among patients but not controls, EM encoding correlated with WM volume in the orbitofrontal cort...
Concussion is common in the sporting arena and is often challenging to diagnose. The development ... more Concussion is common in the sporting arena and is often challenging to diagnose. The development of wearable head impact measurement systems has enabled measurement of head kinematics in contact sports. The objective of this systematic review was to determine the characteristics of head kinematics measured by an accelerometer system among male athletes diagnosed with concussion. A systematic search was conducted in July 2015. Inclusion criteria were English-language studies published after 1990 with a study population of male athletes, in any sport, where objectively measured biomechanical forces were reported in the setting of a concussive event. The random effects meta-analysis model was used to combine estimates of biomechanical force measurements in concussed athletes. Thirteen studies met the inclusion criteria, the majority of which were conducted with high school and college football teams in the US. Included studies measured a combination of linear and rotational acceleratio...
Journal of psychiatry & neuroscience : JPN, Jan 7, 2016
Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) ... more Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance). We recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate. A ...
Previous studies suggest that altered corneal temperature may be a feature of schizophrenia, but ... more Previous studies suggest that altered corneal temperature may be a feature of schizophrenia, but the association between major depressive disorder (MDD) and corneal temperature has yet to be assessed. The aim of this study is to investigate whether eye temperature is different among MDD patients than among healthy individuals. We used a thermographic camera to measure and compare the temperature profile across the corneas of 16 patients with MDD and 16 age- and sex-matched healthy subjects. We found that the average corneal temperature between the two groups did not differ statistically, although clinical severity correlated positively with right corneal temperature. Corneal temperature may be an indicator of clinical severity in psychiatric disorders, including depression.
Transcranial magnetic stimulation (TMS) is an increasingly popular tool in treating psychiatric c... more Transcranial magnetic stimulation (TMS) is an increasingly popular tool in treating psychiatric conditions. The dorsal lateral prefrontal cortex (DLPFC) is typically targeted for stimulation, with magnetic field intensity being calibrated by establishing resting motor threshold (RMT) at hand region of primary motor cortex (M1 hand). This presumes that scalp-to-cortex distance (SCD) and cortical thickness is similar at both sites. We present data from a patient who had very asymmetrical RMTs (47 and 78). We investigated SCDs in this patient at the M1 hand and DLPFC, and the M1 hand cortical thickness. We also investigated TMS electric field distribution. The M1 hand SCD and cortical thickness of the M1 hand was larger on the side with higher RMT. Electric field finite element modelling demonstrated the focal point did not effectively reach the M1 hand with higher RMT as the postcentral gyrus was shunting it. Hence, successful DLPFC treatment was based upon the side with lower RMT. Th...
A number of genome-wide association studies (GWAS) have investigated risk factors for major depre... more A number of genome-wide association studies (GWAS) have investigated risk factors for major depressive disorder (MDD), however there has been little attempt to replicate these findings in population-based studies of depressive symptoms. Variants within three genes, BICC1, PCLO and GRM7 were selected for replication in our study based on the following criteria: they were identified in a prior MDD GWAS study; a subsequent study found evidence that they influenced depression risk; and there is a solid biological basis for a role in depression. We firstly investigated whether these variants were associated with depressive symptoms in our population-based cohort of 929 elderly (238 with clinical depressive symptoms and 691 controls), and secondly to investigate associations with structural brain alterations. A number of nominally significant associations were identified, but none reached Bonferroni-corrected significance levels. Common SNPs in BICC1 and PCLO were associated with a 50% and 30% decreased risk of depression, respectively. PCLO rs2522833 was also associated with the volume of grey matter (p=1.6×10(-3)), and to a lesser extent with hippocampal volume and white matter lesions. Among depressed individuals rs9870680 (GRM7) was associated with the volume of grey and white matter (p=10(-4) and 8.3×10(-3), respectively). Our results provide some support for the involvement of BICC1 and PCLO in late-life depressive disorders and preliminary evidence that these genetic variants may also influence brain structural volumes. However effect sizes remain modest and associations did not reach corrected significance levels. Further large imaging studies are needed to confirm our findings.
Traumatic brain injury (TBI) is a complex pathophysiological process resulting from external forc... more Traumatic brain injury (TBI) is a complex pathophysiological process resulting from external forces applied to the skull and affecting the brain. TBI is a significant global contributor to disability and death, particularly in children and young adults. The severity of a TBI may range from " mild " (a brief change in mental status or consciousness) to " severe " (an extended period of unconsciousness or amnesia after the injury), with mild TBI (mTBI) the most common form, diagnosed in 80-90% of cases. Sports-related concussion contributes significantly to mTBI accounting for nearly 20% of all mTBI cases. In the past decade there has been increasing growing public concern regarding the association of sports concussion; in particular further chance of recurrent injury following a concussion due to transient cognitive impairments, and long-term detrimental mental health issues and deterioration in brain function as a consequence of multiple concussions. Attention is...
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, Jan 27, 2015
No electrophysiological neuroimaging or genetic markers have been established that strongly relat... more No electrophysiological neuroimaging or genetic markers have been established that strongly relate to a diagnosis of major depression or its severity. The objective of this paper is to describe the preliminary evaluation of a potential new biomarker for depression utilizing the recording of electrical activity from the outer ear canal referred to as electrovestibulography (EVestG). Sensory oto-acoustic features were extracted from EVestG data to compare 31 healthy age- and gender-matched individuals as controls to 43 major depressive disorder (MDD) subjects (22 symptomatic (MDD-S), 21 reduced symptomatic (MDD-R)). The stimulus was a single supine-vertical translation. The six features examined were based on the measured firing pattern interval histogram and the shape of the average field potential response. An unbiased classification accuracy of 85, 87 and 77% was achieved for separating Control from MDD-S, Control from MDD, and MDD-S from MDD-R groups respectively. Features used sh...
Recent theorising on the nature of racism suggests that over the last few decades it has come to ... more Recent theorising on the nature of racism suggests that over the last few decades it has come to be expressed in more subtle and ambiguous ways because while many Whites proclaim egalitarian values, their cognitions and behaviour are influenced by prejudices ...
Alterations to functional connectivity following a traumatic brain injury (TBI) may lead to impai... more Alterations to functional connectivity following a traumatic brain injury (TBI) may lead to impaired cognitive performance and major depressive disorder (MDD). In particular, functional gamma band connectivity is thought to reflect information binding important for working memory. The objective of this study was to determine whether altered functional gamma connectivity may be a factor in MDD following TBI (TBI-MDD). This study assessed individuals with TBI-MDD, as well as individuals with TBI alone and MDD alone using electroencephalographic recordings while participants performed a working memory task to assess differences in functional connectivity between these groups. Functional connectivity was compared using the debiased weighted phase lag index (wPLI). wPLI was measured from a group of healthy controls (n = 31), participants with MDD (n = 17), participants with TBI (n = 20) and participants with TBI-MDD (n = 15). Contrary to the predictions, this study found both the groups ...
Ultrasound (US) at diagnostic frequency and power is known to alter nerve potentials; however, th... more Ultrasound (US) at diagnostic frequency and power is known to alter nerve potentials; however, the precise mechanism of action is unknown. We investigated whether US alters resting nerve potential to lower the threshold for magnetic nerve stimulation. Seventeen healthy subjects were recruited. For each subject, a 1.5 MHz US imaging probe was placed onto the elbow with the beam directed at the ulnar nerve. The probe was coupled to the skin using standard acoustic coupling gel as would be done for a routine clinical US scan. Ulnar nerve stimulation was performed simultaneously with magnetic stimulation (MS). Successful magnetic stimulation of the ulnar nerve was confirmed with nerve potentials measured by electromyography. There was no significant change in electromyography signal when MS was performed during US exposure. US at the diagnostic frequency and power tested does not alter nerve thresholds with MS. Testing at other frequencies is required, however, before US is negated as a...
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, Jan 15, 2016
The impact of stressful life events (SLEs) on brain anatomy is poorly understood, particularly it... more The impact of stressful life events (SLEs) on brain anatomy is poorly understood, particularly its long-term neural consequences. We tested the hypothesis that a serious SLE (repatriation of French citizens living in Algeria in 1962) is associated with changes in brain regions previously implicated in psychopathology (hippocampus, amygdala, corpus callosum, prefrontal cortex, anterior, posterior and isthmus cingulate cortex (ICC)) in a large elderly population. Structural magnetic resonance imaging was used to acquire anatomical scans from 82 subjects repatriated from Algeria and 339 subjects without this experience or any other trauma. We derived quantitative regional estimates of subcortical volume using FreeSurfer Software. The General Linear Model was used to test the association between repatriation and changes in brain volume adjusted for confounders (gender, age, education, total brain volume, traumatic brain injury, Mini Mental State Examination score at baseline, current an...
Recent neuroimaging studies in body dysmorphic disorder (BDD) have implicated abnormal structure ... more Recent neuroimaging studies in body dysmorphic disorder (BDD) have implicated abnormal structure and function of occipito-temporal and fronto-limbic regions in the potential pathophysiology of the disorder. To date, morphometric investigations have yielded inconsistent results, and have suggested that clinical symptoms may mediate structural brain abnormalities in BDD. We measured Grey Matter (GM) cortical thickness in 20 participants with BDD and 20 healthy control participants matched on age, gender, estimated IQ and handedness. We observed cortical thinning in BDD patients compared with healthy control participants within the left middle temporal and left inferior parietal gyrus. No significant relationships between cortical thickness and BDD symptom severity, insight, social anxiety and depression were observed within the BDD group. Thinning within left temporal and left inferior parietal regions supports the involvement of these regions in the pathophysiology of BDD.
Episodic memory (EM) impairments in schizophrenia (SZ) are predictive of functional outcome and a... more Episodic memory (EM) impairments in schizophrenia (SZ) are predictive of functional outcome and are a potential endophenotype of the disorder. The current study investigated the neuroanatomical correlates of EM encoding and retrieval in SZ with structural magnetic resonance and diffusion tensor imaging (DTI) measures in 22 patients with SZ and 22 age- and gender-matched healthy controls. Tract-based Spatial Statistics (TBSS) was used to investigate microstructural alterations in white matter (WM), while FreeSurfer surface-based analysis was used to determine abnormalities in grey matter (GM) and WM volumetrics and cortical thickness. Compared to controls, patients demonstrated GM deficits in temporal and parietal regions and lower fractional anisotropy (FA) of WM in diffuse brain regions. Patients also demonstrated reduced functioning in both encoding and retention of auditory-verbal EM. Among patients but not controls, EM encoding correlated with WM volume in the orbitofrontal cort...
Concussion is common in the sporting arena and is often challenging to diagnose. The development ... more Concussion is common in the sporting arena and is often challenging to diagnose. The development of wearable head impact measurement systems has enabled measurement of head kinematics in contact sports. The objective of this systematic review was to determine the characteristics of head kinematics measured by an accelerometer system among male athletes diagnosed with concussion. A systematic search was conducted in July 2015. Inclusion criteria were English-language studies published after 1990 with a study population of male athletes, in any sport, where objectively measured biomechanical forces were reported in the setting of a concussive event. The random effects meta-analysis model was used to combine estimates of biomechanical force measurements in concussed athletes. Thirteen studies met the inclusion criteria, the majority of which were conducted with high school and college football teams in the US. Included studies measured a combination of linear and rotational acceleratio...
Journal of psychiatry & neuroscience : JPN, Jan 7, 2016
Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) ... more Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance). We recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate. A ...
Previous studies suggest that altered corneal temperature may be a feature of schizophrenia, but ... more Previous studies suggest that altered corneal temperature may be a feature of schizophrenia, but the association between major depressive disorder (MDD) and corneal temperature has yet to be assessed. The aim of this study is to investigate whether eye temperature is different among MDD patients than among healthy individuals. We used a thermographic camera to measure and compare the temperature profile across the corneas of 16 patients with MDD and 16 age- and sex-matched healthy subjects. We found that the average corneal temperature between the two groups did not differ statistically, although clinical severity correlated positively with right corneal temperature. Corneal temperature may be an indicator of clinical severity in psychiatric disorders, including depression.
Transcranial magnetic stimulation (TMS) is an increasingly popular tool in treating psychiatric c... more Transcranial magnetic stimulation (TMS) is an increasingly popular tool in treating psychiatric conditions. The dorsal lateral prefrontal cortex (DLPFC) is typically targeted for stimulation, with magnetic field intensity being calibrated by establishing resting motor threshold (RMT) at hand region of primary motor cortex (M1 hand). This presumes that scalp-to-cortex distance (SCD) and cortical thickness is similar at both sites. We present data from a patient who had very asymmetrical RMTs (47 and 78). We investigated SCDs in this patient at the M1 hand and DLPFC, and the M1 hand cortical thickness. We also investigated TMS electric field distribution. The M1 hand SCD and cortical thickness of the M1 hand was larger on the side with higher RMT. Electric field finite element modelling demonstrated the focal point did not effectively reach the M1 hand with higher RMT as the postcentral gyrus was shunting it. Hence, successful DLPFC treatment was based upon the side with lower RMT. Th...
A number of genome-wide association studies (GWAS) have investigated risk factors for major depre... more A number of genome-wide association studies (GWAS) have investigated risk factors for major depressive disorder (MDD), however there has been little attempt to replicate these findings in population-based studies of depressive symptoms. Variants within three genes, BICC1, PCLO and GRM7 were selected for replication in our study based on the following criteria: they were identified in a prior MDD GWAS study; a subsequent study found evidence that they influenced depression risk; and there is a solid biological basis for a role in depression. We firstly investigated whether these variants were associated with depressive symptoms in our population-based cohort of 929 elderly (238 with clinical depressive symptoms and 691 controls), and secondly to investigate associations with structural brain alterations. A number of nominally significant associations were identified, but none reached Bonferroni-corrected significance levels. Common SNPs in BICC1 and PCLO were associated with a 50% and 30% decreased risk of depression, respectively. PCLO rs2522833 was also associated with the volume of grey matter (p=1.6×10(-3)), and to a lesser extent with hippocampal volume and white matter lesions. Among depressed individuals rs9870680 (GRM7) was associated with the volume of grey and white matter (p=10(-4) and 8.3×10(-3), respectively). Our results provide some support for the involvement of BICC1 and PCLO in late-life depressive disorders and preliminary evidence that these genetic variants may also influence brain structural volumes. However effect sizes remain modest and associations did not reach corrected significance levels. Further large imaging studies are needed to confirm our findings.
Traumatic brain injury (TBI) is a complex pathophysiological process resulting from external forc... more Traumatic brain injury (TBI) is a complex pathophysiological process resulting from external forces applied to the skull and affecting the brain. TBI is a significant global contributor to disability and death, particularly in children and young adults. The severity of a TBI may range from " mild " (a brief change in mental status or consciousness) to " severe " (an extended period of unconsciousness or amnesia after the injury), with mild TBI (mTBI) the most common form, diagnosed in 80-90% of cases. Sports-related concussion contributes significantly to mTBI accounting for nearly 20% of all mTBI cases. In the past decade there has been increasing growing public concern regarding the association of sports concussion; in particular further chance of recurrent injury following a concussion due to transient cognitive impairments, and long-term detrimental mental health issues and deterioration in brain function as a consequence of multiple concussions. Attention is...
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, Jan 27, 2015
No electrophysiological neuroimaging or genetic markers have been established that strongly relat... more No electrophysiological neuroimaging or genetic markers have been established that strongly relate to a diagnosis of major depression or its severity. The objective of this paper is to describe the preliminary evaluation of a potential new biomarker for depression utilizing the recording of electrical activity from the outer ear canal referred to as electrovestibulography (EVestG). Sensory oto-acoustic features were extracted from EVestG data to compare 31 healthy age- and gender-matched individuals as controls to 43 major depressive disorder (MDD) subjects (22 symptomatic (MDD-S), 21 reduced symptomatic (MDD-R)). The stimulus was a single supine-vertical translation. The six features examined were based on the measured firing pattern interval histogram and the shape of the average field potential response. An unbiased classification accuracy of 85, 87 and 77% was achieved for separating Control from MDD-S, Control from MDD, and MDD-S from MDD-R groups respectively. Features used sh...
Recent theorising on the nature of racism suggests that over the last few decades it has come to ... more Recent theorising on the nature of racism suggests that over the last few decades it has come to be expressed in more subtle and ambiguous ways because while many Whites proclaim egalitarian values, their cognitions and behaviour are influenced by prejudices ...
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Papers by Jerome Maller