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Working memory function in post-traumatic stress disorder: An event-related potential study
Abstract
Previous studies using event-related potentials (ERPs) in post-traumatic stress disorder (PTSD) have demonstrated reduced P3 amplitude during target detection and working memory (WM) processes. This study investigated effects of psychotropic medication (primarily antidepressants) on these ERP components.
ERPs were recorded from 26 scalp sites in 34 PTSD patients (20 unmedicated, 14 medicated) with age- and gender-matched controls during a WM paradigm that involved detection of target letters on a visual display.
As expected, PTSD patients showed a reduced amplitude P3wm component during WM updating and a reduced and delayed target P3 component. Contrary to expectation, these ERP effects were most apparent in the medicated subgroup of PTSD patients. The medicated PTSD subgroup showed a trend towards reduced P3wm amplitude compared with controls and a significant amplitude reduction and delay of target P3 component, while there was little difference between the non-medicated PTSD subgroup and controls. Neither ERP nor behavioural measures were related to Clinician Administered PTSD Scale (CAPS) symptom severity measures.
These results are consistent with research that suggests antidepressant medication may impair working memory performance.
The present study illustrates the importance of monitoring medication effects on cognitive performance during clinical efficacy studies.
... These findings demonstrate that the P300 current source density might reflect the pathophysiology of PTSD and that various neural networks might contribute to the symptom characteristics of PTSD. A visual working memory task was used to investigate associations between PTSS and P3 responses (Veltmeyer et al., 2009). PTSD subjects (divided into a medicated and non-medicated group) performed a visual working memory task that consisted of a series of letters for which participants were asked to respond when any letter that was identical to the one presented previously (1-back) appeared. ...
... In emotion paradigms, slow wave activity indicates elevated positivity in response to highly arousing stimuli (Cuthbert et al., 2000;Mocaiber et al., 2010Mocaiber et al., , 2009. In fact, using distinct tasks, three studies found positive correlations between these variables: increased severity of PTSS was related to greater P3-family ERP amplitudes (Covey et al., 2013;Lobo et al., 2014;Veltmeyer et al., 2009). This evidence is consistent with a study that found that compared with healthy control subjects, traumatized groups (with and without PTSD) exhibited increased P300 and late positive complex amplitudes in response to traumaspecific questions (Wessa et al., 2006). ...
... It is possible that mixed-trauma samples prevent significant results from being achieved in the EEG studies. In fact, most of the studies that used a mixed-trauma sample found no significant correlation between EEG parameters and the severity of symptoms-very few exceptions were found (Lobo et al., 2014;Veltmeyer et al., 2009Veltmeyer et al., , 2006. ...
... Although post-traumatic stress disorder (PTSD) is classified as an 'anxiety disorder', evidence of cognitive and information processing (IP) abnormalities in PTSD has been accumulating [1]. While many studies on emotional processing abnormalities in PTSD exist, event-related potentials (ERPs) studies focusing on early stages of IP abnormalities in PTSD are limited in number. ...
... at Pz. [12] STAI, BDI (Beck Depression Inventory), CAPS Negative relationship between P550 amplitude and trait anxiety. Negative relationship between P550 amplitude and depression CAPS scores; negative relationship between P550 amplitude and intrusions. [36] Brief Symptom Inventory (BSI), MMN was significantly correlated with the total PTSD score. [1] CAPS Neither P300 nor behavioral measures were related to CAPS symptom severity measures. ...
... Although Metzger and colleagues [41] reported smaller P300 amplitude to all the stimuli in the PTSD patients, they found a smaller response to the neutral words as compared to the positive and negative words. Ehlers and colleagues [42] reported reduced amplitude to neutral faces in the PTSD patients and Veltmeyer and colleagues [1] in an N-back working memory task found reduced P300 amplitude in the PTSD group. We also reviewed P300 responses to TR/aversive stimuli and neutral stimuli separately irrespective of the modality of stimulus presentation (auditory or visual). ...
Despite the sparseness of the currently available data, there is accumulating evidence of information processing impairment in post-traumatic stress disorder (PTSD). Studies of event-related potentials (ERPs) are the main tool in real time examination of information processing. In this paper, we sought to critically review the ERP evidence of information processing abnormalities in patients with PTSD. We also examined the evidence supporting the existence of a relationship between ERP abnormalities and symptom profiles or severity in PTSD patients. An extensive Medline search was performed. Keywords included PTSD or post-traumatic stress disorder, electrophysiology or EEG, electrophysiology, P50, P100, N100, P2, P200, P3, P300, sensory gating, CNV (contingent negative variation) and MMN (mismatch negativity). We limited the review to ERP adult human studies with control groups which were reported in the English language. After applying our inclusion-exclusion review criteria, 36 studies were included. Subjects exposed to wide ranges of military and civilian traumas were studied in these reports. Presented stimuli were both auditory and visual. The most widely studied components included P300, P50 gating, N100 and P200. Most of the studies reported increased P300 response to trauma-related stimuli in PTSD patients. A smaller group of studies reported dampening of responses or no change in responses to trauma-related and/or unrelated stimuli. P50 studies were strongly suggestive of impaired gating in patients with PTSD. In conclusion, the majority of reports support evidence of information processing abnormalities in patients with PTSD diagnosis. The predominance of evidence suggests presence of mid-latency and late ERP components differences in PTSD patients in comparison to healthy controls. Heterogeneity of assessment methods used contributes to difficulties in reaching firm conclusions regarding the nature of these differences. We suggest that future ERP-PTSD studies utilize standardized assessment scales that provide detailed information regarding the symptom clusters and the degree of symptom severity. This would allow assessment of electrophysiological indices-clinical symptoms relationships. Based on the available data, we suggest that ERP abnormalities in PTSD are possibly affected by the level of illness severity. If supported by future research, ERP studies may be used for both initial assessment and treatment follow-up.
... A second variant of P3, which we have labelled P3wm on the basis of two prior studies (Galletly, McFarlane, & Clark, 2008;Veltmeyer, McFarlane, Moores, Bryant, & Gordon, 2009), is elicited in the context of the Two In A Row (TIAR) task. P3wm is thought to reflect the processes that occur when information is maintained and updated in working memory. ...
... P3wm is thought to reflect the processes that occur when information is maintained and updated in working memory. The amplitude of P3 in this context has been shown to differentiate people with PTSD and schizophrenia from controls (Galletly et al., 2008;Johnson et al., 2013;Veltmeyer et al., 2009), and we were interested in whether people with somatic hypervigilance, often associated with PTSD, also produced an altered performance on this task. P3wm is typically measured at central parietal sites, and a higher amplitude reflects the resources allocated to task performance (Saliasi, Geerligs, Lorist, & Maurits, 2013). ...
Objective: Somatic hypervigilance describes a clinical presentation in which people
report more, and more intense, bodily sensations than is usual. Most explanations
of somatic hypervigilance implicate altered information processing, but strong
empirical data are lacking. Attention and working memory are critical for information
processing, and we aimed to evaluate brain activity during attention/working
memory tasks in people with and without somatic hypervigilance. Method: Data
from 173 people with somatic hypervigilance and 173 controls matched for age,
gender, handedness, and years of education were analyzed. Event-related potential
(ERP) data, extracted from the continuous electroencephalograph recordings
obtained during performance of the Auditory Oddball task, and the Two In A
Row (TIAR) task, for N1, P2, N2, and P3, were used in the analysis. Betweengroup
differences for P3 amplitude and N2 amplitude and latency were assessed
with two-tailed independent t tests. Between-group differences for N1 and P2
amplitude and latency were assessed using mixed, repeated measures analyses
of variance (ANOVAs) with group and Group × Site factors. Linear regression
analysis investigated the relationship between anxiety and depression and any
outcomes of significance. Results: People with somatic hypervigilance showed
smaller P3 amplitudes—Auditory Oddball task: t(285) = 2.32, 95% confidence
interval, CI [3.48, 4.47], p = .026, d = 0.27; Two-In-A-Row (TIAR) task: t(334) =
2.23, 95% CI [2.20; 3.95], p = .021, d = 0.24—than case-matched controls. N2
amplitude was also smaller in people with somatic hypervigilance—TIAR task: t
(318) = 2.58, 95% CI [0.33, 2.47], p = .010, d = 0.29—than in case-matched controls.
Neither depression nor anxiety was significantly associated with any outcome.
Conclusion: People with somatic hypervigilance demonstrated an event-related
potential response to attention/working memory tasks that is consistent with
altered information processing.
... Notably, deficits in attention, concentration, and working memory are common in individuals suffering from mental conditions associated with tobacco dependency such as depression [7-9], schizophrenia [10-12], and PTSD [13][14][15][16][17], and are currently undertreated in most patients [18]. Cognitive impairment in patients with schizophrenia includes deficits in several cognitive abilities including executive function, memory and learning, and social knowledge. ...
... SSRIs are the first-line treatments for PTSD [78,79] and several of these drugs including paroxetine and sertraline have received US Food and Drug Administration (FDA) approval [80][81][82]. Some of these drugs can ameliorate PTSD symptoms and the cardiovascular disturbances associated with them [83] but are not able to target or can worsen cognitive deficits [14]. Since available therapies including behavioral and pharmacological approaches do not help a large percentage of PTSD patients, it is imperative to find new drugs that can be used alone or in conjunction with current therapies in order to reduce PTSD symptoms and reestablish their cognitive abilities. ...
Neuroinflammation is a common characteristic of many neurodegenerative conditions including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), stroke, and epilepsy. Neuroinflammation is also associated with mental health conditions such as depression, bipolar disorder, posttraumatic stress disorder (PTSD), and schizophrenia. Recent evidence suggests that individuals with these conditions have inflammatory and oxidative processes in the brain, which are susceptible to being alleviated by analgesic, anti-inflammatory, pro-neurogenic, and pro-neurotrophic treatments. The neuroinflammatory process in the brain is characterized by the activation of glial cells, changes in glucose metabolism and perfusion, and the activation of several pro-inflammatory factors. Such factors include the eicosanoids, cRaf-1, nuclear factor kappa B (NF-κB), cycloxygenase-2 (Cox-2), tumor necrosis factor-α (TNF-α), interleukins, and the inducible nitric oxide synthase (iNOS). The activation of individual factors such as NF-κB can further increase the expression of other pro-inflammatory "partners in crime" including interleukins, eicosanoids, and iNOS. For example, the inhibition of the cRaf-1/NF-κB signaling pathway protects neurons against amyloid β peptide (Aβ) toxicity, considered the main cause of neurodegeneration in AD. Moreover, the multikinase and cRaf-1 inhibitor sorafenib restored memory and inhibited the expression of amyloid precursor protein (APP), NF-κB, Cox-2, and iNOS in the brains of transgenic AD mice. In this chapter, we will discuss potential benefits of targeting neuroinflammatory factors for the treatment of psychiatric and neurological disorders.
... Since the patients were hospitalized, acute patients we could not obtain medication-free recordings for ethical reasons. Antidepressant treatment has been shown to either improve working memory and attention (e.g., Herrera-Guzmán et al., 2010), increase N1 amplitudes (Normann et al., 2007) and to either alter or normalize P3b parameters (Karaaslan et al., 2003;Veltmeyer et al., 2009). Accuracy has also been shown to be affected by antidepressant treatment during a working memory task (Veltmeyer et al., 2009). ...
... Antidepressant treatment has been shown to either improve working memory and attention (e.g., Herrera-Guzmán et al., 2010), increase N1 amplitudes (Normann et al., 2007) and to either alter or normalize P3b parameters (Karaaslan et al., 2003;Veltmeyer et al., 2009). Accuracy has also been shown to be affected by antidepressant treatment during a working memory task (Veltmeyer et al., 2009). The fact that in the current study patients displayed attenuated N1 amplitudes and that P3b changes were specific to context-dependent stimuli, suggests that these changes are likely related to the illness itself rather than medication effects, although the behavioral and ERP findings were not correlated with the clinical scores. ...
The study investigated local contextual processing in patients with major depressive disorder (MDD). This was defined as the ability to utilize predictive contextual information to facilitate detection of predictable versus random targets.
We recorded EEG in 15 MDD patients and 14 age-matched controls. Recording blocks consisted of targets preceded by randomized sequences of standards and by sequences of standards that included a predictive sequence signaling the occurrence of a subsequent target event.
Both MDD patients and age-matched controls demonstrated a significant reaction time (RT) and P3b latency differences between predicted and random targets. However, patients demonstrated a specific prolongation of these measures during processing of predicted targets, as well as an attenuation of P3b amplitudes for the predictive sequence. In addition, patients target N1 amplitudes were attenuated compared with controls.
MDD patients were able to utilize predictive context in order to facilitate processing of deterministic targets, however, this ability was limited compared to controls, as demonstrated by context-dependent P3b deficits.
These findings suggest that patients with major depression have altered processing of local contextual processing.
... Nicotine treatment had been shown to improve cognitive function including attention, concentration, executive function, and learning and memory (Elzinga and Bremner, 2002;Horner and Hamner, 2002;Bowie and Harvey, 2005;Gray and Roth, 2007;Tapia et al., 2007;Burriss et al., 2008;Luck and Gold, 2008;Terry et al., 2008;Hinkelmann et al., 2009;Johnsen and Asbjornsen, 2009;Veltmeyer et al., 2009;Baune et al., 2010). However, nicotine's undesirable cardiovascular and addictive side-effects have limited its therapeutic use (Karaconji, 2005). ...
... Because serotonin promotes acetylcholine release, and acetylcholine signaling positively affects attention and memory, an increase of serotonin levels in the brain, may simultaneously improve mood, reduce aggressiveness (Buhot et al., 2000), and positively affect cognitive abilities. Although SSRIs are useful in the treatment of PTSD (Cohen et al., 2000), they are effective only in a small percentage of patients (approximately 30%; Veltmeyer et al., 2009). ...
A greater incidence of tobacco consumption occurs among individuals with psychiatric conditions including post-traumatic stress disorder (PTSD), bipolar disorder, major depression, and schizophrenia, compared with the general population. Even when still controversial, it has been postulated that smoking is a form of self-medication that reduces psychiatric symptoms among individuals with these disorders. To better understand the component(s) of tobacco-inducing smoking behavior, greater attention has been directed toward nicotine. However, in recent years, new evidence has shown that cotinine, the main metabolite of nicotine, exhibits beneficial effects over psychiatric symptoms and may therefore promote smoking within this population. Some of the behavioral effects of cotinine compared to nicotine are discussed here. Cotinine, which accumulates in the body as a result of tobacco exposure, crosses the blood-brain barrier and has different pharmacological properties compared with nicotine. Cotinine has a longer plasma half-life than nicotine and showed no addictive or cardiovascular effects in humans. In addition, at the preclinical level, cotinine facilitated the extinction of fear memory and anxiety after fear conditioning, improved working memory in a mouse model of Alzheimer’s disease (AD) and in a monkey model of schizophrenia. Altogether, the new evidence suggests that the pharmacological and behavioral effects of cotinine may play a key role in promoting tobacco smoking in individuals that suffer from psychiatric conditions and represents a new potential therapeutic agent against psychiatric conditions such as AD and PTSD.
... Some studies indicated changes in P300 characteristics in patients with Parkinson's disease (the changes correlated with the degree of the disease determined according to the Hoehn and Yahr scale), growth hormone deficiency, Huntington's disease, Tourette syndrome, and narcolepsy (2,9,(24)(25)(26)(27). Changes of P300 characteristics, lowered amplitude, and extended latency have also been noticed in schizophrenia (28)(29)(30)(31)(32)(33)(34)(35)(36), post-traumatic stress disorder (36,37,40), endogenous psychoses (38)(39)(40)(41), panic disorder (42)(43)(44)(45), and depressive patients (46,47). Additionally, a few papers described changes of P300 in impulsive aggressive criminals and obsessive-compulsive disorder (48,49). ...
Cognitive functions can be assessed and followed up over a period of time with cognitive evoked potentials (CEP) P300. In this context, brainstem auditory evoked potentials (BAEP) are most commonly used, but visual evoked potentials (VEP) are utilized as well. The research in this area has demonstrated that these techniques could be used as a supplemental method in diagnostics of numerous diseases such as Alzheimer's disease, mild cognitive impairment, vascular dementia, epilepsy, craniocerebral trauma, Parkinson's disease, multiple sclerosis, and other degenerative diseases. In addition, P300 can also be used as an auxiliary method in the diagnostics of mental disorders conditions such as schizophrenia, panic disorders, narcotic drug addiction, nicotinism, alcoholism, etc. The method assists in monitoring the course of diseases leading to encephalopathy, such as liver and kidney damage and grave anaemia. The advantages of P300 testing are easy application, non-invasiveness, and an unlimited number of potential applications. Moreover, the results obtained with this method are measurable and can be compared.
... Greater IIV was also associated with greater PTSD symptoms. Veltmeyer (2005) also reported that PTSD subjects had greater IIV on an auditory oddball task as well as on a visual target detection task (Veltmeyer and Clark, 2009). ...
Posttraumatic Stress Disorder (PTSD) is associated with alterations in attention at the behavioral and neural levels. However, there are conflicting findings regarding the specific type of attention impairments present in PTSD, as the commonly used tests of attention do not isolate the mechanisms behind attention abnormalities, and the constructs measured do not map onto the neurocircuits governing attention. Here we review the literature on attention processing in PTSD and offer directions for future research to clarify these unanswered questions. First, using instruments that allow assessment of behavioral and neurophysiological attention components will be necessary to understand attention deficits in PTSD. Second, focus on intra-individual variability in addition to assessment of central tendency may help clarify some of the mixed findings. Third, longitudinal studies on attentional processes are warranted to determine how attention contributes to the development and maintenance of PTSD. Integration of behavioral and neural measures of attention will be useful in understanding the pathophysiology of PTSD.
... Most of these studies have focused on patients with post-traumatic stress disorder (PTSD). For example, they found that PTSD patients showed smaller P3 amplitudes than healthy controls in n-back tasks 31,32 . To our knowledge, however, little is known about how long-term stress affects the neural dynamics associated with WM processing in otherwise healthy people. ...
This study examined the neural dynamics of working memory (WM) processing under long-term stress. Forty participants who had been exposed to a long period of major exam preparation (six months) and twenty-one control participants performed a numerical n-back task (n = 1, 2) while electroencephalograms were recorded. Psychological and endocrinal measurements confirmed significantly higher levels of long-term stress for participants in the exam group. The exam group showed significantly increased P2 amplitude in the frontal-central sites in the 1-back and 2-back conditions, whereas other ERP components, including the P1, N1 and P3 and behavioral performance, were unchanged. Notably, the P2 effect was most pronounced in participants in the exam group who reported perceiving high levels of stress. The perceived stress scores positively correlated with the P2 amplitude in the 1-back and 2-back conditions. These results suggest that long-term stress has an impact on attention and the initiation of the updating process in WM.
... SSRIs are the first-line treatments for PTSD [78,79] and several of these drugs including paroxetine and sertraline have received US Food and Drug Administration (FDA) approval [80][81][82]. Some of these drugs can ameliorate PTSD symptoms and the cardiovascular disturbances associated with them [83] but are not able to target or can worsen cognitive deficits [14]. Since available therapies including behavioral and pharmacological approaches do not help a large percentage of PTSD patients, it is imperative to find new drugs that can be used alone or in conjunction with current therapies in order to reduce PTSD symptoms and reestablish their cognitive abilities. ...
Epidemiological studies have associated tobacco consumption with a lower incidence of Alzheimer's disease (AD) and Parkinson's disease (PD). The neuroprotective effect of tobacco has been mainly attributed to the stimulation by nicotine of the α7 nicotinic acetylcholine receptors (nAChRs), which are implicated in neuronal survival, attention, and memory. A reduction in cholinergic function including lower levels of the expression of nAChRs in the hippocampus correlates with memory impairment in AD and schizophrenia. Although nicotine improves memory, sensory gating, and attention, its toxicity and undesired effects such as negative cardiovascular effects have terminated its therapeutic applications. Interestingly, its main metabolite cotinine shows similar neuroprotective and mnemonic properties but has a ten-fold longer half-life than nicotine and a good safety profile in humans. In neurodegenerative conditions including AD and PD, the accumulation of aggregated forms of the P-amyloid peptide correlates with cognitive impairment. Cotinine has been shown to reduce Ap aggregation in vitro. Additionally, since cotinine is a weak agonist of the nAChRs, we postulate that cotinine improves neuronal survival and memory at least in part by acting as a positive modulator of the α7 nAChRs. The potentiation of α7 nAChRs by cotinine can be beneficial in a broad range of neurological disorders such as schizophrenia, AD, attention-deficit hyperactivity disorder, and PD in which the modulation of these receptors can ameliorate working memory and attention. Based on actual evidence and these ideas, the relevance and potential therapeutic use of cotinine in several neurological disorders are discussed in this chapter. "Only do not forget, if I wake up crying it's only because in my dream I'm a lost child hunting through the leaves of the night for your hands...." - Pablo Neruda [1].
... Individuals suffering from stress-related dysfunction such as depression [110] and PTSD [111][112][113] often present with deficits in working memory. These deficits largely impair their abilities to work and interact socially. ...
Tobacco consumption is far higher among a number of psychiatric and neurological diseases, supporting the notion that some component(s) of tobacco may underlie the oft-reported reduction in associated symptoms during tobacco use. Popular dogma holds that this component is nicotine. However, increasing evidence support theories that cotinine, the main metabolite of nicotine, may underlie at least some of nicotine's actions in the nervous system, apart from its adverse cardiovascular and habit forming effects. Though similarities exist, disparate and even antagonizing actions between cotinine and nicotine have been described both in terms of behavior and physiology, underscoring the need to further characterize this potentially therapeutic compound. Cotinine has been shown to be psychoactive in humans and animals, facilitating memory, cognition, executive function, and emotional responding. Furthermore, recent research shows that cotinine acts as an antidepressant and reduces cognitive-impairment associated with disease and stress-induced dysfunction. Despite these promising findings, continued focus on this potentially safe alternative to tobacco and nicotine use is lacking. Here, we review the effects of cotinine, including comparisons with nicotine, and discuss potential mechanisms of cotinine-specific actions in the central nervous system which are, to date, still being elucidated.
... In recent years, various neuroimaging techniques have been used to investigate neural mechanisms underlying stress-related and trauma-related memory impairments. Such imaging techniques include event-related potentials (ERPs) (Galletly et al., 2001 ; Weber et al., 2005 ; Veltmeyer et al., 2009) , positron emission tomography (PET) ( Shaw et al., 2002 ; Clark et al., 2003) , functional magnetic resonance imaging (fMRI) ( Elzinga et al., 2007 ; Moores et al., 2008 ; Shaw et al., 2009) , and functional near infrared spectroscopy (fNIRS) (Matsuo et al., 2003) . The most replicable findings from the neuroimaging studies suggest abnormal activities in the frontal and parietal cortices, two of the key cerebral regions consistently implicated in the neurobiology of PTSD (Bremner, 2002 ; Francati et al., 2007 ; Aupperle et al., 2012) . ...
Neuroimaging studies of post-traumatic stress disorder (PTSD)-related memory impairments have consistently
implicated abnormal activities in the frontal and parietal lobes. However, most studies have used
block designs and could not dissociate the multiple phases of working memory. In this study, the involvement
of the prefrontal cortex in working memory phases was assessed among veterans with PTSD and age- /
gender-matched healthy controls. Multichannel functional near infrared spectroscopy (fNIRS) was utilized
to measure prefrontal cortex hemodynamic activations during memory of neutral (i.e., not trauma-related)
forward and backward digit span tasks. An event-related experimental design was utilized to dissociate the
different phases (i.e., encoding, maintenance and retrieval) of working memory. The healthy controls showed
robust hemodynamic activations during the encoding and retrieval processes. In contrast, the veterans with
PTSD were found to have activations during the encoding process, but followed by distinct deactivations
during the retrieval process. The PTSD participants, but not the controls, appeared to suppress prefrontal
activity during memory retrieval. This deactivation was more pronounced in the right dorsolateral prefrontal
cortex during the retrieval phase. These deactivations in PTSD patients might implicate an active inhibition
of dorsolateral prefrontal neural activity during retrieval of working memory.
... In recent years, various neuroimaging techniques have been used to investigate neural mechanisms underlying stress-related and trauma-related memory impairments. Such imaging techniques include event-related potentials (ERPs) (Galletly et al., 2001 ; Weber et al., 2005 ; Veltmeyer et al., 2009) , positron emission tomography (PET) ( Shaw et al., 2002 ; Clark et al., 2003) , functional magnetic resonance imaging (fMRI) ( Elzinga et al., 2007 ; Moores et al., 2008 ; Shaw et al., 2009) , and functional near infrared spectroscopy (fNIRS) (Matsuo et al., 2003) . The most replicable findings from the neuroimaging studies suggest abnormal activities in the frontal and parietal cortices, two of the key cerebral regions consistently implicated in the neurobiology of PTSD (Bremner, 2002 ; Francati et al., 2007 ; Aupperle et al., 2012) . ...
Neuroimaging studies of post-traumatic stress disorder (PTSD)-related memory impairments have consistently implicated abnormal activities in the frontal and parietal lobes. However, most studies have used block designs and could not dissociate the multiple phases of working memory. In this study, the involvement of the prefrontal cortex in working memory phases was assessed among veterans with PTSD and age-/gender- matched healthy controls. Multichannel functional near infrared spectroscopy (fNIRS) was utilized to measure prefrontal cortex hemodynamic activations during memory of neutral (i.e., not trauma-related) forward and backward digit span tasks. An event-related experimental design was utilized to dissociate the different phases (i.e., encoding, maintenance and retrieval) of working memory. The healthy controls showed robust hemodynamic activations during the encoding and retrieval processes. In contrast, the veterans with PTSD were found to have activations during the encoding process, but followed by distinct deactivations during the retrieval process. The PTSD participants, but not the controls, appeared to suppress prefrontal activity during memory retrieval. This deactivation was more pronounced in the right dorsolateral prefrontal cortex during the retrieval phase. These deactivations in PTSD patients might implicate an active inhibition of dorsolateral prefrontal neural activity during retrieval of working memory.
... In addition, the reduced P3 amplitude in the PTSD group is consistent with previous ERP studies investigating neuropsychological activity during working memory updating [13,14] and tone stimuli task [7]. Previous studies [15,16] indicated that the P3b might represent individuals' ability to allocate attentional resources and to maintain their focus on target stimuli. ...
Previous studies have provided electrophysiological evidence for attentional abnormalities in patients with post-traumatic stress disorder (PTSD). The present study examined the electrophysiological activity of trauma-exposed patients with or without a PTSD during a modified Stroop task. The PTSD group showed a reduced P2 and P3 amplitude relative to the non-PTSD group under both the earthquake-related and earthquake-unrelated words conditions. Importantly, the earthquake-related words elicited a greater P3 amplitude (350-450 ms after stimulus) than did unrelated words in the non-PTSD group, whereas no significant difference was found in the PTSD group. This indicates that PTSD patients had some attention deficits compared with non-PTSD individuals, and that these attention deficits were not just limited to earthquake-related words.
Working Memory (TM) is a cognitive domain related to the temporary manipulation of information. Although its impact on stress and anxiety situations is assumed to be evident, few studies have investigated its functioning in individuals exposed to traumatic situations. The aim of this study was to investigate the relationship between Working Memory and Post-Traumatic Stress Disorder (PTSD). A systematic review was carried out based on the PRISMA method using the Medline, Web of Science and Scielo databases. The final sample included 12 studies that, in their prevalence, indicate WM damage in subjects with PTSD. In addition, it was observed that the most studied population is composed of military personnel exposed to combat related traumas, and the most investigated WM subcomponente was the phonological loop, based on the digit task. These results contribute to an integrated neurocognitive approach for the formulation of cases and treatment planning for people with post-traumatic symptoms, which may contribute to the development of future research and to fill in gaps of the understanding between emotion-cognition in psychopathological cases.
Post-traumatic stress disorder (PTSD) is associated with neural processing deficits affecting early automatic and later conscious processing. Event-related Potentials (ERPs) are high resolution indices of automatic and conscious processing, but there are no meta-analyses that have examined automatic and conscious ERPs in PTSD across multiple paradigms. This systematic review examined 69 studies across affective and non-affective auditory and visual paradigms. Individuals with PTSD were compared to trauma-exposed and non-trauma controls on ERPs reflecting automatic (N1, P1, N2, P2) and conscious (P3, LPP) processing. Trauma exposure was associated with increased automatic ERP amplitudes to irrelevant auditory information. PTSD further showed increased automatic and conscious allocation of resources to affective information, reduced automatic attending and classification as well as reduced attention processing and working memory updating of non-affective information. Therefore, trauma exposure is associated with enhanced early processing of incoming stimuli, and PTSD with enhanced processing of affective stimuli and impaired processing of non-affective stimuli. This review highlights the need for longitudinal ERP studies in PTSD, adopting standardized procedures and methodological designs.
This review aims to identify patterns of electrical signals identified using electroencephalography (EEG) linked to posttraumatic stress disorder (PTSD) diagnosis and symptom dimensions. We filter EEG findings through a clinical lens, evaluating nuances in findings according to study criteria and participant characteristics. Within the EEG frequency domain, greater right than left parietal asymmetry in alpha band power is the most promising marker of PTSD symptoms and is linked to exaggerated physiological arousal that may impair filtering of environmental distractors. The most consistent findings within the EEG time domain focused on event related potentials (ERPs) include: 1) exaggerated frontocentral responses (contingent negative variation, mismatch negativity, and P3a amplitudes) to task-irrelevant distractors, and 2) attenuated parietal responses (P3b amplitudes) to task-relevant target stimuli. These findings suggest that some individuals with PTSD suffer from attention dysregulation, which could contribute to problems concentrating on daily tasks and goals in lieu of threatening distractors. Future research investigating the utility of alpha asymmetry and frontoparietal ERPs as diagnostic and predictive biomarkers or intervention targets are recommended.
Assessing Trauma History Conclusion
Introduction: Some studies of Posttraumatic Stress Disorder (PTSD) find executive dysfunction, whereas others do not. We meta-analytically examined the association between executive function and PTSD and used meta-regression to examine the potential moderating effect of PTSD severity on executive function.
Methods: We conducted a meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We identified published peer-reviewed articles containing measures of executive function and PTSD symptom severity in subjects with PTSD compared to trauma-unexposed controls or trauma-exposed controls without PTSD, or both. We calculated an effect size for each study containing at least one measure of executive function and PTSD symptom severity.
Results: PTSD subjects for whom the Clinician-Administered PTSD Scale (CAPS) score was available had worse executive function compared to both trauma-unexposed controls (g = 0.464, p < .001) and to trauma-exposed controls without PTSD (g = 0.414, p = .001), as did PTSD subjects for whom the Mississippi Scale for Combat-Related PTSD (M-PTSD) score was available (g = 0.390, p < .001). Neither CAPS nor M-PTSD scores significantly moderated the effect size of executive function.
Conclusions: PTSD is associated with executive dysfunction, but this association was not moderated by PTSD symptom severity, suggesting that once PTSD occurs, executive dysfunction may occur regardless of PTSD severity.
Cognitive deficits are now widely recognized to be an important component of anxiety. In particular, anxiety is thought to restrict the capacity of working memory by competing with task-relevant processes. The evidence for this claim, however, has been mixed. Although some studies have found restricted working memory in anxiety, others have not. Within studies that have found impairments, there is little agreement regarding the boundary conditions of the anxiety/WMC association. The aim of this review is to critically evaluate the evidence for anxiety-related deficits in working memory capacity. First, a meta-analysis of 177 samples (N = 22,061 individuals) demonstrated that self-reported measures of anxiety are reliably related to poorer performance on measures of working memory capacity ( g = −.334, p< 10
−29). This finding was consistent across complex span (e.g., OSPAN; g = −.342, k = 30, N = 3,196, p = .000001), simple span (e.g., digit span; g = −.318, k = 127, N = 17,547, p < 10
−17), and dynamic span tasks (e.g., N -Back; g = −.437, k = 20, N = 1,318, p = .000003). Second, a narrative review of the literature revealed that anxiety, whether self-reported or experimentally induced, is related to poorer performance across a wide variety of tasks. Finally, the review identified a number of methodological limitations common in the literature as well as avenues for future research.
Posttraumatic Stress Disorder and Alzheimer's Disease have many similarities and only some differences. The main similarities are that both disorders have as risk factor a severe traumatic event (100% in PTSD and 80% in AD), the prevalence F/M ratio of PTSD is the same as in AD, (2:1), stress hormones and other neurotransmitters are involved in both diseases, the areas of brain which are involved in both disorders are about the same (hippocampus, amygdale, prefrontal cortex, anterior cingulated gyrus) and finally the areas that are activated in fMRI are about the same in both conditions. Perhaps there are some differences in genes, but this area needs more research and the age of onset is the point which is different in vast majority of patients with AD, because the mean age in AD patients is 75 years old. This is the reason which leads to different therapeutic strategies.
Posttraumatic Stress Disorder and Alzheimer's Disease have many similarities and only some differences. The main similarities are that both disorders have as risk factor a severe traumatic event (100% in PTSD and 80% in AD), the prevalence F/M ratio of PTSD is the same as in AD, (2:1), stress hormones and other neurotransmitters are involved in both diseases, the areas of brain which are involved in both disorders are about the same (hippocampus, amygdale, prefrontal cortex, anterior cingulated gyrus) and finally the areas that are activated in fMRI are about the same in both conditions. Perhaps there are some differences in genes, but this area needs more research and the age of onset is the point which is different in vast majority of patients with AD, because the mean age in AD patients is 75 years old. This is the reason which leads to different therapeutic strategies.
Background:
Posttraumatic stress disorder (PTSD) is associated with executive functioning deficits, including disruptions in working memory. In this study, we examined the neural dynamics of working memory processing in veterans with PTSD and a matched healthy control sample using magnetoencephalography (MEG).
Methods:
Our sample of recent combat veterans with PTSD and demographically matched participants without PTSD completed a working memory task during a 306-sensor MEG recording. The MEG data were preprocessed and transformed into the time-frequency domain. Significant oscillatory brain responses were imaged using a beamforming approach to identify spatiotemporal dynamics.
Results:
Fifty-one men were included in our analyses: 27 combat veterans with PTSD and 24 controls. Across all participants, a dynamic wave of neural activity spread from posterior visual cortices to left frontotemporal regions during encoding, consistent with a verbal working memory task, and was sustained throughout maintenance. Differences related to PTSD emerged during early encoding, with patients exhibiting stronger α oscillatory responses than controls in the right inferior frontal gyrus (IFG). Differences spread to the right supramarginal and temporal cortices during later encoding where, along with the right IFG, they persisted throughout the maintenance period.
Limitations:
This study focused on men with combat-related PTSD using a verbal working memory task. Future studies should evaluate women and the impact of various traumatic experiences using diverse tasks.
Conclusion:
Posttraumatic stress disorder is associated with neurophysiological abnormalities during working memory encoding and maintenance. Veterans with PTSD engaged a bilateral network, including the inferior prefrontal cortices and supramarginal gyri. Right hemispheric neural activity likely reflects compensatory processing, as veterans with PTSD work to maintain accurate performance despite known cognitive deficits associated with the disorder.
An evoked potential (or “evoked response”) is an electrical potential recorded from the nervous system of a human, following presentation of a stimulus (visual, auditory, somatosensory) as distinct from spontaneous potentials as detected by electroencephalography (EEG). Evoked potential amplitudes tend to be low, ranging from less than a microvolt to several microvolts, compared to tens of microvolts for EEG. To resolve these low-amplitude potentials against the background of ongoing EEG and ambient noise, signal averaging is usually required. The signal is time-locked to the stimulus and most of the noise occurs randomly, allowing the noise to be averaged out with averaging of repeated responses. An event-related potential (or cognitive evoked potential) measured brain response directly resulting of a thought or perception. It is any stereotyped electrophysiological response to an internal or external stimulus. The P300 (P3) wave is an event related potential which can be recorded via EEG as a positive deflection in voltage at latency of roughly 300 ms regardless of the stimulus presented: visual, tactile, auditory or olfactory. The signal is typically measured most strongly by the electrodes covering the parietal lobe. The presence, magnitude, topography and time of this signal are often used as metrics of cognitive function in decision-making processes. The N400 is an event-related potential component typically elicited by unexpected linguistic stimuli. It is characterized as a negative voltage deflection (topologically distributed over central-parietal sites on the scalp), peaking approximately 400 ms (300–500 ms) after the presentation of the stimulus. The N400 plays a significant role in language processing. The mismatch negativity is an event-related potential to an odd stimulus in a sequence of stimuli. It has most frequently been studied for audition and for vision, with a rare deviant stimuli occuring after an infrequent change in a repetitive sequence of stimuli (the entire sequence is called an oddball sequence). The evoked potential are very useful in the study of the chronology of neurocognitive process. The interest of evoked potential has been shown in several neurological disorders and aging. Their application in the understanding of brain ageing make up a challenge for physicians.
Patients with posttraumatic stress disorder (PTSD) exhibiting disturbances in information processing, including trouble with attention, were studied. Event-related potentials (ERPs)-specifically, the P3 components (P3a, P3b, and P3 working memory {P3wm})-provide an objective, non-invasive, and cost-effective method for evaluating such disturbances. We evaluated the potential clinical utility of P3 components by examining the differences between PTSD and several control groups: normal participants, non-PTSD patients with trauma, and medicated patients with PTSD. We performed a meta-analysis of the ERP literature between 1990 and 2010 using a random effects model. P3a amplitude was larger in patients with PTSD compared to non-PTSD patients having trauma in the context of trauma-related distracters. P3b amplitude was also larger in patients with PTSD than in patients having trauma without PTSD, but in the context of trauma-related stimuli. P3b amplitude was smaller in patients with PTSD compared to normal controls in the context of neutral stimuli. P3wm signals were smaller with shorter latencies in patients with PTSD compared to normal controls or medicated patients with PTSD. The receiver-operator characteristic (ROC) analysis revealed that each P3 component had some potential to accurately classify patients, typically using amplitude for at least one lead. In conclusion, differences in P3 amplitude and latency between patients with PTSD and control patients confirm the results of Karl et al and extend our understanding of P3 as a neural correlate of working memory. These results further provide guidance on the potential design of future clinical trials supporting the development of P3 components as a PTSD diagnostic aid.
Notes that to understand the endogenous components of the event-related potential (ERP), data about the components' antecedent conditions to form hypotheses about the information-processing function of the underlying brain activity must be used. These hypotheses generate testable predictions about the consequences of the component. The application of this approach to the analysis of the P300 component is reviewed. Certain factors suggest that P300 is a manifestation of activity occurring whenever one's model of the environment must be revised. Tests of 3 predictions based on this "context updating" model are reviewed. Open peer commentary follows. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The prefrontal cortex (PFC) utilizes working memory to guide behavior and to release the organism from dependence on environmental cues and is commonly disrupted in neuropsychiatric disorders, normal aging, or exposure to uncontrollable stress. This review posits that the PFC is very sensitive to changes in the neuromodulatory inputs it receives from norepinephrine (NE) and dopamine (DA) systems and that this sensitivity can lead to marked changes in the working-memory functions of the PFC. While NE and DA have important beneficial influences on processing in this area, very high levels of catecholamine release, for example, during exposure to uncontrollable stress, disrupt the cognitive functions of the PFC. This fresh understanding of the neurochemical influences on PFC function has led to new treatments for cognitive disorders such as Attention Deficit Hyperactivity Disorder (ADHD), and may help to elucidate the prevalence of PFC dysfunction in other mental disorders.
Changes in cortical activity during working memory tasks were examined with electroencephalograms (EEGs) sampled from 115 channels and spatially sharpened with magnetic resonance imaging (MRI)-based finite element deblurring. Eight subjects performed tasks requiring comparison of each stimulus to a preceding one on verbal or spatial attributes. A frontal midline theta rhythm increased in magnitude with increased memory load. Dipole models localized this signal to the region of the anterior cingulate cortex. A slow (low-frequency), parietocentral, alpha signal decreased with increased working memory load. These signals were insensitive to the type of stimulus attribute being processed. A faster (higher-frequency), occipitoparietal, alpha signal was relatively attenuated in the spatial version of the task, especially over the posterior right hemisphere. Theta and alpha signals increased, and overt performance improved, after practice on the tasks. Increases in theta with both increased task difficulty and with practice suggests that focusing attention required more effort after an extended test session. Decreased alpha in the difficult tasks indicates that this signal is inversely related to the amount of cortical resources allocated to task performance. Practice-related increases in alpha suggest that fewer cortical resources are required after skill development. These results serve: (i) to dissociate the effects of task difficulty and practice; (ii) to differentiate the involvement of posterior cortex in spatial versus verbal tasks; (iii) to localize frontal midline theta to the anteromedial cortex; and (iv) to demonstrate the feasibility of using anatomical MRIs to remove the blurring effect of the skull and scalp from the ongoing EEG. The results are discussed with respect to those obtained in a prior study of transient evoked potentials during working memory.
A PET study of 10 normal individuals was carried out to investigate the cerebral regions involved in the controlled updating of verbal working memory. Subjects viewed single concrete words on a computer monitor and detected occasional target words in an attended color. In the activating condition, a target was defined as a word that was identical to the previous word presented in the attended color. In the control condition, the target was a predesignated word. The same word lists, target probabilities, and target response demands were used for both conditions, with interword intervals constrained to ensure equivalence in the demand for target rehearsal. A comparison of the conditions found bilateral activation of dorsolateral prefrontal (middle frontal gyrus; MFG) and inferior parietal (supramarginal gyrus; SMG) cortical regions. Activation of the MFG is taken to reflect executive control by prefrontal regions over the working memory updating process linking posterior representations of the anticipated target stimulus to anterior representations of the planned response. It is proposed that the updating of the stimulus link is mediated via connections between the MFG and SMG. The role of the SMG as an amodal region binding the various modal representations in posterior association cortex of the word being retained in working memory is considered and reviewed. It is suggested that the combined activation of these regions is related to the executive control of goal-setting in planned behavior.
Although the mechanism responsible for cognitive deficits in stress-related neuropsychiatric disorders has been obscure, prefrontal cortical (PFC) dopaminergic dysfunction is thought to be involved. In animals, the mesoprefrontal dopaminergic system is particularly vulnerable to stress, and chronic stress induces working memory impairment. However, the relation between the working memory impairment and altered dopaminergic activity in chronically stressed rats is unclear. Furthermore, the change of dopaminergic activity in the PFC induced by stress is thought to express as a stress response, not as a disorder of organic function. We have previously reported that chronic stress administered by water immersion and restraint for 4 weeks induces a organic disorder such as hippocampal neuronal degeneration. We therefore examined whether chronically stressed (4 weeks) and recovered (10 d) rats show a working memory impairment caused by reduced dopamine (DA) transmission in the PFC, as suspected in the neuropsychiatric disorders. The stress impaired the spatial working memory evaluated by T-maze task and induced a marked reduction of DA transmission concomitant with an increase in DA D1 receptor density in the PFC. This memory impairment was sufficiently ameliorated by intra-PFC infusion of 10 ng SKF 81297, a D1 receptor-specific agonist. Pretreatment with intraperitoneal injection of 20 microgram/kg SCH 23390, a D1 receptor antagonist, reversed the SKF 81297 response. These results indicate that chronic stress induces working memory impairment through a D1 receptor-mediated hypodopaminergic mechanism in the PFC. These findings provide important information for understanding of the mechanisms underlying PFC dysfunction in stress-related neuropsychiatric disorders.
The purpose of this study was to examine electrophysiological response to trauma-relevant stimuli in combat-related post-traumatic stress disorder (PTSD). Study design incorporated comparison of 10 Vietnam War veterans with PTSD diagnosis to 10 Vietnam War veterans with no mental disorder diagnosis on P3 components in a series of two oddball tasks (trauma-relevant threat, trauma-irrelevant threat) counterbalanced for order. Each task included high probability emotionally neutral distractor words and low probability neutral target words, but differed in the content of low probability threat words. Whereas threat words in the trauma-relevant oddball task pertained directly to combat trauma, threat words in the trauma-irrelevant oddball task were socially threatening words. Results revealed that, in comparison to healthy combat veterans, those diagnosed with PTSD demonstrated: (a) attenuated P3 response to neutral target items at selected electrode sites across both oddball tasks; and (b) increased responsivity to trauma-relevant combat stimuli but not to trauma-irrelevant social-threat stimuli at frontal electrode sites (F3, F4). Results are consistent with resource allocation models of PTSD, which suggest that PTSD is characterized by attentional bias to threat stimuli at the expense of attention to emotionally neutral information.
Dorsal anterior cingulate cortex (dACC) is a brain region that subserves cognition and motor control, but the mechanisms of these functions remain unknown. Human neuroimaging and monkey electrophysiology studies have provided valuable insights, but it has been difficult to link the two literatures. Based on monkey single-unit recordings, we hypothesized that human dACC is comprised of a mixture of functionally distinct cells that variously anticipate and detect targets, indicate novelty, influence motor responses, encode reward values, and signal errors. As an initial test of this conceptualization, the current event-related functional MRI study used a reward-based decision-making task to isolate responses from a subpopulation of dACC cells sensitive to reward reduction. As predicted, seven of eight subjects showed significant (P < 10(-4)) dACC activation when contrasting reduced reward (REDrew) trials to fixation (FIX). Confirmatory group analyses then corroborated the predicted ordinal relationships of functional MRI activation expected during each trial type (REDrew > SWITCH > CONrew > or = FIX). The data support a role for dACC in reward-based decision making, and by linking the human and monkey literatures, provide initial support for the existence of heterogeneity within dACC. These findings should be of interest to those studying reward, cognition, emotion, motivation, and motor control.
This study investigated the efficacy of a combined multivariate/resampling procedure for the analysis of PET activation studies. The covariance-based multivariate analysis was used to investigate distributed brain systems in posttraumatic stress disorder (PTSD) patients and matched controls during performance of a working memory task. The results were compared to univariate results obtained in an earlier study. We also examined whether the PTSD patients demonstrated a breakdown in functional connectivity that may be associated with working memory difficulties often experienced by these patients. A resampling procedure was used specifically to test the reliability of measured between-group effects, to avoid mistaken inference on the basis of random intersubject differences. Significant and reproducible differences in network connectivity were obtained for the two groups. The functional connectivity pattern of the patient group was characterized by relatively more activation in the bilateral inferior parietal lobes and the left precentral gyrus than the control group, and less activation in the inferior medial frontal lobe, bilateral middle frontal gyri and right inferior temporal gyrus. The resampling procedure provided direct evidence that working memory updating was abnormal in PTSD patients relative to matched controls. This work focuses on the need to identify extended brain networks (in addition to regionally specific changes) for the full characterization of brain responses in neuroimaging experiments. Our multivariate analysis explicitly measures the reliability of the patterns of functional connectivity we obtain and demonstrates the potential of such analyses for the study of brain network dysfunction in psychopathology.
Considerable ambiguity exists about the generators of the scalp recorded P300, despite a vast body of research employing a diverse range of methodologies. Previous investigations employing source localization techniques have been limited largely to equivalent current dipole models, with most studies identifying medial temporal and/or hippocampal sources, but providing little information about the contribution of other cortical regions to the generation of the scalp recorded P3. Event-related potentials (ERPs) were recorded from 5 subjects using a 124-channel sensor array during the performance of a visuo-verbal Oddball task. Cortically constrained, MRI-guided boundary element modeling was used to identify the cortical generators of this target P3 in individual subjects. Cortical generators of the P3 were localized principally to the intraparietal sulcus (IPS) and surrounding superior parietal lobes (SPL) bilaterally in all subjects, though with some variability across subjects. Two subjects also showed activity in the lingual/inferior occipital gyrus and mid-fusiform gyrus. A group cortical surface was calculated by non-linear warping of each subject's segmented cortex followed by averaging and creation of a group mesh. Source activity identified across the group reflected the individual subject activations in the IPS and SPL bilaterally and in the lingual/inferior occipital gyrus primarily on the left. Activation of IPS and SPL is interpreted to reflect the role of this region in working memory and related attention processes and visuo-motor integration. The activity in left lingual/inferior occipital gyrus is taken to reflect activation of regions associated with modality-specific analysis of visual word forms.
The P300 components of auditory event related potentials (ERPs) are objective measures related to information and cognitive processing.
To assess P300 ERPs in female patients with fibromyalgia (FM) in comparison with healthy age matched controls. To investigate the relationship between P300 potentials and pain threshold levels of patients, and subsequent effect of sertraline treatment on P300 potentials.
P300 auditory ERPs were studied in 13 untreated female patients with FM and 10 healthy controls matched for age, sex, and education. Pain pressure thresholds and total myalgic scores (TMS) were assessed with an algometer. Patients were evaluated for clinical measures and P300 potentials (recorded from the vertex) at the first visit, and then in the fourth and eighth weeks of sertraline treatment.
Patients with FM had significantly lower P300 amplitudes, but not significantly different P300 latencies, than controls at entry. P300 latencies in patients correlated negatively with TMS (r(s)=-0.79, p<0.01) and P300 amplitudes correlated significantly with TMS (r(s)=0.53, p<0.05). Anxiety and depression scores did not correlate significantly with P300 latencies or amplitudes at the study entry. P300 auditory ERPs had increased amplitudes that had reached nearly the same levels as those of the controls at the eighth week without any significant change in their latencies.
The results show reduced P300 amplitudes in patients with FM. Further studies assessing the relationship between P300 ERPs and neuropsychiatric tests are required for better clarification of the clinical relevance of P300 potentials in FM.
Subchronic treatment with the selective serotonergic reuptake inhibitors (SSRIs) fluoxetine, venlafaxine and paroxetine, but not sertraline, were previously shown to specifically impair vigilance performance. The current study was designed to compare the vigilance effects of subchronic treatment with the SSRIs sertraline and citalopram in healthy volunteers, according to a placebo-controlled, double-blind, three-way cross-over design. Twenty-four healthy subjects, aged 30-50 years, of whom 21 completed the study, underwent three treatment periods of 2 weeks in which they received sertraline (50 mg on days 1-8, 100 mg on days 8-15), citalopram (20 mg on days 1-8, 40 mg on days 8-15) and placebo. Treatment periods were separated by 14 days washout periods. Vigilance performance was assessed through a 45-min Mackworth Clock Test at days 1, 8 and 15 of each treatment period. It was found that citalopram impaired vigilance performance acutely after the first 20 mg dose and subchronically after 40 mg daily doses. By contrast, no vigilance impairment was found during sertraline treatment. Sertraline is the only SSRI studied so far with no detrimental effects on vigilance. This may be due to the affinity of sertraline for the dopamine reuptake site. Because citalopram is the most specific SSRI showing this effect, it is concluded that the SSRI-induced decrement of vigilance performance is specifically associated with serotonergic reuptake inhibition.
Individuals with posttraumatic stress disorder (PTSD) have been found to show several event-related brain potential (ERP) abnormalities including reduced target P3b amplitude, P50 suppression, and P2 amplitude/intensity slope. Female Vietnam nurse veterans with (n = 29) and without (n = 38) current PTSD completed P50 paired-click, three-tone "oddball" and four-tone stimulus-intensity modulation procedures. Opposite to previous findings, the current PTSD group had larger target P3b amplitudes and increased P2 amplitude/intensity slopes. Reduced P50 suppression was associated with increased severity of general psychopathology, but not with PTSD diagnosis. Findings suggest that target P3b amplitude and P2 amplitude/intensity slope abnormalities reflect different pathophysiological processes. Future research is needed to determine whether the opposite ERP abnormalities observed in this PTSD sample reflect gender-, trauma-, or sample-specific findings.
Twelve Post-Traumatic Stress Disorder (PTSD) patients, 12 psychiatric patients matched for severity of psychopathology, and 12 normal controls were assessed for cognitive functioning by means of a comprehensive test battery. Both patient groups felt subjectively more impaired than normals. Performance on measures of intelligence, organicity, verbal fluency, memory, and attention was significantly poorer in patients than in normals. The performance of the PTSD patients and that of the psychiatric controls was, however, very similar. The premorbid intelligence of both the PTSD patients and the psychiatric controls was average and had deteriorated significantly by the time of current testing. These cognitive problems were not secondary to alcohol, drug abuse, or head injury. The results suggest a cognitive impairment in post-traumatic patients.
Stress can exacerbate a number of psychiatric disorders, many of which are associated with prefrontal cortical (PFC) cognitive deficits. Biochemical studies demonstrate that mild stress preferentially increases dopamine turnover in the PFC. Our study examined the effects of acute, mild stress exposure on higher cognitive function in monkeys and the role of dopaminergic mechanisms in the stress response.
The effects of loud (105-dB) noise stress were examined on a spatial working memory task (delayed response) dependent on the PFC, and on a reference memory task with similar motor and motivational demands (visual pattern discrimination) dependent on the inferior temporal cortex. The role of dopamine mechanisms was tested by challenging the stress response with agents that decrease dopamine receptor stimulation.
Exposure to noise stress significantly impaired delayed-response performance. Stress did not impair performance on "0-second" delay control trials and did not alter visual pattern discrimination performance, which is consistent with impaired PFC cognitive function rather than nonspecific changes in performance. Stress-induced deficits in delayed-response performance were ameliorated by pretreatment with drugs that block dopamine receptors (haloperidol, SCH 23390) or reduce stress-induced PFC dopamine turnover in rodents (clonidine, naloxone hydrochloride).
These results indicate that stress impairs PFC cognitive function through a hyperdopaminergic mechanism. Stress may take the PFC "off-line" to allow more habitual responses mediated by posterior cortical and subcortical structures to regulate behavior. This mechanism may have survival value, but may often be maladaptive in human society, contributing to the vulnerability of the PFC in many neuropsychiatric disorders.
We applied a covariance-based multivariate analysis to functional magnetic resonance imaging (fMRI) data to investigate abnormalities in working memory (WM) systems in patients with post-traumatic stress disorder (PTSD). Patients (n=13) and matched controls (n=12) were scanned with fMRI while updating or maintaining trauma-neutral verbal stimuli in WM. A multivariate statistical analysis was used to investigate large-scale brain networks associated with these experimental tasks. For the control group, the first network reflected brain activity associated with WM updating and principally involved bilateral prefrontal and bilateral parietal cortex. Controls' second network was associated with WM maintenance and involved regions typically activated during storage and rehearsal of verbal material, including lateral premotor and inferior parietal cortex. In contrast, PTSD patients appeared to activate a single fronto-parietal network for both updating and maintenance tasks. This is indicative of abnormally elevated activity during WM maintenance and suggests inefficient allocation of resources for differential task demands. A second network in PTSD, which was not activated in controls, showed regions differentially activated between WM tasks, including the anterior cingulate, medial prefrontal cortex, fusiform and supplementary motor area. These activations may be linked to hyperarousal and abnormal reactivity, which are characteristic of PTSD.
Electroencephalographic data recorded for topographical analysis constitute multidimensional observations, and the present paper illustrates methods of data analysis of multichannel recordings where components of evoked brain activity are identified quantitatively. The computation of potential field strength (Global Field Power, GFP) is used for component latency determination. Multivariate statistical methods like Principal Component Analysis (PCA) may be applied to the topographical distribution of potential values. The analysis of statistically defined components of visually elicited brain activity is illustrated with data sets stemming from different experiments. With spatial PCA the dimensionality of multichannel data is reduced to only three components that account for more than 90% of the variance. The results of spatial PCA relate to experimental conditions in a meaningful way, and this method may also be used for time segmentation of topographic potential maps series.
We confirm that the latency of the P300 component of the human event-related potential is determined by processes involved
in stimulus evaluation and categorization and is relatively independent of response selection and execution. Stimulus discriminability
and stimulus-response compatibility were manipulated independently in an "additive-factors" design. Choice reaction time and
P300 latency were obtained simultaneously for each trial. Although reaction time was affected by both discriminability and
stimulus-response compatibility, P300 latency was affected only by stimulus discriminability.
We examined the effects of varying the scoring rules for the CAPS (Clinician Administered PTSD Scale) on the diagnosis of PTSD in a sample of 100 victims of recent motor vehicle accidents. This was done by assessing, for each scoring rule, the rate of categorical diagnosis and the effect on group mean scores on measures of subjective distress and role impairment. Changing from the most liberal to the most conservative scoring rule results in a change in diagnosis of PTSD from 44% to 29% of the sample. Comparisons of those included as PTSD under the most conservative scoring criteria vs those excluded (who had previously been included) reveal significantly greater subjective distress and role impairment among those who continue to be included in the PTSD category. Thus, changes in scoring rules have clinically significant effects on the incidence and severity of diagnosed PTSD. This indicates that the selection of scoring rules has important implications for epidemiological estimates of the prevalence of PTSD, and that PTSD studies using different scoring rules as inclusion criteria may be using somewhat different samples.
This study investigated event-related potential (ERP) indices of information processing in sufferers of posttraumatic stress disorder (PTSD). ERPs were obtained from 18 PTSD patients and 20 controls while they performed a target discrimination task requiring the detection of infrequent target tones from a background sequence of frequent and infrequent distractor tones. A delayed N2 and an attenuated P3 that failed to differentiate target from distractor tones indicated that patients had abnormal difficulty distinguishing task stimuli of differing relevance. It is proposed that this difficulty is reflected behaviorally in the slowed reaction time by patients to target stimuli and may underlie the disturbed concentration and memory impairments found in PTSD. It may also be related to dysfunction in central noradrenaline function, which has been shown to be both crucial in selective attention and abnormal in PTSD.
Seventeen patients with major affective disorder completed a 10-week, placebo-controlled, randomized trial of the serotonin reuptake inhibitor sertraline. Patients underwent positron emission tomography with 18F-deoxyglucose and were assessed with the Hamilton Depression Rating Scale at baseline and 10 weeks after treatment with sertraline or placebo. The middle frontal gyrus, an area previously characterized by decreased metabolic activity in depressive patients, showed relatively increased activity on both sides after sertraline when contrasted with temporal and some occipital areas. Sertraline was associated with a significantly increased relative metabolic rate in right parietal lobe and in left occipital area 19, and a decreased metabolic rate in right occipital area 18. Other areas that differed between controls and a larger cohort of 39 depressive patients--including medial frontal lobe, cingulate gyrus, and thalamus--also showed a normalization of metabolic rate after sertraline.
We tested 186 children ranging in age from 6 years, 10 months to 13 years, 7 months; 174 suffered either physical and/or sexual abuse, and 12 were nonabused children. Abused subjects were grouped in four different ways. The primary grouping was based on whether subjects satisfied the DSM III-R criteria for posttraumatic stress disorder (PTSD). Secondary groupings were based upon the three symptom clusters used to make the PTSD diagnosis (arousal, avaidance, and reexperiencing). In each of these groupings three separate subgroups were formed with approximately 25 percent in the high and low symptom count subgroups and the remaining 50 percent in the middle symptom count subgroup.
Subjects listened to four different intensity levels (65, 80, 95, and 102 dB) of a 1 KHz tone, pseudo-randomly ordered, while event-related brain potentials (ERPs) were recorded. Two separate blocks were used, one with short intervals (4±1 sec) between tones and the other with longer intervals (17±2 sec). PTSD subjects presented a greater P2-N2 ERP intensity gradient (i.e., a larger increase in the P2-N2 ERP component as tone intensity increased) than did abused subjects without PTSD. Abused subjects with the highest number of reexperiencing symptoms showed a similar P2-N2 augmenting effect when compared to those with the lowest number of reexperiencing symptoms. Subjects with the highest number of arousal symptoms showed a shallower intensity gradient for the N1-P2 ERP component than did those with fewer arousal symptoms. The results are discussed in relation to previous results reported on adults with PTSD and in terms of CNS processing of stimulus intensity information.
This study attempted to replicate findings of abnormal auditory event-related potentials (ERPs) in posttraumatic stress disorder (PTSD) in a sample of Vietnam combat veterans. Veterans with combat-related PTSD, divided into unmedicated (unmed-PTSD, n = 12) and medicated (med-PTSD, n = 22) groups, and veterans without PTSD (non-PTSD, n = 10) completed a three-tone "oddball" target detection task while ERPs were measured. Individuals with comorbid panic disorder (PD) were excluded from the primary analyses. Parietal P3 amplitude to the target tone was significantly smaller in unmed-PTSD compared to med-PTSD and non-PTSD groups. These differences did not remain significant when an adjustment was made for level of depression. Parietal P3 amplitude was also negatively correlated with state anxiety. Secondary analyses within the unmed-PTSD group indicated that participants with comorbid PD (n = 3) had the largest parietal P3 amplitudes to target tones. Results are consistent with attentional or concentration deficits in PTSD and highlight the importance of considering comorbid diagnoses. The absence of ERP differences between med-PTSD and non-PTSD participants suggests that psychotropic medication may normalize these deficits.
There is growing evidence that posttraumatic stress disorder (PTSD) is characterized by specific psychobiological dysfunctions, contributing to a growing interest in the use of medication in its treatment. This is a systematic review, following the guidelines and using the software of the Cochrane Collaboration, of randomized controlled trials (RCTs) of the medication treatment of PTSD. A search was undertaken for all RCTs, published and unpublished, completed prior to the end of 1999, and data was collated and analysed using Review Manager (RevMan) software. 15 short-term (12 weeks or less) RCTs were available for analysis. Despite potentially important differences between the trials, many trials demonstrated efficacy for medication over placebo. Summary statistics for the Clinical Global Impressions scale change item (CGI-C) or close equivalent and for the intrusion, avoidance and total scales of the Impact of Events Scale (IES) indicated that medication was significantly more effective than placebo. Thus, medication treatments can be effective in PTSD, acting to reduce its core symptoms, and should be considered as part of the treatment of this disorder. Although the existing evidence base does not provide sufficient data to suggest particular predictors of response to treatment, or to demonstrate that any particular class of medication is more effective or better tolerated than any other, the largest trials showing efficacy to date have been with the selective serotonin reuptake inhibitors (SSRIs). Given the high prevalence and enormous personal and societal costs of PTSD, there is a need for additional controlled trials in this area.
Treatment of major depression with antidepressants is generally associated with a delay in onset of clinical response. Functional brain correlates of this phenomenon have not been previously characterized.
Time course of changes in brain glucose metabolism were measured using positron emission tomography in hospitalized unipolar depressed patients treated with fluoxetine. Time-specific and response-specific effects were examined at 1 and 6 weeks of treatment.
Changes were seen over time, and characterized by three distinct patterns: 1) common changes at 1 and 6 weeks, 2) reversal of the 1-week pattern at 6 weeks, and 3) unique changes seen only after chronic treatment. Fluoxetine responders and nonresponders, similar at 1 week, were differentiated by their 6-week pattern. Clinical improvement was uniquely associated with limbic and striatal decreases (subgenual cingulate, hippocampus, insula, and pallidum) and brain stem and dorsal cortical increases (prefrontal, parietal, anterior, and posterior cingulate). Failed response was associated with a persistent 1-week pattern and absence of either subgenual cingulate or prefrontal changes.
Chronic treatment and clinical response to fluoxetine was associated with a reciprocal pattern of subcortical and limbic decreases and cortical increases. Reversal in the week-1 pattern at 6 weeks suggests a process of adaptation in specific brain regions over time in response to sustained serotonin reuptake inhibition. The inverse patterns in responders and nonresponders also suggests that failure to induce these adaptive changes may underlie treatment nonresponse.
Neuropsychological findings in obsessive-compulsive disorder (OCD) have been explained in terms of reduced cognitive shifting ability as a result of low levels of frontal inhibitory activity. This deficit could be reflected in an abnormal P300 component of the event-related potential. The improvement in cognitive processing due to pharmacological treatment would modify the P300 component, bringing it close to that of normal controls. Nineteen patients suffering from OCD and 19 normal controls were recorded. We used a computerized version of the auditory 'odd-ball paradigm' to obtain the P300 component at the Pz electrode. Patients were tested twice, drug-free and under treatment with clomipramine in 250-300 mg doses. We observed the P300 component to have lower amplitude and longer latency in drug-free OCD patients when compared with controls. P300 amplitude in OCD increased after treatment, although this was supported only by a statistical trend. There was no modification in P300 latency after treatment. It is possible that inhibitory activity improves with treatment and allows patients to answer with more confidence, which results in an increase in P300 amplitude. This study suggests that cognitive dysfunction in OCD fluctuates with changes in the clinical associated with treatment, probably in relationship to central serotoninergic transmission.
This study examined ERP topography during the updating and the utilization of working memory in subjects with PTSD. Event-related potentials of 18 participants with PTSD and 18 controls were recorded from 32 scalp electrodes during an auditory target detection task requiring the constant updating of target identity. Midline N2 and P3 abnormalities previously noted in PTSD during target detection were replicated. Scalp topographic data revealed sustained reduction in activity over the right hemisphere during working memory updating. Executive processes were associated with brief but widespread right hemisphere reductions during the P3, followed by sustained, bilateral reduction frontally. This study identifies an abnormal pattern of cortical network function during both the updating and use of working memory in PTSD.
Finding objective and effective thresholds for voxelwise statistics derived from neuroimaging data has been a long-standing problem. With at least one test performed for every voxel in an image, some correction of the thresholds is needed to control the error rates, but standard procedures for multiple hypothesis testing (e.g., Bonferroni) tend to not be sensitive enough to be useful in this context. This paper introduces to the neuroscience literature statistical procedures for controlling the false discovery rate (FDR). Recent theoretical work in statistics suggests that FDR-controlling procedures will be effective for the analysis of neuroimaging data. These procedures operate simultaneously on all voxelwise test statistics to determine which tests should be considered statistically significant. The innovation of the procedures is that they control the expected proportion of the rejected hypotheses that are falsely rejected. We demonstrate this approach using both simulations and functional magnetic resonance imaging data from two simple experiments.
The selective serotonin uptake inhibitor (SSRI) fluoxetine has been shown to not only increase the extracellular concentrations of serotonin, but also dopamine and norepinephrine extracellular concentrations in rat prefrontal cortex. The effect of other SSRIs on monoamine concentrations in prefrontal cortex has not been thoroughly studied.
The aim of this study was to compare the ability of five systemically administered selective serotonin uptake inhibitors to increase acutely the extracellular concentrations of serotonin, norepinephrine and dopamine in rat prefrontal cortex.
The extracellular concentrations of monoamines were determined in the prefrontal cortex of conscious rats using the microdialysis technique.
Fluoxetine, citalopram, fluvoxamine, paroxetine and sertraline similarly increased the extracellular concentrations of serotonin from 2- to 4-fold above baseline. However, only fluoxetine produced robust and sustained increases in extracellular concentrations of norepinephrine and dopamine after acute systemic administration. Fluoxetine at the same dose blocked ex vivo binding to the serotonin transporter, but not the norepinephrine transporter, suggesting that the increase of catecholamines was not due to non-selective blockade of norepinephrine uptake. Prefrontal cortex extracellular concentrations of fluoxetine at the dose that increased extracellular monoamines were 242 nM, a concentration sufficient to block 5-HT(2C) receptors which is a potential mechanism for the fluoxetine-induced increase in catecholamines.
Amongst the SSRIs examined, only fluoxetine acutely increases extracellular concentrations of norepinephrine and dopamine as well as serotonin in prefrontal cortex, suggesting that fluoxetine is an atypical SSRI.
The purpose of this study was to examine the relationship between disturbance in event-related potentials (ERPs) and symptom clusters in posttraumatic stress disorder (PTSD). ERPs were recorded in 17 unmedicated civilian PTSD patients and 17 age- and sex-matched controls during a conventional auditory oddball task. PTSD symptom clusters (re-experiencing, active avoidance, numbing, hyperarousal) were correlated with ERP measures. The PTSD group showed ERP disturbances to target stimuli (reduced P200 and P300 and increased N200 amplitude, increased N200 and P300 latency) and reduced P200 amplitude to common stimuli compared to the control group. A significant negative correlation was found between the intensity of numbing symptoms and parietal P300 amplitude. This study replicates findings of disturbed N200 and P300 components in PTSD, reflecting impairments in stimulus discrimination and attention. The finding that numbing was associated with reduced attention processing (P300) is consistent with models positing a relationship between disordered arousal and attention in PTSD.
Antidepressants may vary widely in their potential to impair cognitive and psychomotor functions. Little is known about their effects on event-related brain potentials (ERPs).OBJECTIVES. To compare the effects of three pharmacologically different antidepressants on performance and ERPs in tasks of selective attention and working memory.
Subjects were treated for 8 days with amitriptyline (sedative/anticholinergic TCA), nefazodone (5-HT(2) receptor antagonist), paroxetine (SSRI) and placebo, in a double-blind, crossover design. Measurements were carried out on day 1 and 8 of each treatment period. A task was used in which memory load (two and four items) and attention (focused, divided) were orthogonally varied.
On day 1 amitriptyline increased reaction times (focused attention) and the percentage of misses (load 4>load 2) and false alarms. Sensitivity (A') was reduced as a function of memory load. Effects were greatly diminished on day 8. The ERP analysis yielded a reduced early frontal positive difference wave related to memory load (day 1). Attention-related search negativity was slightly prolonged. P3 latency (stimulus evaluation time) was prolonged. P3 amplitude was reduced (mainly on day 8) suggesting diminished attention capacity. Nefazodone increased reaction times and miss rates and reduced sensitivity (A') on day 8 only. Paroxetine speeded responses on day 1 and slightly increased miss rates on day 8. Performance effects of nefazodone and paroxetine did not interact with the task factors. Search negativity and P3 measures were not affected.
The results suggest that the pharmacologically selective serotonergic antidepressants lack the specific memory and attention deficits seen with amitriptyline. Both performance and ERP data suggest that paroxetine and nefazodone may influence response-related processes, while for nefazodone an effect on other processes cannot be excluded.
Individuals with posttraumatic stress disorder (PTSD) have been found to show several event-related brain potential (ERP) abnormalities including reduced target P3b amplitude, P50 suppression, and P2 amplitude/intensity slope. Female Vietnam nurse veterans with (n = 29) and without (n = 38) current PTSD completed P50 paired-click, three-tone "oddball" and four-tone stimulus-intensity modulation procedures. Opposite to previous findings, the current PTSD group had larger target P3b amplitudes and increased P2 amplitude/intensity slopes. Reduced P50 suppression was associated with increased severity of general psychopathology, but not with PTSD diagnosis. Findings suggest that target P3b amplitude and P2 amplitude/intensity slope abnormalities reflect different pathophysiological processes. Future research is needed to determine whether the opposite ERP abnormalities observed in this PTSD sample reflect gender-, trauma-, or sample-specific findings.
We examined P300 measures in patients with posttraumatic stress disorder (PTSD) and control subjects at two different time points to determine event-related potential (ERP) stability over time and the relationship of changes in ERPs to changes in symptom levels.
Auditory and visual P300 was recorded in a three-condition novelty oddball task in 25 male subjects with combat-related PTSD and 15 male combat-exposed normal control subjects at two time points separated by 6-12 months. Regression analyses were conducted to compare the temporal stability of ERP measures in PTSD and control subjects. Variability in ERP measures over time within PTSD subjects was examined for association with changes in symptom levels.
There were no significant differences in P300 amplitude or latency in PTSD versus control subjects at either time point, regardless of stimulus type (target, novel) or modality (auditory, visual). Nine of 24 P300 measures were significantly less predictable over time in the PTSD group compared to control subjects. Variability of P300 measures over time was not associated with fluctuations in symptoms of depression or PTSD.
P300 ERPs are more variable cross-sectionally and over time in PTSD subjects compared to trauma exposed control subjects. Measures of variability about the group mean appear to be more informative about the cognitive electrophysiology of PTSD than measures of central tendency.
This study examined cerebral function in posttraumatic stress disorder (PTSD) during the updating of working memory to trauma-neutral, verbal information.
Ten PTSD and matched control subjects completed a visuoverbal target detection task involving continuous updating (Variable target condition) or no updating (Fixed target condition) of target identity, with updating activity estimated by condition comparison.
Normal updating activity using this paradigm involved bilateral activation of the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobe. The PTSD group lacked this activation in the left hemisphere and was significantly different from control subjects in this regard, but showed additional activation in the superior parietal lobe, bilaterally.
The pattern of parietal activation suggests a dependence on visuospatial coding for working memory representation of trauma-neutral, verbal information. Group differences in the relative involvement of the DLPFC indicate less dependence in PTSD on the executive role normally attributed to the left DLPFC for monitoring and manipulation of working memory content in posterior regions of the brain.
Brain imaging studies have mapped out the neural circuitry of posttraumatic stress disorder (PTSD), implicating brain areas sensitive to stress such as the hippocampus. Animal studies show that antidepressants promote hippocampal neurogenesis and block the effects of stress on the hippocampus. We found that treatment of PTSD patients for a year with the serotonin reuptake inhibitor (SSRI) paroxetine resulted in a 5% increase in hippocampal volume and a 35% improvement in verbal declarative memory function. Patients subjectively reported an improvement in cognition and work performance. These studies are consistent with the idea that antidepressants have a beneficial effect on hippocampal function in PTSD patients.
Previous investigations of auditory P300 event-related potentials have provided electrophysiological evidence for attentional problems in patients with posttraumatic stress disorder (PTSD). The present study sought to evaluate the relationship between P300 deficits and underlying brain morphological abnormalities in never-treated, comorbidity-free patients with PTSD following the Tokyo subway sarin attack. Out of 47 victims recruited, 8 victims with PTSD and 13 victims without PTSD were identified. Correlational analyses were performed between auditory P300 amplitude at Pz electrode site elicited in an oddball task and anterior cingulate gray matter volume that was shown to be reduced in our previous study using voxel-based morphometry on magnetic resonance imaging. Victims with PTSD showed significantly lower amplitudes of P300 compared with victims without PTSD, and the lower P300 amplitudes at Pz were significantly associated with higher avoidance/numbing scores in the PTSD group. Furthermore, in the PTSD group only, the P300 amplitudes showed a trend toward significant positive correlation with voxel densities of the anterior cingulate cortex gray matter. These results provide the first evidence that electrophysiological deficits of controlled attention observed in patients with PTSD may be linked to underlying brain morphological abnormalities.
This study used event-related potentials (ERPs) to investigate the timing and scalp topography of working memory in post-traumatic stress disorder (PTSD). This study was designed to investigate ERPs associated with a specific working memory updating process. ERPs were recorded from 10 patients and 10 controls during two visual tasks where (a) targets were a specific word or (b) targets were consecutive matching words. In the first task, nontarget words are not retained in working memory. In the second task, as in delay-match-to-sample tasks, a non-target word defines a new target identity, so these words are retained in working memory. This working memory updating process was related to large positive ERPs over frontal and parietal areas at 400-800 ms, which were smaller in PTSD. Estimation of cortical source activity indicated abnormal patterns of frontal and parietal activity in PTSD, which were also observed in regional cerebral blood flow [Clark, C.R., McFarlane, A.C., Morris, P., Weber, D.L., Sonkkilla, C., Shaw, M., Marcina, J., Tochon-Danguy, H., Egan, G., 2003. Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Biological Psychiatry 53, 474-481]. Frontal and parietal cortex are known to be involved in distributed networks for working memory processes, interacting with medial temporal areas during episodic memory processes. Abnormal function in these brain networks helps to explain everyday concentration and memory difficulties in PTSD.
Intracranial recordings, lesion studies, and the combination of functional imaging with source analysis have produced a solid body of evidence about the generators of the P300 event-related potential. Although it is impossible to square all findings obtained across and within methodologies, a consistent pattern of generators has emerged, with target-related responses in the parietal cortex and the cingulate and novelty-related activations mainly in the inferior parietal and prefrontal regions. Stimulus modality-specific contributions come from the inferior temporal and superior parietal cortex for the visual and from the superior temporal cortex for the auditory modality. The P300 continues to be an important signature of cognitive processes such as attention and working memory and of its dysfunction in neurologic and mental disorders. It is increasingly being investigated as a potential genetic marker of mental disorders. Knowledge about the generators of the P300 will be crucial for a better understanding of its cognitive significance and its continuing clinical application.
In healthy humans, there is an apparent dissociation between cognitive and affective consequences of reduced brain serotonin (5-HT), as rapid tryptophan depletion (RTD) causes alterations in a consistent constellation of cognitive processes in the general absence of mood deterioration. This study aimed to investigate possible neural mechanisms underlying this relative dissociation by measuring the effects of reduced 5-HT on regional cerebral blood flow (rCBF). A total of 16 healthy, euthymic male subjects (mean age 39+/-9 years) without a personal or family history of affective disorder had mood ratings and single photon emission computed tomography scans with the rCBF tracer 99mTc-HMPAO under reduced 5-HT (RTD) and control conditions. Across individuals, modest positive and negative changes in subjective happiness associated with RTD were significantly correlated with change of rCBF in a cluster comprising subgenual (affective) anterior cingulate cortex (ACC) and associated regions (Brodmann's area (BA) 25, posterior BA11 and 47, caudate nucleus and ventral striatum; SPM99 p<0.05, corrected). The covariation was such that increasing sadness was associated with increased rCBF and vice versa. Independent of mood change, RTD was associated with reduced rCBF in the dorsal (cognitive) ACC (BA32; SPM99 p<0.05, corrected). The subgenual prefrontal cortex and dorsal ACC are important components of the ventral and dorsal neural systems that regulate and integrate affective and cognitive functions. The results therefore suggest that the dissociation between affective and cognitive consequences of RTD may possibly be attributable to differential effects of reduced 5-HT on these neural systems.
Posttraumatic Stress Disorder (PTSD) is characterized by symptoms of hyperarousal, avoidance and intrusive trauma-related memories and deficits in everyday memory and attention. Separate studies in PTSD have found abnormalities in electroencephalogram EEG, in event-related potential (ERP) and behavioral measures of working memory and attention. The present study seeks to determine whether these abnormalities are related and the extent to which they share this relationship with clinical symptoms. EEG data were collected during an eyes-open paradigm and a one-back working memory task. Behavioral and clinical data (CAPS) were also collected. The PTSD group showed signs of altered cortical arousal as indexed by reduced alpha power and an increased theta/alpha ratio, and clinical and physiological measures of arousal were found to be related. The normal relationship between theta power and ERP indices of working memory was not affected in PTSD, with both sets of measures reduced in the disordered group. Medication appeared to underpin a number of abnormal parameters, including P3 amplitude to targets and the accuracy, though not speed, of target detection. The present study helps to overcome a limitation of earlier studies that assess such parameters independently in different groups of patients that vary in factors such as comorbidity, medication status, gender and symptom profile. The present study begins to shed light on the relationship between these measures and suggests that abnormalities in brain working memory may be linked to underlying abnormalities in brain stability.
Post-traumatic stress disorder (PTSD) is characterised by disturbances in concentration and memory, symptoms which are a source of further distress for patients. Related to this, abnormalities in underlying working memory (WM) systems have been identified [Clark, C.R., McFarlane, A.C., Morris, P., Weber, D.L., Sonkkilla, C., Shaw, M.E., Marcina, J., Tochon-Danguy, H.J., Egan, G.F., 2003. Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Biological Psychiatry 53, 474-481.], indicating dysfunction in left hemisphere brain regions. In this study, we performed functional magnetic resonance imaging (fMRI) in 13 patients with severe PTSD and matched non-traumatized Controls, during performance of visuo-verbal tasks that involved either maintenance or continual updating of word stimuli in WM. The PTSD group failed to show differential activation during WM updating, and instead appeared to show abnormal recruitment of WM updating network regions during WM maintenance. These regions included the bilateral dorsolateral prefrontal cortex (DLPFC) and the inferior parietal lobe (IPL). Several other regions were significantly more activated in Controls than in PTSD during WM updating, including the hippocampus, the anterior cingulate (AC), and the brainstem pons, key regions that are consistently implicated in the neurobiology of PTSD. These findings suggest compensatory recruitment of networks in PTSD normally only deployed during updating of WM and may reflect PTSD patients' difficulty engaging with their day-to-day environment.