Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV

HIV-infected women may be particularly vulnerable to verbal learning and memory deficits. One factor contributing to these deficits is high perceived stress, which is associated with prefrontal cortical (PFC) atrophy and memory outcomes sensitive to PFC function, including retrieval and semantic clustering. We examined the association between stress and PFC activation during a verbal memory task in 36 HIV-infected women from the Chicago Consortium of the Women’s Interagency HIV Study (WIHS) to better understand the role of the PFC in this stress-related impairment. Participants completed standardized measures of verbal learning and memory and stress (perceived stress scale-10). We used functional magnetic resonance imaging to assess brain function while participants completed encoding and recognition phases of a verbal memory task. HIV-infected women with higher stress (scores in top tertile) performed worse on all verbal memory outcomes including strategic encoding (p?<?0.05) compared to HIV-infected women with lower stress (scores in lower two tertiles). Patterns of brain activation during recognition (but not encoding) differed between women with higher vs. lower stress. During recognition, women with higher stress demonstrated greater deactivation in medial PFC and posterior cingulate cortex compared to women with lower stress (p?<?0.05). Greater deactivation in medial PFC marginally related to less efficient strategic retrieval (p?=?0.06). Similar results were found in analyses focusing on PTSD symptoms. Results suggest that stress might alter the function of the medial PFC in HIV-infected women resulting in less efficient strategic retrieval and deficits in verbal memory.     

Post-traumatic stress disorder is associated with altered modulation of prefrontal alpha band oscillations during working memory

ObjectiveTo investigate the relationship between the severity of PTSD symptoms, modulation of alpha band oscillations, and behavioral performance in a working memory task.MethodsMagnetoencephalography data were recorded in 35 participants with combat exposure and various degrees of PTSD symptom severity while they performed a modified Sternberg working memory task: briefly presented sets of two or six letters had to be held in memory and participants indicated whether subsequent probe letters were present or absent from these sets.ResultsPTSD scores were positively correlated with the false positive rate in the high memory load condition. Higher rates of false recognition were associated with negative probes that were seen in recent previous trials (negative probe recency effect) or were physically similar with the list letters. The relative alpha band power in the left middle frontal gyrus was negatively correlated with both PTSD scores and false positive rates.ConclusionsReduced task specific modulation of alpha band oscillations in left middle frontal cortex may reflect alterations in the functions of pattern separation and suppression of memory traces for irrelevant or no longer relevant information in PTSD.SignificanceThe lower amplitude of prefrontal alpha band oscillations may represent an important physiological basis for core PTSD symptoms and can provide a target for interventions to augment response to treatment.     

Delayed motor learning and psychomotor slowing in HIV-infected children

OBJECTIVE: To find out whether HIV-associated subclinical psychomotor slowing is present in HIV-infected children despite effective highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: An electrophysiological motor test battery shown to sensitively describe HIV-associated CNS disease in adults (tremor peak frequency []TPF], most rapid alternating movements [MRAM], reaction time [RT] and contraction time [CT]) was performed in 17 HIV seropositive (+) right-handed children. Results were compared to 16 HIV seronegative (-) children. RESULTS: HIV (-) children showed slower frequencies (TPF, MRAM) and longer RT and CT than (-) adults. They showed a significant correlation (p = 0.0263) between RT (right = dominant hand) and age. HIV (+) children showed significant prolongations of RT (right hand) and CT (both hands) compared to HIV (-) children. RT right hand did not accelerate with age in HIV (+) children. CT were significantly prolonged in 10 children with detectable HIV plasma viral burden and normal in 7 children with no detectable HIV plasma viral load. There was no correlation between CT and CD 4 cell counts. CONCLUSIONS: Despite effective HAART, electrophysiological motor testing in HIV (+) children reveals significant subclinical CNS dysfunction, especially in children with insufficient viral load suppression.     

Effects of hostility and stress on affective verbal learning in women

The current experiment investigated the effects of hostility on affective verbal learning and physiological regulation in high and low hostile women. The Auditory Affective Verbal Learning Test (AAVLT) was administered to women in either a cold pressor or no cold pressor condition. Systolic blood pressure, diastolic blood pressure, and heart rate were recorded before and after the cold pressor or no cold pressor manipulation. Results indicated that high hostile women learned fewer words across conditions. The cold pressor primarily influenced neutral learning in high and low hostile participants. Additionally, primacy and recency effects of the AAVLT were replicated.     

Intrusive trauma recollections is associated with impairment of interference inhibition and psychomotor speed in PTSD

Background

Intrusive cognitions that enter consciousness involuntarily are prominent symptoms of posttraumatic stress disorder (PTSD). The present study aimed to identify neuropsychological mechanisms involved.

Method

Fifty PTSD outpatients and 50 healthy controls were tested using Finger Tapping, Simple and Choice Reaction Times and Stroop Tasks, to measure motor, psychomotor speed, response selection, and interference inhibition ability respectively.

Results

PTSD patients performed poorly in all tests, presumably owing to their generalized slowness of information processing and motor reaction. Psychomotor speed was a predictor of slowness and high error rate during the Stroop. Impaired inhibition, as measured by the interference index of the Stroop task, explained 9.7% of the predicated variance in frequency of re-experiencing PTSD symptoms and 23.5% of the predicated variance in augmentation of the interference response time.

Conclusion

Impaired interference control may be related to internal (re-experiencing) and external (sensory) stimuli that leads to cognitive deficits in PTSD patients.     

Deficits in verbal declarative memory function in women with childhood sexual abuse-related posttraumatic stress disorder

Several studies have shown deficits in verbal declarative memory function in posttraumatic stress disorder (PTSD). Most of these studies have been performed in men with combat-related PTSD compared with healthy subjects; relatively little is known about memory function in women with abuse-related PTSD, or whether these effects are specific to PTSD or are a nonspecific outcome of exposure to early abuse. The purpose of this study was to assess declarative memory function in women with and without a history of early childhood sexual abuse and PTSD. Forty-three women with and without a history of early childhood sexual abuse and PTSD underwent neuropsychological testing with subtests of the Wechsler Memory Scale--Revised for measurement of verbal and visual memory and subtests of the Wechsler Adult Intelligence Scale for measurement of IQ, and behavioral ratings of PTSD and other psychiatric symptoms. Abused women with PTSD had deficits in verbal declarative memory as measured with the subtests of the Wechsler Memory Scale--Revised compared with women with early abuse without PTSD and nonabused women without PTSD. There were no significant differences in IQ. These findings suggest that early abuse with PTSD is associated with deficits in verbal declarative memory, and that these effects are not related to the nonspecific effects of childhood abuse.     

Processing speed mediates the relationship between verbal memory, verbal fluency, and functional outcome in chronic schizophrenia

Verbal fluency and verbal memory have been reported to be diminished in patients with schizophrenia. These deficits could partially predict functional disability in this pathology. However, processing speed often mediates the relationship among cognitive processes in the disorder. Our goal was to analyse the influence of processing speed as mediator of the relation between verbal fluency–verbal memory and functional disability in chronic schizophrenia. We examined 90 hospitalized patients and 30 healthy controls (matched for gender, age and years of education). The neuropsychological battery included tests for verbal fluency, verbal memory, motor speed and processing speed. Outcome measures included Disability Assessment Schedule (DAS-WHO) and number of hospitalizations (NH). Results confirmed chronicity on clinical symptoms (PANSS total X = 48.94 + 14.97 PANSS negative X = 27.81 + 10.18, PANSS positive X = 23.51 + 10.81) and impairment on functional disability (DAS-WHO X = 13.62 +4.28). As expected, verbal fluency was severely impaired in patients and significantly predicted functional outcome. Immediate and Delayed Verbal Memory were also severely impaired and predicted functional outcome. However, when processing speed was entered in the regression analyses the significance of verbal fluency and verbal memory decreased significantly. Sobel's equation was significant, suggesting full mediation. Our findings suggest that processing speed may be a central factor in the relation between cognitive symptoms and functional outcome in chronic schizophrenia.     

Post-traumatic stress disorder in HIV-positive incarcerated women

The primary objective of this study was to examine a sample (n = 81) of HIV-positive incarcerated women to compare those with and those without a diagnosis of lifetime post-traumatic stress disorder (PTSD) with respect to demographics and legal, psychiatric, and health utilization histories. A secondary objective was to describe the prevalence of psychiatric disorders in the sample. Eighty-one women were interviewed with the Structured Clinical Interview for DSM-IV (SCID-P), SCID II, and the Clinician Administered Post-traumatic Stress Scale for DSM-IV (CAPS). Women with lifetime PTSD (n = 60) were more likely than those without (n = 21) to be white or Hispanic and to have a history of arrests for prostitution, risky sexual behavior, and intravenous drug use. Women with lifetime PTSD were also more likely to have had outpatient psychiatric treatment, treatment with psychiatric medications, suicide attempts, lifetime cannabis abuse/dependence, lifetime major depression, and antisocial personality disorder. These results suggest that HIV-positive female inmates with lifetime PTSD are a complex population who are likely to need careful psychiatric assessment, and medical and mental health treatment.     

Longitudinal improvement in psychomotor processing speed is associated with potent combination antiretroviral therapy in HIV-1 infection

This longitudinal natural history study aimed to assess the pattern and durability of neurocognitive benefits of progressively more potent combination antiretroviral therapy in HIV-1 infection. A cohort of 141 homosexual or bisexual men were assessed semiannually for CD4 count, HIV RNA viral load, medical and depressive symptoms, and a neuropsychological test battery, including psychomotor speed, verbal memory, and executive function. In a mixed-effects model, increasingly potent antiretroviral therapy was associated with improvement in tests of psychomotor processing speed. This study contributes to the growing literature documenting the longitudinal benefit provided by potent antiretroviral therapy for neuropsychological function, particularly psychomotor processing speed, in patients with HIV illness.     

Cortisol level predicts executive and memory function in depression, symptom level predicts psychomotor speed

OBJECTIVE: On a group level depression is related to hypercortisolism and to psychomotor retardation, executive dysfunction and memory impairment. However, intra-group heterogeneity is substantial. Why some are impaired while others remain in the normal range, is not clear. The present study aims at discerning the relative contribution of present symptom severity and hypercortisolism to impairment in the three domains of cognition. METHOD: Morning saliva cortisol was measured in 26 subjects with recurrent major depression prior to a neuropsychological examination with tests known to be sensitive to cognitive impairment in depression. RESULTS: Cortisol level correlated with executive dysfunction and post-encoding memory deficits, but not with processing speed. Depression level correlated with processing speed. These patterns remained significant after controlling for confounders through partial correlations. CONCLUSION: The association between cortisol and cognition is not an artifact of psychiatric symptom load. High level of saliva cortisol is associated with aspects of cognition that can be dissociated from psychomotor retardation, which is dependent on symptom load.     

Hyperhomocysteinemia is associated with lower performance on memory tasks in post-menopausal women

Increased levels of total homocysteine (tHcy) have been associated with lower performance on tests of cognitive function, and may be a potential preclinical marker for Alzheimer's disease. Most reports have focused on older cohorts, but raised tHcy levels, in association with cognitive changes may be occurring in earlier years. Scores for verbal and working memory were compared to plasma homocysteine levels for 200 healthy women aged 56--67 (mean=60). Smoking, hormone therapy and age were significantly associated with increased levels of tHcy, whilst vitamin B or folate supplements were significantly associated with lower tHcy levels. Hyperhomocysteinemia (>13 micromol/l) was significantly associated with poor performance for combined verbal and working memory, and there was a trend for hyperhomocysteinemia to be associated with the learning trials for 2 word lists, but not for the delayed trial. As hyperhomocysteinemia is associated with memory changes in women aged 56--67, it may be playing a role in the early dementia processes.     

Human verbal working memory impairments associated with thalamic damage

Although animal studies, human neuroimaging studies, and numerous theoretical models suggest possible contributions of the thalamus to working memory, there are very few reported deficits in human working memory following thalamic lesions. The present study examined working memory performance in six individuals with isolated thalamic stroke and found evidence of impairment on a number of working memory span tasks, but not on a forward digit-span measure. Examination of additional aspects of working memory performance (e.g., spatial and object working memory), analysis of subjects with other sites of thalamic stroke, and functional neuroimaging suggest a role of the thalamus in working memory.     

LTP-like cortical plasticity is associated with verbal memory impairment in Alzheimer's disease patients

Background

Alzheimer's disease (AD) is characterized by a primary impairment of long-term declarative memory caused by deposition of misfolded protein aggregates. Experimental studies showed that AD neuropathological alterations impair synaptic plasticity and memory performance. Transcranial Magnetic Stimulation protocols have been recently introduced to investigate altered mechanisms of cortical plasticity in AD patients.

Impaired verbal memory is associated with impaired motor performance in schizophrenia: relationship to brain structure

Deficient ability to take advantage of predictable elements in the performance of cognitive tasks has been proposed as an underlying factor for a number of deviances in schizophrenia. In a schizophrenic sample (n=39), we propose and test the view that certain memory and motor anomalies arise because of a compromise in the capacity to take advantage of the redundant (predictable) features of cognitive tasks. Results demonstrate a relationship between reduced capacity to take advantage of predictable features of two different cognitive processing tasks, one verbal memory, and the other motor. Poorer verbal recall on high-redundancy word lists was associated with a reduced ability to produce synchronous finger tapping in response to a high redundancy auditory stimulus, and inversely correlated with formal thought disorder ratings. These relationships, we suggest, reflect a specific and common schizophrenic deficit in the use of redundancies, not attributable to a generalized deficiency in performance. Structural imaging evidence from a subsample of these subjects (n=16) implicates frontal areas as the locus of this cognitive impairment.     

Expression of HIV-Tat protein is associated with learning and memory deficits in the mouse

HIV-Tat protein has been implicated in the pathogenesis of HIV-1 neurological complications (i.e., neuroAIDS), but direct demonstrations of the effects of Tat on behavior are limited. GT-tg mice with a doxycycline (Dox)-inducible and brain-selective tat gene coding for Tat protein were used to test the hypothesis that the activity of Tat in brain is sufficient to impair learning and memory processes. Western blot analysis of GT-tg mouse brains demonstrated an increase in Tat antibody labeling that seemed to be dependent on the dose and duration of Dox pretreatment. Dox-treated GT-tg mice tested in the Barnes maze demonstrated longer latencies to find an escape hole and displayed deficits in probe trial performance versus uninduced GT-tg littermates, suggesting Tat-induced impairments of spatial learning and memory. Reversal learning was also impaired in Tat-induced mice. Tat-induced mice additionally demonstrated long-lasting (up to one month) deficiencies in novel object recognition learning and memory performance. Furthermore, novel object recognition impairment was dependent on the dose and duration of Dox exposure, suggesting that Tat exposure progressively mediated deficits. These experiments provide evidence that Tat protein expression is sufficient to mediate cognitive abnormalities seen in HIV-infected individuals. Moreover, the genetically engineered GT-tg mouse may be useful for improving our understanding of the neurological underpinnings of neuroAIDS-related behaviors.     

Inflammatory markers are associated with decreased psychomotor speed in patients with major depressive disorder

Previous data have demonstrated that administration of inflammatory cytokines or their inducers leads to altered basal ganglia function associated with reduced psychomotor speed. Decreased psychomotor speed, referred to clinically as psychomotor retardation, is a cardinal symptom of major depressive disorder (MDD) and has been associated with poor antidepressant treatment response. We therefore examined the association between plasma inflammatory markers and psychomotor speed in ninety-three un-medicated patients with MDD. Psychomotor speed was assessed by a range of neuropsychological tests from purely motor tasks (e.g. movement latency and finger tapping) to those that involved motor activity with increasing cognitive demand and cortical participation (e.g. Trails A and Digit Symbol Substitution Task (DSST)). Linear regression analyses were performed to determine the relationship of inflammatory markers and psychomotor task performance controlling for age, race, sex, education, body mass index, and severity of depression. MDD patients exhibited decreased psychomotor speed on all tasks relative to normative standards. Increased IL-6 was associated with decreased performance on simple and choice movement time tasks, whereas MCP-1 was associated with decreased performance on the finger tapping task and DSST. IL-10 was associated with increased performance on the DSST. In an exploratory principle component analysis including all psychomotor tasks, IL-6 was associated with the psychomotor speed factor. Taken together, the data indicate that a peripheral inflammatory profile including increased IL-6 and MCP-1 is consistently associated with psychomotor speed in MDD. These data are consistent with data demonstrating that inflammation can affect basal ganglia function, and indicate that psychomotor speed may be a viable outcome variable for anti-inflammatory therapies in depression and other neuropsychiatric disorders with increased inflammation.     

Computerized cognitive remediation improves verbal learning and processing speed in schizophrenia

Computerized cognitive remediation has resulted in improved executive function in schizophrenia, whereas results with regard to verbal memory were inconsistent. In the present study, 42 inpatients with schizophrenia were randomly assigned to a computerized cognitive remediation group or to a treatment-as-usual (TAU) control group. The remediation group received 15 sessions of computerized cognitive training (Cogpack) over a 3-week period. Neurocognitive functions were assessed at the beginning and end of this period. Compared to the control condition, remediation training resulted in improvements in verbal learning, processing speed and executive function (verbal fluency). The results indicate that cognitive remediation may lead to improvements beyond those of executive function.