Cerebral blood flow velocity changes to visual stimuli in patients with multiple sclerosis

We assessed the blood flow velocity (BFv) changes to visual stimuli using transcranial Doppler (TCD) in patients with multiple sclerosis (MS) during an exacerbation period by means of vasoneuronal coupling. Eighty-four patients (19 men, 75 women) and 45 healthy subjects (14 men, 31 women) were studied. Both posterior cerebral arteries (PCAs) were simultaneously monitored by TCD sonography during 10 cycles of 20 s eyes open observing complex moving visual images, and 20 s eyes closed at the end of every cycle. TCD sonography was performed at least at the first 2 days of exacerbation. Mean cerebral BFv throughout the procedure (p=0.003, p=0.001; right and left sides, respectively), velocity at rest (p=0.001, p<0.001), and velocity at stimulation (p=0.021, p=0.01) on both PCAs were significantly lower in patients than controls. However, BFv changes to visual stimulation on both sides were significantly higher in patients (p=0.01, p=0.031) compared to controls. There were negative correlations between P100 latencies and relative blood flow changes on both sides, but it was not significant on the left side. These results may suggest that patients with MS during exacerbation have more reactive vessels in the posterior circulation and! or more reactive neurons in the occipital cortex.     

Identification of pleasant, neutral, and unpleasant odors in schizophrenia

Recent work on odor hedonics in schizophrenia has indicated that patients display abnormalities in hedonic judgments of odors in comparison to healthy comparison participants. In the current study, identification accuracy for pleasant, neutral, and unpleasant odors in individuals with schizophrenia and healthy controls was examined. Thirty-three schizophrenia patients (63% male) and thirty-one healthy volunteers (65% male) were recruited. The groups were well matched on age, sex, and smoking status. Participants were administered the University of Pennsylvania Smell Identification Test, which was subsequently divided into 16 pleasant, 15 neutral, and 9 unpleasant items. Analysis of identification z-scores for pleasant, neutral, and unpleasant odors revealed a significant diagnosis by valence interaction. Post-hoc analysis revealed that schizophrenia participants made more identification errors on pleasant and neutral odors compared to healthy controls, with no differences observed for unpleasant odors. No effect was seen for sex. The findings from the current investigation suggest that odor identification accuracy in patients is influenced by odor valence. This pattern of results parallels a growing body of literature indicating that patients display aberrant pleasantness ratings for pleasant odors and highlights the need for additional research on the influence of odor valence on olfactory identification performance in individuals with schizophrenia.     

Cerebral blood flow in subjects with social phobia during stressful speaking tasks: a PET study

OBJECTIVE: The central nervous system representation of social phobia (social anxiety disorder) is largely unknown. The aim of this study was to examine brain activity during symptom provocation in social phobics. METHOD: Positron emission tomography with the use of (15)O water was used to measure regional cerebral blood flow (rCBF) in 18 subjects with DSM-IV-defined social phobia and a nonphobic comparison group while they were speaking in front of an audience and in private. Heart rate and subjective anxiety were also recorded. RESULTS: During public versus private speaking, subjective anxiety increased more in the social phobics than in the comparison group. Increased anxiety was accompanied by enhanced rCBF in the amygdaloid complex in the social phobics relative to the comparison subjects. Cortically, brain blood flow decreased in the social phobics and increased in the comparison subjects more during public than private speaking in the orbitofrontal and insular cortices as well as in the temporal pole and increased less in the social phobics than in the comparison group in the parietal and secondary visual cortices. Furthermore, rCBF increased in the comparison group, but not in the social phobics, in the perirhinal and retrosplenial cortices. CONCLUSIONS: An rCBF pattern of relatively increased cortical rather than subcortical perfusion was observed in the nonphobic subjects, indicating that cortical evaluative processes were taxed by public performance. In contrast, the social phobia symptom profile was associated with increased subcortical activity. Thus, the functional neuroanatomy of social phobia involves the activation of a phylogenetically older danger-recognition system.     

Central and cardiovascular responses to emotional stimuli are normal in non-phobic subjects with Reflex Syncope.

OBJECTIVE: Reflex Syncope (RS) is a self-limited loss of consciousness due to systemic arterial hypotension resulting from widespread vasodilatation and/or bradycardia. Higher neural centres have been implicated in the pathophysiology of RS, particularly in blood/injury phobic patients. We investigated interictal central autonomic functions in non-phobic RS subjects compared to non-phobic controls evaluating their central and cardiovascular responses to emotional stimuli. METHODS: Cardiovascular responses to Valsalva Manoeuvre (VM), Deep Breathing (DB) and during presentation of 108 slides selected from the International Affective Picture System were assessed in 20 non-phobic RS subjects and 20 controls. Slide onset visual event-related potentials (ERPs) were also computed. RESULTS: No significant difference in cardiovascular responses and ERP amplitude were found in non-phobic RS subjects and controls at rest, in response to VM and DB or during picture presentation. CONCLUSIONS: Non-phobic patients with RS not only have a normal interictal autonomic control of the cardiovascular system but also a normal modulation and adaptation of central and cardiovascular response to emotional processing, in our experimental setting. SIGNIFICANCE: Non-phobic patients with RS present normal interictal central and cardiovascular responses. Autonomic dysfunction observed in phobic RS patients could be related to mechanisms underlying the phobia itself rather than the mechanisms causing RS.     

Neuropsychological correlates of normal variation in emotional response to visual stimuli

Although the neural substrates of induced emotion have been the focus of numerous investigations, the factors related to individual variation in emotional experience have rarely been investigated in older adults. Twenty-six older normal subjects (mean age, 54) were shown color slides to elicit emotions of sadness, fear, or happiness and asked to rate the intensity of their emotional responses. Subjects who experienced negative emotion most intensely showed relative impairment on every aspect of the Wisconsin Card Sorting Test. Intense positive emotion was associated with relatively impaired performance on the Rey Complex Figure Test. The volume of frontal brain structures, however, was not associated with emotion responses. Hemisphere-specific executive dysfunction was associated with greater intensity of emotional experience in normal older subjects. The role of these differences in intensity of induced emotion and impairment in executive function in daily social and vocational activity should be investigated.     

Cerebral blood flow changes associated with Schneiderian first-rank symptoms in schizophrenia

The authors examined the severity of Schneiderian first-rank symptoms in relation to regional cerebral blood flow (rCBF) with the use of PET. Eighty-seven schizophrenic patients were imaged during an eyes-closed condition during which they were instructed to relax and not perform any specific task (random episodic silent thought, or REST). Schneiderian symptoms were rated by using structured assessment instruments. The Schneiderian score of the patients was positively correlated with rCBF in right superior parietal cortex and negatively correlated with rCBF in left posterior cingulate gyrus and in left lingual gyrus. The results of this study demonstrate a cerebral pattern of activation related to Schneiderian symptoms and reinforce the hypothesis of an involvement of cortical areas that mediate space and body representation in such phenomena.     

Cerebral blood flow during anticipation of public speaking in social phobia: a PET study.

BACKGROUND: The aim was to examine the neural correlates of anxiety elicited by the anticipation of public speaking in individuals with social phobia.Positron emission tomography and (15)O-water was used to measure regional cerebral blood flow in subjects with DSM-IV defined social phobia during anxiety anticipation. Heart rate and subjective anxiety were also recorded. While being scanned, subjects were speaking alone either before or after speaking in public. To evaluate anticipatory anxiety we compared individuals speaking alone before they were speaking in front of an audience with those who did the reverse. RESULTS: Heart rate and subjective anxiety measures confirmed anticipatory anxiety in social phobics who performed their private speech before their public. This was accompanied by enhanced cerebral blood flow in the right dorsolateral prefrontal cortex, left inferior temporal cortex, and in the left amygdaloid-hippocampal region. Brain blood flow was lower in the left temporal pole and bilaterally in the cerebellum in the anticipation group. CONCLUSIONS: Brain regions with altered perfusion presumably reflect changes in neural activity associated with worry about anticipated public performance. We speculate that anticipatory anxiety in social phobics originates in an affect sensitive fear network encompassing the amygdaloid-hippocampal region, prefrontal, and temporal areas.     

An fMRI study investigating cognitive modulation of brain regions associated with emotional processing of visual stimuli

Brain regions modulated by cognitive tasks during emotional processing were investigated using fMRI. Participants performed indirect and direct emotional processing tasks on positive and negative faces and pictures. We used a multivariate technique, partial least squares (PLS) to determine spatially distributed patterns of brain activity associated with different tasks and stimulus conditions, as well as the interaction between the two. The pattern of brain activity accounting for the most task-related covariance represented a task x stimulus interaction and distinguished indirect processing of pictures and direct processing of faces from direct processing of pictures and indirect processing of faces. The latter two conditions were characterised by limbic (e.g. amygdala, insula, thalamus) and temporal lobe activity, in addition to greater activity in the ventral prefrontal cortex. Indirect and direct processing of pictures and faces, respectively, were represented by more dorsal prefrontal and parietal activity. These findings indicate that brain activity during processing of emotional content is critically dependent on both the type of stimulus and processing task. In addition, these results support the idea that the pattern of activity in the emotional network can be influenced in a 'top-down' fashion via cognitive factors such as attentional control, and as such, have important clinical implications for emotional disorders, such as depression and anxiety.     

Anticipation of aversive visual stimuli is associated with increased insula activation in anxiety-prone subjects.

BACKGROUND: Anticipation is a critical component of affective processing in general and for anxiety in particular. Prior research suggests that the right insula plays an important role in anticipation of affective processing during aversive images. This study aimed to test the hypothesis that individuals with increased anxiety-related temperamental traits (anxiety-prone [AP]) relative to anxiety-normative (AN) subjects would show an exaggerated insula response during anticipation of an aversive image. METHODS: 16 AP and 16 AN individuals performed a task in the functional magnetic resonance imaging scanner, during which they viewed pictures of spiders and snakes. Subjects were prompted 4-6 sec before the onset of each aversive image. Blood oxygenation level-dependent signal was contrasted during cued anticipation of images versus non-anticipatory task performance as well as viewing images. RESULTS: As hypothesized, AP subjects showed greater response than AN subjects in the bilateral insula during anticipation. In addition, these individuals had lower activity within the superior/medial frontal gyrus. During the image presentation phase, AN subjects showed greater activation than AP subjects in the bilateral temporal lobes and left superior frontal gyrus. Moreover, bilateral temporal lobe activation during image presentation was inversely correlated with bilateral insula activation during anticipation both within groups and in the combined group. CONCLUSIONS: These data suggest that greater activation of the insula during visual anticipation is associated with visual processing of aversive stimuli in AP individuals. Insula hyperactivity might be a common feature in persons with elevated trait anxiety and, as such, might be a neuroimaging marker for anxiety proneness.     

Abnormal neural responses to emotional visual stimuli in adolescents with conduct disorder.

BACKGROUND: It is widely held that aggression and antisocial behavior arise as a consequence of a deficiency in responding to emotional cues in the social environment. We asked whether neural responses evoked by affect-laden pictures would be abnormal in adolescents with conduct disorder (CD). METHODS: Functional magnetic resonance imaging during passive viewing of pictures with neutral or strong negative affective valence was performed in 13 male adolescents with severe CD aged 9 to 15 years and in 14 healthy age-matched control subjects. RESULTS: Main effects for negative-neutral affective valence included activations in the amygdala and hippocampus, ventral extrastriate visual cortex, and intraparietal sulcus bilaterally. There was a significant group-by-condition interaction in the right dorsal anterior cingulate cortex that was due to a pronounced deactivation in the patient group during viewing of negative pictures. When correcting for anxiety and depressive symptoms, we additionally found a reduced responsiveness of the left amygdala to negative pictures in patients compared with control subjects. CONCLUSIONS: We suggest that these findings reflect an impairment of both the recognition of emotional stimuli and the cognitive control of emotional behavior in patients with CD, resulting in a propensity for aggressive behavior.     

Cerebral blood flow changes associated with different meditation practices and perceived depth of meditation

Our goal in this study was to advance the understanding of the neural pathways of meditation by addressing the cerebral blood flow (CBF) responses associated with two different meditation practices performed by the same individuals and how such changes related to the “stress” circuits in the brain. Ten experienced meditators performed two types of meditation, a “focused-based” practice and a “breath-based” practice. Subjects were scanned using perfusion functional magnetic resonance imaging (fMRI) during a baseline state, both meditation states, and a post meditation baseline state. Using general linear model, we found that the frontal regions, anterior cingulate, limbic system and parietal lobes were affected during meditation and that there were different patterns of CBF between the two meditation states. We observed strong correlations between depth of meditation and neural activity in the left inferior forebrain areas including the insula, inferior frontal cortex, and temporal pole. There were persistent changes in the left anterior insula and the precentral gyrus even after meditation was stopped. This study revealed changes in the brain during two different meditation practices in the same individuals and that these changes correlated with the subjective experiences of the practitioners.     

Patterns of emotional experience in schizophrenia: differences in emotional response to visual stimuli are associated with clinical presentation and functional outcome

Second generation antipsychotics (SGA) are associated with new onset diabetes, dyslipidemia and significant weight gain. Patients with schizophrenia are also at an increase risk of developing metabolic disorders, making routine metabolic monitoring important in patients with schizophrenia. The objective of our study was to identify glucose and lipid monitoring rates in Kansas Medicaid beneficiaries with schizophrenia who received long-term SGA therapy both before and after metabolic concerns of SGA had been introduced in the medical literature and after publication of metabolic monitoring guidelines from professional organizations in 2004. A retrospective cohort study was conducted using health care claims of Kansas Medicaid enrollees (age 18-64 years) with a diagnosis of schizophrenia and receiving long-term SGA. Proportions of these patients receiving annual blood glucose and serum lipid laboratory tests were calculated for two periods: 2002-2003 and 2005-2007. Bivariate and multivariate analyses were conducted to determine associations between demographic characteristics and monitoring outcomes. Among 2204 persons in the 2002 cohort, 23% received annual blood glucose monitoring and 10.1% received lipid monitoring. Among 1646 persons in the 2006 cohort, 75.3% received blood glucose monitoring and 52.5% received lipid monitoring. Our findings showed significant increases in blood glucose and lipid monitoring rates observed across a 4-year period in Kansas Medicaid enrollees with schizophrenia receiving SGA. The large rise in monitoring over time may be due to increase awareness of metabolic concerns by mental health care specialists, whom patients with schizophrenia are likely to receive their care from.     

Cerebral blood flow, haematocrit and viscosity in subjects with a high oxygen affinity haemoglobin variant

The cerebral blood flow is low in primary polycythaemia, and it has been suggested that this is due to the increase in viscosity which accompanies the elevated haematocrit. In the present study cerebral blood flow has been measured by a non-invasive ¹³³Xenon technique in six subjects with an elevated haematocrit secondary to a haemoglobin variant with increased oxygen affinity. Flow was significantly higher than normal and 81 % higher than in 11 subjects of comparable age, matched for haematocrit and viscosity, but without the haemoglobin variant. In patients with this unusual type of polycythaemia, cerebral blood flow is high despite the elevated blood viscosity and the implications of these results are discussed.     

Quantitative EEG changes due to cerebral vasoconstriction. Indomethacin versus hyperventilation-induced reduction in cerebral blood flow in normal subjects.

Hyperventilation leads to an increase in slow EEG activity as well as to a decrease in alpha activity. These effects may be considered a result of reduction in cerebral blood flow due to vasoconstriction, but metabolic factors, such as alkalosis and the increased formation of cerebral lactate, may also have to be taken into account. As indomethacin decreases cerebral blood flow it is possible to study cerebral vasoconstriction, without concomitant metabolic alkalosis or cerebral lactate formation. Two parallel groups of 12 healthy male subjects (age 20-25) were studied with quantitative EEG (qEEG) and cerebral blood flow velocity as parameters. In the first group the effect of 100 mg indomethacin was studied. In the parallel group a standardized hyperventilation procedure was performed. In the indomethacin group the blood flow velocity decreased to 60% of the initial value; the qEEG showed a 0.5 Hz slowing of the alpha peak frequency (P less than 0.01) and a decrease in the power of the alpha band without any change in the delta or theta band. In the hyperventilation group the blood flow velocity decreased to 63% of the initial value and the qEEG showed a marked increase in delta and theta activity (P less than 0.01), but a non-significant change in alpha peak frequency. Indomethacin and hyperventilation caused similar degrees of vasoconstriction; however, the increase in qEEG slow wave activity, which was observed only in the hyperventilation group, is apparently related to metabolic rather than haemodynamic factors.     

Cerebral blood flow abnormalities in cerebral palsied children with a normal CT scan

Cerebral palsy (CP) is often a consequence of a hypoxic-ischemic encephalopathy and/or intracerebral hemorrhage secondary to pre- and peri-natal asphyxia. Hypodense lesions on the CT-scan are found in about 70 to 80% of CP-patients. In the present study, regional cerebral blood flow (CBF) was measured in CP-patients having a normal CT-scan. The aim was to correlate the CBF changes with the clinical and the etiologic findings. CBF was measured by xenon-133 inhalation and single photon emission computer tomography. The mean CBF value in 20 CP-patients, age 6-19 years, was 67 +/- 11 (1 SD) ml/100g/min, the same value as found in the 9 normal children. However, 16 of the 20 CP-patients had focal hypoperfused areas on the tomographic flow map. In the preterm infants (n = 7) the hypoperfused areas were mainly located in the posterior watershed areas, often in one hemisphere only. In the term infants (n = 13) both asymmetrical and symmetrical hypoperfused areas were observed in the anterior and posterior watershed areas. In addition, several children had larger low flow areas in the frontal and fronto-parietal lobes. In both groups, a relatively poor concordance was observed between the clinical findings and the expected location of the low flow area.