Maintenance of an adequate pH balance in all tissues and organs is important for good health. Decreased levels of brain pH are associated with increased levels of lactate, and vise versa. Lactate is an acidic source of fuel that is constantly generated and consumed in the brain. An imbalance in pH, particularly a shift toward high acidity, is associated with numerous physical and mental disorders.

What is the evidence for brain pH and lactate in people with schizophrenia?

Moderate quality evidence suggests no significant differences in brain pH between people with schizophrenia and controls. Lower quality evidence is unclear of changes in lactate concentrations.

October 2020

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Pending enough primary studies, we invite reviews on this topic to be conducted. Alternatively we will endeavour to conduct our own review to fill this gap in the Library.

October 2020

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Pending enough primary studies, we invite reviews on this topic to be conducted. Alternatively we will endeavour to conduct our own review to fill this gap in the Library.

October 2020

The post Cholesterol appeared first on NeuRA Library.

Pending enough primary studies, we invite reviews on this topic to be conducted. Alternatively we will endeavour to conduct our own review to fill this gap in the Library.

October 2020

The post Cortical release signs appeared first on NeuRA Library.

Dopamine is a neurotransmitter that is important for emotional and cognitive processing in the brain, particularly rewarding and pleasurable stimuli or experiences. Alterations of the dopamine system have been suggested in schizophrenia. This may be assessed as changes in levels of dopamine or its metabolites, or as changes in levels or activity of the mechanical components of the dopamine system, such as the receptors that receive dopamine, or the transporters that remove it.

What is the evidence for dopamine?

Moderate quality evidence suggests elevated striatal dopamine synthesis and release capacities and increased synaptic dopamine levels in people with schizophrenia compared to controls. The finding for dopamine synthesis was apparent in treatment-responsive and treatment-naive patients, but not in treatment-resistant patients. There were no differences in dopamine D2/3 receptor or transporter availability. Within-group variability was similar in patient and control groups for dopamine synthesis and release capacities, but there was greater variability in synaptic dopamine levels, and in dopamine D2/3 receptor and transporter availability in the patient groups.

Moderate to low quality evidence suggests an association between dopamine receptor occupancy and clinical improvement on the PANSS following treatment with antipsychotic medications. Greatest D2 receptor occupancy occurs with haloperidol (91.9%), then risperidone, olanzapine, clozapine, quetiapine, aripiprazole, ziprasidone, and then amisulpride (85%).

October 2020

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Electroencephalography (EEG) uses electrodes on the scalp to measure electrical activity from the brain. Quantitative spectral EEG investigates several waveforms, and so the activity can be measured, but EEG also gives rise to event related potentials (ERP), which measure the EEG activity directly evoked by a stimulus, often using cognitive or perceptual stimuli. Error-related negativity is a response-locked ERP that has been associated with monitoring of actions and detecting errors. Error-related negativity is typically followed by the error positivity component. In contrast to error-related negativity and error positivity, feedback negativity is elicited by externally provided feedback about positive rather than negative outcomes. Spectral waveforms measured by EEG include delta waves (up to 4 Hz), which are slow waves with high amplitude; theta waves (4-7 Hz), which are also slow waves; alpha waves (8-12 Hz), which occur mostly at rest, beta waves (12-30 Hz), which are fast waves with low amplitude, occurring during times of alert concentration, and gamma waves (30-100+ Hz) which occur during certain cognitive and motor functions. One example of an ERP is the P300 wave, which is measured primarily over the parietal lobe and is used as a measure of cognitive function. EEG is also used to measure electrical activity during sleep, to identify disruptions to sleeping patterns.

What is the evidence for EEG?

Moderate to high quality evidence finds theta and delta wave activity are increased and P300 amplitude is decreased in people with schizophrenia. Moderate quality evidence also finds increased beta wave activity and decreased alpha wave activity.

Moderate to high quality evidence finds a large effect of reduced error-related negativity in people with psychosis and a medium-sized effect in those at risk of psychosis. There were no differences in error positivity or feedback negativity.

Moderate quality evidence finds people with schizophrenia had large effects of shorter total sleep time, more awake time, longer sleep onset latency, and lower sleep efficiency. There were medium-sized effects of increased stage 1 sleep, decreased stage 4 sleep, decreased slow wave sleep, and decreased REM latency. There were small effects of decreased stage 3 sleep and increased REM duration. Moderator analyses found medication-naïve patients had shorter total sleep time, longer sleep onset latency, decreased sleep efficacy, and longer awake time. Patients recently withdrawn from antipsychotics had shorter total sleep time, longer sleep onset latency, decreased sleep efficacy, longer awake time, increased stage 1 sleep, decreased stage 2, 3, and 4 sleep, decreased slow wave sleep and shorter REM latency. Patients on antipsychotics had significantly longer sleep onset latency, increased stage 2 sleep, and decreased total REM sleep.

October 2020

The post Electroencephalography appeared first on NeuRA Library.

The endocannabinoid system is an endogenous biological system that regulates functions including cognition, sleep, energy metabolism, and inflammation. It modulates different neurotransmitter systems in the brain, including dopamine, glutamate, and GABA using two major lipid-based mediators, anandamide and arachidonoyl-sn-glycerol, that act through type one and type two cannabinoid receptors.

Exogenous cannabinoids, such as delta-9-tetrahydrocannabinol (THC), the main psychoactive components of cannabis, and cannabidiol (CBD), impact on the endocannabinoid system. While disturbance of the endocannabinoid system after cannabis consumption has been associated with increased risk of psychotic illness, CBD alone has shown anti-inflammatory and antipsychotic properties.

What is the evidence on endocannabinoids in schizophrenia?

Moderate to high quality evidence finds a large effect of higher concentrations of anandamide in the cerebrospinal fluid of patients, a medium-sized effect of higher concentrations of anandamide in the blood of patients, and a medium-sized effect of higher expression of type one cannabinoid receptors on peripheral immune cells of patients. There were insufficient usable data for a meta-analysis on type two cannabinoid receptors, and authors report mixed findings.

Increased severity of positive and negative symptoms was associated with decreased anandamide levels in cerebrospinal fluid and increased expression of type one and two cannabinoid receptors in peripheral blood mononuclear cells.

Poor cognitive performance was associated with decreased anandamide levels in serum and cerebrospinal fluid, increased expression of type one and two cannabinoid receptors in peripheral blood mononuclear cells, decreased expression of endocannabinoid system-synthesizing enzymes in peripheral blood mononuclear cells, and increased expression of endocannabinoid system-degrading enzymes in peripheral blood mononuclear cells.

October 2020

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Smooth pursuit eye movement is a visual tracking reflex evoked by a smoothly moving target, usually elicited by stimuli presented on a computer monitor. Deficits in smooth pursuit and an excess of ‘jerky’ eye movements were one of the earliest reported phenotypes associated with schizophrenia, and smooth pursuit has since been identified as a candidate endophenotype (phenotype with a clearer genetic connection) for schizophrenia. The aim of the smooth pursuit reflex is to maintain the image of the moving target on the fovea, the region of the retina with the highest density of photoreceptors. The neural pathways involved in generating smooth pursuit are a complex network from the cortical visual pathways through to the brainstem ocular motor nuclei (III, IV and VI), and consequently an alteration in smooth pursuit performance may not in itself shed light on the actual nature of the dysfunction. Components of smooth pursuit which are quantified include gain in the open and closed loops, as well as rates and amplitudes for both intrusive and anticipatory saccades (fast eye movements). Closed loop gain is an index of temporal synchrony of the eye and the target during pursuit, and is estimated as the ratio of the respective velocities. Open loop gain is the average acceleration during the initiation of pursuit, in the first 100ms. During this period there is no visual feedback and so the movement is solely a result of visual motion signal input. Spontaneous saccades can occur during smooth pursuit: these can either be anticipatory saccades which facilitate movement towards the target, such as reflexive visually guided saccades; or intrusive saccades, which interrupt the smooth tracking of the target, such as catch-up saccades, back-up saccades, and memory-guided saccades.

What is the evidence on eye movement dysfunction?

Moderate to high quality evidence suggests reduced eye tracking performance in people with schizophrenia compared to controls, particularly in maintenance (closed loop) gain. Moderate quality evidence also suggests increased saccadic intrusion during eye tracking, with the effect largest for leading saccades and catch-up saccades. High quality evidence suggests relatives of people with schizophrenia also show impairment in closed loop gain during smooth pursuit eye movement. Moderate quality evidence suggests they show increased error rate of visually and memory guided saccades, impairment in fixational stability, and increased intrusive anticipatory saccades during smooth pursuit eye movement.

October 2020

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Functional laterality refers to a natural asymmetry in left or right-side dominance, for example in terms of handedness, or brain function. Handedness refers to the preference for using one hand over the other for certain tasks. Right-handed people show increased dexterity in their right hand, left-handed people show increased ability the left hand. People may also be ‘mixed’ handed and show different hand preference for different tasks. Listening tasks can be used to assess language lateralisation. People with schizophrenia may show differences in handedness or footedness, as well as altered visual and auditory dominance that may reflect abnormalities in brain laterality and dominance.

What is the evidence for altered functional laterality?

High quality evidence shows that people with schizophrenia are more likely to be left or mixed-handed than people without schizophrenia, including people with other psychiatric disorders. Moderate to high quality evidence suggests this finding is similar for males and females. Moderate to high quality evidence suggests people with schizophrenia have less right-ear dominance, which may be most apparent in people who experience auditory hallucinations. Moderate to low quality evidence suggest people with schizophrenia show an absence of normal leftward asymmetry in the planum temporale and Sylvian fissure brain regions, and an excess rightward asymmetry in the superior temporal gyrus (particularly posterior). There is also a higher frequency of abnormal (reversed) asymmetry in the frontal and occipital lobes.

February 2022

Image: ©arkalyk – Fotolia – stock.adobe.com

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Functional magnetic resonance imaging (fMRI) is used to determine functional activation of brain regions when an individual performs tasks (or rests) inside an MRI scanner. Most commonly fMRI studies use visual, auditory, motor or sensory stimuli to evoke neural responses in the brain. Recent fMRI studies also examine activity of the brain at rest. Changes in blood flow are interpreted to represent brain activation (or deactivation) associated with a particular brain state (i.e, while performing a particular activity, or while the brain is at rest). Functional activity has been investigated in people with schizophrenia compared to people without schizophrenia to identify regions of increased or decreased brain function on the basis of blood flow.

What is the evidence for fMRI brain function?

Moderate quality evidence suggests decreased local organisation and small-worldness (balance of local organisation and global integration) in people with schizophrenia compared to controls. There was reduced connectivity within the default network (self-related thought), the affective network (emotion processing), the ventral attention network (processing of salience), the thalamus network (gating information) and the somatosensory network (sensory and auditory perception). There was reduced connectivity between the ventral attention network and the thalamus network, the ventral attention network and the default network, the ventral attention network and the frontoparietal network (external goal-directed regulation), the frontoparietal network and the thalamus network, and the frontoparietal network and the default network. There was increased connectivity between the affective network and the ventral attention network.

During executive functioning and working memory tasks, there was decreased activation in the frontal lobe, including the dorsolateral prefrontal cortex, and in neocortical regions, including the parietal and occipital cortices and bilateral claustrum, fusiform gyrus, and cerebellum, and in subcortical regions, including the right putamen, hippocampus and left mediodorsal thalamus. Moderate to low quality evidence suggests significant increases in functional activation in the anterior cingulate cortex, temporal lobe, parietal cortex, lingual gyri, insula and the amygdala.

During cognitive control tasks, there was decreased activation in the bilateral anterior cingulate/paracingulate gyrus, left inferior parietal gyrus, right middle/inferior frontal gyrus, bilateral middle frontal gyrus, right thalamus, and left cerebellum. There was increased activation in the right middle occipital and bilateral precentral gyri.

During timing tasks, there was decreased activation in the bilateral caudate nuclei, left middle occipital gyrus, right inferior occipital gyrus, bilateral supplementary motor area, and right putamen. There was increased activation during timing tasks in bilateral superior parietal gyri, right inferior frontal gyrus, and right middle temporal gyrus.

During memory encoding tasks, there was decreased activation in the medial frontal gyri and the hippocampus. During memory retrieval tasks, decreased activation was seen in the medial and inferior frontal gyri, the cerebellum, hippocampus, and the fusiform gyrus, with increases in the anterior cingulate cortex and the medial temporal gyrus. During episodic memory encoding, there was decreased activation in the right superior frontal gyrus, bilateral inferior frontal gyri, right inferior parietal gyrus, right lingual gyrus, left hippocampus, and right posterior cingulate. There was increased activation in the left precentral gyrus, left middle temporal gyrus, left post-central gyrus, left cingulate and left parahippocampal gyrus. During episodic memory retrieval, there was decreased activation in the left inferior frontal gyrus, left middle frontal gyrus, right cuneus, right cingulate gyrus, bilateral thalamus, and bilateral cerebellum. There was increased activaton in the left precentral gyrus, right middle frontal gyrus, right thalamus and right parahippocampal gyrus.

During emotion processing tasks, there was decreased activation in the parahippocampus, superior frontal gyrus, middle occipital gyrus, fusiform gyrus, lentiform nucleus, and thalamus. There was increased activation in left amygdala, left hippocampus, left medial frontal region, left cuneus, and bilateral parietal cortex. During explicit threat processing, there was decreased activation in the inferior frontal gyrus, right cerebellum lobule VI, left fusiform gyrus, and thalamus, and increased activation in the medial prefrontal gyrus to superior prefrontal gyrus. During implicit threat processing, there was decreased activation in bilateral amygdala extending into putamen, hippocampus and parahippocampal gyrus, and fusiform gyrus extending into the cerebellum lobule IV/VI.

During theory of mind tasks, there was decreased activation in the medial prefrontal cortex (frontal medial and paracingulate), right premotor cortex (central opercular, postcentral, precentral), medial occipitoparietal, right lingual gyrus, left orbitofrontal cortex, left lateral occipitotemporal, left cingulate gyrus, and left middle temporal gyrus. There was increased activation in the left inferior parietal cortex and right inferior parietal cortex. During empathy tasks, there was decreased activation the right inferior frontal gyrus.

During inhibition tasks, there was decreased activation in the anterior and middle cingulate cortex, and increased activation in parietal and occipital regions. There was also decreased activation in the basal ganglia and inferior frontal cortex, and increased activation in the superior temporal gyrus during inhibition tasks.

During attention tasks, there was decreased activation in the anterior and middle cingulate cortex and the basal ganglia, and increased activation in the left supramarginal gyrus.

During linguistic tasks (mostly semantic reading), there was decreased activation in the lateral temporal regions and left putamen, and increased activation in bilateral frontal cortex and left putamen.

During reward stimuli tasks, there was decreased activation in the right ventral striatum.

During auditory hallucinations, there was increased activation in Broca’s area of the temporal lobe, insula, hippocampus, left parietal operculum, left and right postcentral gyrus, and left inferior frontal gyrus, and decreased activation of Broca’s area, the left middle temporal gyrus, left premotor cortex, anterior cingulate cortex, and left superior temporal gyrus.

In people with schizophrenia and formal thought disorder, moderate quality evidence found functional alterations (hyperactivation or hypoactivation) in the left superior and middle temporal gyrus.

Following cognitive remediation (40 session over 10 weeks), moderate to low quality evidence found increased activation in the left middle frontal gyrus, left inferior frontal gyrus, left superior frontal gyrus, pre- and postcentral gyrus, bilateral insula, parietal lobe, and medial frontal gyrus.

October 2020

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