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

The post Functional magnetic resonance imaging appeared first on NeuRA Library.

MRS is a specialised imaging technique that utilises magnetic resonance imaging to investigate biochemical alterations within tissues. Two notable methods of MRS are 1H-MRS (proton-MRS) and 31P-MRS (phosphorus-MRS). Each technique is sensitive to different metabolic compounds. 1H-MRS can be used to measure N-acetylaspartate, an amino acid that is used as a marker of neuronal viability. Decreased levels are associated with neuron death or dysfunction. 1H-MRS is also used to measure creatine, a compound involved in energy metabolism, glutamate, a neurotransmitter, and glutamine, a metabolite of glutamate. 31P-MRS is used to measure phospholipid levels, such as phosphomonoesters and phosphodiesters, that provide information about cellular energy metabolism and membrane synthesis.

What is the evidence for MRS?

All patients versus controls

High quality evidence finds decreases in glutathione in the anterior cingulate and myo-inositol in the medial prefrontal region of people with schizophrenia. Moderate or moderate to high quality evidence finds N-acetylaspartate is decreased in the frontal lobe, temporal lobe, thalamus, hippocampus, cerebellum, and cingulate cortex. N-acetylaspartate may also be reduced in the parietal cortex, basal ganglia and occipital lobe (white matter only) and increased in the striatum and lenticular nucleus. There were reductions in frontal glutamate, phosphomonoesters, and hippocampal choline/creatine, and increases in frontal glutamine and temporal phosphodiesters. There were no differences in GABA levels in the medial frontal cortex.

Unmedicated patients (drug free or drug naive) versus controls

Moderate to high quality evidence finds decreases in N-acetylaspartate in the thalamus and decreases in frontal white matter (using <3T MRI scanners only),. There are also increases in glutamate+glutamine in the medial prefrontal cortex, and increases in choline in the basal ganglia. There were no differences in glutamate, creatine or myo-inositol.

First-episode psychosis patients versus controls

Moderate quality evidence finds decreased phosphomonoesters levels and increased phosphodiesters levels in both the prefrontal cortex and temporal cortex.

People at clinical or genetic high risk versus controls

Moderate to high quality evidence finds a medium-sized decrease in glutamate in the thalamus of people at clinical high risk of psychosis, and a medium-sized increase in glutamate+glutamine in the frontal lobe of first-degree relatives. Moderate to low quality evidence finds N-acetylaspartate/creatine reductions in the anterior cingulate and hippocampus of first-degree relatives. People at clinical or genetic high-risk of schizophrenia showed N-acetylaspartate reductions in the thalamus and N-acetylaspartate/creatine reductions in the prefrontal cortex. There were also reduced prefrontal phosphomonoester levels and increased prefrontal phosphodiester levels in first-degree relatives.

October 2020

The post Magnetic resonance spectroscopy appeared first on NeuRA Library.

Positron emission tomography (PET) is a nuclear based imaging technique that utilises a radioactive tracer to visualise functional brain activity. PET imaging is frequently used in combination with anatomical imaging such as computed tomography (CT) or structural magnetic resonance imaging (MRI). The radioisotopes tracers are coupled with a biological molecule such as glucose, which is used during cellular metabolism and can be used to highlight areas with changes in metabolic activity. Using PET, functional brain activity has been investigated in people with schizophrenia compared to people without schizophrenia to identify regions of increased or decreased metabolic function or blood flow.

What is the evidence for PET brain functioning?

During executive functioning and working memory tasks, moderate quality evidence suggests significant decreases in functional 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 memory encoding tasks, moderate quality evidence suggests significant decreases in functional activation in the medial frontal gyri and the hippocampus. During memory retrieval tasks, decreased activation is 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 emotion processing tasks, moderate and moderate to low quality evidence suggests decreased activation in the amygdala, parahippocampus, superior frontal gyrus and middle occipital gyrus. There is also lower magnitude of activation in the fusiform gyrus, lentiform nucleus, and parahippocampal gyrus. During explicit (effortful) emotion tasks, there is decreased activation in the fusiform gyrus, while during implicit (automatic) emotion tasks, there are decreases in the superior frontal and middle occipital gyri.

During auditory hallucinations, moderate and moderate to low quality evidence suggests 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 during external auditory stimulation.

During cognitive tasks and rest periods, moderate to high quality evidence shows a medium to large effect of reduced functional activity in bilateral frontal lobes in people with schizophrenia. Moderate quality evidence suggests increased functional activity in the left temporal lobe during cognitive tasks, but no differences between patients and controls during rest periods.

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 significant in treatment-resistant patients. There were no differences in dopamine D2/3 receptor or transporter availability. Within-group variability was similar for dopamine synthesis and release capacities, but there was greater variability in synaptic dopamine levels, and dopamine D2/3 receptor and transporter availability in the patient groups than in the control groups.

Moderate quality evidence finds greatest D2 receptor occupancy with haloperidol (92%), then risperidone, olanzapine, clozapine, quetiapine, aripiprazole, ziprasidone, and then amisulpride (85%). There may be an association between dopamine receptor occupancy and clinical improvement following treatment with antipsychotic medications.

There was also a small to medium-sized increase in translocator protein in people with schizophrenia when measured using binding potential, but not when measured using volume of distribution.

October 2020

The post Positron emission tomography appeared first on NeuRA Library.

Single-photon emission computed tomography (SPECT) is a nuclear based imaging technique that uses radioactive tracers to visualise functional brain activity. SPECT imaging is frequently used in combination with anatomical imaging such as computed tomography (CT) or structural magnetic resonance imaging (MRI). The radioisotope tracers are coupled with a biological molecule such as glucose, which is used during cellular metabolism and can be used to highlight areas with changes in metabolic activity. Functional brain activity has been investigated in people with schizophrenia compared to people without schizophrenia to identify regions of increased or decreased metabolic function or blood flow.

What is the evidence from SPECT studies?

Moderate quality evidence suggests elevated striatal dopamine synthesis and release capacities and increased striatal synaptic dopamine levels in people with schizophrenia compared to controls. The finding for elevated 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 for dopamine synthesis and release capacities, but there was greater variability in synaptic dopamine levels, and dopamine D2/3 receptor and transporter availability in the patient groups than in the control groups.

Moderate to low quality evidence finds associations between dopamine receptor occupancy and clinical improvements following treatment with antipsychotic medications. There is greatest dopamine D2 receptor occupancy with haloperidol (91.9%), then risperidone, olanzapine, clozapine, quetiapine, aripiprazole, ziprasidone, and then amisulpride (85%). First-generation antipsychotics in general are associated with higher receptor occupancy in the striatum and temporal cortex than second-generation antipsychotics.

Moderate to high quality evidence suggests significant reductions in functional activity in the whole brain of people with schizophrenia compared to controls. During cognitive tasks and rest periods, there is a medium to large effect of reduced functional activity in bilateral frontal lobes. Moderate quality evidence suggests increased functional activity in the left temporal lobe during cognitive tasks, but no differences between patients and controls during rest periods.

October 2020

The post Single photon emission computed tomography appeared first on NeuRA Library.