The amygdala is located deep in the medial temporal lobe, and has reciprocal connections with many regions of the cortex, such as prefrontal and cingulate cortex, as well as sub-cortical regions such as the brainstem and hippocampus. The amygdala is implicated in the processing and memory of emotional responses, particularly emotional learning, as well as mediating the autonomic expression of emotion.

What is the evidence for amygdala alterations?

Moderate to high quality evidence found reduced grey matter volume in the amygdala and the amygdala-hippocampus region of people with schizophrenia compared to controls. There were also reductions in the amygdala of first-episode patients and relatives of people with schizophrenia.

Compared to people with bipolar disorder, moderate to low quality evidence finds a medium-sized effect of reduced amygdala volume in people with schizophrenia.

Moderate quality evidence found people with schizophrenia showed increased activity in the amygdala during executive function tasks, and increased or decreased activity during emotion processing tasks.

October 2020

The post Amygdala appeared first on NeuRA Library.

The arcuate fasciculus is a bundle of axons that connects the temporal cortex and inferior parietal cortex to locations in the frontal lobe. One of the key roles of the arcuate fasciculus is connecting Broca’s and Wernicke’s areas, which are involved in producing and understanding language. Therefore, there may be anomalies in the arculate fasciculus of people with schizophrenia who experience auditory-verbal hallucinations.

What is the evidence for changes in the arculate fasciculus?

Moderate quality evidence found reduced white matter integrity in the bilateral arcuate fasciculus, including bilateral anterior and posterior segments, and the left long segment.

There was reduced white matter integrity in the left, but not the right arcuate fasciculus in people with schizophrenia who experience auditory-verbal hallucinations.

October 2020

The post Arcuate fasciculus appeared first on NeuRA Library.

The basal ganglia is a group of sub-cortical nuclei thought to be involved in motor control and learning. The nuclei comprising the basal ganglia include the caudate, putamen, globus pallidus, the subthalamic nucleus, and the substantia nigra. The caudate and putamen together form the striatum, while the globus pallidus and the putamen together form the lenticular nucleus. The striatum is the principal input centre, receiving afferents primarily from the cortex, but also from the substantia nigra, thalamus, and external globus pallidus. There are two primary pathways from the striatum through the basal ganglia (‘direct’ and ‘indirect’), which incorporate different components of the basal ganglia circuitry, and play different roles in controlling and planning movements and cognition.

What is the evidence for basal ganglia alterations?

Structural changes

Moderate to high quality evidence found increased globus pallidus volume in medicated people with schizophrenia compared to controls. In mediation-naïve patients, the caudate nucleus was reduced. Moderate quality evidence found increases in the left caudate head of people with schizophrenia, but decreases in the left caudate head in those with persistent negative symptoms.

In people with first-episode schizophrenia, there was decreased grey matter in the bilateral caudate head (but not nucleus) and increased grey matter in the left putamen compared to controls. There was also increased grey matter in the left putamen of people with schizophrenia (not necessarily first-episode) compared to relatives of people with schizophrenia. Moderate to low quality evidence found greater reductions in the bilateral caudate in first-episode treatment-naïve patients (vs. controls) than in first episode treated patients (vs. controls). Moderate to high quality evidence suggests increased antipsychotic use was associated with increased basal ganglia volume over time (>2 years).

Moderate to low quality evidence found similar grey matter volume decreases in the right putamen in people with schizophrenia and people with an autistic spectrum disorder compared to controls.

Functional changes

Moderate quality evidence found reduced activity in the right putamen of people with schizophrenia during executive functioning and timing tasks compared to controls. Moderate quality evidence found increased activations in the left putamen of people with schizophrenia compared to controls during emotionally neutral tasks.

Moderate to low quality evidence finds increased activation in the right caudate of relatives of people with schizophrenia compared to controls during cognitive tasks, and increased activation in the left lentiform nucleus during emotion tasks.

Moderate quality evidence finds unmedicated people with schizophrenia have a medium to large increase in choline in the basal ganglia. Moderate to low quality evidence found no differences in D2/D3 receptor availability in the substantia nigra of unmedicated people with schizophrenia compared to controls, and no differences in GABA levels in the striatum of people with schizophrenia.

Structural and functional changes

Moderate quality evidence found decreased grey matter volume and decreased functional activity in the left caudate nucleus of drug-free first-episode patients.

October 2020

The post Basal ganglia appeared first on NeuRA Library.

The cerebellum sits below the larger cerebrum of the brain, and is connected via the brainstem. The cerebellum is divided into two hemispheres separated dorsally by a midline zone called the vermis. It contains three primary lobes, the flocculonodular lobe, anterior lobe, and posterior lobe. Broadly, the cerebellum is thought to function in fine motor control (coordination and precision) and motor learning, balance, posture, as well as some cognitive and emotional capacity. The interaction of sensory, cognitive and motor functions may also contribute to proprioception (the awareness of self in space), planning movements, and evaluating information for action. The detailed functions of each region of the cerebellum are determined largely by their connectivity.

What is the evidence for cerebellum alterations?

Structural changes

Moderate quality evidence found grey matter reductions in the bilateral cerebellum of people with schizophrenia, particularly in medication-naïve patients, compared to controls. There were also white matter reductions in the bilateral cortico-ponto-cerebellum tract, and in the bilateral inferior and superior cerebellar penduculus. High quality evidence found no

Moderate to high quality evidence found better overall functioning was associated with larger cerebellum volume, and moderate to low quality evidence found reduced white matter volume in the cerebellum was associated with increased severity of neurological soft signs.

Functional changes

Moderate to high quality evidence found decreased functional activity in the right cerebellum (lobule VIII and crus I) and the left cerebellum (lobule IX), with no increases in functional activity. Functional connectivity strength was decreased in the left cerebellum (lobule IV/V) extending to the left fusiform gyrus (BA 30), and increased in the left cerebellum (crus I/II) of medication-naïve patients with first-episode schizophrenia compared to controls. Moderate to low quality evidence found increased activity in the cerebellum during auditory hallucinations in people with schizophrenia.

Moderate quality evidence found decreased functional activity in the left cerebellum of people with schizophrenia (vs. controls) during episodic memory retrieval. There was reduced activity in the right cerebellum lobule VI during explicit threat processing, and decreased activity in the fusiform gyrus extending into the cerebellum lobule IV/VI during implicit threat processing. There was decreased activity in the cerebellum during reward anticipation tasks. There was increased activity in the cerebellum during facial emotion recognition. Moderate to low quality evidence found decreased functional activity in the cerebellum of first- degree relatives of people with schizophrenia (compared to controls) during working memory and executive functioning, but not during cognitive control, long-term memory, or language processing.

Moderate quality evidence found decreased metabolic N-acetyl aspartate in the cerebellum of people with schizophrenia compared to controls.

Structural and functional changes

Moderate quality evidence found increased grey matter volume and decreased functional activity in the left cerebellum, and increased grey matter volume and increased functional activity in the left cerebellum lobule IX.

October 2020

The post Cerebellum appeared first on NeuRA Library.

The cingulate cortex is part of the medial frontal cortex, located immediately dorsal to the corpus callosum along the sagittal midline. The anterior cingulate cortex has three key divisions which may be functionally distinct (dorsal, rostral, subcallosal). The dorsal part of the anterior cingulate cortex has reciprocal connections with the prefrontal and parietal cortices as well as the frontal eye fields, and plays a primary role in balancing top-down and bottom-up processing of external stimuli; that is, monitoring behaviour and incoming stimuli in the context of current goals, and assigning control to other areas in the brain when required. By contrast, the ventral (rostral and subcallosal) parts of the anterior cingulate cortex are connected with amygdala, nucleus accumbens, hypothalamus, and insula, and are implicated in assessing the salience of sensory information, and regulating emotion and autonomic activity.

What is the evidence for cingulate cortex anomalies?

Structural changes

Moderate to high quality evidence found reductions in grey and white matter in bilateral regions of the cingulate cortex of people with schizophrenia. Specifically, there were grey matter reductions in the anterior and posterior cingulate gyrus of people with schizophrenia and reduced grey matter in the left anterior cingulate/paracingulate gyrus and right dorsal anterior cingulate of first-episode patients. High-risk individuals showed decreases in bilateral median cingulate and the right anterior cingulate gyrus compared to controls and increases in the left anterior cingulate compared to first-episode patients.

Functional changes

Moderate quality evidence found decreased activity in the posterior cingulate cortex of people with schizophrenia at rest compared to controls. There was under-activation in the anterior and middle cingulate cortex of people with schizophrenia during attention and inhibition tasks, and over-activation in the anterior cingulate cortex during working memory tasks. During executive functioning, there was increased activity in the left cingulate gyrus and decreased activity in right cingulate gyrus. During cognitive control, there was decreased activity in the bilateral anterior cingulate/paracingulate gyrus. During auditory stimulation, there was decreased activation in the anterior cingulate cortex, and during theory of mind tasks, there was decreased activity in the left cingulate gyrus. During reward anticipation tasks there was reduced activation in the right median cingulate/paracingulate gyri. In relatives of people with schizophrenia, there was decreased activity in the left cingulate gyrus during executive functioning and working memory tasks compared to controls.

Moderate quality evidence found decreased N-acetylaspartate and N-acetylaspartate/creatine ratio in the anterior cingulate gyrus of people with schizophrenia and their first-degree relatives. High quality evidence finds a small decrease in glutathione in the anterior cingulate of people with schizophrenia.

Structural and functional changes

Moderate to high quality evidence found decreased grey matter volume and decreased functional activity in the left medial posterior cingulate/paracingulate gyrus in drug-free, first-episode patients. Moderate quality evidence found decreased grey matter volume and decreased functional activation in the right medial frontal/anterior cingulate, and decreased grey matter volume and increased functional activation in the left medial frontal/anterior cingulate of people with first-episode schizophrenia, regardless of medication status.

Moderate quality evidence finds decreased activation in the bilateral anterior cingulate and left posterior cingulate of people with schizophrenia compared to people with an autism spectrum disorder during facial emotion recognition tasks. During theory of mind tasks, there was increased activation in the left posterior cingulate cortex in people with schizophrenia compared to people with an autism spectrum disorder. Moderate to low quality evidence found similar grey matter volume decreases in the right posterior cingulate cortex of people with schizophrenia and people with an autism spectrum disorder.

October 2020

The post Cingulate cortex appeared first on NeuRA Library.

The claustrum is a thin irregular sheet of grey matter located sagitally between the external capsule and the extreme capsule fibre tracts. The connectivity of the claustrum has not been extensively determined, however it appears to have connections with almost all cortical regions, as well as some subcortical connections such as the hippocampus, amygdala and basal ganglia. The function of the claustrum is also largely unclear, but may be involved in some functions of the neighbouring insula. The widespread connectivity of the claustrum places it in a prime position for multimodal integration and processing of perceptual, cognitive and motor capacities. Definitive understanding of the function of the claustrum is somewhat limited by the spatial resolution of current imaging technologies. Likewise, singular inactivation of the claustrum (whether pharmacologically or surgically) for inferring function is difficult, as the claustrum is at most only a few millimetres wide.

What is the evidence for claustrum alterations?

Moderate quality evidence found greater reduction in the right claustrum in people with treatment naïve, first-episode schizophrenia compared to people with treated first-episode schizophrenia or compared to people without schizophrenia. People with schizophrenia also showed reduced functional activity in the bilateral claustrum during executive function tasks compared to people without schizophrenia.

October 2020

The post Claustrum appeared first on NeuRA Library.

The corpus callosum is the bundle of inter-hemispheric white matter tracts that plays an essential role in the transfer and integration of sensory, motor and cognitive information between homologous regions in opposite hemispheres. It is the primary source of contralateral connections between the hemispheres and contains as many as 250 million axons.

What is the evidence for corpus callosum alterations?

Moderate to high quality evidence found volume and white matter reductions in the corpus callosum of people with schizophrenia compared to controls. There were reductions in frontal white matter via genu of the corpus callosum extending to the body of the corpus callosum, incorporating fibers joining the left anterior thalamic radiation, cingulum fibers, inferior fronto-occipital fasciculus, and uncinate fasciculus.

High quality evidence found both male and female patients showed decreases of white matter in the genu, but not in the splenium, of the corpus callosum when compared to controls. The effect was non-significantly higher in females than in males.

There were similar decreases in white matter integrity in people with schizophrenia and people with bipolar disorder in the genu of the corpus callosum extending to the anterior thalamic radiation/cingulum, and inferior fronto-occipital fasciculus.

October 2020

The post Corpus callosum appeared first on NeuRA Library.

The ‘default mode’ system refers to a network of regions including the precuneus, posterior cingulate cortex, medial prefrontal cortex, and medial, lateral and inferior parietal cortices, that appear to be active in the resting brain, and consistently show attenuations of activity following onset of a task-related activity. Default mode network (DMN) attenuation is not task specific; however the magnitude of reduction is dependent on the cognitive load and task requirements. The more demanding the task being performed, the stronger the deactivation. DMN activity is characterised by coherent low frequency (less than 0.1 Hz) neural oscillations. The functional connectivity of DMN regions is determined through the temporal correlation of blood oxygen level dependent activity in discrete anatomical regions. A ‘task-positive’ network of regions including the dorsolateral prefrontal cortex, inferior parietal cortex and supplementary motor area has been identified that is strongly anti-correlated with DMN activity. The DMN is thought to facilitate adaptive functioning, working memory, and processing emotionally salient stimuli.

What is the evidence for default mode network alterations?

Moderate to low quality evidence is unclear of alterations in functional activity in schizophrenia in default mode networks when the brain is at rest or during stimulus or task performance.

October 2020

The post Default mode network appeared first on NeuRA Library.

The frontal lobe comprises the anterior portion of the brain and is anatomically defined by four key gyri – the superior, middle, inferior and medial frontal gyri. The prefrontal cortex forms the rostral pole of the frontal lobe and is one of the most highly developed brain regions. The frontal lobe and its regions have widespread connections throughout the brain, particularly the prefrontal cortex. Proposed functions of the prefrontal cortex are involved mainly with executive functions and higher level cognition, such as working memory, problem solving and planning. The prefrontal cortex has also been implicated as a storage site for declarative memory such as semantic and episodic knowledge. This region has reciprocal connectivity with the amygdala, and is in a position to use experience and learning to influence behavioural responses and evaluate situations. The most posterior section of the frontal lobe is the pre-central gyrus, the primary motor cortex, also surrounded by associative and supplementary motor regions.

What is the evidence for frontal lobe alterations?

Structural changes

High quality evidence found schizophrenia is associated with significant reductions in grey and white matter volume of the frontal lobe, with greater reductions over time in people with schizophrenia than in controls. Specifically, moderate to high quality evidence found reduced grey matter in the prefrontal cortex, left orbito-frontal gyrus, left superior frontal gyrus, and bilateral medial, middle and inferior frontal gyri in chronic patients. There was also an absence of normal leftward asymmetry in the Sylvian fissure, and a higher frequency of abnormal (reversed) asymmetry in the frontal lobe of patients.

People with first-episode schizophrenia showed reduced grey matter in inferior, middle and medial frontal and precentral gyri. There was decreased right superior frontal grey matter in medication-naïve first-episode patients and increased right superior frontal grey matter in treated first-episode patients. A high risk of schizophrenia was particularly associated with reduced grey matter in superior and inferior frontal gyri.

Functional changes

Moderate quality evidence found increased activation during auditory hallucinations in the inferior and superior frontal gyri, and decreased activation during auditory tasks in the superior frontal gyrus of people with schizophrenia. Compared to controls without schizophrenia, there was decreased activation during cognitive control tasks in the right middle/inferior frontal gyrus and bilateral middle frontal gyrus. During timing tasks, there was increased activation in the right inferior frontal gyrus. During executive functioning tasks, there was decreased activation in the middle and medial frontal gyri, and decreased activation in the superior and inferior frontal gyri. During episodic memory encoding, there was reduced activity in the right superior frontal gyrus and bilateral inferior frontal gyri, and increased activity in the left precentral gyrus. During episodic memory retrieval, there was reduced activity in the left inferior frontal gyrus and left middle frontal gyrus, but increased activity in the left precentral gyrus and right middle frontal gyrus. During emotion processing tasks, there was reduced activity in the superior frontal gyrus. There was decreased activity in the inferior frontal gyrus and increased activity in the medial to superior prefrontal gyrus during explicit threat processing of facial stimuli. There was decreased activity in the medial prefrontal cortex and left orbito-frontal cortex during theory of mind tasks. Following cognitive remediation, patients showed increased activity in the left middle frontal gyrus, left inferior frontal gyrus, left superior frontal gyrus, and medial frontal gyrus. There was decreased activation in the left middle frontal gyrus during reward anticipation tasks and decreased activation in the right inferior frontal gyrus during empathy tasks.

In first-degree relatives of people with schizophrenia, there was decreased resting-state brain activity in the right inferior frontal gyrus compared to controls. The right inferior frontal gyrus showed increased activation during cognitive tasks and decreased activation during emotion tasks in relatives. There was also increased activation in the right superior frontal gyrus and decreased activation in the left medial frontal gyrus during emotion tasks. There was decreased activity in the right middle frontal gyrus and right inferior frontal gyrus, and increased activity in the right frontopolar region during working memory tasks in relatives.

Moderate quality evidence found decreased phosphomonoester (PME) levels in the prefrontal cortex of people with first-episode psychosis and people with schizophrenia when compared to controls. There were increased phosphodiester (PDE) levels in the prefrontal cortex of first-episode patients. Moderate to low quality evidence found decreased PME and increased PDE levels in the frontal lobe of first-degree relatives of people with schizophrenia.

Moderate quality evidence found N-acetylaspartate (NAA) and creatine (Cr) levels were reduced in frontal grey and white matter, particularly the prefrontal cortex and frontal pole, in both first episode and chronic schizophrenia. NAA/Cr ratio was reduced in the prefrontal cortex of people at clinical or familial risk of schizophrenia.

Moderate to high quality evidence found reduced glutamate (Glu) and increased glutamine (Gln) levels in the frontal cortex of people with schizophrenia. There was a medium-sized increase in Glu+Gln in the medial prefrontal cortex of unmedicated people with schizophrenia, and increased Glu/Gln ratio and glutamate+glutamine levels in the frontal lobe of first-degree relatives of people with schizophrenia.

High quality evidence found a small decrease in myo-inositol levels in the medial prefrontal region in people with schizophrenia, while moderate quality evidence found reduced translocator protein.

October 2020

The post Frontal lobe appeared first on NeuRA Library.

The hippocampus is located deep within the medial temporal lobe and has extensive connections, largely to cortical association areas including the sensory modalities. This widespread connectivity facilitates multimodal integration of sensory information, and likely contributes to the role of the hippocampus in generating memory and facilitating spatial navigation. The medial temporal lobes, particularly the hippocampus and the surrounding cortical regions, have been implicated as crucial facilitators in the formation of new declarative memories.

What is the evidence for changes in the hippocampus?

Structural changes

Moderate or high quality evidence found hippocampal and parahippocampal grey and white matter reductions in people with schizophrenia and in people at risk of schizophrenia compared to controls. People at high clinical risk (with subclinical symptoms) showed decreases in the left hippocampus and the right parahippocampus. People at high genetic risk (relatives) showed increases in the right hippocampus and decreases in bilateral parahippocampus. There were decreases in the left parahippocampus in people at high genetic risk compared to people at high clinical risk.

Compared to people with bipolar disorder, there were small reductions in hippocampal subregions in the left cornu ammonis (CA)1, left CA2/3, left CA4/dentate gyrus, right presubiculum, and right subiculum of people with schizophrenia. There were overlapping grey matter volume decreases (when compared to controls) in the right parahippocampus of people with schizophrenia and people with autism.

Functional changes

Moderate quality evidence found decreased activation in the left hippocampus of people with schizophrenia compared to controls at rest. There was increased activity in the hippocampus during auditory hallucinations, and decreased activation in the retrosplenial/hippocampus during external auditory stimulation. There was decreased activation in the hippocampus during memory encoding and retrieval tasks, increased activation in the left parahippocampal gyrus during episodic memory encoding, and increased activation in the right parahippocampal gyrus during episodic memory retrieval compared to controls. There was increased activation in the left hippocampus and decreased activation in the parahippocampus during emotion processing tasks. During implicit, but not explicit threat processing, there was decreased activity in bilateral amygdala extending into the putamen, hippocampus and parahippocampal gyrus. There was increased activity in the parahippocampus and hippocampus during emotionally neutral tasks. There was increased activation in the left parahippocampal gyrus during emotion tasks of first-degree relatives compared to controls. There was increased activation in the left parahippocampus during facial emotion recognition tasks in people with schizophrenia compared to people with autism.

For neurometabolites, there was reduced hippocampal N-acetyl aspartate/creatine (NAA/Cr) and choline/creatine (Cho/Cr) ratios in people with schizophrenia. NAA/Cr was also reduced in first-degree relatives. There was reduced translocator protein in the hippocampus of people with schizophrenia.

October 2020

The post Hippocampus appeared first on NeuRA Library.