Brodmann area 32
The Brodmann area 32 known in the human brain as the dorsal anterior cingulate area 32, refers to a subdivision of the cytoarchitecturally defined cingulate cortex. In the human it forms an outer arc around the anterior cingulate gyrus; the cingulate sulcus defines its inner boundary and the superior rostral sulcus its ventral boundary. Cytoarchitecturally it is bounded internally by the ventral anterior cingulate area 24, externally by medial margins of the agranular frontal area 6, intermediate frontal area 8, granular frontal area 9, frontopolar area 10, prefrontal area 11-1909.. The dorsal region of the anterior cingulate gyrus is associated with rational thought processes, most notably active during the Stroop task. In the guenon, Brodmann area 32 is a subdivision of the cytoarchitecturally defined cingulate region of cerebral cortex; this area was named 25 in Brodmann-1905 and labeled 25 in a figure contributed by Brodmann in Mauss-1908. In Brodmann-1909, the area was labeled 32 and the name "area 25" was attached to the area that has since been the accepted area 25 of Brodmann-1909.
Distinguishing features according to Brodmann-1905: in contrast with area 6 of Brodmann-1909 the cortex of area 32 is thick. Brodmann-1909 regarded area 32 as topologically, but not cytoarchitecturally, homologous to the human dorsal anterior cingulate area 32. Brodmann area See BrainInfo for Brodmann area 32 3D representation
Brodmann area 8
Brodmann area 8 is one of Brodmann's cytologically defined regions of the brain. It is involved in planning complex movements. Brodmann area 8, or BA8, is part of the frontal cortex in the human brain. Situated just anterior to the premotor cortex, it includes the frontal eye fields. Damage to this area, by stroke, trauma or infection, causes tonic deviation of the eyes towards the side of the injury; this finding occurs during the first few hours of an acute event such as cerebrovascular infarct or hemorrhage. The term Brodmann area 8 refers to a cytoarchitecturally defined portion of the frontal lobe of the guenon. Located rostral to the arcuate sulcus, it was not considered by Brodmann-1909 to be topographically homologous to the intermediate frontal area 8 of the human. Distinctive features: compared to Brodmann area 6-1909, area 8 has a diffuse but present internal granular layer; the area is involved in the management of uncertainty. A functional magnetic resonance imaging study demonstrated that brodmann area 8 activation occurs when test subjects experience uncertainty, that with increasing uncertainty there is increasing activation.
An alternative interpretation is that this activation in frontal cortex encodes hope, a higher-order expectation positively correlated with uncertainty. Brodmann area List of regions in the human brain
Brodmann area 5
Brodmann area 5 is one of Brodmann's cytoarchitectural defined regions of the brain. It is involved in somatosensory association. Brodmann area 5 is a subdivision of part of the cortex in the human brain. BA5 is the superior parietal part of the postcentral gyrus, it is situated posterior to the primary somatosensory cortex. It is bounded cytoarchitecturally by Brodmann area 2, Brodmann area 7, Brodmann area 4, Brodmann area 31. In guenon Brodmann area 5 is a subdivision of the parietal lobe defined on the basis of cytoarchitecture, it occupies the superior parietal lobule. Brodmann-1909 considered it topologically and cytoarchitecturally homologous to the preparietal area 5 of the human. Distinctive features: compared to area 4 of Brodmann-1909 area 5 has a thick self-contained internal granular layer. In the macaque monkey the area PE corresponds to BA5. Brodmann area List of regions in the human brain Visit BrainInfo for Neuroanatomy of this area Brodmann area 5 in the Brede Database at the Technical University of Denmark
Brodmann area 6
Brodmann area 6 part of the frontal cortex in the human brain. Situated just anterior to the primary motor cortex, it is composed of the premotor cortex and, the supplementary motor area, or SMA; this large area of the frontal cortex is believed to play a role in the planning of complex, coordinated movements. Brodmann area 6 is called agranular frontal area 6 in humans because it lacks an internal granular cortical layer, it is a subdivision of the cytoarchitecturally defined precentral region of cerebral cortex. In the human brain, it is located on the portions of the precentral gyrus that are not occupied by Brodmann area 4, it extends from the cingulate sulcus on the medial aspect of the hemisphere to the lateral sulcus on the lateral aspect. It is bounded rostrally by the granular frontal region and caudally by the gigantopyramidal area 4. Brodmann area 6 is a cytoarchitecturally defined portion of the frontal lobe of the guenon. Brodmann-1909 regarded it as topographically and cytoarchitecturally homologous to the human agranular frontal area 6 and noted that, in the monkey, area 4 is larger than area 6, whereas, in the human, area 6 is larger than area 4.
Distinctive features: It is thick relative to other cortical areas. Brodmann area List of regions in the human brain Korbinian Brodmann ancil-41 at NeuroNames – agranular frontal area 6 ancil-1044 at NeuroNames – Brodmann area 6
Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin-norepinephrine reuptake inhibitor class. It is used to treat major depressive disorder, generalized anxiety disorder, panic disorder, social phobia, it is taken by mouth. Common side effects include loss of appetite, dry mouth, dizziness and sexual problems. Severe side effects include an increased risk of suicide and serotonin syndrome. Antidepressant withdrawal syndrome may occur. There are concerns that use during the part of pregnancy can harm the baby. How it works is not clear but it is believed to involve alterations in neurotransmitters in the brain. Venlafaxine was approved for medical use in the United States in 1993, it is available as a generic medication. In the United States the wholesale cost per dose is less than US$0.20 as of 2018. In 2016 it was the 51st most prescribed medication in the United States with more than 15 million prescriptions. Venlafaxine is used for the treatment of depression, general anxiety disorder, social phobia, panic disorder, vasomotor symptoms.
Some doctors may prescribe venlafaxine off label for the treatment of diabetic neuropathy and migraine prophylaxis. Studies have shown venlafaxine's effectiveness for these conditions, although agents that are marketed for this purpose are preferred, it has been found to reduce the severity of'hot flashes' in menopausal women and men on hormonal therapy for the treatment of prostate cancer. Due to its action on both the serotoninergic and adrenergic systems, venlafaxine is used as a treatment to reduce episodes of cataplexy, a form of muscle weakness, in patients with the sleep disorder narcolepsy; some open-label and three double-blind studies have suggested the efficacy of venlafaxine in the treatment of attention deficit-hyperactivity disorder. Clinical trials have found possible efficacy in those with post-traumatic stress disorder. A comparative meta-analysis of 21 major antidepressants found that venlafaxine, amitriptyline, mirtazapine and vortioxetine were more effective than other antidepressants although the quality of many comparisons was assessed as low or low.
Venlafaxine was similar in efficacy to the atypical antidepressant bupropion. In a double-blind study, patients who did not respond to an SSRI were switched to venlafaxine or citalopram. Similar improvement was observed in both groups. Studies of venlafaxine in children have not established its efficacy. Venlafaxine is not recommended in patients hypersensitive to it, nor should it be taken by anyone, allergic to the inactive ingredients, which include gelatin, ethylcellulose, iron oxide, titanium dioxide and hypromellose, it should not be used in conjunction with a monoamine oxidase inhibitor, as it can cause fatal serotonin syndrome. Venlafaxine can increase eye pressure, so those with glaucoma may require more frequent eye checks; the US Food and Drug Administration body requires all antidepressants, including venlafaxine, to carry a black box warning with a generic warning about a possible suicide risk. A 2014 meta analysis of 21 clinical trials of venlafaxine for the treatment of depression in adults found that compared to placebo, venlafaxine reduced the risk of suicidal thoughts and behavior.
A study conducted in Finland followed more than 15,000 patients for 3.4 years. Venlafaxine increased suicide risk by 60%, as compared to no treatment. At the same time, fluoxetine halved the suicide risk. In another study, the data on more than 200,000 cases were obtained from the UK general practice research database. At baseline, patients prescribed venlafaxine had a greater number of risk factors for suicide than patients treated with other anti-depressants; the patients taking venlafaxine had higher risk of completed suicide than the ones on fluoxetine or citalopram. After adjusting for known risk factors, venlafaxine was associated with an increased risk of suicide relative to fluoxetine and dothiepin, not statistically significant. A statistically significant greater risk for attempted suicide remained after adjustment, but the authors concluded that it could be due to residual confounding. An analysis of clinical trials by the FDA statisticians showed the incidence of suicidal behaviour among the adults on venlafaxine to be not different from fluoxetine or placebo.
Venlafaxine is contraindicated in children and young adults. According to the FDA analysis of clinical trials venlafaxine caused a statistically significant 5-fold increase in suicidal ideation and behaviour in persons younger than 25. In another analysis, venlafaxine was no better than placebo among children, but improved depression in adolescents. However, in both groups and suicidal behaviour increased in comparison to those receiving a placebo. In a study involving antidepressants that had failed to produce results in depressed teenagers, teens whose SSRI treatment had failed who were randomly switched to either another SSRI or to venlafaxine showed an increased rate of suicide on venlafaxine. Among teenagers who were suicidal at the beginning of the study, the rate of suicidal attempts and self-harm was higher, by about 60%, after the switch to venlafaxine than after the switch to an SSRI. People stopping venlafaxine experience discontinuation symptoms such as dysphoria, hea
Brodmann area 46
Brodmann area 46, or BA46, is part of the frontal cortex in the human brain. It is between BA10 and BA45. BA46 is known as middle frontal area 46. In the human brain it occupies the middle third of the middle frontal gyrus and the most rostral portion of the inferior frontal gyrus. Brodmann area 46 corresponds with the dorsolateral prefrontal cortex, although the borders of area 46 are based on cytoarchitecture rather than function; the DLPFC encompasses part of granular frontal area 9, directly adjacent on the dorsal surface of the cortex. Cytoarchitecturally, BA46 is bounded dorsally by the granular frontal area 9, rostroventrally by the frontopolar area 10 and caudally by the triangular area 45. There is some discrepancy between the same area as described by Walker; the dorsolateral prefrontal cortex plays a central role in sustaining attention and managing working memory, has been shown to regulate self-control. It is one of the few cortical areas; the high connectivity of this area within the frontal lobe as well as other parts of the brain means that damage can have a wide variety of effects.
Lesions impair short-term memory, cause difficulty inhibiting responses, impair the ability to judge the relevance of stimuli, cause problems in organization. Recent research has shed light on the mechanism of working memory and the role of the dorsolateral prefrontal cortex. Studies using transcranial direct current stimulation observe changes in cortical activity due to either depolarization or hyperpolarization of underlying areas; the effect of these voltage shifts on activity in other structures is measured. The goal of the studies is to identify the role of the dorsolateral prefrontal cortex in memory circuit modulation and learning. In a limited research study, participants tested their baseline working memory with digit span exercises underwent tDCS for ten minutes before being retested with the exercises. Contrary to expectations, tDCS showed only minimal effects on working memory. Due to the lack of coherent resources and data of the experiment, more WM experiments using tDCS need to be evaluated.
Some applications being discussed involve using tDCS adjunctively with cognitive remediation to enhance WM in neurologic and psychiatric conditions. A recent study found that targeting Transcranial magnetic stimulation to Brodmann area 46 has better clinical efficacy treating depression, as its functionally is connected to Brodmann area 25. Brodmann area List of regions in the human brain Petrides, M.. M.. "Dorsolateral prefrontal cortex: comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns". European Journal of Neuroscience. 11: 1011–1036. Doi:10.1046/j.1460-9568.1999.00518.x. Andrews S, Hoy K, Enticott P, Daskalakis Z, Fitzgerald P. Improving working memory: The effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex. Brain Stimulation. April 2011. Available from: PsycINFO, Ipswich, MA. Accessed February 19, 2013. Http://search.ebscohost.com.leo.lib.unomaha.edu/login.aspx?direct=true&db=psyh&AN=2010-16899-001&site=ehost-live For Neuroanatomy of the area visit BrainInfo
Biology of depression
Scientific studies have found that numerous brain areas show altered activity in people with major depressive disorder, this has encouraged advocates of various theories that seek to identify a biochemical origin of the disease, as opposed to theories that emphasize psychological or situational causes. Factors spanning these causative groups include nutritional deficiencies in magnesium, vitamin D, tryptophan with situational origin but biological impact. Several theories concerning the biologically based cause of depression have been suggested over the years, including theories revolving around monoamine neurotransmitters, neurogenesis and the circadian rhythm. Physical illnesses, including hypothyroidism and mitochondrial disease, can trigger depressive symptoms. Neural circuits implicated in depression include those involved in the generation and regulation of emotion, as well as in reward. Abnormalities are found in the lateral prefrontal cortex whose putative function is considered to involve regulation of emotion.
Regions involved in the generation of emotion and reward such as the amygdala, anterior cingulate cortex, orbitofrontal cortex, striatum are implicated as well. These regions are innervated by a monoaminergic nuclei, tentative evidence suggests a potential role for abnormal monoaminergic activity. Genetic factors involved in depression have been difficult to identify. Candidate gene studies have been a major focus of study. However, as the number of genes reduces the likelihood of choosing a correct candidate gene, Type I errors are likely. Candidate genes studies possess a number of flaws, including frequent genotyping errors and being statistically underpowered; these effects are compounded by the usual assessment of genes without regard for gene-gene interactions. These limitations are reflected in the fact that no candidate gene has reached genome-wide significance. A 2003 study study proposed that a gene-environment interaction may explain why life stress is a predictor for depressive episodes in some individuals, but not in others, depending on an allelic variation of the serotonin-transporter-linked promoter region.
As of 2018, five meta analyses of the 5-HTTLPR GxE interaction have been performed. Two 2009 meta analyses reported null findings, while a 2011 meta analysis with more liberal inclusion criteria reported a significant relationship. A 2016 meta analysis concluded. A 2018 meta analysis reported a weak but significant relationship, limited by significant heterogeniety. BDNF polymorphisms have been hypothesized to have a genetic influence, but replication results have been mixed and, as of 2005, were insufficient for a meta-analysis. Studies indicate an association of decreased BDNF production with suicidal behavior. However, findings from gene-environment interactions studies suggest that the current BDNF models of depression are too simplistic. A 2008 study found interactions in the signaling pathways of the serotonin transporter. Thus, the BDNF-mediated signalling involved in neuroplastic responses to stress and antidepressants is influenced by other genetic and environmental modifiers; the largest genome meta analysis to date failed to identify variants with genome-wide significance, with a study size of 18,000 participants of European ancestry.
A 2015 GWAS study in Han Chinese women positively identified two variants in intronic regions near SIRT1 and LHPP with a genome-wide significant association. Attempts to find a correlation between norepinephrine transporter polymorphisms and depression have yielded negative results. One review identified multiple studied candidate genes; the genes encoding for the 5-HTT and 5-HT2A receptor were inconsistently associated with depression and treatment response. Mixed results were found for brain-derived neurotrophic factor Val66Met polymorphisms. Polymorphisms in the tryptophan hydroxylase gene was found to be tentatively associated with suicidal behavior. A meta analysis of 182 case controlled genetic studies published in 2008 found Apolipoprotein verepsilon 2 to be protective, GNB3 825T, MTHFR 677T, SLC6A4 44bp insertion or deletions, SLC6A3 40 bpVNTR 9/10 genotype to confer risk. Depression may be related to biological clock. For example, rapid eye movement sleep—the stage in which dreaming occurs—may be quick to arrive and intense in depressed people.
REM sleep depends on decreased serotonin levels in the brain stem, is impaired by compounds, such as antidepressants, that increase serotonergic tone in brain stem structures. Overall, the serotonergic system is most active during wakefulness. Prolonged wakefulness due to sleep deprivation activates serotonergic neurons, leading to processes similar to the therapeutic effect of antidepressants, such as the selective serotonin reuptake inhibitors. Depressed individuals can exhibit a significant lift in mood after a night of sleep deprivation. SSRIs may directly depend on the increase of central serotonergic neurotransmission for their therapeutic effect, the same system that impacts cycles of sleep and wakefulness. Research on the effects of light therapy on seasonal affective disorder suggests that light deprivation is related to decreased activity in the serotonergic system and to abnormalities in the slee