Brodmann Area 21: A Brief Review of the Literature

Brodmann Area 21, Derived from Gray’s Anatomy 20th Edition 1918 Lithograph Reproduction, Public Domain

A brief review of the literature on Brodmann Area 21 (BA21) was conducted on Medline using the search term “Brodmann Area 21”. Relevant papers were identified from the returned abstracts. The search returned 123 results. Brodmann Area 21 (BA21) is part of the Temporal Cortex and is known also as the Middle Temporal Area 21 although in at least one study it is described as part of the Insular Cortex. Broadly speaking the research can be divided into studies investigating physiological parameters and those investigating characteristics of BA21 in pathological conditions.

In one fMRI study, children who were homozygous for the T allele in rs4675890 near the CREB1 gene (there is evidence of an association between CREB1 and mood disorders) showed a different pattern of neural activity to children who were homozygous for the C allele. In the former group there was significantly greater BOLD activity in BA21 amongst other differences. Amongst other areas there was found to be a decrease in alpha-2, beta-1 and gamma activities in BA21 15 minutes after exercise in this electrotomography study involving 22 runners. Differential patterns of 3[H] Nicotine-binding were found in BA21 in this Autoradiographic study. In a post-mortem grey matter analysis of 3 areas including BA21 in 51 brains there was found to be a reduction in 5-HT1A and 5-HT2A receptors in these areas compared to a control group amongst other findings. The researchers in this study compared the cytoarchitecture of the Hippocampus and Temporal Lobe and found a number of differences. In an fMRI study, sleep deprived subjects showed compensatory responses in BA21 amongst several other areas (paper freely available here).

BA21 was one of the areas associated with vestibular symptoms evoked during intraoperative electrical cortical stimulation. Presentation of pure auditory tones was associated with increased activity in BA21 amongst other areas in this fMRI study. Complex auditory stimuli activated BA21 in contrast with simple auditory stimuli in one PET study. In an fMRI study of 15 children (mean age 6.8) there was significant activation in the Left BA21 amongst other areas during an auditory comprehension task. The researchers interpreted this and other findings as suggesting that language was already lateralised by this age. In an fMRI study word lists were presented visually. BA21 was one of the regions activated preferentially when attention was focused on semantic relations. In a PET and event-related potential (ERP) study, semantic retrieval was associated with increased blood flow in the left BA21. In an fMRI study looking at semantic processing in 9-15 year old children (paper freely available here), the researchers found that activation of BA21 amongst other areas was associated with tasks in which word pairs were assessed as similar in meaning. In this PET study investigating music and language, BA21 was one of several areas in which activity was associated with the generation of sentences. In a 3T fMRI study (paper freely available here) researchers found that linguistic inference was associated with increased activation of BA21 amongst other areas compared with logic inference. In one fMRI study, people were asked to generate words silently and there was found to be an increase in activity in the left BA21 amongst other areas. Increased activity in the left BA21 was found with performance of reasoning tasks in one PET study. Bilateral activation of BA21 was associtated with processing of word-form in one fMRI study. In a small PET study (n=9), BA21 was one of several areas activated during a ‘Theory of Mind’ task.

In an fMRI study looking at 29 people with Alzheimer’s Disease, awareness of functional difficulties in Alzheimer’s Disease was examined using the ‘Awareness of Deficit Questionnaire-Dementia Scale’. People who were classed as being unaware exhibited reduced activity in BA21 amongst other areas. In this particular study the researchers concluded that awareness of difficulties involved the recruitment of cingulate, frontal, parietal and temporal cortices. The laminar binding distribution of 3 nicotinic acid receptors was characterised in one post-mortem study looking at BA21 in people who had been diagnosed with Alzheimer’s Disease as well as in controls. Synaptophysin mRNA was reduced in BA21 in people who had been diagnosed with Alzheimer’s Disease and Non-Alzheimer’s Disease Dementia compared to a control group in one study. Binding to Benzodiazepine and  NMDA receptors was reduced in most lamina in BA21 in people who had been diagnosed with Alzheimer’s Disease compared to a control group in this post-mortem study. Creatinine Kinase – BB levels were similar in BA21 in the brains of people who had been diagnosed with Alzheimer’s Disease compared to controls in this autopsy study. In people who had been diagnosed with Alzheimer’s Disease, ChAT activity and plaque levels were correlated in BA21 in this study. BA21 was one of several areas involving cortical atrophy in a small (n=6) case series of semantic dementia. Somatostatin receptors were reduced to 50% of control values in BA21 in people who had been diagnosed with Alzheimer’s Disease in this postmortem study. Neuropeptide Y-like immunoreactivity and Somatostatin-like immunoreactivity were increased in BA21 in people who had been diagnosed with Huntington’s Disease in this study.  Somatostatin-like immunoreactivity was decreased in BA21 in people who had been diagnosed with Parkinson’s Disease compared to a control group in this postmortem study whilst it was found to be reduced in people who had been diagnosed with Alzheimer’s Disease compared to a control group in this study.

The C-allele of a GSK3-beta promoter single-nucleotide polymorphism (rs334558) was associated with increased grey matter volume in BA21 in people with schizophrenia in this study. Activity in the posterior part of the right BA21 was associated with the number of complex sentences in a control group compared with people with schizophrenia in this fMRI study (paper freely available here). Compared to a control group, people with Schizophrenia were found to have altered cortical electrical activity in the left BA21 amongst other areas in this 123-channel EEG and current density reconstruction study. In a post-mortem study [3H]SCH23390 bindings were used to examine Dopamine-1 like receptors in people who had been diagnosed with Schizophrenia. The researchers found an increase in the receptors in BA21. People with depression exhibited reduced activity in the right BA21 compared to controls whilst performing the Tower of London task in this 99mTc-ethyl cysteinate dimer SPECT study. In an fMRI study of girls (age range 8-10) bilateral activity in several regions including BA21 was associated with sad feelings experienced when watching sad films.

In a replication of an important neuroimaging study of stuttering, researchers used Positron Emission Tomography to investigate stuttering. They found an inverse correlation between cerebral blood flow in BA21 and stuttering and in conjunction with their other findings they concluded that stuttering resulted from an alteration in the communication between the auditory and speech-motor areas. In a PET study involving right-handed stutterers and 10 right-handed controls, researchers identified negative regional Cerebral Blood Flow correlates of stuttering in the Right BA21 in female stutterers (more broadly speaking the researchers found bilateral associations with stuttering in female speakers and right sided associations in male stutterers).  In an fMRI study, people with a diagnosis of Borderline Personality Disorder read a dissociation-inducing script as well as a neutral script. The former script was associated with reduced activity in the right BA21 amongst other differences. In an fMRI study of people with temporal lobe epilepsy and a control group, an auditory language task activated contralateral Right BA21. BA21 grey matter volume reductions were found in people with panic disorder compared to a control group in this structural MRI study. In a SPECT study people with Wilson’s disease were found to have diffuse/focal hypoperfusion in BA21 amongst other areas. Researchers found reduced perfusion in BA21 amongst other areas in people with REM sleep behaviour disorder compared to a control group in this (99m)Tc-Ethylene Cysteinate Dimer (ECD) SPECT study. In people with refractory angina, stimulation of the spinal cord was associated with decreased regional Cerebral Blood Flow was noticed in BA21 amongst other areas in this PET study.

Appendix – Articles Reviewed in relation to Brodmann Areas or other Structures

Brodmann Area 1 – Somatosensory Cortex: An Investigation of D3 Receptors and Brodmann Area 1 in Schizophrenia, YouTubing the Somatosensory Cortex Brodmann Area 4 – The Primary Motor Cortex: Brodmann Areas– Part 2: Area 4. The Primary Motor Cortex – A Brief Literature Review, YouTubing the Motor Cortex Brodmann Area 6 (Agranular Frontal Area 6): FDG-PET, Frontal Dysfunction and Mild Cognitive Impairment, Brodmann Area 6 – Premotor Cortex and the Supplementary Motor Area , YouTubing Brodmann Area 6 Brodmann Areas 5 and 7 (Somatosensory Association Cortex): Brodmann Areas 5 and 7 (Somatosensory Association Cortex) Brodmann Area 8: Brodmann Area 8 Youtubing Brodmann Area 8 Brodmann Area 9: Brodmann Area 9 YouTubing Brodmann Area 9 Brodmann Area 10: Brodmann Area 10 YouTubing Brodmann Area 10 Brodmann Area 11: Brodmann Area 11. A Brief Review of the Literature. Brodmann Area 12 YouTubing Brodmann Area 12  Brodmann Area 12: A Brief Overview of the Literature Brodmann Areas 13, 14 and 52 (Insular Cortex) YouTubing the Insular Cortex  What does the Insular Cortex Do Again? Insular Cortex Infarction in Acute Middle Cerebral Artery Territory Stroke The Insular Cortex and Neuropsychiatric Disorders Developing a Model of the Insular Cortex and Emotional Regulation Part 1 Developing a Model of the Insular Cortex: A Recap  The Relationship of Blood Pressure to Subcortical Lesions  Pathobiology of Visceral Pain  Interoception and the Insular Cortex  A Case of Neurogenic T-Wave Inversion   Video Presentations on a Model of the Insular Cortex  MR Visualisations of the Insula  The Subjective Experience of Pain*  How Do You Feel? Interoception: The Sense of the Physiological Condition of the Body  How Do You Feel – Now? The Anterior Insula and Human Awareness   Role of the Insular Cortex in the Modulation of Pain  The Insular Cortex and Frontotemporal Dementia   A Case of Infarct Connecting the Insular Cortex and the Heart  The Insular Cortex: Part of the Brain that Connects Smell and Taste?   Stuttered Swallowing and the Insular Cortex  Brodmann Area 15 (Anterior Temporal Lobe – Controversial Area in Humans): Review: The Anterior Temporal Lobes and Semantic Memory   Brodmann Area 17  Turning a Person’s Visual Experiences into a Movie  Brodmann Area 20 Brodmann Area 20: A Brief Review of the LiteratureBrodmann Area 25 – Anterior Cingulate Cortex: Brodman Areas Part 3. Brodmann Area 25 – The Anterior Cingulate Cortex  Brodmann Area 27 (Piriform Cortex): Anosmia in Lewy Body Dementia   Brodmann Area 28  (Entorhinal Cortex): MRI Measures of Temporoparietal Atrophy During Prodromal Alzheimer Disease*   Brodmann Areas 45, 46, 47 (Inferior Frontal Gyrus): Which Bit of the Brain Detects the Emotions in Speech? Medial Temporal Lobe: The Medial Temporal Lobe and Recognition Memory  Hippocampus: Review: Differences in Hippocampal Metabolism Between Amnestic and Non-Amnestic MCI Subjects Anatomy of the Hippocampus Review: Involvement of BDNF in Age-Dependent Alterations in the Hippocampus Miscellaneous Subcortical Structures: Book Review: Subcortical Vascular Dementia Review: Subcortical Vascular Ischaemic Dementia Review: Psychiatric Disturbances in CADASIL  Review: Cognitive Decline in CADASIL  Review: Relationship Between 24-hour Blood Pressure, Subcortical Ischemic Lesions and Cognitive Impairment    Hypocretin and Neurological Disorders    A Case of Pontine and Extrapontine Myelinolysis with Catatonia   Generic Articles Relating to Localisation: A History of Human Brain Mapping  Book Review: Brain Architecture  Brain Folding and the Size of the Human Cerebral Cortex

An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail Disclaimer: The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.


  1. Youre not the regular blog author, man. You definitely have something important to contribute to the World Wide Web. Such a wonderful blog. I will revisit again for more.


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